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Pharmacology Current Practice

5 Contact Hours including 5 Advanced Pharmacology Hours
This peer reviewed course is applicable for the following professions:
Advanced Registered Nurse Practitioner (ARNP), Certified Registered Nurse Anesthetist (CRNA), Clinical Nurse Specialist (CNS), Licensed Practical Nurse (LPN), Licensed Vocational Nurses (LVN), Nursing Student, Registered Nurse (RN)
This course will be updated or discontinued on or before Monday, August 15, 2022
Outcomes

≥92% of participants will enhance their knowledge of pharmacology with the end goal of improving patient outcomes and reducing errors in patients prescribed medications.

Objectives

After completing this continuing education course, the participants will be able to meet the following objectives:

  1. Relate the ten rules that serve as the standard for legal accountability in drug administration.
  2. Identify the types of patients who require special consideration when administering drugs.
  3. Discuss common principles of pharmacokinetics.
  4. Discuss the role of drugs and therapeutic devices in the prevention of disease and maintenance of health.
  5. Discuss the indications and adverse effects of major categories of drugs.
  6. List common agents included in each category of drugs.
  7. Identify nursing considerations for each category of drug.
  8. List common drug errors that are avoidable and strategies to avoid them.
  9. Relate drug-specific categories for the prevention of drug errors.
CEUFast Inc. did not endorse any product, or receive any commercial support or sponsorship for this course. The Planning Committee and Authors do not have any conflict of interest.

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To earn of certificate of completion you have one of two options:
  1. Take test and pass with a score of at least 80%
  2. Reflect on practice impact by completing self-reflection, self-assessment and course evaluation.
    (NOTE: Some approval agencies and organizations require you to take a test and self reflection is NOT an option.)
Author:    Raymond Lengel (MSN, FNP-BC, RN)

Nurses' Accountability

Nurses have a significant role in medication safety. However, a recent study showed that nurses make an error in 27.6 percent of drug administrations.1 It has been estimated by the Institute of Medicine that drug errors lead to 1 of 131 outpatient and 1 of 854 inpatient deaths.2

Research has found that drug administration guideline adherence was low.3 Their results showed that at least one of the ten drug rights were regularly violated. Most of these errors are preventable, and according to the Institute of Medicine Report, The Future of Nursing, nurses are pivotal in reducing drug errors.4

The Ten Rights

  1. Right Patient: Use two identifiers. The room number is not an identifier. Ask the patient to identify himself or herself, check the name on the order and the patient. If available, use technology such as barcoding. For patients not wearing ID bands or those that are not able to identify themselves, extra caution is necessary. A system should be in place to identify patients without name bands or who are incompetent.
  2. Right Drug: Every drug administered must have an order from the provider. Compare the order with the drug administration record (MAR) for accuracy. Compare the label on the drug to the information on the MAR three times: 1) before removing the container from the drawer, 2) as the drug is removed from the container, and 3) at the bedside before administering it to the patient. Do not prepare unmarked drug containers or illegible containers. Be sure to verify drugs at the patients’ bedside with the MAR and two identifiers.5
  3. Right Dose: Have a second nurse check any calculations that need to be done. Use standard measuring devices such as syringes, graduated cups, or scaled droppers. See if the pharmacists can split any required pills for safety.5 If drugs need to be crushed, be sure to clean the devices used before and after. Nurses should have access to information on therapeutic doses, therapeutic serum levels if applicable, and laboratory results when needed. If there is any doubt as to the dose on the MAR, or if there is a question on the drug, stop and verify all information before administering.
  4. Right Route: Drug errors involving the wrong route of drug administration are common. Be sure to verify if there is any question as to the drug route. The nurse must know the appropriate route for the drug. Giving drugs via the wrong route can cause serious harm to patients. If possible, when using a syringe or other device, label the appropriate route.
  5. Right Time: Nurses need to understand why drugs are given at certain times. Although some drugs require clinical judgments as to when to administer, such as an as-needed sleeping drug, other drugs are labeled as time-critical.6 Studies show that giving drugs at incorrect times results in 30-40% of all drug errors.7,8 Giving drugs at an incorrect time can impact the bioavailability and efficacy of the drug. Likewise, drugs should not be prepared or mixed in advance for the same reason.
  6. Right Documentation: Write down the drug after you give the dose. Note injection sites.
  7. Right Patient Education: Educate the patient on what to expect, side-effects, benefits, reactions, and when to seek medical help.
  8. Right to Refuse: Patients have a right to refuse any drug. Document refusal of the drug.
  9. Right Assessment: Assess the patient. Note the patient’s history and any perimeters around drug administration.
  10. Right Evaluation: Check for drug allergies and interactions.

Special Considerations

The elderly, children, and pregnant women have physiologic differences that need to be considered when administering drugs.

Due to physiological changes, particularly in hepatic metabolism and renal elimination, dosing in the elderly population can be challenging. The elderly may experience an increase in side effects or toxicity more easily. Awareness of side effects in the elderly is particularly important as most elderly patients are on more than one drug. Care should be taken when combining drugs.

Pediatric doses are very different from adult doses. Differences in dosing are not merely due to bodyweight but must include physiological differences.9 Rates of renal clearance can be different in each age group. The liver and kidneys impact the pharmacokinetics of a child’s dose versus an adult dose. Bodyweight, which most drugs are based on, does not indicate how organs are functioning. Therefore, developmental growth must also be considered when administering drugs to this population.9

Pregnant women present another population where careful consideration must be taken when administering drugs. The effect of the drug on the fetus may be detrimental. An understanding of how the fetus develops during pregnancy must be considered. The risks of not treating a disorder must be contemplated, as well.

Pharmacokinetic Principles and Clinical Application

Pharmacodynamics is what a drug does to the body, whereas pharmacokinetics is what the body does to the drug. Pharmacodynamics includes receptor binding, chemical interactions, and post-receptor effects. Pharmacokinetics includes the terms absorption, distribution, excretion, and metabolism. The pharmacokinetics determines the onset of the drug in addition to its duration and intensity of the effect. Clinical pharmacokinetics is when pharmacokinetic principles are applied to the appropriate and effective therapeutic management of drugs in patients.

A common acronym that is used to remember key principles in pharmacokinetics is ADME, which describes the four main aspects of pharmacokinetics.

  • A = Absorption
  • D = Distribution
  • M = Metabolism
  • E = Excretion

pharmacokinetics

Chart from the US Department of Health and Human Services

The above graph shows when a drug is taken to when it reaches a concentration maximum, also known as Cmax until it is eliminated from the body. The Cmax is the maximum concentration of the drug and will help predict the therapeutic benefit as well as the most likely time side effects are seen. The time that the maximum concentration is reached is called the Tmax. At this point, the drug concentration starts to go down (gets eliminated), and the amount of time that the drug goes down 50 percent is known as the half-life.

Absorption is how the drug enters the body. Except in intravenous administration, drugs are absorbed across a tissue membrane to enter the bloodstream. Absorption depends on how the drug is administered. Drugs that are given orally are typically swallowed and absorbed through the stomach or small intestine. Then they enter into the portal venous system, and pass through the liver, move through the cardiopulmonary system, and then the arterial system.

Parental administration involves giving a drug that avoids the gastrointestinal tract. Parental administration includes a transdermal application, injection, and inhalation. These drugs avoid first-pass metabolism, which includes potential alterations that may occur by stomach acid, food, liver enzyme, or gut wall interference. Bioavailability is the quantity of a dose that enters the systemic circulation. The bioavailability of the drug is significantly less when given by the oral route when compared to the intravenous route.

Drugs that are given through the intravenous route tend to reach a high Cmax in a shorter period when compared to orally taken drugs. The half-life is the same for the drug, no matter the route of administration.

Distribution is how the drug moves in the body. The drug moves between many compartments of the body, including the blood, fat, extracellular fluid, intracellular fluid, fat, cerebral spinal fluid, and other body compartments. The ability of the drug to move between compartments is dependent on multiple factors, including the pH in the different compartments, the permeability between compartments, and the binding capacity in the compartments.

The volume of distribution (Vd) is another concept that is commonly discussed under distribution but is beyond a basic pharmacology introduction. In general, the volume of distribution describes how extensively the drug is dispersed to the rest of the body when compared to the plasma. To determine the Vd, the amount of the drug in the body is divided by the plasma concentration.

Metabolism is how the drug is chemically changed to be excreted. Drugs need to be made water-soluble enough to be excreted in the stool or urine. Metabolism occurs mainly in the liver, kidney, gut wall, and skin.

In the liver, drugs are metabolized by cytochrome P450 enzymes. Many different cytochrome P450 enzymes metabolize drugs. It is estimated that there are 50 cytochrome P450 enzymes, but ten are responsible for metabolizing 90% of the drugs.10

The metabolism of drugs occurs in either phase I or phase II. Phase I metabolism involves chemically altering the drug to allow it to go through phase II metabolism or to be excreted. There are multiple methods that phase I metabolism may occur, including oxidation, reduction, or hydrolysis. Oxidation is the most common reaction. It mainly involves the cytochrome P450 family of membrane-bound enzymes in the liver. Most products of the drugs that go through phase I metabolism become pharmacologically inactive, but some drug metabolites retain some of the original drug activity.

Phase II metabolism converts a parent drug to a more water-soluble metabolite, which is inactive. These drugs are then renally excreted.

Genetic and environmental factors affect the rate of drug metabolism. These factors account for varying drug plasma concentrations when a standard dose is given.

Excretion is how the drug leaves the body. A water-soluble drug will be excreted in the urine. Lipid-soluble drugs must be changed to water-soluble metabolites before excretion, which will occur in the stool or kidney.

Urinary excretion typically occurs for water-soluble drugs that have a low-molecular-weight. The urinary system also excretes drugs that are made water-soluble by liver metabolism.

In patients with chronic kidney disease, it is essential to note that these patients may not excrete drugs as efficiently through the urinary system. In these cases, a lower dose of the drug needs to be administered.

Larger molecular weight drugs prefer to leave the body through fecal excretion. These drugs include those that are not absorbed and those that are metabolized in the liver. If the drug is still significantly lipid-soluble, they may be reabsorbed and enter the portal vein in a process called enterohepatic circulation.

Most drugs are eliminated by first-order kinetics, and because of this, prescribers can estimate their concentration by knowing the drug’s half-life. Repeat dosing is necessary with most drugs, and knowing the half-life helps providers understand when the drug’s concentration gets to a point where it loses effectiveness and how often repeat dosing should occur. Drugs with short half-lives may need to be given by continuous infusion. Also, drugs with long-half-lives may require a loading dose to accelerate their clinical effects.

Pharmacodynamics includes how the drug works in the body, including the intensity of its effects, its adverse effects, and its time course. Receptors on different body organs bind to drugs to give a therapeutic effect. For example, a drug that acts on a receptor on the cardiac tissue may increase the force of contraction of the heart. Generally, the drug’s intensity is determined by the concentration of the drug at the receptor, the density of the receptors on the cell’s surface, how the signal is transmitted into the cell, and factors that affect the protein production of a drug’s effect.

With continued use of some individuals, develop tolerance, and the drug becomes less effective. Tolerance may occur because of increased drug metabolism. A typical example of drug tolerance is the chronic use of opiates. The chronic use of opiates leads to less effect with a given dose requiring a patient to require an escalating dose to get the same pain relief. Another commonly used drug that the body develops a tolerance to is nitrates. Nitrates require a drug-free interval to maintain effectiveness.

Understanding pharmacokinetics improves the prescriber’s ability to prescribe safely and effectively. It will help the prescriber understand the proper dose, frequency of dosing, and route of dosing. Understanding pharmacokinetics helps the prescriber to know how to prescribe to assure the effective drug concentrations reach the target tissue for adequate amounts of time to treat the condition.

Some key points to understand from pharmacokinetics:11

  • Drugs with narrow therapeutic indexes are at higher risk for adverse effects. These drugs include warfarin, digoxin, benzodiazepines, lithium, and amiodarone.
  • Some drugs metabolized by the cytochrome P450 enzymes and can lead to toxic levels or low levels in other drugs that are metabolized by the same enzyme system. An example of this interaction includes combining statins with carbamazepine or phenytoin. This interaction will significantly reduce the statin’s bioavailability.
  • Certain drugs bind to circulating proteins, but only the unbound drug has a pharmacological effect. This protein binding is only clinically relevant for highly protein-bound drugs, e.g., warfarin and phenytoin. Therefore, patients with low protein levels in their blood may have more unbound drug and may become toxic on a standard dose.
  • Age also affects pharmacokinetics. Older patients have a reduced ability to metabolize and excrete drugs. Therefore, older adults often need lower doses when compared to younger patients. Utilizing the same dose in older patients when compared to younger patients may lead to potentially more side effects.
  • The first-pass metabolism may be increased as patients age reducing the levels of certain drugs.
  • Diet can affect how drugs are absorbed. Some drugs are absorbed best on an empty stomach, such as levothyroxine, and large quantities of food slow many drugs in the gut.
  • Grapefruit juice is known to interact with many drugs, including statins.

The Use of Drugs and Therapeutic Devices in the Prevention of Illness and Maintenance of Health

Preventative health care is meant to reduce death and disability and maintain health in the targeted population. Its primary goal is to implement cost-effective measures to help most of the population. The goals look not only to the individual but to the community at large.

The major goals of prevention are to:

  • Lessen the burden for preventable disease
  • Manage costs by lowering the need for intensive treatment in end-stage illness

Preventative health care is a critical component of ongoing health care and can significantly reduce morbidity and mortality. Preventative health care can occur in the setting of an annual physical exam or during a “sick visit.” There are four main types of clinical prevention; chemoprevention, immunizations, behavioral counseling, and screening. Chemoprevention is the use of drugs to prevent disease. Behavioral counseling is when the health care provider motivates patients to engage in lifestyle change and include items such as exercise, diet, smoking cessation, and counseling on drug abstinence. Immunizations are injecting pharmacological agents to reduce the risk of infectious disease. Screening is looking for disease in asymptomatic individuals.

Drugs and therapeutic devices (a product that helps people deal with physical illness, for example – hearing aids, mobility devices, or pacemakers) have the potential to prevent disease, prevent complications of the disease, and help individuals maintain health. Three types of preventative health care exist: primary, secondary, and tertiary.

Primary preventative health care prevents the disease from happening by eliminating its causes. Examples of primary prevention include immunizations, bariatric surgery, and smoking cessation.

Secondary prevention looks to find a disease early before symptoms have occurred and implementing interventions to stop its progression. This prevention involves doing a screening test to detect the problem and then implement interventions. Examples are screening for HIV in people who are asymptomatic and routine Pap smears.

Tertiary prevention looks to stop deterioration after a disease process is identified. Examples include giving a statin to a patient after a heart attack. It is another term for disease treatment.

There can be some confusion around these terms, with some overlap occurring. For example, a patient can undergo a colonoscopy to have a polyp removed, and this is classified as primary prevention. The colonoscopy can also find an early colon cancer that is not causing any symptoms, which would be classified as secondary prevention. The colonoscopy could also be done on a patient who had treated colon cancer to look for recurrence, which would be classified as tertiary prevention.

Chemoprevention is done when drugs are used to prevent disease. While there are many examples of chemoprevention, some have excellent benefits. Some examples include:

  • Ocular antibiotics to prevent gonorrhea infection in newborns
  • Folate during pregnancy to stop neural tube defects in the infant
  • Fluorination in the water to prevent cavities
  • Low dose aspirin in some patients to prevent cardiovascular disease
  • Statin therapy to prevent cardiovascular disease
  • Trimethoprim-sulfamethoxazole to prevent Pneumocystis jiroveci pneumonia in patients with HIV and a CD4 count less than 200

It is essential to weigh the harms and benefits of any drug or therapeutic device. While there may be a benefit, if the harm is greater than the intervention is likely not indicated.

Methods used to evaluate the harms versus the benefits may include:

  • Based on research determining the number needed to treat (NNT) to provide benefit versus the number needed to harm (NNH) is favorable
  • Determining the quality-adjusted life-year (QALY) of the intervention; Generally, in the United States, the upper limits of acceptable cost-effectiveness are approximately $50,000 to $100,000 per QALY gained
  • Cost-effectiveness. One study on the use of the HPV vaccine and regular Pap smears reduced the lifetime risk of cervical cancer by 94 percent at the cost of 57,400 to 58,500 per QALY

Preventative health care can have a profound effect on lowering health care costs. When steps are taken to prevent patients from developing an acute illness and having to go to the hospital or get urgent treatment in the emergency room, costs can be significantly reduced. Care in the hospital, and the emergency room is expensive.

It is estimated that the cost of an ED visit is 2,032 dollars, which is 12 times more expensive than the same condition treated in the primary care office, which costs 167 dollars. The same condition treated in the urgent care center is estimated at 193 dollars.12 The cost of care at the ED is higher for multiple reasons, including hospital facility fees, more diagnostic testing (labs, pathology, and radiology), and more specialty care.

Most of the leading causes of deaths are preventable, heart disease, cancer, stroke, and chronic obstructive pulmonary disease. Lifestyle choices are strongly linked to all these diseases, including smoking, which is a primary cause of each disease. Likewise, lack of exercise, poor nutritional habits, obesity are also related to cancer, heart disease, and stroke.

Preventive care is important in those with established chronic disease. Heart disease and stroke are the number killer of Americans, and between these two diseases, 859,000 people die per year. Heart disease and stroke cost the health care system 199 billion dollars per year, leading to 131 billion dollars in lost job productivity.13 Cancer is the second leading cause of death and accounts for 600,000 deaths per year, costing 174 billion dollars. Diabetes affects 34.2 million Americans, with the total estimated cost of 327 billion dollars of lost productivity and medical expenses. Arthritis is another common disease that affects 54.4 million people, which is about 25 percent of adults. It is the number one cause of work disability in America. It cost 140 billion dollars for medical expenses and 164 billion dollars for lost earnings.13

The utilization of drugs and therapeutic devices are primary weapons used to combat known medical disease. With proper use of drugs, risk factors for many chronic diseases may help assure that these conditions are controlled to reduce the risk of morbidity and mortality.

The goal of using drugs and therapeutic devices to prevent disease looks to modify factors that can lead to the disease or slow the progression of the disease. The goal of prevention is to extend the disease-free lifespan. This prevention works best on many chronic diseases that progress over the years.

Examples of this include managing risk factors for heart disease. In the overwhelming majority of cases, heart disease develops over the years and is preceded by years of unmanaged risk factors. Identifying the risk factors for heart disease and managing them will increase the amount of time until clinical disease manifests. Many lifestyle interventions can be implemented, including regular exercise, a healthy diet, and smoking cessation.

While these interventions have the potential to significantly reduce the risk of heart disease, drugs and therapeutic devices also have the potential to maintain health and prevent progression to disease significantly. These interventions include the use of blood pressure drugs to maintain a good blood pressure, lipid-lowering agents to keep cholesterol levels in the optimal range, daily aspirin therapy may be beneficial in reducing risk in some patients. Also, the use of the influenza vaccine reduces major cardiovascular events in those with the acute coronary syndrome.14

Another example of drug use and therapeutic devices to maintain health is in a patient with heart failure (HF). Currently, several drugs improve morbidity, mortality, and quality of life in those with HF.

A variety of drug classes are used in the management of HF. Some work by off-loading fluid, while others are involved in adjusting the hormonal balance of the body to improve cardiac function (angiotensin-converting enzyme inhibitor, angiotensin receptor blockers, beta-blockers, spironolactone). The treatment of HF often requires the use of multiple drugs.

Therapeutic devices are used in heart failure in some patients. Cardiac dysrhythmia is a frequent cause of mortality in HF, and antiarrhythmic drugs do not reduce mortality rates in HF, but implantable cardioverter defibrillators (ICD) are helpful. The use of an ICD in those with heart disease and an ejection fraction of less than 30-35% reduces the risk of sudden death from cardiac dysrhythmias.15

Biventricular pacing or cardiac resynchronization therapy should be considered in those with class III or IV New York Association heart failure, a QRS duration longer than 120 milliseconds, and a left ventricle ejection fraction less than 35% who have persistent symptoms.

Major Categories of Drugs

Pharmacology is the study of drugs. The next section will look at some major classes of drugs and provide a basic overview of pharma. It will provide a practical look at the use of selected drugs.

Anti-infective Agents

Antibiotics are a diverse group to fight infection. They are classified by action as bacteriostatic or bactericidal. Bacteriostatic action inhibits growth and bactericidal kill bacteria. These actions are accomplished thru various mechanisms including inhibiting cell wall synthesis, alteration of cell permeability, prohibiting cell protein synthesis, changing nucleic acid metabolism of the cell, blocking metabolic steps of the cell, and blocking DNA synthesis.16

Common classes of antibiotics include:

  • Beta-lactams (Penicillin, Cephalosporins, Monobactams, Carbapenems)
  • Aminoglycoside (Gentamicin, Neomycin, Tobramycin)
  • Sulfonamide (Bactrim, Septra)
  • Tetracycline
  • Clindamycin
  • Macrolides (Erythromycin, Azithromycin, Clarithromycin)
  • Fluoroquinolones (Ciprofloxacin, Levofloxacin)

The effectiveness of an antibiotic can be altered by the way it is taken. Antibiotics should be taken at regular intervals to maintain appropriate concentrations. Some antibiotics must be taken on an empty stomach, while others specifically must be taken with a meal. Most should be taken with a full glass of water, and some should not be taken with dairy products or close to the time dairy products are consumed.

It is good practice to culture the suspected bacteria before administering the drug. Typically, the infection is treated empirically, and once the culture returns, the antibiotic may be changed to assure that the antibiotic will eradicate the organism. It is also essential to assess the severity of the illness.16 This assessment will be a factor in how aggressively and how long to treat.

Allergic reactions can occur even in patients who have not previously shown sensitivity to the drug. It is important to observe the patient closely while the drug is being administered. Reactions may be rapid in onset or may not occur for days or weeks following the initiation of the therapy. Allergic reactions vary in intensity from a mild rash to difficulty breathing.

A significant complication of antibiotic therapy is infection. Antibiotics can eradicate the body’s good bacteria, which generally keep things in balance. When this occurs, other infections may result. Examples of common antibiotic-induced infections include yeast infections and Clostridium difficile infections.

In some individuals, the intestinal tract becomes colonized with Clostridium difficile. When antibiotic therapy is initiated, the intestinal flora is disrupted, and signs and symptoms associated with antibiotic-associated colitis occur. Inflammation of the intestines occurs due to endotoxins binding to receptors in the intestine. This inflammation leads to diarrhea.

Adverse effects are different from allergic reactions. They are often considered expected side effects of the drugs. Common adverse effects of antibiotics are nausea, vomiting, and diarrhea. Some antibiotics have very specific and severe adverse effects and contraindications. Nurses should familiarize themselves with those adverse effects and contraindications in antibiotics that they commonly use.

Nursing Consideration and Patient Education:

  • Antibiotics may interfere with oral contraceptives.
  • The patient should take the drug precisely as ordered since the timing of some antibiotics is crucial to maintain therapeutic levels.
  • Do not stop the drug prematurely, even if the patient feels better. The organism may not have been destroyed.
  • Patients should be instructed to contact their physician if the symptoms worsen or do not improve.
  • Antibiotic induced infections caused by the overgrowth of non-susceptible organisms, like yeast, may occur with antibiotic use. Symptoms may be diarrhea, anogenital itching, or vaginal discharge.
  • Encourage the patient to increase fluid intake, especially water, if it is not contraindicated.

Antivirals

Antivirals are used to treat and manage viral infections, including influenza, HIV, hepatitis, herpes simplex, and herpes zoster. There are several classes of antivirals, each working at a different stage of the viral life cycle. The exact mechanism of action is different for each disease and a particular virus. The most common side effects for any antiviral drug are diarrhea, nausea, vomiting, dizziness, sleep issues, and headaches64. However, there are additional side effects and serious reactions with each type of antiviral classification.

Human Immunodeficiency Virus (HIV)

As of early 2020, there are over 30 drugs FDA approved to treat HIV. The nucleoside reverse transcriptase inhibitors (NRTIs) stop the viral RNA to DNA transcription. The non-nucleoside reverse transcriptase inhibitors (NNRTIs) change the conformation of the reverse transcriptase enzyme, inhibiting the enzyme. The protease inhibitors (PIs) inhibit the protease enzyme, which cuts viral proteins into functional components before placing them into new HIV particles.

HIV enters the CD4 cell by fusing with the cell membrane and attaching to chemokine receptors. Entry and fusion inhibitors block these receptors, stopping the virus from entering the cells. The fusion inhibitors block the fusion of HIV with the host cell at the original point of contact to prevent HIV infection. The entry inhibitors stop HIV from entering the host cell by blocking the cell-surface co-receptor CCR5. The integrase inhibitors halt the integration of the viral DNA into the host genome.

HIV replicates and creates copies that are different from their parent strain. Because of this, many mutations are made. In those who take less potent ART therapy, that less effectively suppresses viral replications. More drug-associated resistant mutations may occur. Those who develop resistance – as evidence by viral load rising despite compliance with therapy - need to have drug resistance testing.

In treating HIV, patients require a combination of two to four drugs. These drugs are often combined into one pill to improve drug compliance.

Goals of antiretroviral therapy (ART) include prevention of HIV transmission, suppression of HIV viral load, improvement in the quality of life, restoration of the immune function, and prevention of drug resistance.

Nucleoside reverse transcriptase inhibitors (NRTIs)
Abacavir (ABC) Ziagen®
Lamivudine (3TC) Epivir®
Didanosine (ddI) Videx®, Videx® EC
Zidovudine (ZDV, AZT) Retrovir®
Emtricitabine (FTC) Emtriva®
Tenofovir disoproxil fumarate (TDF) Viread®*
Non-nucleoside reverse transcriptase inhibitors
Rilpivirine (RPV) Edurant®
Doravirine (DOR) Pifeltro®
Delavirdine (DLV) Rescriptor
Efavirenz (EFV) Sustiva®
Nevirapine (NVP) Viramune®
Protease Inhibitors
Fosamprenavir (FPV) Lexiva®
Ritonavir (RTV) Norvir®
Darunavir (DRV) Prezista®
Lopinavir/ritonavir (LPV/r) Kaletra®
Atazanavir (ATV) Reyataz®
Other Agents
Integrase inhibitors:
  • Elvitegravir (EVG) - as part of the combination drug Stribild
  • Raltegravir (RAL) – Isentress
  • Dolutegravir – Tivacay
  • Bictegravir – as part of the combination Biktarvy
CCR5 antagonist:
  • Maraviroc (MVC) - Selzentry®
Fusion inhibitor:
  • Enfuvirtide (T-20) – Fuzeon®
Post-attachment inhibitors:
  • Ibalizumab-uiyk – Tragarzo®
Pharmacokinetic enhancers:
  • Cobicistat - Tybost®
Selected Fixed-Dose Combinations
Efavirenz + Emtricitabine + Tenofovir disoproxil fumarate Atripla®
Bictegravir + Emtricitabine + Tenofovir alafenamide Biktarvy®
Darunavir + Cobicistat + Emtricitabine + Tenofovir alafenamide Symtuza®
Rilpivirine + Emtricitabine + Tenofovir Complera®
Doravirine + Lamivudine + tenofovir disoproxil fumarate Delstrigo®
Dolutegravir + Lamivudine Dovato®
Zidovudine + Lamivudine Combivir®
Emtricitabine + Tenofovir disoproxil fumarate Truvada®
Dolutegravir + Rilpivirine Juluca®
Lamivudine + Abacavir Epzicom®
Abacavir + Dolutegravir + Lamivudine Triumeq®
Emtricitabine + Tenofovir disoproxil fumarate + rilpivirine Complera®
Emtricitabine + Tenofovir alafenamide Descovy®
Elvitegravir + Cobicistat + Emtricitabine + Tenofovir alafenamide Genvoya®
Elvitegravir + Cobicistat + Emtricitabine + Tenofovir disoproxil fumarate Stribild®

Side Effects

HIV drugs have many side effects. Many drugs lead to nausea, vomiting, and diarrhea. The NNRTIs and PIs are associated with hepatotoxicity and must be used watchfully in patients with liver insufficiency.

Common side effects of NNRTIs are rash and dyslipidemia. The rash may necessitate stopping the drug and using a different class of drugs as the rash may advance to toxic epidermal necrosis, Stevens-Johnson syndrome, or erythema multiforme. Lipid abnormalities may be significant, leading to the need for treatment with drugs to lower lipids.

The NRTIs carry a black box warning for severe hepatomegaly with fatty liver and lactic acidosis and should be used thoughtfully in patients with liver and renal insufficiency.

PIs are associated with nausea, vomiting, diarrhea, elevated liver enzymes, dyslipidemia, hyperglycemia, and lipodystrophy. Approximately 2 in 3 patients on PIs have triglyceride levels higher than 240 mg/dL, and many have triglycerides over 500 mg/dl.17 Atazanavir and darunavir are the least likely to cause dyslipidemia. PIs have multiple drug-to-drug interactions as the CYP450 system metabolizes them.

Other Antiviral Drugs

Drugs for Herpes Simplex 1 and 2

Herpes simplex virus (HSV) is a virus that causes herpes. There are two types, 1 and 2. Type 1 HSV typically causes cold sores but can also cause genital herpes. Type 2 HSV is the most common cause of genital herpes (which is sexually transmitted) but can also cause sores around the mouth. The virus is spread by direct contact and presents with sores that transform into blisters and may become painful and itchy and then heal. Outbreaks tend to reoccur.

Treatment of HSV is with antiviral drugs. Drugs, including - acyclovir, famciclovir, and valacyclovir – are used to lessen symptoms and reduce outbreaks. There are generally two ways to take the drug: suppressive and episodic. Suppressive therapy entails taking drugs every day to suppress outbreaks. Episodic therapy is taking medicine at the first symptom (which is typically a burning or tingling sensation in the area where there is going to be a breakout).

Episodic therapy:

  • Acyclovir is dosed 800 mg 3 times a day for two days, or 800 mg twice a day for five days, or 400 mg 3 times a day for five days
  • Famciclovir is dosed 1000 mg twice a day for one day; or 125 mg twice a day for five days; or 500 mg one time, then 250 mg twice a day for two days
  • Valacyclovir is dosed 500 mg twice a day for three days or 1000 mg once a day for five days

Suppressive therapy:

  • Acyclovir is dosed 400 mg twice a day
  • Famciclovir is dosed 250 mg twice a day
  • Valacyclovir is dosed 500 mg once a day or 1000 mg once a day
Antivirals Side Effects
Acyclovir (Zovirax®) Malaise, GI upset, thrombocytosis, rash, pruritis, pain, burning at the injection site
Famciclovir (Famvir®) Headache, fatigue, dizziness, somnolence, GI upset, pruritis
Valacyclovir (Valtrex®) GI upset, headache, dizziness, depression, dysmenorrhea, arthralgia

Drugs for Influenza

Influenza, which typically occurs in the winter, is an acute respiratory illness triggered by the influenza A or B virus. It is typically a self-limiting disease. In some populations, such as the elderly or immunocompromised, there is a significant increase risk of morbidity and mortality.

There are three classes of antiviral drugs in the management of influenza: adamantanes, neuraminidase inhibitors, and a selective inhibitor of influenza cap-dependent endonuclease.

Adamantanes include amantadine and rimantadine. These agents only work against influenza A and are generally not recommended. The neuraminidase inhibitors include oseltamivir, peramivir, and zanamivir. These agents work against influenza A and B. There is one selective inhibitor of influenza cap-dependent endonuclease named baloxavir. This agent is effective against both influenza A and B.

Generally, most guidelines recommend the use of a neuraminidase inhibitor in the management of influenza.18 Individuals prioritized for treatment include those who have severe disease or those who are high risk (e.g., older adults, pregnancy, extreme obesity, chronic health care problems, or immunosuppressed). It is crucial to start therapy within the first 48 hours of illness, but for those who are at high risk or those requiring hospitalization should receive therapy as soon as possible even after 48 hours.

Antivirals for Influenza Side effects
Oseltamivir (Tamiflu®) - oral Dizziness, fatigue, headache, insomnia, epistaxis, conjunctivitis, GI upset, cough, lymphedema, and dermatitis in children
Zanamivir (Relenza®) - inhaled Hives, difficulty breathing, swelling of the face, lips, tongue, or throat are potentially life-threatening. Other side effects include headache, dizziness, GI upset, joint pain, chills, fever, stuffy nose, sneezing, and sore throat
Peramivir (Rapivab®) -intravenous Abnormal Liver function test, decrease neutrophils, erythema multiform, Stevens-Johnson Syndrome, skin rash, and sloughing are severe reactions. Other side effects include GI upset, high blood pressure, increase glucose and rash
Baloxavir marboxil (Xofluza®) Diarrhea, bronchitis, nausea, runny nose, headache

Nursing Considerations and Patient Education:

  • Monitor for side effects and complete regular assessments
  • Educate patients on side effects
  • Oral contraceptives may be rendered ineffective
  • Antacids should be taken at least an hour before taking an antiviral drug
  • Review laboratory work

Neurological/Psychological

Anticonvulsants

Antiseizure drugs work by reducing the excitability of neurons in the brain. For many drugs, the exact mechanism of action is not known. Some mechanisms that seizure drugs reduce neuronal excitability include:

  • Drugs that affect the voltage-dependent sodium channel – carbamazepine, oxcarbazepine, lacosamide, phenytoin, and lamotrigine
  • Drugs that affect calcium currents – ethosuximide, topiramate, zonisamide, gabapentin and pregabalin
  • Drugs that affect the glutamate receptor – topiramate and felbamate
  • Drugs that affect GABA activity – benzodiazepines and phenobarbital

Some drugs are meant to treat generalized seizures, while others are meant to treat focal seizures.19 Seizure drugs that treat both generalized and focal seizures include felbamate, lamotrigine, levetiracetam, topiramate, valproate, and zonisamide. Drugs used to treat focal seizures include carbamazepine, gabapentin, lacosamide, oxcarbazepine, phenobarbital, phenytoin, pregabalin, and primidone.

Seizure drugs have been around since phenobarbital was first used as an anti-epileptic in 1912.20 The newer drugs, when compared to older drugs (phenytoin, carbamazepine, valproate, and phenobarbital), are easier to use as they typically do not require serum monitoring, have less drug to drug interactions, have more simple dosing and fewer side effects.

Common Drugs

Carbamazepine:

Carbamazepine inactivates sodium channels and inhibits the creation of rapid action potentials. It can be used to treat generalized and focal seizures and other illnesses such as trigeminal neuralgia and bipolar disease. It is effective for adults with focal seizures, likely effective in children with focal seizures, and potentially effective in both kids and adults in generalized-onset tonic-clonic seizures. This drug has many drug-to-drug interactions.

The initial starting dose is 2-3 mg/kg per day, which is most typically given two to four times a day, two times a day for the extended-release form, and 3 to 4 times a day for the immediate release form. The dose can be increased every week to 10 mg/kg day. Levels should be checked at three, six and nine weeks.

Side effects include nausea, vomiting, rash, itch, diarrhea, dizziness, vision change, lethargy, headache, and fluid retention. Also, lower testosterone levels and increased rates of sexual dysfunction may be seen. Hyponatremia may be seen, and it is recommended to measure the level at the start of therapy and then when therapeutic levels are reached. Serious side effects include liver failure, Stevens-Johnson syndrome/toxic epidermal necrolysis, agranulocytosis, aplastic anemia, pancreatitis, and lupus syndrome.

Gabapentin:

Gabapentin appears to inhibit inward calcium currents and reduces neurotransmitter release. It also affects the transport of gamma-aminobutyric acid (GABA). It is used for add-on therapy for focal seizures. It is excreted in the urine, and dosage adjustment is needed in those with renal insufficiency.

This drug has very few drug interactions. Typically, the dose is started at 100-300 mg a day and is titrated up to a maximum of 1800 mg per day split three times a day.

Common side effects include sedation, weight gain, ataxia, and dizziness. Serious side effects include respiratory depression and multiorgan hypersensitivity*.

*Certain seizure drugs can cause a hypersensitivity syndrome, which has the potential to be life-threatening. It is a delayed (typically occurring in the first few weeks of starting a drug) hypersensitivity reaction associated with rash, fever, and multiorgan involvement.

Lacosamide:

Lacosamide inactivates voltage-dependent sodium channels, which stabilizes the neuronal membrane. It is approved as monotherapy or adds on therapy for focal-onset seizures. Its recommended starting dose is 50-100 mg two times a day to a maximum of 400 mg per day.

Side effects include dizziness, ataxia, vertigo, nausea, headache, diplopia, and poor coordination. Syncope has been reported in a small percentage of patients with diabetic neuropathy and those receiving doses of more than 400 mg per day. Serious side effects include neutropenia, multiorgan hypersensitivity, and atrioventricular block.

Lamotrigine:

Lamotrigine has multiple mechanisms of action, including inactivating the voltage-dependent sodium channels. It may also affect neurons that synthesize aspartate and glutamate. It is approved for focal-onset seizures and as adjunctive therapy for generalized tonic-clonic seizures and Lennox-Gastaut syndrome (LGS). It is often thought of as an alternative to valproate with fewer side effects.

Pregnancy and oral contraceptives can affect serum levels. This drug interacts with many other seizure drugs, including valproate, phenytoin, and carbamazepine. The typical starting dose is 25 mg every day and slowly increased. The maximum dose is dependent on other drugs that the patient takes, including valproate, carbamazepine, phenytoin, rifampin, and some protease inhibitors.

Side effects include nausea, rash, dizziness, fatigue, sleepiness, and diplopia. The rash is common and most likely to occur in those who have the dose increased too quickly. Serious side effects include Stevens-Johnson syndrome/toxic epidermal necrolysis, multiorgan hypersensitivity, and aseptic meningitis.

Levetiracetam:

Levetiracetam is a commonly used drug, and the mechanism of action is unknown. It is a drug with broad-spectrum antiseizure properties. Drug interactions are minimal with levetiracetam, as it is independent of the CYP system.

It is started at 250-500 mg two times a day and is often very effective at reducing seizures after the first day. It may be titrated to 4000 mg a day, but 3000 mg a day has similar efficacy and less sedation.

An intravenous form is available, but it is no more bioavailable than oral form. Levels of the drugs do not need to be monitored but may be monitored in renal insufficiency, pregnancy, or to monitor for adherence.

Side effects include somnolence, dizziness, agitation, irritability, fatigue, and upper respiratory tract infection. These side effects are more common during the initial phase of therapy. Serious side effects include Stevens-Johnson syndrome/toxic epidermal necrolysis, pancytopenia, and psychosis.

Oxcarbazepine:

Oxcarbazepine is like carbamazepine and blocks voltage-sensitive sodium channels and affects high voltage calcium channels. In adults, it is indicated for monotherapy or adjunctive therapy in the treatment of partial seizures. It has fewer drug-to-drug interactions when compared to carbamazepine. Dosing for adults is with 300-600 mg per day and may be increased to 900 to 3000 mg per day in divided doses.

Side effects include dizziness, vertigo, rash, ataxia, diplopia, sedation, nausea, headache, and hyponatremia. Serious side effects include Stevens-Johnson syndrome/toxic epidermal necrolysis, multiorgan hypersensitivity, agranulocytosis, and pancytopenia.

Hyponatremia
Carbamazepine and oxcarbazepine are the two seizures drugs most likely to cause hyponatremia. It is more likely to be seen older adults, those on diuretics, those with high serum levels of the seizure drug, and those on polytherapy for seizures. Baseline sodium levels should be checked, and then once levels are therapeutic, sodium levels should be rechecked. If the patient develops any indication of hyponatremia such as headaches, lethargy, confusion, then the sodium levels should be checked.

Phenobarbital:

Phenobarbital works on the GABA receptor to extend GABAs effect. It is the oldest anti-epileptic and is indicated for generalized and focal seizures. It is metabolized in the liver and should be used with caution in those with hepatic impairment. It is a schedule IV-controlled substance and available in intravenous, intramuscular, and oral form. This drug has abuse potential, and it is dosed 1-5 mg/kg/day, and blood levels should be monitored.

Side effects include nausea, rash, mood changes, sedation, tolerance, dependence, and reduced concentration. Chronic use may be associated with frozen shoulder, bone problems, Dupuytren's contractures, and plantar fibromatosis. Serious side effects include liver failure, agranulocytosis, and Stevens-Johnson syndrome/toxic epidermal necrolysis.

Phenytoin:

Phenytoin works by blocking the sodium channels, thereby reducing synaptic transmission. It is another older drug that was first used in the 1930s. It can be used for those with generalized and focal seizures as well as for status epilepticus.

Phenytoin interacts with many drugs, which can affect phenytoin levels. Phenytoin is available as an oral agent and an intravenous agent. The maintenance dose is typically 300-400 mg a day in 2-3 divided doses. The loading dose may be 15mg/kg in three divided diseases. Target doses should control seizures without significant side effects, which generally correlates with a serum concentration between 10-20 mcg/mL. Caution must be used with dosing as small changes in dose may cause significant changes in drug levels.

Side effects include rash, reduced bone density, gingival hypertrophy, folic acid depletion, an increase in body hair, slurred speech, ataxia, confusion, and double vision. If they develop a rash with phenytoin, they are more likely to get a rash with carbamazepine. Serious side effects include agranulocytosis, liver failure, Stevens-Johnson syndrome/toxic epidermal necrolysis, aplastic anemia, adenopathy, neuropathy, and lupus syndrome.

Pregabalin:

Pregabalin is similar to gabapentin. It binds to the alpha-2-delta subunit of the calcium channel and affects glutamate, substance P, and noradrenaline.

It is used as an adjunctive treatment for focal seizures. It does not have significant interactions with other drugs used to manage seizures and overall, very few drug interactions. It is dosed 150 mg a day in 2 to 3 divided doses, and the dose may be increased up to 600 mg a day.

Side effects include ataxia, dizziness, sedation, weight gain, vision change, tremor, impaired concentration, peripheral edema, and dry mouth. It may also cause euphoria and is classified as a Schedule V controlled substance. Serious side effects include angioedema, hypersensitivity reactions, and rhabdomyolysis.

Topiramate:

Topiramate works through multiple mechanisms, including affecting the sodium channels and the GABA(A) receptor. It is indicated for monotherapy for primary generalized tonic-clonic seizures as well as focal-onset seizures. It may also be used for adjunctive therapy for Lennox-Gastaut syndrome. The dosage is started at 50 mg/day and increased in 50 mg increments every week to a maximum of 400 mg a day divided twice per day.

Side effects include weight loss, fatigue, dizziness, cognitive impairment, sedation, paresthesia, depression, kidney stones, reduced appetite, nervousness, mood disturbance, and tremor. Serious side effects include hyperthermia, acute myopia, glaucoma, and kidney stones.

Valproate:

Valproate blocks sodium channels, as well as the calcium channels. It also affects the GABA system. It has a broad spectrum of activity and is used in both focal and generalized seizures. It is metabolized in the liver, and the dose may need to be decreased in those with hepatic insufficiency. It is also bound to protein, so those with low albumin in the blood may have elevated levels despite a low serum value.

Dosing is between 10-15 mg/kg and may be increased weekly. Serum levels should be checked in about one to two weeks after starting the drug.

Side effects include tremor, hair loss, nausea, vomiting, dizziness, easy bruising, weight gain, and may increase alanine aminotransferase levels. In rare situations, it may cause elevated ammonia levels leading to encephalopathy, acute liver injury, or pancreatitis. It can also cause thrombocytopenia and elevations in thyrotropin (TSH) levels. It has a high rate of teratogenicity when compared to other anti-seizure drugs.

Serious side effects include liver failure, agranulocytosis, Stevens-Johnson syndrome/toxic epidermal necrolysis, aplastic anemia, and pancreatitis.

Zonisamide:

Zonisamide blocks the sodium and calcium channels and is indicated for generalized and focal seizures. It is mainly metabolized in the liver. It interacts with multiple other anti-seizure drugs. It is dosed at 100 to 200 mg per day in two doses. To minimize side effects starting at 25 mg a day and increase it 25 mg a week until the patient is on 100 mg twice day can be tried. The dose is increased at two-week intervals to a typical dose of 400-600 mg/day.

Common side effects include fatigue, dizziness, somnolence, mental status changes, ataxia, anorexia, nausea, concentration problems, and depression. Serious side effects include Stevens-Johnson syndrome/toxic epidermal necrolysis, aplastic anemia, agranulocytosis, nephrolithiasis, acute myopia, glaucoma, hyperammonemia, and encephalopathy.

Patient Education:

  • To avoid danger, patients on these drugs should not drive or participate in activities requiring alertness.
  • Patients with a seizure history should carry an ID card or medic alert bracelet that includes the drugs they take.
  • Patients should take the drug with food or milk to decrease GI symptoms.
  • Patients on prolonged therapy should have an adequate intake of Vitamin D foods and sufficient exposure to sunlight.
  • Since the liver metabolizes some anticonvulsants, caution the patient to report any jaundice immediately.
  • Caution the patient to take the drug as prescribed. Abrupt discontinuation may precipitate seizures and status epilepticus.
  • Alcohol intake may increase drug levels leading to toxicity. When taking barbiturates, the patient should abstain from alcohol or psychotropic drugs unless directed by a physician.
  • Patients should use good oral hygiene, including flossing daily to control gingival hyperplasia.

Nursing Considerations:

  • Be sure to check required laboratory tests.
  • Monitor the patient for changes in behavior.
  • Monitor for hepatotoxicity.
  • Monitor therapeutic range.
  • When giving an anticonvulsant IV, frequently observe for signs of infiltration at the IV site since these drugs can destroy soft tissue. Continuously monitor vital signs closely during IV infusion and for 1 hour following completion. A cardiac monitor should be used. Watch for respiratory depression.

Mental Health Drugs

Depression and Anxiety:

Drugs are frequently used to treat depression and anxiety. The major classes of drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs) and other agents.

Serotonin reuptake inhibitors:

Serotonin reuptake inhibitors (SSRIs) are first-line agents for depression and work by increasing the amount of the neurotransmitter serotonin in the brain. They are first-line treatment options primarily because of their safety profile, efficacy, and limited drug-to-drug interactions.

Fluoxetine:

Fluoxetine (Prozac) is dosed at 20 mg in the morning and may be increased up to 80 mg a day. Each titration must occur after a few weeks on the drug. It is not indicated for those less than eight years old. Fluoxetine has a long half-life and is less likely to lead to withdrawal symptoms if abruptly discontinued. A weekly formulation is available that is dosed 90 mg once a week.

Fluoxetine can increase the levels of warfarin, phenytoin, carbamazepine, TCAs, and benzodiazepines. It may lower the therapeutic effect of codeine. It may cause serotonin syndrome when combined with other SSRIs and other antidepressants.

Sertraline:

Sertraline (Zoloft) is started at 25-50 mg orally every day, and the dose can be increased gradually to a maximum of 200 mg per day. It is not indicated for those less than six years old. Common side effects include dizziness, fatigue, headache, insomnia, somnolence, diarrhea, nausea, tremor, and diaphoresis. It may interact with warfarin, cimetidine, digoxin, and diazepam. It is indicated for major depressive disorder, premenstrual dysphoric disorder, panic disorder, posttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and social anxiety disorder.

Paroxetine:

Paroxetine (Paxil) has a short half-life and may lead to discontinuation syndrome when the drug is stopped, or doses are missed. It has the most potent anticholinergic effects of any of the SSRIs. For major depression, the standard form is dosed 10 mg per day to start to a maximum of 50 mg orally per day, and the extended-release form (Paxil CR) is dosed at 12.5 mg once a day to a maximum of 62.5 mg orally every day. Paroxetine is indicated for major depressive disorder, panic disorder, OCD, social anxiety disorder, generalized anxiety disorder, PTSD, and premenstrual dysphoric disorder. Side effects include somnolence, insomnia, dizziness, headache, nausea, xerostomia, constipation, diarrhea, weakness, tremor, and diaphoresis. Sexual dysfunction is most problematic with paroxetine among the SSRIs.21

Citalopram:

Citalopram (Celexa) is indicated for depression and is dosed at 20 mg once a day, and the dose can be increased to 40 mg once a day after one week. It interacts with macrolide antibiotics, cimetidine, azole antifungal, omeprazole, and carbamazepine. Side effects include sleep disturbance, xerostomia, nausea, and diaphoresis.

Escitalopram:

Escitalopram (Lexapro) is dosed at 10 mg once a day and may be increased to 20 mg after one week. It has few interactions but may interact with other SSRIs, cimetidine, and alcohol. The FDA warns that both citalopram (more than 40 mg/day) and escitalopram (more than 20 mg/day) have the potential to prolong the QT interval and may be fatal. They should be used cautiously in those with underlying heart disease and those who are prone to becoming hypokalemic.

Serotonin and norepinephrine reuptake inhibitors:

Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a newer class of drugs to treat depression and anxiety. Drugs in this class include venlafaxine (Effexor), duloxetine (Cymbalta), and desvenlafaxine (Pristiq), milnacipran (Savella), and levomilnacipran (Fetzima). This class has a similar safety profile to SSRIs, but occasionally they may be associated with an increase in blood pressure. They can be used as a first-line agent to treat depression/anxiety or in those who do not respond to SSRIs. The SNRIs work on multiple neurotransmitters and do a better job of reducing the pain and other somatic complaints in depression when compared to other antidepressants.22

Venlafaxine:

Venlafaxine (Effexor) comes as an extended-release form and is dosed 37.5 to 75 mg a day and may be titrated up to 225 mg a day. It may interact with other antidepressants, cimetidine, diuretics, and alcohol. It should not be used in those with severe uncontrolled hypertension. At doses less than 150 mg a day, it mainly affects serotonin levels, but at higher doses effects dopamine and norepinephrine levels. Discontinuation syndrome is high with this drug.

Desvenlafaxine:

Desvenlafaxine (Pristiq) is dosed 50 mg once a day for adults. It may be titrated up to 400 mg once a day, but positive effects are not proven with higher doses (as reported by the manufacturer). Common side effects include nausea, headache, dizziness, dry mouth, insomnia, fatigue, and bowel disturbance. It may interact with other SSRIs or blood thinners.

Milnacipran:

Milnacipran (Savella) is dosed 12.5 mg once a day on the first day and is titrated upwards to a maximum of 200 mg a day divided every 12 hours. It should be used cautiously in those with moderate to severe renal impairment and severe hepatic impairment. Those who take it may suffer from nausea, headache, dizziness, sleep disturbance, and constipation.

Levomilnacipran:

Levomilnacipran (Fetzima) is started at 20 mg once a day and increased to 40 mg once a day. The maximum dose is 120 mg a day. Doses should be reduced in those with moderate and severe renal insufficiency. Common side effects include nausea but may also be associated with sexual dysfunction, constipation, urinary hesitancy, and elevated heart rate.

Duloxetine:

Duloxetine (Cymbalta) is dosed 20 mg twice a day to start and may be increased to 30 mg twice a day or 60 mg once a day in the adult. The maximum dose is 120 mg a day. It may interact with ciprofloxacin, SSRIs, TCAs, antiarrhythmic agents, and anticoagulants. Common adverse effects include nausea, headache, dry mouth, dizziness, sleep disturbance, and fatigue.

Duloxetine has multiple indications. It is approved for the treatment of depression in addition to diabetic peripheral neuropathy, chronic musculoskeletal pain, fibromyalgia, and generalized anxiety disorder. This drug is often used by those who have depression in addition to one of these co-morbid conditions.

Other Antidepressants:

Other antidepressants include bupropion (Wellbutrin), mirtazapine (Remeron), vortioxetine (Brintellix), vilazodone (Viibryd) and trazodone (Desyrel). Generally, this group has low toxicity in overdose and may have an advantage over the SSRIs by causing less sexual dysfunction and gastrointestinal distress.

  • Bupropion is indicated for major depression, seasonal affective disorder, and smoking cessation. It is indicated for those over 17 years old. It comes in many brand names, including Wellbutrin XL, Wellbutrin SR and Aplenzin, and Forfivo XL. It increases the risk of seizure at higher doses, particularly in those with a history of seizures. Common side effects include headache, nausea, dry mouth, weight loss, dizziness, and insomnia.
  • Mirtazapine (Remeron) is dosed 15 mg at bedtime and may be increased every 1-2 weeks up to 45 mg a day in adults. It is given at bedtime because one of its significant side effects is sedation. Another common side effect is weight gain. Other side effects include dry mouth, constipation, and dizziness.
  • Vortioxetine (Brintellix) starting dose is 10 mg once a day and may be increased to 20 mg a day. The dose may be lowered to 5 mg a day in those who do not tolerate the higher dose. It works on multiple receptors and leads to increases in noradrenaline, dopamine, and glutamatergic transmission. The half-life of the drug is long at approximately 57 hours, leading to a low rate of withdrawal effects. Major interactions include linezolid, other antidepressants, fentanyl, ritonavir, tramadol, and clopidogrel. Nausea is the most common side effect, but other side effects include diarrhea, constipation, dry mouth, headache, and dizziness.
  • Vilazodone (Viibryd) selectively inhibits serotonin reuptake and does not work on dopamine or norepinephrine reuptake. It is dosed at 10 mg once a day for seven days then may be titrated up to 20 mg then 40 mg once a day. This drug should be taken with food. It is commonly associated with diarrhea and nausea, and other side effects may include dizziness, dry mouth, insomnia, and fatigue. Vilazodone showed favorable effects on weight gain and possibly less sexual dysfunction than other SSRIs.23
  • Trazodone is indicated for those 18 years of age and older. It is not commonly used as an antidepressant because it is very sedating.

Nursing Consideration:

  • Educate the patient not to stop drugs abruptly
  • Assess for adverse reactions
  • Educate the patient on drug interactions and side effects
  • When starting an antidepressant, the patient must be assessed for suicide. Suicide is more common among youths and young adults, but it can also affect the elderly. As the patient starts to feel better from being on the drug, some energy may return, which may increase the risk of suicide. An increase in agitation, irritability, or other behavior change may indicate a pending suicide attempt.
  • The patient should be told that side effects may initially be more intense and fade over time. Patients should be encouraged to work through minor side effects until the body gets used to the drug. It may take a few weeks until symptoms start to improve, and it is important to encourage the patient to keep taking the drug.

Antipsychotics:

Antipsychotics can be classified as typical (first-generation) or atypical (second-generation). Antipsychotic drugs are used to manage schizophrenia, bipolar disease, and some cases of depression.

Typical antipsychotics existed since the 1950s and included Haloperidol (Haldol), Thioridazine (Mellaril), Molindone (Moban), Fluphenazine (Prolixin), and Perphenazine (Trilafon). Typical antipsychotics have more neurological side effects. Prescribers frequently dose antipsychotics at the EPS threshold, which is the dose that brings on minimal rigidity on the exam. This dosing method is the most effective, and higher doses are no more effective and are typically associated with poor compliance due to side effects.

Atypical antipsychotics have existed since the late 1980s. These drugs are less likely to lead to neurological side effects, which results in better compliance. This class of drugs is associated with other side effects such as weight gain, diabetes, and elevated cholesterol.

Antipsychotic Drugs
First-generation antipsychotics Second-generation antipsychotics
High Potency Ziprasidone (Geodon®)
Thiothixene (Navane®) Aripiprazole (Abilify®)
Fluphenazine (Prolixin®) Risperidone (Risperdal®)
Perphenazine (Trilafon®) Quetiapine (Seroquel®)
Haloperidol (Haldol®) Olanzapine (Zyprexav®)
Low potency Clozapine (Clozaril®)
Thioridazine (Mellaril®) Lurasidone (Latuda®)
Chlorpromazine (Thorazine®) Paliperidone (Invega®)
  Asenapine (Saphris®)
  Cariprazine (Vraylar®)
  Brexpiprazole (Rexulti®)
  Iloperidone (Fanapt®)

Being able to recognize and treat side effects is a key component of pharmacotherapy with antipsychotics. Those who are afflicted with too many side effects will discontinue therapy and likely relapse.

The first-generation antipsychotic drugs, known as typical antipsychotics, generally have more neurological side effects than second-generation antipsychotics. High potency drugs have more side effects. High potency first-generation antipsychotics have a high risk of extrapyramidal side effects (EPS) and medium risk of sedation. Low potency first-generation drugs have a lower risk of EPS side effects and a high risk of sedation and anticholinergic effects.24 As a class, antipsychotics often lead to weight gain and sexual side effects (breast tenderness, lack of sexual interest, or erectile dysfunction).

Extrapyramidal side effects include Parkinsonism, tardive dyskinesia, dystonia, and akathisia. The most worrisome neurological side effect is a neuroleptic malignant syndrome. Other side effects include constipation, blurred vision, sedation, urinary retention, dry mouth, confusion, and orthostatic hypotension.

The atypical antipsychotic drugs have less risk of neurological side effects but are not without risk. These agents may cause weight gain, diabetes, and abnormal cholesterol levels. Antipsychotics may cause weight gain and diabetes, but weight gain and diabetes may be reversed when the drug is stopped.

Nursing Considerations:

  • Inform patients on home therapy not to alter or discontinue their drug. These drugs should be tapered gradually to discontinue treatment.
  • Educate the patient to wear sunscreen when outside, rise slowly from a lying or sitting position, and avoid hot tubs.
  • Monitor blood pressure.
  • Evaluate for extrapyramidal symptoms such as akathisia, dystonia, pseudo-Parkinsonism, and dyskinesia.
  • Wear sunscreen or protective clothing to prevent sunburns.
  • Take extra precautions during hot weather to avoid heatstroke.
  • Drowsiness or impaired mental and motor activity occurs during the first two weeks of taking the drug but tends to decrease over time.
  • The sudden appearance of sores in the mouth or a sore throat may indicate agranulocytosis. The patient should contact the prescribing physician if this occurs.

Dementia:

Two classes of drugs are used to manage Alzheimer’s disease - cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists.

Patients with Alzheimer’s disease have a reduced amount of acetylcholine with resultant reduced cortical cholinergic function. Cholinesterase inhibitors enhance the cholinergic transmission in the synaptic cleft as it inhibits the enzyme cholinesterase.

Donepezil, galantamine, and rivastigmine are three currently available cholinesterase inhibitors. Patients show variable responses to cholinesterase inhibitors, with some patients having profound benefits and others demonstrating minimal to no benefit. Therefore, nurses should assess the efficacy of these drugs on all patients. Patients who do not have a good clinical benefit from one drug may benefit from another drug in the same class.

Common side effects of cholinesterase inhibitors include headaches, dizziness, diarrhea, nausea, anorexia, muscle cramps, and nightmares. Side effects may be minimized by slow titration.

Donepezil (Aricept®) is started at 5 mg every night for four weeks and then titrated up to 10 mg every night. It is well tolerated and available as a pill and an orally disintegrating tablet. It is approved for mild, moderate, and severe dementia.

Donepezil also comes as a 23 mg dose, and it is approved for those with moderate to severe Alzheimer’s disease who have been on donepezil 10 mg for at least three months. In those with moderate to severe dementia25, the 23 mg dose was associated with improved cognition, but no difference in overall functioning and more side effects.

Common side effects of donepezil include nausea, vomiting, and diarrhea. Bradycardia can arise and may slow the heart rate to a point where it is associated with syncope.

Rivastigmine (Exelon®) is approved for mild to moderate dementia and Parkinson’s disease dementia. Common side effects include headache, nausea, vomiting, anorexia, and weight loss. Rivastigmine should be taken with food to reduce gastrointestinal (GI) side effects.

Rivastigmine also comes in a patch form that is associated with less nausea and vomiting. The patch is available in two doses: 4.6 mg/24 hours and 9.5 mg/24 hours. The lower dose patch has fewer side effects than the oral form or the high dose patch.26

Galantamine (Razadyne®) is used in mild to moderate Alzheimer’s dementia. It is dosed twice a day in the standard form and once a day in the extended-release form. Side effects include anorexia, weight loss, nausea, vomiting, and diarrhea.

Memantine (Namenda®) is the only N-methyl-D-aspartate (NMDA) receptor antagonist and is approved for moderate-to-severe dementia. Side effects include dizziness, confusion, headache, cough, and constipation, but they are not common. Like cholinesterase inhibitors, the side effects are minimized when the dose is titrated.

Memantine may aid in the treatment of dementia partly through its ability to help control behavior issues as it has been shown to manage agitation and aggression.27 The combination of memantine and a cholinesterase inhibitor may have extra benefits when combined.

Attention Deficit Hyperactivity Disorder

Attention deficit hyperactivity disorder (ADHD) results in many problems for children and adolescents. They have problems with impulse control, paying attention, and being overactive. In addition to the symptoms above, those with ADHD tend to forget or lose things, talk excessively, take unnecessary risks, have trouble taking turns, daydream excessively, fidget, and do not get along well with others. While many people will have features of ADHD from time to time, those with ADHD have severe symptoms that cause difficulty in their lives.

ADHD is a condition of distractibility and inattention. It may or may not be associated with hyperactivity. It is the most common neuropsychiatric disorders of childhood and adolescence, and many of these cases persist into adulthood.28 The pathology of ADHD is unknown, but it is theorized that certain parts of the brain linked to attention lack in neural transmission. The incidence of ADHD is 3-7 percent in school-aged children and is more common in boys than in girls, but the inattentive type is more common in girls. Those with ADHD are at increased risk of having substance abuse problems. In adults, its prevalence is estimated at 2-7%.29

While the exact etiology is unknown, it is known that genetics plays a significant role. Other potential causes include low birth weight, alcohol, and tobacco use during pregnancy, brain injury, exposure to lead, and premature delivery.28

There are three types of ADHD:

  • Predominantly hyperactive
  • Predominantly inattentive
  • Combined

The inattention type must have at minimum six symptoms (at least five symptoms if an adolescent 17 years old or older) of inattention persisting for at minimum six months to a point it is maladaptive and not consistent with the developmental level.30 These include: difficulty maintaining attention in play or tasks, forgetful in daily activities, avoids tasks/strongly dislikes tasks that require mental effort, easily distracted, loses items necessary for tasks or activities, does not seem to listen, difficulty organizing tasks and activities, fails to pay close attention to details or makes careless mistakes and does not follow through on instructions.

The hyperactive/impulsive type30 must have at minimum six of the following symptoms (at least five symptoms if an adolescent 17 years old or older) for at minimum six months to a point it is maladaptive and not consistent with the developmental level. These include: hyperactive with difficulty playing or engaging in leisure activities quietly; fidgeting with feet and hands or squirming in the seat; running around, climbing excessively when it is inappropriate; impulsive with blurting out answers to questions before the question being asked; difficulty waiting in line or waiting for their turn in a group situation; and leaving the seat when the individual is expected to remain sitting.

Other features include30: be present before the age of 12; symptoms present in two or more situations (e.g., work, home, or school); these symptoms cause significant distress or impairment in academic, occupational, or social functioning; and another mental illness does not better explain symptoms.

Before prescribing drugs for ADHD, the clinician must assure that the patient:

  • Does not have a history of seizures, Tourette syndrome, significant anxiety, or pervasive developmental delay
  • The child has normal blood pressure and heart rate
  • There is a complete diagnostic assessment that confirms ADHD
  • The parents accept drugs as a method to manage the condition
  • The school is cooperative in monitoring and administering
  • No prior sensitivities are noted to the drug
  • No concern for substance abuse with the patient or among those that live the with the patient (particularly with immediate-release stimulants)

Treatment

In children aged 4-6 years old, the first-line treatment should include parent training in behavioral management and behavioral classroom inventions. The use of methylphenidate can be used if behavior interventions do not provide significant clinical improvement, and the child still has significant problems.31

Considering current medical data, children aged 4-6 should only be given drugs when they have moderate to severe disease. No drugs are FDA approved to treat ADHD in the child below 6, but the American Academy of Pediatrics recommends the use of stimulants if needed in those 4-6 years old. The criteria for the moderate-to-severe disease include symptoms at least nine months, symptoms that have not been controlled behavioral therapy, and symptoms that are seen in the home and other settings.31

There are concerns regarding drug treatment in the pre-school child, including lack of data on long-term effects. Research suggests that methylphenidate is metabolized slower in those under six years old, and therefore the dose should be started low and titrated slowly.31

Other than methylphenidate, no drug has adequate research backing on safety and effectiveness in those under six years old.31

In children between 6-12 years old, the use of stimulants has shown good effectiveness. Non-stimulant drugs that are effective, but not as effective, include atomoxetine, extended-release guanfacine, and extended-release clonidine.31, 32

In those between 6-18 years old, combining treatments work best. Drugs should be FDA approved. The school should be included in the treatment plan. Schools often implement an individualized education program as part of the plan to manage ADHD.29, 31

For those 12 to 18, the use of FDA approved drugs for ADHD is strongly recommended in combination with behavioral interventions.31

When the drug is used, the prescriber needs to adjust the drug dose to manage symptoms while minimizing side effects optimally. In adolescents, the patient should be involved in the decision to use the drug. A list of FDA-approved drugs for ADHD is available here.

Treatment with stimulants for ADHD constitutes the best first-line treatment.32 Stimulants have similar effectiveness, but they have different dosing, duration of action, and side effects. When used, the dose should be started low and titrated upwards while monitoring for symptoms.

Stimulants come in an immediate-release formulation, which is typically dosed every 4-6 hours and longer-acting formulations, which are typically dosed one time a day. Dosing should not be done close to bedtime, as this may lead to sleep impairment. Common side effects of stimulants include insomnia, headaches, depression, irritability, weight loss, and poor appetite. There is also concern that they may lead to substance abuse, but recent studies have shown that there is no link between stimulant therapy and future substance abuse.33

Multiple formulations of stimulants exist in the management of ADHD (See tables below). The short-acting stimulants have a longer history of safety and a lot of data efficacy, but they need to be taken multiple times a day. The long-acting stimulants are only dosed once a day but are more expensive and have side effects that last into the evening.

Sustained-release preparations (e.g., Dexedrine Spansule®, Ritalin® LA, Focalin® XR, Adderall® XR, and Metadate® CD) can be sprinkled onto soft food for those who are unable to swallow pills. They should not be taken with a high-fat meal (delays onset of action) or drugs that lower the acidity of the stomach.

Methylphenidate is available as a transdermal patch, Daytrana®, which is placed on for 9 hours and off for 15 hours each day. The patch should be applied two hours before the effect is needed, and the patch may be removed when effects are no longer needed. The effect lasts about 2-3 hours after the patch is removed.

Lisdexamfetamine (Vyvanse®) is a stimulant that has a lower abuse potential than other stimulants. The capsule may be opened and mixed with water for those who cannot swallow the capsule.

Stimulants are sometimes abused. They can be used to stay awake or improve cognitive performance.34 They may also be used to get high. Some individuals will crush the tablets and snort or inject them.

Stimulants

Methylphenidate:

Methylphenidate is a Schedule II stimulant approved for ADHD in those six and older. It comes in multiple formulations including Ritalin, Ritalin LA, Daytrana, Metadate CD, Metadate ER, Adhansia XR, Aptensio XR, Methylin, Concerta, and Quillivant XR, Daytrana, Cotempla XR-ODT, Relexxii, and QuiliChew ER (see table below for dosing).

Methylphenidate – particularly the short-acting formulation - has the potential to be chronically abused and should be used carefully in those with a history of drug dependence. Methylphenidate is contraindicated in those with glaucoma, hypersensitivity to the drug; marked agitation, anxiety, or tension; those with a family history of Tourette syndrome or motor tics; and within two weeks of taking a MAO inhibitor.It should be used carefully in those with hypertension, bipolar disease, psychosis, and those with seizures.

Potential side effects include headache, nausea, seizures, increased blood pressure, increased heart rate, arrhythmias, anxiety, angina, fatigue, anger, irritability, rash, constipation, cough, blurred vision, and priapism.

Methylphenidate has multiple interactions; always check all other drugs before prescribing methylphenidate. Compliance is an issue, and therefore long-acting (once a day) drug is better at improving compliance.

The exact mechanism of action of this drug is unknown, but it may work by stimulating the CNS, stimulating the cerebral cortex, and blocking the reuptake of norepinephrine and dopamine.

Dexmethylphenidate (Focalin, Focalin XR):

Dexmethylphenidate is available as Focalin or Focalin XR. The immediate-release tablet is dosed 2.5 mg twice a day and increased every week by 2.5 to 5 mg increments with a maximum dose of 20 mg a day. The extended-release formulation is dosed 5-10 mg a day and increased to a maximum of 30 mg in children and 40 mg in adults.

Common side effects of dexmethylphenidate include headache, insomnia, abdominal pain, anxiety, and restlessness. Other side effects include poor appetite, dizziness, nausea, sore throat, irritability, dyspepsia, blurred vision, and priapism.

This drug is contraindicated in those who have a hypersensitivity to dexmethylphenidate, those with Tourette syndrome, motor tics, significant agitation, glaucoma, or anxiety. It should not be used within 14 days of taking a MAO inhibitor.

It should be used carefully in those with a history of drug dependence, bipolar disease, hypertension, or any structural cardiac abnormalities.

This drug acts as a stimulant and blocks the reuptake of dopamine and norepinephrine.

Non-stimulant Drugs

Non-stimulant drugs that are effective for ADHD, but not as effective, as stimulants include atomoxetine, extended-release guanfacine (Intuniv), and extended-release clonidine (Kapvay).31, 32

Atomoxetine (Strattera) is a second-line agent for ADHD and has a delayed onset of therapeutic action. It is a norepinephrine reuptake inhibitor. It may take up to four weeks before effectiveness is noted. When switching from stimulants to atomoxetine, both drugs are given to allow atomoxetine time to reach full effect. It is FDA approved for children as well as adults and is often used in those with a history of substance abuse.35

Atomoxetine is well tolerated, and side effects may include slight increases in heart-rate/blood pressure. Other common side effects include headache, drowsiness, insomnia, sweating, dry mouth, anorexia, abdominal pain, nausea, constipation, and erectile dysfunction.

Extended-release guanfacine (Intuniv) and extended-release clonidine (Kapvay) are classified as alpha-2-adrenergic agonists and are used in children when the use of stimulants or atomoxetine is not effective, have significant side effects or co-morbid conditions exist. The use of guanfacine or clonidine is sometimes used in combination with stimulants as adjunctive therapy.31

Research has shown effectiveness in these agents, but the effectiveness is not as robust as what is seen in those with stimulants. These agents are not approved in adults. Some argue that the effectiveness of clonidine is due to its sedating effects, which reduces agitation.36

Common side effects of guanfacine include drowsiness, fatigue, dizziness, headache, abdominal pain, and anorexia. Common side effects of clonidine include drowsiness, fatigue, dizziness, headache, dry mouth, abdominal pain, rash, and low blood pressure.

Table 1: ADHD Drugs – Adult Dosing
DrugsStarting DoseTitrationUsual dosage
Methylphenidate
Short-Acting (Ritalin®, Methylin®)5 mg two times a day before breakfast and lunchIncreased 5 or 10 mg weekly40 to 60 mg per day divided two or three times
Long-Acting
Metadate® CD and Quillivant® XR20 mg each morningIncrease 10 or 20 mg weekly40 to 60 mg once each morning
Ritalin® LA10 or 20 mg each morningIncrease 10 mg weekly40 to 60 mg once per morning
Concerta®18 or 36 mg per morningIncrease 18 mg weekly54 to 72 mg each morning
Dexmethylphenidate
Focalin®2.5 mg two times a dayIncrease 2.5-5 mg weekly10-20 mg a day
Focalin® XR10 mg each morningIncrease 10 mg weekly20-40 mg a day
Dextroamphetamine and amphetamine (mixed salts)
Short-acting - Adderall®10 mg one time a dayIncrease 5-10 mg weekly5 to 60 mg a day in 1 to 3 divided doses
Long-acting - Adderall® XR20 mg each morningIncrease 10 mg weekly5 to 60 mg each morning
Other
Lisdexamfetamine (Vyvanse®)30 mg each morningIncrease 10-20 mg weekly30 to 70 mg each morning
Table 2: ADHD Drug - Pediatric Dosing
DrugsStarting DoseTitrationMaximum Dose
Methylphenidate
Short-acting (Ritalin®, Methylin®)2.5 to 5 mg before breakfast and lunch if less than 25 kg - 2.5 mg per dayIncrease 5-10 mg weekly60 mg
Long-acting
Metadate® CD and QuilliVant® XR 20 mg per morningIncrease 10-20 mg weekly 60 mg
Ritalin® LA 10 or 20 mg each morningIncrease 10 mg weekly 60 mg
Daytrana® transdermal patch (on for 9 hours and off for 15 hours each day
Apply patch two hours before needed onset)
10 mg once dailyIncrease to next transdermal dose each week 30 mg
Concerta® 18 mg per morningIncrease 18 mg each week Less than 13 years: 54 mg; 13 years-old or older: 72 mg
Dexmethylphenidate
Focalin® 2.5 mg two times each day (at least 4 hours apart)Increase 2.5 to 5 per week 20 mg
Focalin® XR 5 mg per morningIncrease 5 mg per week 30 mg
Dextroamphetamine
Short-acting 2.5-5 mg one or two times a dayIncrease 2.5-5 mg each week 40 mg
Long-acting Dexedrine® spansule 5 mg once or twice a dayIncrease 5 mg each week 40 mg
Dextroamphetamine and amphetamine (mixed salts)
Short-acting - Adderall 2.5 - 5 mg one or two times a dayIncrease by 2.5 - 5 mg each week 40 mg
Long-acting - Adderall® XR 5-10 mg each morningIncrease 5-10 mg weekly, may be increased by 20 mg in those over 13 years old 20-30 mg
Other
Lisdexamfetamine -Vyvanse® 20-30 mgIncrease 10 or 20 mg each week 70 mg
Non-Stimulant Drugs for Adults for ADHD
DrugStarting doseTitrationsUsual Dose
Strattera® (atomoxetine) 40 mg once a dayIncreased after at least three days to 80 mg once daily or divided twice a day; 80 mg PO per day

Max dose 100 mg/day
Non-Stimulant Drugs
Intuniv® (guanfacine, extended release) ≤45 kg: 0.5 mg once daily at bedtime
>45 kg: 1 mg once daily at bedtime
may titrate every 3 to 4 days in 0.5 mg/day increments to 0.5 mg four times daily; max 2-3 mg/day
may titrate every 3 to 4 days in 1 mg/day increments to 1 mg four times daily; maximum daily dose: 4 mg/day
Target dose based effect vs. adverse effects
Strattera® (atomoxetine) Greater than 6 years and ≤70 kg: 0.5 mg/kg once/day After 3 days target dosage of 1.2 mg/kg once daily or divided 2 times/day; max dose 1.4 mg/kg or 100 mg
>70 kg: adult dosing
Target dose based effect vs. adverse effects
Kapvay® (clonidine, extended release) ≤45 kg: 0.05 mg at bedtime

>45 kg: 0.1 mg at bedtime
increase every 3 to 7 days in 0.05 mg/day increments up to a maximum of 4 times daily;
increase every 3 to 7 days in 0.1 mg/day increments up to a maximum of 4 times a day
maximum daily dose 27 to 40.5 kg - 0.2 mg/day; 40.5 to 45 kg - 0.3 mg/day.>br/> maximum dose: 0.4 mg/day

Case Study

Sam is an eight-year male who is in second grade. He has no known medical or surgical history. His parents are generally healthy, but his mother was diagnosed with ADHD as a child and depression and anxiety as an adult.

He is described by his parents as a “normal” child who spends time with friends, playing video games, and playing soccer. He enjoys social events and is often invited to friend’s houses for playdates.

Sam interacts well with his friends but is easily influenced by others and has made some poor decisions when with friends, such as staying out too late and vandalizing some property in the neighborhood. Sam gets upset when he does not receive the attention that he wants.

He does fair academically and gets mostly C’s. At the last teacher conference, the teacher reports that he sometimes engages in attention-seeking behavior and has a difficult time maintaining attention. Also, she said that she often interrupts other students when they are answering questions in class. His teacher also reports that he does not listen to instructions but interacts with his peers well.

When Sam is interviewed, he admits to having difficulty focusing on boring things but can focus well when it is something he is interested in, like video games. He admits that school is boring and reports he has a difficult time focusing at school. He reports poor sleep both in falling asleep and waking up in the middle of the night with difficulty getting back to sleep.

Sam’s parents report he is a very active child, and the only time he sits still is when he is playing video games. He often needs to be reminded to stay on task. At home, his parents report he has problems following instructions. His parents also report he is very emotional, getting upset and crying very easily. Other behavioral concerns include lying, arguing, and aggression.

Sam is diagnosed with ADHD of the hyperactive/impulsive type. He is treated with a combination of drug and behavior treatments. The consultant psychologist manages the behavioral treatments in combination with the school psychologist. Strategies implemented include counseling, behavioral parent training, and behavioral classroom management.

The drug of choice in a patient over six is a stimulant that is the most effective. While stimulants have similar efficacy choosing the most appropriate one depends on the side effect profile and the duration of action. It is recommended to start the lowest dose and increase slowly while assessing the effectiveness and adverse effects.

Sam’s physician chose dexmethylphenidate extended-release because it was felt that once a day, dosing was optimal. Dexmethylphenidate (Focalin XR) was started at 10 mg each morning with reevaluation in one week, at which point the dose was increased to 20 mg. The next week's symptoms were reasonably well controlled with minimal side effects (he did report some reduction in appetite and an occasional mild headache).

Over the next year, he was assessed regularly by a school psychologist, an outside psychologist, and his primary care provider. It was noted that he had significant improvement in symptoms, and his grades improved to all A’s and B’s with much fewer behavior problems.

Cardiac Agents

Antihypertensive Drugs:

Globally, approximately one billion individuals have hypertension, which makes up about 25% of the adult population.37 Males are more likely to have hypertension at a younger age, but after menopause, the rates equalize. Blacks are more commonly afflicted with hypertension than whites.

Drugs are used when lifestyle modifications do not control blood pressure. Multiple drug classes are available to control blood pressure. Each medicine has a unique mechanism of action, and individuals will respond differently to different drug classes.

Four classes of medicine are recommended as initial therapy for hypertension:

  • diuretics
  • angiotensin-converting enzyme inhibitors
  • angiotensin receptor blockers
  • calcium channel blockers

Diuretics:

Diuretics are equivalent to other antihypertensive drugs as a first-line drug in the treatment of high blood pressure.39 Diuretics help the body excrete excess fluid and lower peripheral vascular resistance. There are three classes of diuretics: loop diuretics, thiazide diuretics, and potassium-sparing diuretics. Each type works at a different site within the kidney. Although these drugs are widely used and cost-effective, care should be taken with special populations such as the elderly. Diuretics are particularly helpful in those with diabetes, congestive heart failure, at high risk for cardiovascular disease and in the prevention of a second stroke.

Common side effects of diuretics include dehydration, orthostatic hypotension (which increases the risk of falls), electrolyte imbalance (usually low potassium or low sodium), photosensitivity, GI upset, and high blood sugars. Those with gout or a predisposition to gout may develop a gout flair while on thiazide diuretics.

Common interactions include:

  • Digoxin with a thiazide diuretic increases the risk of digoxin toxicity
  • Angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB) used in combinations with diuretics elevate the risk of low blood pressure, especially with the first few doses
  • Nonsteroidal anti-inflammatory drugs lower the effectiveness of diuretics
  • A high sodium diet while on diuretics increases hypokalemia risk
  • Diuretics are classified as thiazide, loop, potassium sparing and aldosterone antagonists

Thiazide diuretics, hydrochlorothiazide (HydroDIURIL®) and indapamide (Lozol®) are commonly used as first-line blood pressure drugs. They are effective at managing blood pressure in those with normal renal function.

Loop diuretics, including - furosemide (Lasix®), torsemide (Demadex®), and bumetanide (Bumex®) – are more useful in those with renal dysfunction, do not respond to thiazide diuretics or those who need a drug that more robustly off-loads fluid.

Aldosterone antagonists are also used in those with chronic heart failure. The two major drugs in this class are aldactone (Spironolactone®) and Eplerenone (Inspra®).

Potassium-sparing diuretics are often combined with other diuretics to offset the hypokalemic effects of those drugs. Triamterene (Dyazide®) is a common drug in this class.

Thiazide diuretics are recommended as first-line drugs in uncomplicated hypertension as well as part of the combination in controlling those with blood pressure more than 20/10 mm Hg over the goal.38 Diuretics should also be considered in those with a history of stroke, heart disease, heart failure, and diabetes.

Thiazide diuretics are more effective than calcium channel blockers in those with heart failure and angina and better than ACE-I in cardiovascular disease and stroke, but no overall mortality benefit was shown.39

Class of DiureticSite of ActionExamplesNotes
Loop Ascending limb of the loop or HenleFurosemide, bumetanide, Torsemide Most powerful
Thiazide and Thiazide like Distal convoluted tubule Bendroflumethiazide, indapamide, Metolazone, Chlortalidone Preferred for hypertension
Potassium-sparing Collecting tubules; block the loss of potassium Spironolactone, Eplerenone, Amiloride, Triamterene Some inhibit aldosterone; slower acting but effects last longer

Nursing Considerations:

  • Use diuretics with caution in the elderly because electrolyte disturbances and dehydration can occur rapidly
  • The nursing assessment should include a daily weight, intake and output, and a check of skin turgor for dehydration
  • Monitor for signs of metabolic alkalosis, including drowsiness and restlessness
  • Monitor for signs of hypokalemia, including postural hypotension, malaise, fatigue, tachycardia, leg cramps and weakness, confusion, and anuria
  • Monitor electrolytes
  • Thiazide can exacerbate diabetes and gout40
  • Avoid potassium supplements with a potassium-sparing diuretic
  • Avoid ACE inhibitors with potassium-sparing diuretics

Angiotensin-Converting Enzyme Inhibitors:

Angiotensin-converting enzyme inhibitors (ACE-I) include agents such as quinapril (Accupril®), captopril (Capoten®), benazepril (Lotensin®) and ramipril (Altace®). Angiotensin II is a hormone that constricts blood vessels and subsequently raises blood pressure. Angiotensin-converting enzyme inhibitors prevent the conversion of angiotensin I to angiotensin II and, in so doing, drops blood pressure. Angiotensin II also elevates blood pressure by contributing to water and sodium retention.

ACE-I can be used as first-line agents, particularly in patients with heart failure, diabetes, proteinuria, peripheral vascular disease, cerebral vascular disease, and diabetic nephropathy.

Common side effects include hypotension (especially in those on diuretics or those who are dehydrated), dizziness, dry hacking cough, hyperkalemia, headache, and nausea. Infrequently does angioedema happen, but this can be severe, so monitor patients carefully during the first few doses. ACE-I can result in worsening in kidney function, so blood urea nitrogen and creatinine along with potassium levels should be monitored while on ACE-I.

Angiotensin Receptor Blockers:

Angiotensin Receptor Blockers (ARB) include the drugs candesartan (Atacand®), losartan (Cozaar®), and valsartan (Diovan®). They work by dilating blood vessels and lowering blood pressure.

Hyperkalemia, dizziness, headache, fatigue, and angioedema are side effects associated with ARB. This drug has similar indications and works through a similar mechanism to ACE-I and is often substituted in those who are unable to tolerate the ACE-I secondary to a dry hacking cough.

Nursing Considerations with ACE-I and ARB:

  • These drugs can become less effective when used with NSAIDs and antacids.
  • They enhance the hypotensive effect of diuretics.
  • They can increase serum lithium levels.
  • Food decreases absorption.
  • They can also cause an increase in serum potassium and an elevation of BUN and creatinine levels. Up to a 30 percent increase in creatinine is considered normal.
  • Monitor vital signs regularly.
  • Check for adverse reactions.
  • Monitor weight, electrolytes, and fluid status.
  • Instruct the patient to take with food or at bedtime.
  • Instruct the patient to get up slowly as orthostatic hypotension can occur when rising.
  • Help the patient maintain a diet and exercise program.

Calcium Channel Blockers:

Calcium channel blockers (CCB) result in vasodilatation and lower blood pressure. Non-dihydropyridine and dihydropyridines are two broad categories that makeup calcium channel blockers. Verapamil (Calan®) and diltiazem (Cardizem®) are the primary non-dihydropyridines. Amlodipine (Norvasc®), felodipine (Plendil®), nicardipine (Cardene®), and nifedipine (Procardia®) are examples of dihydropyridines. The non-dihydropyridines have negative chronotropic and ionotropic actions and should not be used in those with heart failure or those on beta-blockers. The dihydropyridines may result in vasodilatation and may lead to reflex tachycardia.

CCB is used in those with uncomplicated hypertension, as well as those with hypertension and comorbid diabetes, those at high risk for coronary disease and tachydysrhythmia (non-dihydropyridines).

Common side effects of this class include low blood pressure, edema, constipation, headache, dizziness, fatigue, nausea, and bradycardia.

Interactions can occur with beta-blockers since they both interfere with the AV node resulting in bradycardia, heart block, and asystole. Calcium channel blockers should not be taken with grapefruit juice or cimetidine (Zantac®), as it may lead to decrease cardiac output and hypotension. Also, phenytoin and carbamazepine may interfere with the calcium channel blocker to work and may cause hypertension and angina. These drugs may alter the effects of other drugs such as theophylline, digoxin and cyclosporine.65

Nursing Considerations:

  • Monitor apical pulse. Report an irregular beat or a rate below 60 beats/minute
  • Assess for edema, crackles, dyspnea, weight gain, and jugular distention
  • Assess for hypotension and bradycardia
  • Educate the patient on orthostatic hypotension and how to rise slowly
  • Review the diet and exercise plan as sodium may need to be reduced
  • Assess blood pressure. If systolic is below 90mm HG, report to the prescriber

B-adrenergic blockers (beta-blockers):

Beta-Blockers (BBs) regulate blood pressure by affecting the heart’s response to epinephrine and norepinephrine, in so doing reducing heart rate and cardiac output, resulting in lower blood pressure. Also, beta-blockers lower renin release and tend to be most effective in blood pressure lowering in those with elevated renin levels, which include younger, white individuals.

Adverse reactions include bradycardia, angina, syncope, heart failure, arrhythmias, fluid retention, peripheral edema, nausea, vomiting, diarrhea, and difficulty breathing due to bronchiole constriction.64

BBs are often used in those with hypertension and co-morbid conditions such as heart failure, diabetes, tachyarrhythmia, coronary heart disease, or migraine. BB may mask hypoglycemia, so beware of BBs in those with diabetes on agents that lower blood sugar. BBs have the potential to worsen depression, peripheral vascular disease, asthma, and chronic obstructive pulmonary disease.

Commonly used beta-blockers include atenolol (Tenormin®), metoprolol (Lopressor®), nadolol (Corgard®), and propranolol (Inderal®).

It is important to note that several drugs interact with beta-blockers:

  • Antacids can delay absorption
  • NSAIDs can decrease the hypotensive effects
  • Lidocaine toxicity can occur

Nursing Consideration:

  • Check the apical pulse. Some drugs such as metoprolol should be held if the apical pulse is less than 50-60 beats/minute.
  • Educate the patient not to stop this drug suddenly. Suddenly stopping drugs can cause angina, arrhythmia, and MI.
  • Monitor renal and liver laboratory results.
  • Assess for adverse reactions.
  • Educate the patient on drug interactions.

Other agents:

While the five classes listed above are commonly used, there are many other drugs available to manage blood pressure:

  • Doxazosin (Cardura®) and prazosin (Minipress®) are centrally acting agents that dilate vessels and are known as alpha-blockers.
  • Hydralazine (Apresoline®) can also be used to treat blood pressure as it results in vasodilatation and is dosed two to four times a day.
  • Tekturna is a renin inhibitor and was approved in 2007. Its most common side effect is diarrhea.
  • Central alpha agonists reduce peripheral vascular resistance. Agents in this class include clonidine (Catapres®), guanfacine (Tenex®) and methyldopa (Aldomet®). Common side effects include dry mouth, sedation, and depression. Clonidine (Catapres® patch) is available as a patch and is easier to take than oral clonidine, which should be taken three times a day.

Other Cardiac Drugs

Antianginals:

Antianginal agents reduce oxygen demand, increasing the oxygen to the heart or both. At therapeutic doses, they reduce systolic, diastolic, and mean arterial blood pressures and improve coronary circulation. There are three classes of these drugs; they are nitrates, calcium channel blockers, and beta-adrenergic blockers. While beta-blockers and calcium channel blockers were discussed in the previous section, all antianginal drugs will be briefly discussed here.

Nitrates decrease peripheral vascular resistance or afterload and decrease preload. They also cause vasodilation and are typically used for acute angina as they have a rapid onset. Side effects are typically a headache, dizziness, orthostatic hypotension, flushing, and palpitations. Drugs in this class are amyl nitrate, isosorbide dinitrate, isosorbide mononitrate, and nitroglycerin. These drugs are given sublingually, as a patch, as a pill or as an aerosol.

Beta-adrenergic drugs are used for long-term prevention of angina. These include atenolol, metoprolol, nadolol, and propranolol. These drugs reduce oxygen demand as they cause a decrease in heart rate and reduces the contraction force.

Calcium channel blockers are used to prevent angina that does not respond to the other antianginal drugs. These drugs include amlodipine, diltiazem, nifedipine, and verapamil. These drugs block the calcium ions from entering the cell membrane and smooth muscle cells, causing dilation of peripheral and coronary arteries. This drug decreases the contraction force of the heart and decreases afterload, increasing the oxygen supply.

Nursing Considerations and Patient Education:

  • Assess for adverse reactions
  • Assess apical pulse and vital signs
  • Monitor serum drug levels
  • Monitor liver function and renal function laboratory tests
  • Monitor ECG as required
  • Educate patient to change positions slowly, avoid alcohol and report side effects

Antiarrhythmics:

Antiarrhythmic drugs are used to treat disturbances in normal heart rhythms by altering the conductivity and automaticity of the cells. All cardiac cells can generate excitatory impulses, which can affect the contractility of the heart as well as the cardiac output. Careful monitoring must be observed as these drugs can worsen conditions with the heart. There are four classes of antiarrhythmics. The desired endpoint of this therapy includes eliminating the dysrhythmias, controlling the heart rate, and preventing the dysrhythmias from returning. Monitoring EKGs and the heart rate are integral parts of the therapy.41

Common adverse effects are syncope, vision change, dizziness, drowsiness, hypotension, nausea, vomiting, diarrhea, respiratory depression, hair loss, rash, bone marrow suppression. Symptoms of overdosage are hypokalemia, seizures, and tachydysrhythmias.

Class 1A:

This class includes Quinidine, disopyramide phosphate (Norpace), and procainamide hydrochloride (Pronestyl®). These drugs are quickly absorbed and metabolized. There are extended-release versions to prolong their effects. Quinidine does cross the blood-brain barrier. All are metabolized by the liver and excreted through the kidneys. Class 1A Antiarrhythmic works by blocking sodium channels, which changes the impulses along cardiac cells. This effect occurs during different phases of the heart action potential. They also block parasympathetic stimulation of the sinoatrial and AV nodes, which increases the conduction of the AV node. These drugs increase action potential duration and the refractory period and slow the conduction velocity. Class 1A drugs are used to treat premature ventricular contractions, ventricular tachycardia, atrial fibrillation, atrial flutter, and paroxysmal atrial tachycardia. Side effects particular to this class of drugs are GI symptoms and a bitter taste.

Class 1B:

This class of drugs includes mexiletine (Mexiletine®) and lidocaine. These drugs work by blocking the influx of sodium during the depolarization phase, especially in the Purkinje fiber system. This drug results in a decrease refractory period and reduces the risk of arrhythmia. Class 1B drug is used only on ventricular arrhythmias. Side effects seen with this class of drugs are drowsiness, light-headedness, parenthesis, hypotension, and bradycardia. Particular to mexiletine are AV block, confusion, ataxia, double vision, nausea, vomiting, and tremors. Lidocaine can cause seizures as well as respiratory and cardiac arrest.

Class 1C:

Class 1C antiarrhythmics are used to treat severe, resistant ventricular arrhythmias. Drugs include flecainide acetate (Tambocor®) and propafenone (Rythmol®). These drugs slow the conduction rate but do not have much of an effect on the action potential. Side effects include the development of new arrhythmias, aggravation of current arrhythmia, palpitations, shortness of breath, chest pain, heart failure, and cardiac arrest.

Class II:

Class II antiarrhythmics are beta-adrenergic blockers. These drugs block beta-adrenergic receptors on the conduction system of the heart. This drug slows the firing of the SA Node and the AV Node, which decreases conductivity. These drugs also reduce the strength of the contractions, so less force is needed with each beat, and therefore less oxygen is required. Class II drugs are used for atrial flutter, atrial fibrillation, and paroxysmal atrial tachycardia. Drugs include Propranolol, Timolol, Metoprolol, and Atenolol. Side effects include arrhythmia, bradycardia, heart failure, hypotension, GI reactions, bronchoconstriction, and fatigue.

Class III:

Class III drugs treat ventricular arrhythmias. These drugs bind and block the potassium channels for phase 3 repolarization. This drug delays repolarization and increases potential action time in the effective refractory period. Drugs in this class are amiodarone (Cordarone®), sotalol (Betapace®), bretylium tosylate (Bretylium®) and Ibutilide (Corvert®). Side effects include aggravation of current arrhythmia, hypotension, bradycardia, nausea, and anorexia. Amiodarone can cause vision issues. Ibutilide may prolong the QT interval. Sotalol may cause AV block, bradycardia, bronchospasm, and hypotension. Amiodarone is indicated for ventricle fibrillation and pulseless ventricle tachycardia. Ibutilide and dofetilide exacerbate AV block.

Class IV:

Class IV drugs are calcium channel blockers and used to treat supraventricular arrhythmias. These drugs block calcium ions in cardiac and smooth muscle cells, which decreases contractility. This drug decreases oxygen requirements and dilates coronary arteries and arterioles. Examples of Class IV drugs are verapamil (Calan®, Covera®-HS, Verelan®) and diltiazem (Cardizem®).

Nursing Considerations and Patient Education:

  • Assess for any contraindications
  • Perform complete evaluation before therapy to determine baseline status
  • Monitor EEG, vital signs, and apical pulse
  • Monitor drug levels when indicated
  • Monitor complete blood count, liver function and renal function laboratory results
  • Assess for adverse reaction
  • Educate patients on drugs including indications and side effects
  • Monitor weight as required
  • Monitor fluid intake and output when indicated
  • Monitor compliance

Cardiac Glycosides:

Cardiac glycosides are used to treat heart failure and some arrhythmias. The main ingredient is Digitalis purpurea. Digitalis (Lanoxin®), which has been around since the 1700s, works by increasing cardiac muscle contraction and slowing the heart rate. Because it is a heart stimulant, digoxin acts indirectly as a diuretic by promoting greater perfusion of blood through the kidneys. Furthermore, digoxin acts on the central nervous system to slow heart rate.

In heart failure, digoxin (Lanoxin®) has been shown to improve symptoms but does not improve survival.42 It works by increasing the strength of heart muscle contractions. It was once a mainstay of treatment for heart failure, but it is used less frequently today. Digoxin can be used in those with systolic heart failure and atrial fibrillation. It can also be used in systolic dysfunction in those adequately treated with ACE-I, BBs, and diuretics who remain symptomatic.42 Digoxin does not prolong life but reduces hospitalizations and improves symptoms in those with systolic heart failure.43 Digoxin levels do not need to be routinely checked, but levels should be less than 1.0 ng/ml and when checked, should be measured at least 6 hours after dosing. Side effects of digoxin include bradycardia, anorexia, nausea, vomiting, and diarrhea.

Digoxin has a long half-life (40 hours), and it takes multiple days to reach a steady state. This drug has a very narrow therapeutic window, and caution should be implemented to getting outside the therapeutic concentration range of 0.5 to 1.5 ng/ml.

Adverse side effects of cardiac glycosides include dysrhythmias (AV block, atrial tachycardia) anorexia, nausea, vomiting, electrolyte disturbances, bradycardia, and headache. Dysrhythmias are more common when the dose is above the therapeutic window.

Common drug interactions include quinidine, non-steroidal anti-inflammatory agents, calcium channel blockers, amiodarone, diuretics, and beta-blockers.

Nursing Consideration and Patient Education:

  • Before giving every dose of digoxin, an apical heart rate must be taken. If the heart rate has slowed, or a change in rhythm is detected, the dose should be withheld, and the physician should be notified. A heart rate of 60 or below is usually used to decide to hold the drug.

In atrial fibrillation and flutter, digoxin can lower ventricular rate when an elevated atrial rate causes it. Digoxin activates vagal efferent nerves, which diminishes the conduction of electrical impulses in the AV node, thereby blocking some impulses. Also, it increases the refractory period in the AV node. Recent evidence suggests that digoxin is associated with an increased mortality rate in individuals with atrial fibrillation, with higher levels more likely to be associated with mortality.44

Agents for Gastrointestinal Problems – Gastroesophageal Reflux Disease

In the United States, heartburn affects approximately 7% of the population daily and up to 25-40% experience symptomatic gastroesophageal reflux disease (GERD).45 Heartburn causes a burning sensation that starts in the stomach or lower chest and rises to the throat and neck.

When lifestyle modifications do not sufficiently manage the disease, drugs are used. Using drugs does not mean that lifestyle interventions are stopped when the drug is added – they are used together.

First-line treatment for GERD is antacids, which are bought over the counter. Common brands include Alka-Seltzer, Maalox, Mylanta, Pepto-Bismol, and Rolaids. Antacids neutralize the acid in the stomach and provide fast, short-term relief. Antacids can be taken as needed or after each meal and at bedtime to control stomach acid.

The main side effects of antacids are diarrhea or constipation. Magnesium based antacids – such as Maalox and Mylanta – cause diarrhea while aluminum or calcium-containing antacids – such as Rolaids and Tums - lead to constipation. Some antacids are mixed with alginic acid (Gaviscon). The addition of alginic acid to an antacid is more effective than an antacid alone but is more expensive. If lifestyle changes and antacids do not help symptoms, a stronger drug is needed.

Antacids may interact with other drugs. Some interactions to be aware of include angiotensin-converting enzyme inhibitors, beta-blockers, levodopa, oral anticoagulants, some antibiotics (quinolones), some anti-diabetic agents, and anticonvulsants.

The next drug to treat GERD controls acid production in the stomach. The drugs cimetidine (Tagamet®), famotidine (Pepcid®), nizatidine (Axid®), and ranitidine (Zantac®) are in a class of drugs called histamine two receptor antagonists (H2RA). Drugs in this class provide similar efficacy to each other.45 H2RAs block histamine from binding to the histamine two receptors on the parietal cell, leading to a decrease amount of acid production.

H2RA can be used in the treatment of grade 1 and 2 esophagitis and mild to moderate symptoms.45 Long-term use is not recommended because tolerance can develop.

H2RA has a slower onset of action than antacids but work for longer periods. As opposed to antacids, H2RA has the potential to stop heartburn before it starts.

Proton pump inhibitors (PPIs) are the most potent acid inhibitors and are considered to be the gold standard for GERD treatment. This drug class blocks the final step in the hydrogen ion secretion of the parietal cell. Some PPIs are available over the counter, and some are available by prescription. PPIs include omeprazole (Prilosec®) and lansoprazole (Prevacid®) pantoprazole (Protonix®), rabeprazole (Aciphex®) and esomeprazole (Nexium®).

PPIs have increased efficacy in the treatment of GERD when compared to H2RA, with individual PPIs being equally effective.45

The PPIs provide a slower onset of relief when compared to the H2RA. It may take 1-4 days before complete relief is noticed with PPIs. PPIs have multiple indications. Treatment of GERD or GERD symptoms is a common indication in all PPIs. Other indications of PPIs include treatment of duodenal and gastric ulcers, treatment of erosive esophagitis, and treatment of Zollinger-Ellison syndrome.

Less commonly, metoclopramide (Reglan®) is used to treat GERD. Metoclopramide increases the speed at which food goes through the digestive tract, but this drug has many side effects that limit its usefulness.

Problems with Treatments

Long-term use of acid suppression with PPIs may lead to:

  • Increased incidence of community-acquired pneumonia.46
  • Fundic polyps are increased in those who take PPIs over five years. Research has demonstrated that the progression to malignancy is rare.45
  • An increased risk of hip fractures in those at high risk for osteoporosis; The risk was lowered after the drug was stopped.
  • Impaired intestinal absorption of calcium carbonate reduces the amount of calcium available for bone development.47 It is recommended that individuals who take calcium supplements should take calcium citrate instead of calcium carbonate.
  • Increased risk for Clostridium difficile infection and an increased risk of re-infection.48
  • Selected drug interaction for PPIs include: some HIV drugs, bisphosphonates, cefuroxime (reduces absorption), clopidogrel (diminishes anti-platelet effect), citalopram, iron (decreases absorption), methotrexate (increases serum concentration) and phenytoin.

Corticosteroids

Corticosteroids are a class of drugs that include glucocorticoids and mineralocorticoids. Corticosteroids have many uses in managing inflammation and diseases of immune function based on their immunosuppressive and anti-inflammatory properties.49 Glucocorticoids decrease inflammation, increase capillary permeability, and modify the body's immune response. Mineralocorticoids act by increasing the reabsorption of sodium by increasing the excretion of hydrogen and potassium.

Glucocorticoids are used to treat asthma, allergic reactions, and in conjunction with antineoplastic agents. Mineralocorticoids are used to treat adrenal insufficiency.

Side effects include suppression of the immune response, euphoria, insomnia, GI irritation, hypokalemia, hyperglycemia, carbohydrate intolerance, and sodium and fluid retention. The salt or sodium retention properties of mineralocorticoids are counterbalanced by increased potassium excretion. Thus, electrolyte imbalances may occur, and patients need to be monitored for sodium retention and potassium depletion.

These agents have many adverse effects including:

  • Use more than two weeks leads to suppression of the hypothalamic-pituitary-adrenal (HPA) axis
  • Long-term effects include cataract formation, diabetes, osteoporosis, eye disease, growth suppression in children/adolescents
  • Short-term use of corticosteroids adverse effects includes elevated blood glucose, immunosuppression, GI bleeding, poor wound healing, elevated blood pressure, edema, and electrolyte disorders

These drugs include:

  • Hydrocortisone (Cortef®)
  • Prednisone (Sterapred®)
  • Dexamethasone (Decadron®)
  • Methylprednisolone (Depo-Medrol®)

Common mineralocorticoids include:

  • Fludrocortisone (Florinef®)
  • Nursing Considerations and Patient Education
  • Monitor weight daily, blood pressure and electrolyte status
  • Assure tapering occurs when corticosteroids are given for over two weeks
  • Monitor for adverse effects
  • Assess for Cushingoid effect: moon face, buffalo hump, central obesity, thinning hair, hypertension, and increased susceptibility to infections
  • Assess for signs of adrenal insufficiency: fatigue, muscle weakness, joint pain, fever, anorexia, nausea, shortness of breath, dizziness, and fainting

Pain Drugs

Non-Opioid Pain Drugs

Acetaminophen is very common over the counter drug used in the management of pain. In the past, it was recommended as a primary agent in the management of hip and knee osteoarthritis. Recently it was found in many trials to be only slightly better than placebo with minimal clinically important differences.50

Acetaminophen is dosed 325 to 650 mg every four hours or 500-1000 mg every 6 hours, not to exceed 3000 to 3250 mg a day. In the pediatric population, acetaminophen is dosed at 10-15 mg/kg/dose every 4-6 hours with a maximum of 75 mg/kg/day, but no more than 3000-4000 mg a day. The dose should be reduced in those with hepatic insufficiency or alcohol abuse. Absolute contraindication to acetaminophen is liver failure, while relative contraindications include chronic alcohol abuse or hepatic insufficiency. Those who are on a statin cholesterol drug may need a lower dose of acetaminophen.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are used for the management of acute and chronic painful and inflammatory conditions. Agents that are short-to-moderate acting are the preferred agents in this class, which include ibuprofen or naproxen. NSAIDs are used for anti-inflammatory, analgesic, and antipyretic effects.

There are over 20 different types of NSAIDs, and individual patients have different responses to different NSAIDs. NSAIDs work by inhibiting the cyclooxygenase (COX) enzyme. NSAIDs inhibit two major isoforms of the enzyme (COX-1 and COX-2). Many different genes are known to affect COX-1 and COX-2 metabolism which may explain some for variations in response to the drug.

The majority of NSAIDs are equally effective,51 but if one agent is ineffective, it may be reasonable to try a different NSAID as there is individual variation in response to different drugs.

Absolute contraindications to NSAIDs include an active peptic ulcer, chronic kidney disease, or heart failure. Relative contraindications include a history of history peptic ulcer disease, Helicobacter pylori infection, hypertension, or concomitant use of selective serotonin receptor inhibitors or corticosteroids.

Side effects of NSAIDs include gastrointestinal bleeding, renal insults, adverse cardiovascular effects, headaches, constipation, and mental status changes. Gastrointestinal effects may include gastric ulceration and dyspepsia. Taking the drug with food or antacids may reduce the risk of dyspepsia. Those at high risk of gastric ulceration – older age, on corticosteroids, bleeding problems, or a history of gastric ulceration – should likely not use NSAIDs. The use of a proton pump inhibitor reduces the risk of gastric ulceration with the use of NSAIDs.

The use of misoprostol or proton pump inhibitors may be considered with NSAIDs to reduce the risk of gastrointestinal ulceration. It may be reasonable to use a COX-2 inhibitor in those at high risk for gastrointestinal bleeding. In very high-risk patients, a COX-2 agent, along with a proton pump inhibitor, can be considered. It is also important to check for and eradicate Helicobacter pylori in those when it is present to reduce the risk of NSAID induced gastrointestinal injury.

NSAIDs have the potential to cause nephrotoxicity. NSAIDs inhibit prostaglandin synthesis, which leads to vasoconstriction of the afferent arteriole in the kidney. This vasoconstriction results in a reduction in the glomerular filtration rate. NSAIDs should be used cautiously in those with renal impairment.

NSAIDs have the potential to lead to cardiovascular complications. The use of NSAIDs interferes with the cardioprotective effect of aspirin, raises blood pressure, and may exacerbate heart failure. NSAIDs also may increase the risk of clotting and should be used extremely cautiously in those with a history of venous thrombosis. For those with high cardiovascular risk, the use of NSAIDs should be limited.52

NSAIDs may interfere with the antiplatelet activity of aspirin therapy.53 Chronic NSAID use should be avoided in those who are on chronic aspirin therapy. They should also be avoided in those with thrombocytopenia (low platelet count). Patients receiving warfarin or heparin should not receive NSAIDs.

Common NSAIDs

Aspirin is typically dosed 325-650 mg every 4-6 hours. It is less commonly used for chronic pain. It will irreversibly inhibit platelet function for 7-10 days.

Naproxen is given as 250 to 500 mg every 12 hours for naproxen base and 275 to 550 for naproxen sodium. It may have less cardiac toxicity compared to other NSAIDs. The dose may be increased to 1500 mg (base) and 1650 mg (sodium) for those with a rheumatologic disorder.

Ibuprofen is typically dosed 400-600 mg every 4-6 hours and may be given up to 3200 mg a day in acute pain, but only 2400 mg in chronic pain.

Oxaprozin is typically dosed at 1200 mg a day.

Diclofenac is typically dosed 50 mg every 8 hours. In addition to the oral formulation, it comes as a topical patch and gel.

Indomethacin is dosed at 25-50 mg every 8-12 hours for the immediate release and 75 mg one or two times a day for the controlled release. This drug has been traditionally used for acute gout. It is frequently associated with headache as a side effect.

Meloxicam is dosed 7.5 to 15 mg a day. This agent is relatively COX-2 selective.

Nabumetone is dosed up to 2000 mg a day and is relatively COX-2 selective at doses less than 1000 mg a day.

Celecoxib is dosed 200 mg a day and is a selective COX-2 inhibitor and is associated with less GI toxicity. It does not affect platelet function.

Other NSAIDs include ketoprofen, etodolac, sulindac, piroxicam, and mefenamic acid.

NSAIDs have many interactions. Common interactions include:

  • Methotrexate - (higher methotrexate drug levels)
  • Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers -(reduced blood pressure lowering effects and increase the risk of hyperkalemia)
  • Aspirin - (attenuates the cardioprotective benefits of aspirin)
  • Other antiplatelet agents - (increased risk of bleeding)
  • Anticoagulants – (increased risk of bleeding)
  • Glucocorticoids - (increased risk of gastrointestinal toxicity)
  • Selective serotonin reuptake inhibitors - (increased risk of gastrointestinal toxicity)

Research suggests that the dose of the given NSAID should be started at the lowest effective dose but may be titrated up to the maximal anti-inflammatory range. When the patient has a history of an inadequate response to an NSAID, the health care provider should determine if an adequate dose was tried.

An adequate trial to determine effectiveness should last about two weeks.54 Individuals who have a good response at two weeks are more likely to have a good response for at least three months.55

Nursing Considerations and Patient Education:

  • When these drugs are administered for their antipyretic effect, the temperature must be rechecked an hour following administration.
  • In adults, sensations of fullness in the ears, tinnitus, and a decreased or muffled hearing are common symptoms associated with chronic overdose.
  • Because of the possible association of Aspirin usage with Reye's Syndrome, do not give aspirin to children or teens with symptoms of chickenpox or influenza-like illnesses without consulting a physician.
  • Monitor for adverse effects includes nausea, dizziness, drowsiness, GI bleeding, prolonged bleeding time, nephrotoxicity, blood dyscrasias, and cholestatic hepatitis.
  • Review renal and liver function periodically.
  • Assess for GI ulceration and bleeding as evidenced by tarry stools, blood in the urine or vomit, or coffee-ground emesis.
  • Assess for cardiovascular history or current symptoms.
  • Educate patients that full effect may not be for 1-2 weeks for inflammation and 2-4 weeks for arthritis.

Narcotic Analgesics (Opioid Analgesics)

NSAIDs are laced with risks, and some patients are unable to tolerate NSAIDs due to side effects and co-morbid conditions. The risk associated with NSAIDs is one reason many clinicians choose an opioid to manage pain. Opioid therapy is effective in the management of many chronic pain conditions including osteoarthritis, low back pain, neuropathic pain, and postherpetic neuralgia.

A position paper from the American Academy of Neurology suggested that there is evidence for good short-term pain relief with opioids. However, no good evidence exists for the continuation of pain relief or improved function for extended periods without sustaining serious risk of dependence, overdose, or addiction.56

When non-opioid therapy is ineffective, or there is severe nociceptive pain, opioid therapy may be considered. In chronic back pain, opioids do not improve pain scores any more than non-opioid therapy.57 Opioid therapy is often used to manage neuropathic pain but is thought to be the second line to antidepressants and anticonvulsants.

When opioids are used for chronic pain. Treatment is typically started with a short-acting drug, and the drug is titrated upwards to control pain while side effects are monitored. After determining the dose of the drug required to provide adequate pain relief with minimal side effects, the drug can then be converted to a sustained release form and be administered once or twice a day. When a long-acting drug is used, a breakthrough drug can be given.

Side Effects

Opioid drugs are associated with multiple side effects, including constipation, nausea, vomiting, pruritus, abdominal cramping, sedation, and mental status changes. Multiple interventions are available to reduce side effects.

Constipation is a frequent issue in those who use opioids. Risk factors for constipation include older age, those with intra-abdominal pathology, and those who eat a low fiber diet. Those on opiates should be encouraged to increase fiber intake, drink plenty of fluids, and be encouraged to exercise. Stool softeners (e.g., docusate sodium) and stimulants (e.g., bisacodyl) may be needed to manage constipation. An osmotic laxative such as polyethylene glycol or lactulose may also be considered, which may be added to stools softeners/stimulants for resistant constipation.

An antiemetic drug can help treat nausea.

Antihistamines can treat pruritus.

Opioids are associated with somnolence and other mental status changes. Patients do develop tolerance to these symptoms over weeks. Reducing the dose may lessen the mental status changes. An adjunctive drug may be added to allow a lower dose of opioids to manage the pain. Rarely, the use of a stimulant can be used to manage sedation due to opioid use.

Respiratory depression may occur, but it is uncommon when the drug is used carefully. Starting low and slowly titrating the dose will reduce the risk of respiratory depression. Problems arise with rapid titration, the addition of another drug that may suppress the respiratory drive (benzodiazepine, alcohol, or a barbiturate) or the patient overdoses. Sedation precedes respiratory depression, so when starting a patient on opioid therapy, encourage them to take the first dose in the office to be monitored or in the presence of a responsible adult who can help monitor the patient.

Individual drugs

Key Terms
Opioid naïve - those who have not had opioids in the last 30 days
Opioid tolerant - someone who has taken 60 mg daily of oral morphine, 30 mg daily of oral oxycodone, or equianalgesic dosages of other opioids for at minimum one week58

Morphine:

While there are many opioids, morphine is considered by many as a standard comparator for other drugs. Morphine can be given orally, rectally, intravenously, subcutaneously, or intramuscularly.

Morphine is used for moderate to severe acute pain and chronic severe pain. It comes in multiple formulations. For acute pain, there is an oral and rectal formulation, and it is dosed at 5-30 mg every 4 hours. It is available as a tablet, solution, suppository, and parenteral solution. Morphine also comes in a controlled release form, a sustained-release form, and an extended-release form.

Longer-acting formulations include:

  • Arymo ER and MorphaBond ER are extended-release tablets. The initial dose is 15 mg every 8 to 12 hours in those who are not opioid-tolerant or as the first opioid used. It can be titrated every 1-2 days.
  • Kadian is not indicated for initial opioid analgesia. For non-opioid tolerant patients, 10-30 mg once a day is recommended. Higher doses are indicted for opioid-tolerant patients. Titration may be done every 1- 2 days. When converting from other forms of morphine, it may be given once or twice a day.
  • MS Contin is started at 15 mg every 8-12 hours, with the dosage being adjusted every 1-2 days.

Morphine should not be used in those with a hypersensitivity to morphine, those with toxin-mediated diarrheal disease, and those with severe/acute asthma, paralytic ileus, or severe respiratory depression. The extended-release form should not be used in those with GI obstruction.

The extended-release forms of morphine are not interchangeable. Changing from one drug to another should be done only by those experienced in how to do this. Extreme caution should be used when using a highly concentrated solution, so overdoses do not occur.

Fentanyl:

Fentanyl can be given as an injection, transdermal patch (Duragesic®), an oral transmucosal lozenge (Actiq®), a sublingual tablet (Abstral®), a sublingual spray (Subsys®), a buccal tablet (Fentora®), a buccal film (Onsolis®) and a nasal spray (Lazanda®). The transdermal patch is used in opioid-tolerant patients with moderate to severe pain and is often started at 25 mcg per hour and changed every 72 hours.

Fentanyl can be used for multiple reasons, including pre-drug for surgery, for general anesthesia, as an adjunct to general and regional anesthesia, and chronic pain management. The transdermal patch is indicated for around the clock pain management in those with chronic severe pain. Fentanyl transmucosal and intranasal is indicated for cancer pain.

While no precise dosage adjustment is recommended in those with renal or hepatic impairment, those with mild to moderate renal or hepatic impairment should likely have the dose reduced by 50 percent with the patch, and the use is not recommended in severe renal or hepatic impairment. Transmucosal and nasal spray have no specific recommendations for dose reduction in renal or hepatic impairment.

As with most opioids, contraindications include hypersensitivity, toxin-mediated diarrheal disease, and paralytic ileus. It should not be used for short-term pain, post-operative pain, and should not be used for those who have severe respiratory disease. The transmucosal and nasal form of fentanyl are typically only used by specialists for opioid-tolerant cancer patients.

The patch form should not be exposed to external heat, as this may increase the absorption of the drug. Also, patients with a fever may notice an increase in the absorption of the drug. The patch should only be applied to intact skin, and it contains aluminum and must be removed before an MRI.

Cutting patches can sometimes be done, depending on patch type, but may adversely affect their adhesiveness. In the case of reservoir patches, such as fentanyl, it can potentially lead to harmful immediate drug release.

Oxycodone:

Oxycodone is a schedule II-controlled substance and is available in multiple forms.

Immediate release is dosed 5-20 mg every 4-6 hours (lower range for opioid-naive patients).

The controlled release tablet is indicated for those who require around the clock pain control. It is dosed 10 mg every 12 hours to start and titrated carefully. There is also an extended-release capsule, which is started at 9 mg every 12 hours.

It also comes as an oral concentrate and oral solution.

Oxycodone is often combined with other analgesic agents such as acetaminophen, aspirin, and ibuprofen.

Those with a creatinine clearance less than 60 mL/min should have the dose adjusted down as serum concentration of oxycodone will increase in renal insufficiency. Those with hepatic impairment should have doses reduced. The starting dose should be lowered one-third to one-half and slowly titrated up to effect.

Oxycodone is contraindicated in those with paralytic ileus, significant respiratory depression, hypercarbia, acute or severe bronchial asthma, and GI obstruction.

Caution should be used in those with biliary tract impairment, such as acute pancreatitis, as it may lead to constriction of the sphincter of Oddi. It may lead to an elevation of intracranial pressure (ICP) and should be used carefully for those with intracranial lesions, elevated ICP, or a head injury.

Hydrocodone:

Hydrocodone, which was classified as a Schedule II Controlled Substance in October of 2014, is available as a combination pill with non-narcotic analgesic and by itself in an extended-release form. The combination pill has a short-acting version of hydrocodone and is dosed 2.5 to 10 mg of hydrocodone every 4-6 hours as needed for moderate to severe pain.

Hydrocodone extended-release (Zohydro® ER) is typically dosed 10 mg every 12 hours in treatment-naive patients. It is used for severe pain requiring around the clock dosing of hydrocodone. The dose may be increased every 3-7 days in 10 mg increments. Hysingla ER is dosed 20 mg once a day while increased the dose of 10-20 mg every three to five days. Vantrela ER is also available and is initially dosed at 15 mg every 12 hours.

Those with severe hepatic impairment should start at the lowest dose and titrate up very slowly while monitoring for side effects. Caution should be used with renal impairment as plasma concentration may rise.

Contraindications to hydrocodone include paralytic ileus, severe asthma, severe respiratory depression, and hypercarbia.

Tramadol:

As of August 18, 2014, the DEA placed tramadol into a Schedule IV of the Controlled Substance Act. It is indicated for chronic moderate-to-severe pain. For those who do not need a rapid onset of pain relief and affected by side effects, it may be dosed at 25 mg/day and titrated up every three days to 50-100 mg every 4-6 hours to a maximum of 400 mg a day.

Tramadol also comes in an extended-release form, which is dosed 100 mg once a day and may be titrated by 100 mg every five days to a maximum dose of 300 mg a day.

When prescribing tramadol to older adults, use the lower end of the dosage range and titrate slowly. In those over 75 years old, 300 mg a day should not be exceeded and utilize extreme caution with the extended-release form.

In those with a creatinine clearance less than 30 mL/min, only the immediate release formulation should be used with doses of 25-100 mg split every 12 hours (maximum dose of 200 mg a day). In those with severe liver impairment, the immediate release form should be given at a maximum of 50 mg every 12 hours.

Patients may experience withdrawal symptoms from tramadol that may include nausea, diarrhea, anxiety, pain, sweating, tremor, and rigors. Extended use of tramadol may lead to dependence, and these drugs should be tapered slowly to reduce the risk of withdrawal symptoms.

Tramadol has been shown to increase the risk of seizures. This risk is increased in those who take serotonin reuptake inhibitors, tricyclic antidepressants, neuroleptics, other opioids, or other drugs that lower the seizure threshold. The risk may also be increased in those who have seizures or are at risk for seizures, such as those who have a CNS infection, cancer, history of head trauma, or while patients are going through drug or alcohol withdrawal.

Other Drugs:

Oxymorphone, a schedule II drug, can be given intravenously, subcutaneously, intramuscularly, or orally. For acute pain, the immediate-release tablet (Opana) is used at 5-20 mg every 4-6 hours as needed for opioid naïve patients. Caution should be used in those with a creatinine clearance less than 50 mL/minute, and the drug should not be used in moderate to severe hepatic impairment.

Hydromorphone can be given orally, rectally, subcutaneously, intramuscularly, or intravenously. The oral drug comes in standard and extended-release forms. The standard form is used for moderate to severe pain and is often dosed 2 to 4 mg tablets every 4-6 hours. The oral liquid is typically dosed 2.5 to 10 mg every 3 to 6 hours. Parental and oral doses are not equivalent. The parenteral dose is five times more potent than the oral dose. The long-acting form (Exalgo) is used for opioid-tolerant patients who have chronic severe pain. It is dosed 8-64 mg once a day.

Methadone can be given intravenously, subcutaneously, intramuscularly, or orally. The oral dose is started in the opioid naïve patient at 2.5 every 8-12 hours. Methadone is a high-risk drug to lead to overdose. It has a half-life of up to five days and may accumulate in the body. Methadone may also prolong the QT interval leading to cardiac arrhythmias, especially at doses higher than 120 mg a day. Methadone should be used for severe pain that has not been responsive to other agents and only by clinicians with specific training in the use of methadone. Methadone is also used in detoxification.

Tapentadol (Nucynta®, Nucynta® ER) is used for acute moderate to severe pain and started at 50-100 mg every six hours for the immediate-release formulation. The starting dose for the extended-release tablet is 50 mg every 12 hours. For chronic pain, it is typically dosed 100-250 mg two times a day as needed. This drug is not recommended for those with severe liver or renal insufficiency. It is also indicated for diabetic peripheral neuropathy.

Propoxyphene has been taken off the US market as it has been linked with fatal cardiac arrhythmias. Meperidine is not recommended as a first-line agent for chronic pain as it is associated with high rates of central nervous system toxicity.

Nursing Considerations and Patient Education:

  • Never assume the pain is just from one source. Reassess the site, severity, and type of pain each time the patient requires the drug. Always return to the patient within 30 minutes or less to assess the results. The results of the therapy should be documented each time. Remember that the time of the assessment is directly related to the route used for the analgesic.
  • Monitor for overdose (cold, clammy skin, confusion, severe nervousness, restlessness, dizziness, drowsiness, slow breathing, or seizures).
  • Monitor for signs of withdrawal (nausea, vomiting, cramps, fever, faintness, anorexia, rhinorrhea, diaphoresis, tachycardia, or hallucinations).
  • Educate the patient not to use alcohol and not to participate in activities that require alertness.
  • Monitor vital signs.
  • Educate patients on side effects such as constipation and dry mouth and provide instruction for relief such as drinking water or chewing gum.
  • Monitor for the ability to urinate.
  • The level of consciousness should be assessed 30-60 minutes after the opioid is given. The next dose should be held, and the prescriber should be contacted immediately if there is a reduced level of consciousness, hypoxia occurs, or the patient has a respiratory rate of less than 10 per minute.

Case Study

Ms. L is a 52-year-old female with a history of bilateral knee pain; she currently rates the pain as an 8/10 in her right knee and 5/10 in her left knee. She takes meloxicam 7.5 mg twice a day and uses 1000 mg of acetaminophen for breakthrough pain about three times a day. She has been using this regime for the past six months, but over the last month, she has not been getting adequate relief from her pain and has been progressively disabled and has stopped exercising.

The pain is attributed to osteoarthritis and has been progressively worsening over the last 1-2 years. She has a past medical history of hypertension, dyslipidemia, depression, obesity, and osteoarthritis. She has a past-surgical history of a hysterectomy approximately five years ago. She is currently on simvastatin, lisinopril, meloxicam, acetaminophen, and aspirin. She has no known allergies.

She has no history of alcohol, drug, or substance abuse. She has a strong family network, including a supportive husband of 25 years and two sons who live within twenty miles of her home. She has a history of depression but is currently not depressed.

The physical exam is significant for obesity (BMI of 34). She has crepitus to both of her knees and is unable to extend the right knee due to pain.

An x-ray demonstrates moderate arthritic changes in both knees. The patient is unwilling to consider the surgery of her knees.

The prescriber offers tramadol immediate-release 25 mg in the morning, which is titrated every three days in 25 mg increments as distinct doses to 100 mg/day (25 mg four times a day). Pain control was still not adequate, and the dose was then increased by 25 mg every three days to 50 mg every 6 hours.

Pain control was significantly improved, and then the patient was given tramadol extended-release 200 mg once a day. The patient was able to function and exercise. Her quality of life was much improved.

Urinary Incontinence

If, after three months of lifestyle and behavioral therapy, no improvement in urinary incontinence (UI) is noted, the use of pharmacotherapy may be considered. Pharmacological agents are more beneficial than placebo when managing urgency and other symptoms of overactive bladder.59

In those with urgency, frequency, and nocturia options include anticholinergics, antispasmodics (anticholinergic and antispasmodic agents are classified as antimuscarinic agents), and tricyclic antidepressants. Stress incontinence is managed with alpha agonists, estrogen, and tricyclic antidepressants. Switching agents within the class may be tried before disregarding the class of drugs.

Drugs are ideally combined with a pelvic exercise routine. When one drug does not work, combination therapy (e.g., oxybutynin and imipramine) may be tried. A drug trial should be 4-6 weeks at minimum at the maximally tolerated dose. Side effects may be minimized with extended-release forms and slow titration.

Urgency and mixed incontinence are managed with antimuscarinic agents. Antimuscarinic agents increase bladder capacity and reduce urgency as they block the release of acetylcholine when the bladder is filling.60 Antimuscarinics reduce involuntary bladder contractions by affecting afferent signaling and blocking the muscarinic cholinergic receptors on the detrusor muscle cell wall. Continence is achieved in 8.5 to 13.0 percent of females who are treated with antimuscarinic agents.61 Agents showed similar efficacy.

Drugs to Treat Urinary Incontinence
DrugDoseNotes
Antimuscarinic Agents
Oxybutynin (Ditropan® XL, Gelnique®, Oxytrol®) Oral:
Immediate release: 2.5 - 5 mg, 2-3 times a day; the maximum dose is 5 mg, four times daily.
Extended-release: Start: 5-10 mg once a day, increase the dose by 5 mg weekly to a maximum of 30 mg a day.
Transdermal: Apply one 3.9 mg/day patch, twice weekly.
The label does not discuss dosage adjustments for renal or liver impairment, so it should be used with caution in renal and liver insufficiency.
Darifenacin (Enablex®) Start at 7.5 mg once daily. If the response is not sufficient dosage may be increased to 15 mg once daily in two weeks Interactions: azole antifungals, erythromycin, isoniazid, protease inhibitors - with these drugs do not exceed 7.5 mg/day. With moderate liver failure, do not exceed 7.5 mg /day; no adjustment with renal insufficiency.
Fesoterodine (Toviaz®) Start at 4 mg once daily, may be increased to 8 mg once daily Interactions: ketoconazole, itraconazole, clarithromycin – with these drugs or with a creatinine clearance less than 30 mL/minute use a maximum of 4 mg/day.
Solifenacin (VESIcare®) Start oral dosing at 5 mg once a day; may increase to 10 mg a day When the creatinine clearance is less than 30 mL/minute, the maximum dose is 5 mg/day.
Tolterodine (Detrol®, Detrol® LA) Immediate release tablet: 1-2 mg twice daily
Extended-release capsule: 2-4 mg once daily
Dosing adjustment in patients concurrently taking strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir): 1 mg twice daily for immediate release and 2 mg once a day for extended-release
Immediate release tablet: creatinine clearance 10-30 mL/minute): 1 mg twice a day;
Extended-release capsule: creatinine clearance 10-30 mL/minute: 2 mg once daily
creatinine clearance <10 mL/minute: Not recommended
Caution with hepatic impairment
Trospium (Sanctura®, Sanctura® XR) Immediate-release: 20 mg twice a day
Extended-release: 60 mg once a day
In those over 75 years old, a dose of 20 mg once a day with immediate-release may be appropriate.
Creatinine clearance less than 30 mL/min uses 20 mg of immediate-release once a day at bedtime.
Other
Mirabegron(Myrbetriq®) Indicated for overactive bladder with urge incontinence, urgency, and urinary frequency. Dosed at 25 mg once a day. The dose may be increased to 50 mg per day. This drug is classified as a Beta3 agonist. The drug is not recommended for end-stage renal disease and severe hepatic impairment. Those with creatinine clearance between 15-29 mL/min and moderate hepatic impairment the dose should not exceed 25 mg a day

For individuals who do not respond to treatment after 4-6 weeks at the maximum tolerable dose, switching to another antimuscarinic agent may be considered. Also, the use of mirabegron may be tried.

Side effects of antimuscarinics are problematic. Side effects are limited by starting low and going slow. Side effects are variable among drugs, but the dry mouth, blurred vision, constipation, mental status changes, tachycardia, and drowsiness are all common. Antimuscarinic agents should not be used in those with angle-closure glaucoma and those with gastric retention.

Those at risk for urinary retention should have their post-void residual checked while on an antimuscarinic agent.

Stress Incontinence

While no drug in the United States is approved for stress incontinence, many drugs are used.

Duloxetine is a serotonin and norepinephrine reuptake inhibitor that is approved for depression but is occasionally is used for urinary stress incontinence as it stimulates pudendal motor neurons alpha-adrenergic and 5-hydroxytryptamine-2 receptors. While duloxetine can help women with stress incontinence, some believe the harms outweigh the benefits.62 Common side effects include nausea, dry mouth, and headache. It should not be used in those with chronic liver disease.

Topical estrogen treats stress incontinence in those with vaginal atrophy, while oral estrogens may increase urinary incontinence.61

Anticoagulants

Anticoagulants are used to treat or prevent blood clots caused by strokes, myocardial infarctions, deep vein thrombosis, and pulmonary embolisms. These drugs slow down the clotting process. The goal is to promote anticoagulation while minimizing hemorrhagic issues.

Drugs, such as heparin, are used in more serious disease processes and are administered intravenously or by injection. Commonly prescribed drugs in this class are warfarin (Coumadin®), heparin, and direct oral anticoagulants. Low molecular weight heparin (LMWH) therapy has a longer duration and does not need aPTT monitored.

Differences between LMWH versus unfractionated heparin include a more predictable effect on clotting, a lower incidence of heparin-induced thrombocytopenia, lower risk of osteoporosis, and possibly a lower bleeding risk. LMWH drugs include dalteparin (Fragmin®), enoxaparin (Lovenox®), and tinzaparin (Innohep®).63

The most common side effect of anticoagulant drugs is an increased risk of bleeding. Renal excretion must be taken into consideration as these drugs are excreted mostly in the urine.

Anticoagulants are used for the following conditions:

  • Prophylaxis and treatment of venous thrombosis
  • Preventing thromboembolic complications arising from cardiac surgery, vascular surgery, and frostbite
  • Treatment of atrial fibrillation with embolization
  • Anticoagulant during dialysis
  • Heart surgery
  • Treatment of acute stroke or prevention of stroke
  • Treatment of acute MI

Before administering an anticoagulant, coagulation test values must be checked. The tests vary per drug. Below is a chart depicting the most common coagulation tests for the drug prescribed. Note that each facility or laboratory may vary.

Warfarin (Coumadin):

Warfarin inhibits Vitamin K synthesis, which impacts Factors II, VII, IX, and X. At a therapeutic level, warfarin inhibits the ability of the liver to produce vitamin K, which is what creates the therapeutic effect. Although therapeutic ranges may be achieved in 1-2 hours, the full effect is not achieved for 4-5 days until Factor II is depleted. It is important to draw the INR on time and before administering the drug. The INR is one way to determine the dose of the drug. The INR is checked regularly until the therapeutic range is achieved. The INR should be monitored closely after starting or changing the dose or starting another new drug.64

Warfarin has a black box warning as it can cause major bleeding. Bleeding is more likely to occur during the start of the treatment. It is important to monitor INR carefully as well as completing a full assessment of the patient. Warfarin also interacts with several other drugs and foods. Be sure to check all drugs for interactions and assess the patient’s diet and make sure to ask about any herbals or vitamins taken.

IndicationInternational Normalization Ratio (INR) Therapeutic Range
Venous thrombosis
Pulmonary embolism
Prevention of systemic embolism
Tissue heart valves
Acute MI
Atrial Fibrillation
2.0-3.0
Mechanical mitral valve and some mechanical aortic valves
2.5-3.5
Warfarin may impact other laboratory tests
ALT, AST Increase
INR, PT, PTT Increase
Theophylline False decrease

Foods and supplements that interact with warfarin:

  • Grapefruit and cranberry products
  • Green leafy vegetables must be kept consistent in the diet
  • Garlic
  • Ginger
  • Gingko Biloba
  • Feverfew
  • Fish oil
  • Turmeric
  • St John’s Wort
  • Chondroitin sulfate
  • Vitamin supplements

Be sure to assess alcohol intake and vegetable intake, especially vegetables high in vitamin K such as kale, parsley, collards, spinach, turnip greens, mustard greens, and collard greens.

Heparin:

Unfractionated heparin (UFH) is an older form that has been used in clot prevention for many years. It is usually used in the hospital setting as a treatment for acute issues such as DVT, PE, MI, stroke, or atrial occlusion. It can also be given prophylactically before surgery. Check with your institution as to the proper procedural use. Side effects are more significant with UFH and include an increased chance of bleeding as well as pain and bruising at the injection site. Monitoring aPTT begins 3-4 hours after initiation, and doses adjusted accordingly.

What to monitor64, 65
Laboratory TestWhat it measuresResults
Activated partial prothrombin time - aPTT The aPTT evaluates factors I, II, V, VIII, IX, X, XI, and XII. Reference range is generally 30-40.
On heparin, results may be 1.5 -2 times normal
Prothrombin time - PT Monitors extrinsic pathway and Vitamin K dependent clotting factors I, II, V VII, X. Used in warfarin therapy Reported as INR
International Normalization Ratio - INR Mathematical equation used to measure the prothrombin, and the time it takes blood to clot. The INR is typically only used in those on warfarin. Therapeutic ranges from 2-3.5

Nursing Considerations for heparin:

  • Inject between iliac crests in the lower abdomen into the fat layer
  • Do not massage area
  • Alternate sites every 12 hours
  • Draw blood for aPTT 4-6 hours after administration (Therapeutic level is 1.5 to 2 times the baseline)
  • Monitor platelet count
  • Assess patient for bruising, bleeding, petechiae, nosebleed, melena, tarry stool, hematuria, and hematemesis
  • Monitor for agranulocytosis, leukopenia, eosinophilia, thrombocytopenia, tissue irritation and sloughing, and site reactions. Patients should be monitored for signs and symptoms of hemorrhage, like a drop in BP or rapid pulse
  • Monitor vital signs
  • Apply gentle pressure for 5-10 seconds

Patient Teaching for heparin:

  • Instruct patient or caregiver to watch for bleeding or bruising
  • Avoid OTC drugs containing aspirin or salicylates
  • Avoid herbal supplements
  • Encourage smoking cessation as nicotine decreases the effect of heparin
  • Monitor CBC in menstruating females (May see excessive bleeding)
  • Use a soft toothbrush
  • Use an electric razor
  • Wear identification stating the use of heparin
  • Keep in mind that warfarin takes several days to reach therapeutic concentration. It is important to remember to start warfarin before discontinuing heparin therapy. Warfarin is gradually adjusted until the INR of 2 to 3 (or 2.5 to 3.5 for some clinical scenarios) is reached.

Direct Oral Anticoagulants

Direct oral anticoagulants (DOACs) are a newer class of anticoagulants that work at major points in the coagulation cascade to reduce clot formation. These drugs are often used as alternatives to warfarin as they do not require monitoring due to less unpredictability in drug effect at a specified dose. Unfortunately, these drugs are more expensive than warfarin and are not appropriate for all indications. They are not appropriate in those with severe liver or kidney disease as well as those with prosthetic heart valves, pregnant women, and those with antiphospholipid syndrome.

Direct thrombin inhibitors are available parentally and orally. The parenteral version, bivalirudin, and argatroban are used in heparin-induced thrombocytopenia and percutaneous coronary intervention.

The oral DOACs are classified as direct thrombin inhibitors (Dabigatran® [Pradaxa®]) or direct oral factor Xa inhibitors (see below) and are dosed and given without laboratory monitoring. These agents are used for those with deep vein thrombosis, pulmonary embolism, and nonvalvular atrial fibrillation.

Dosages may need to be adjusted in those with liver or kidney disease. Also, before starting these drugs, testing prothrombin time and activated partial thromboplastin time should be done to check coagulation status. Individuals who are morbidly obese (body mass index greater than 40 or over 120 kg) should avoid these drugs.

Direct factor Xa inhibitors:

  • Rivaroxaban (Xarelto) – once a day
  • Edoxaban (Lixiana/Suvaysa) – once a day
  • Apixaban (Eliquis) – twice a day
  • Betrixaban (Bevyxxa)

Side effects of DOACs include increased risk of bleeding. This risk is increased in those with renal failure.66 DOACs are considered by most to be safer than warfarin with fewer drug-drug and drug-food interactions, less bleeding risk, quicker onset of action, and more predictable dose-response. There is concern regarding the reversal of bleeding in life-threatening situations.67

Case Study

A 65-year-old male presents to the emergency room with a two-day history of swelling of the right lower extremity. He was previously healthy before a bout of pneumonia, which required ICU admission and a total hospital stay of 6 days. He was discharged from the hospital three days ago.

In the emergency room, he had an ultrasound of this right leg, which shows an extensive clot burden. He is started on low molecular weight heparin given subcutaneously at a dose of 1 mg per kilogram every 12 hours. Given his weight of 68.5 kg, he is given 70 mg every 12 hours.

Given that this was a provoked DVT (due to prior pneumonia for which he was hospitalized), he will need anticoagulation for three months, given that this is a provoked cause and the risk factor that caused the DVT has abated.

He will need three months of anticoagulation therapy and giving subcutaneous injections twice a day is not optimal for three months. He will be transitioned to Dabigatran (Pradaxa®). Dabigatran cannot be used for a DVT as initial therapy. In this case, LMWH was chosen over an oral anticoagulant due to the extensive clot burden found on ultrasound. Once stabilized, he will be transitioned to an oral agent. In some patients, the use of an oral anticoagulant can be used as initial therapy. Rivaroxaban and apixaban are the two agents that can be used without first starting heparin but cannot be used in all cases.

So, after five days he was transitioned to Dabigatran dosed at 150 mg twice a day and discharged from the hospital.

Before discharge from the hospital, the patient was educated on the dabigatran, including bleeding risks.

Key points of teaching given to the patient included:

  • This drug causes the blood to clot more slowly reducing the risk of clots.
  • Make sure you let health care providers know you are on anticoagulants because it may affect the prescriptions, they prescribe due to drug interactions or procedures they perform due to bleeding risk.
  • Let your provider know if there is any significant bleeding (nose, gums, cuts), bruising, blood in the urine, bruises that do not heal, feeling dizzy, extreme weakness, black/red bowel movements, severe headache, or abdominal pain.
  • Avoid high-risk situations that may lead to injury, carry a card or wear a bracelet telling which anticoagulant you are on, tell health care providers all drugs that you are on, use an electric razor over a straight edge razor and avoid the use of ibuprofen and aspirin unless directed by a prescriber.

Diabetic Drugs (Insulin and Hypoglycemics)

Diabetic patients may be treated with injectable insulin or oral hypoglycemics, depending on the pathophysiology of their disease.

Sulfonylureas:

Sulfonylureas, including glipizide (Glucotrol), glyburide (Micronase, DiaBeta, Glynase), and glimepiride (Amaryl), stimulate the pancreas to release more insulin. These drugs work best in those who are of normal body weight and are dosed one to two times a day before meals.

As a class, sulfonylureas have similar effects on blood glucose levels, but they differ in side effects, how often they are taken, and their interactions with other drugs. On average, sulfonylureas lower the HbA1C by 1-2 points.68 So, if the HbA1C is 9.2%, after being on this drug for a few months, the level would drop to 7.2 – 8.2%. Common side effects include weight gain, hypoglycemia, and increased risk for sunburn.

Factors that increase the risk of hypoglycemia include renal insufficiency, alcoholics, those with poor nutritional status, and advanced age.

Thiazolidinediones:

Rosiglitazone (Avandia®) and pioglitazone (Actos®) are the two thiazolidinediones (TZD). TZDs allow the body to use insulin more effectively and reduces the amount of blood glucose that the liver excretes. TZD lower the HbA1C by 0.4 to 1.4 points when used alone68.

Due to side effects, lack of efficacy, and negative cardiovascular effects, this class of drug is relegated to second- or third-line agents.

These agents have been shown to lower triglyceride levels but may increase LDL cholesterol. They have the potential to cause a liver problem, and liver monitoring should occur while on these drugs. Individuals with symptomatic heart failure or New York Heart Association Class III or IV heart failure should not use this class.

Other side effects include fluid retention, weight gain, headache, sinusitis, muscle aches, and elevated liver enzymes.

Biguanides:

Metformin (Glucophage®, Glucophage® XR, Riomet®, Fortamet®, and Glumetza®) is a biguanide. Metformin reduces the amount of sugar that the liver produces and enhances the cell’s ability to use insulin more effectively.

Metformin – along with lifestyle changes - is recommended for the initial treatment of diabetes, assuming there are no contraindications.68 Metformin significantly improves blood sugar control, has a low risk of hypoglycemia, lacks the side effect of weight gain, and is inexpensive. Metformin lowers HbA1C by 1-2 percentage points 68 and lowers the risk of death and diabetes-related endpoints.69

Side effects of metformin include gastrointestinal upset, diarrhea, and weight loss. An uncommon but potentially fatal side effect is lactic acidosis. It only affects those with renal insufficiency. It is important to assess glomerular filtration rate (GFR) to determine the safety of metformin. Its use is contraindicated when the GFR is less than 30 and should be used with caution when between 30 and 45.

Also, metformin should not be used in those with hemodynamic instability, heart failure, liver disease, or alcohol abuse. Those who are to have radiography with an intravenous iodinated contrast agent should have their metformin held. Those who are to have surgery that compromises circulation should have the metformin held until normal circulation, and renal blood flow is established.

Alpha-glucosidase inhibitors:

Acarbose (Precose®) and miglitol (Glyset®) are alpha-glucosidase inhibitors. They block the breakdown of sugar in the stomach and thereby reduce the amount that gets into the blood. The result is a smaller rise in blood glucose after a meal. When regularly used, alpha-glucosidase inhibitors lower HbA1C 0.5 to 0.8 percent.68 These drugs should be given 30 minutes before a meal. Common side effects include bloating, gas, and abdominal pain. Alpha-glucosidase inhibitors have fallen out of favor because they are not as effective as other agents, have more side effects, and are expensive.

Meglitinides:

Meglitinides lower blood sugar by stimulating the pancreas to release insulin. They are short-acting medicines and are taken 30 minutes before eating. Meglitinides are effective at lowing blood sugars after a meal, and when used regularly, they lower HbA1C 1.0 to 1.5 percent.72 The drugs in this class include repaglinide (Prandin®) and nateglinide (Starlix®). The side effects include hypoglycemia, weight gain, back pain, flu symptoms, and dizziness.

Expense is often a limiting factor for these drugs, and there is no advantage therapeutically with these drugs over sulfonylureas.

The liver metabolizes repaglinide as opposed to nateglinide, which is metabolized by the kidney. Nateglinide is more likely to result in hypoglycemia in those with chronic renal insufficiency. These drugs are sometimes used in those who cannot tolerate sulfonylureas.

Dipeptidyl peptidase 4 (DPP-4) inhibitors:

Drugs in this class include Vildagliptin, Saxagliptin, Linagliptin, Alogliptin, and Sitagliptin. These agents inhibit the enzyme DPP-4. DPP-4 is an enzyme on many cells that neutralize some bioactive peptides and subsequently lower glucose. Also, they stimulate insulin secretion, are associated with weight loss, reduced gastric emptying, and may stimulate beta cell regeneration.

DPP-4 inhibitors are newer drugs, and expenses can be a limiting factor in their use. Common side effects include upper respiratory tract infection, headache, sore throat, abdominal pain, diarrhea, and rarely pancreatitis.

Glucagon-like peptide one agonists:

Glucagon-like peptide-1 (GLP-1) agonists activate the glucagon-like-peptide receptors and reduce glucagon secretion, reduce food intake, increase insulin secretion, and delay gastric emptying. When used alone, they typically do not cause hypoglycemia.

Exenatide (Byetta®) is a popular drug in this class, and it is injected twice a day subcutaneously. Common side effects include nausea, dizziness, and headache. Less common side effects include pancreatitis and kidney dysfunction. Liraglutide (Victoza®) is given by subcutaneous injection once a day, starting at 0.6 mg to a maximum of 1.8 mg. Nausea, vomiting, and diarrhea are common side effects. Other agents in this class include lixisenatide (Lyxumia®), albiglutide (Tanzeum®), dulaglutide (Trulicity®), and semaglutide (Ozempic®).

Sodium-glucose co-transporter 2:

The sodium-glucose co-transporter 2 (SGLT2) promotes the renal excretion of glucose, which reduces the amount of glucose in the blood. Empagliflozin is one of the drugs in this class and is often used because it has data showing that it has cardiovascular benefits.70 Other agents in this class include canagliflozin, ertugliflozin, and dapagliflozin. When using these agents, it is important to assess and monitor renal function and volume status. Common side effects include hypotension and candida infections. Other side effects may include urinary tract infections, acute kidney insufficiency, diabetic ketoacidosis, bone fracture, and lower extremity amputation.

Insulin:

Many different types of insulin exist, including long-acting, short-acting, and medium-acting types. Insulin is titrated upward until blood sugar is well controlled. Eventually, diabetes robs the ability of the pancreas to produce insulin; so many diabetics eventually need to go on insulin.

Insulin is often added to one of the above medicines, to enhance control of blood glucose. Common side effects of insulin include hypoglycemia and pain at the injection site. Insulin has the most potential to lower HbA1C but is associated with the highest risk of hypoglycemia.

Injection of insulin serves as a replacement for the patient's insulin and is used in insulin-dependent diabetes (IDDM or Type I.). These patients cannot produce much if any, insulin, so they need an exogenous source of insulin.

Insulin Activity after SQ Injection
Type InsulinOnsetPeakDuration
Lispro, aspart, glulisine
15 minutes before a meal or immediately after
3-15 mins.0.5-1.5 hrs. 2 – 4 hrs.
Regular
30-60 min before meals
0.5 –1 hr.2-4 hrs. 5-8 hrs.
NPH 1-2 hrs.4-12 hrs. Approx. 12 hrs.
Insulin glargine 2 hrs.None 24 or more hrs.
Insulin detemir 2 hrs.3-9 hrs. 6-24 hrs.
Insulin degludec 2 hrs.None 40 or more hrs.

Animal source insulin (beef or pork) carries a danger of contamination and immunologic reactions, and their use is rapidly decreasing and replaced with synthetic “human” insulin. Synthetic insulin comes in different forms that can be mixed to suit the patient's glucose pattern and lifestyle.

Insulin vials currently being used should be stored at room temperature. Unopened vials should be stored in the refrigerator but never frozen.

All insulin preparations except short-acting insulin should be rolled between the palms to be mixed. Insulin should never be vigorously shaken.

Regular, short-acting insulin should always be drawn up in the syringe first when it is mixed in the same syringe with another type of insulin. Otherwise, a small amount of long-acting insulin may contaminate the regular insulin delaying its action.

Nursing Considerations:

  • Educate the patient on how to inject themselves and when to take the drug
  • Educate the patient on how to measure drug
  • Educate patient on to obtain and read glucose levels
  • Assess patient for rash, shortness of breath, wheezing, hypotension, excess sweating
  • Monitor injection sites
  • Assess for hypoglycemia and hyperglycemia
  • Assess for diabetic nerve disease
  • Review renal and liver function laboratory reports
  • Monitor patients closely if they have a fever, are under stress, surgery, or trauma

Drug Calculations

Commonly used equivalents:

Volume: 1 liter (L) = 1000 milliliters (ml) = 1000 cubic centimeter (cc)
1 ml = 1cc
Weight1 kilogram (kg) = 1000 grams (gm)
1 gm = 1000 milligrams (mg)
1 mg = 1000 micrograms (mcg)

To convert grams to milligrams, you would multiply the known value by the conversion factor.

For example to convert 0.015 gm. to mg. you multiply 0.015 gm. by 1000 (1 gm. =1000 mg.).

 0.015 X 1000 = 15
Therefore, 0.015 gm. = 15 mg.
 

Calculating Dosages:

Calculating dosages for non-parenteral medications such as pill, capsules, unscored tablets or suppositories should be rounded to the nearest whole number. To calculate the dosage for scored tablets round to the nearest half, or quarter, depending on how the tablet is scored. With problems involving oral liquid medication, it is generally accurate enough to round one decimal place. However, remember that drugs for children require a greater degree of accuracy.

Suggested formula for calculation, Method I:

Prescribed dose/Available dose
x Quantity (unit of measure) = Amount to be given.

Example: The physician orders Keflex® 750 mg. On hand, you have Keflex® 250 mg. per capsule. Both the medication ordered and the medication on hand is in the same unit of measure (mg).

(Prescribed dose) 750 mg./(Available dose) 250 mg.
x 1 capsule = = 3 capsules to be given
750/250
x 1 = 3

To check your answer by the alternate method of reasoning:

250 mg. x 3 = 750 mg.

Suggested formula for calculation, method II:

This method allows you to set up a ratio of what you have to what you need.

Example: Using the same example, the physician orders Keflex® 750 mg. and you have Keflex® 250 mg. per tablet.

Available dose : 1 :: Prescribed dose : X

250 mg. : 1 tablet :: 750 mg. : X tablets

250x = 750

X
750/250

X = 3

Calculating mcg/Kg/min.

If you know the rate:

(mcg/ml) (ml/hr)/(60 min/hr)(kg of body weight)
= mcg/kg/min

If you know the dose:

(mcg/kg/min) (60 min/hr) (kg of body weight)/mcg/ml of the solution
= ml/hr

Example: A patient is on a dopamine drip infusing at a rate of 26 ml/hr. The dopamine bag is labeled, 400 mg of dopamine in 250 ml of D5 (1600 mcg/ml). The patient weights 70 kg. To calculate the mcg/kg/min:

(1600 mcg/ml)(26 ml/hr)/(60 min/hr)(70 kg)
= mcg/kg/min
41600/4200
= 9.9047 = 10 mcg/kg/min

Tips for solving problems in dosage calculation:

  1. Know the units of measure that you desire in the answer. This will help you find the information you need to convert to the desired amount.
  2. Recheck your math. Use a calculator if one is available.

Calculating IV Drip Rates:

When you regulate an IV flow rate with a clamp or dial controller, the rate will usually be measured in drips/minute. IV administration sets deliver a specific number of drops per ml. The number is on the package label. Standard drip sets deliver 10-20 drops/ml. Microdrip sets deliver 60 drops/ml and blood sets usually deliver 10 drops /ml.

Suggested formula:

total number of ml to infuse/total number of minutes to infuse
x drip factor (gtts/ml) = flow rate (gtts/min)

Example: Administer 1000ml of D5W over 8 hours using an infusion set that delivers 10 gtts/ml.

1000ml/8 hours x 60 minutes
x 10 gtts/ml = X gtts/min
1000 ml/480 minutes
x 10 gtts/ml = X gtts/min

2.08 ml/minute x 10 gtts/ml = X gtts/min

20.8 gtts/ml = X

Round to the nearest whole for a drip rate of:

21 gtts/min (rate for a clamp or dial controller)

Dial controllers may not be accurate if the IV catheter is less than a 20 gauge.

When you use an infusion pump, the flow rate is measured in ml/hours. To find the rate in ml/hour for an infusion pump, divide the total number of ml. by the total number of hours.

1000ml/8 hr
= 125ml/hr (rate for an infusion pump)

Case Study

Ms. Stevenson, who is a 60-year-old female, presents to the emergency room with the chief complaint of chest pain, dizziness, and palpitations. An EKG shows an irregular-irregular heart rhythm with a rate of 175 beats per minute. The remaining vital signs are normal, but the patient looks anxious and scared. She weighs 60 kilograms.

The physician orders diltiazem for ventricular rate control as an intravenous bolus at 0.25 mg/kg over a two-minute time frame. What is the dose that will be infused?

60 kg x 0.25 mg/kg =15 mg is the proper dose

The nurse gives this as an injection with a solution concentration at 5 mg/mL. How many mL does she need to push over 2 minutes?

15 mg dived by 5 mg/mL = 3 mL

After 20 minutes, the rate is not controlled, and the physician orders a repeat bolus of 0.35 mg/kg over a two-minute time frame? What is the dose?

60 kg x 0.35 mg/kg = 21 mg, which will be rounded down to 20 mg, and then 4 mL will be given.

After the second bolus, Ms. Stevenson’s rate is lowered to 92 beats a minute, and the physician orders a continuous infusion of 5 mg/hr. What rate would you run the Cardizem drip?

The nurse goes into the drug room after she takes the order off and finds a 300 ml bag with 250 mg of diltiazem. The concentration is determined by dividing 300 ml by 250 mg, yielding a concentration of 0.83 mg/mL. At an administration rate of 5 mg/hour, the infusion rate is determined by dividing the dose by the concentration. So...

5 mg/hour 0.83 mg/ml
= 6 mL/hour

Drug Errors

Annually, adverse drug events lead to about 700,000 trips to the emergency room and 100,000 hospitalizations. It is estimated that 5 in 100 patients in the hospital are there due to an adverse drug event.71 It is estimated that preventable adverse reactions account for more than 3.5 billion dollars annually.71

The Institute of Medicine report “To Err is Human: Building a Safer Health Care System” revealed the seriousness of these errors and found that most were preventable.72 Dosing errors are the most common form of drug errors. Other errors occur during ordering and administration and often include the wrong dose, wrong prescription, allergy, wrong time, wrong route, or missed dose. Although several reasons have been found for the errors, communication is a common thread.

Another area of concern is that of handoffs or transitions. As continuity of care is disrupted, the risk for error is higher. This continuity can happen with changes in providers such as shift change or when the patient is moved to a different facility or unit. Communication is, again, a key component. The Joint Commission National Patient Safety Goals require a standardized handoff procedure include discussion of patient information.73 Several errors can occur during handoff including, background noise, inconsistent information, incomplete care responsibility, conflicting communication needs and expectations, and inability to listen.

Handoff tools such as SBAR (Situation, Background, Assessment, Recommendation) are a way to standardize the information that is passed between providers and facilities.74 The situation is described and includes present illness, the reason for transfer, the contact information of referring provider, and patient identification. Background information includes diagnosis, past drug history, surgical history, drugs, allergies, vital signs, laboratory results, code status, significant events during hospitalization, and physical exam findings. The assessment is patient-centered and includes patient-specific needs, concerns, cardiovascular stability, complications, and cultural factors. The recommendation includes information about the treatment plan, discharge plan, and case management.

There are also more specific tools for intrahospital transfers (The Ticket Ride Tool)75 and surgical tools (Postoperative Handover Assessment Tool)76, for example. Other information can also be included for specific purposes such as mental examinations, barriers, diet, or required patient positioning.71

Nurses find themselves as the last link in the chain of drug management. Nurses are habitually blamed for drug errors when, in fact, there are multiple people and tasks involved in drug errors, and nurses discover most drug errors. Studies reveal that several factors are involved in drug errors that can lead to adverse reactions and sentinel events. Causes identified specific to nursing care are unsafe practices, misidentification of the patient or drug, lack of knowledge, violation of policy and procedures, calculation errors, faulty checking procedures, equipment deficits, and not following drug directions.77

The use of technology in drug administration has been somewhat successful in reducing drug errors. Barcoding drug for administration, computerized order entry, education, and electronic drug distribution systems have been helpful to nurses and other health care staff in catching and reducing drug errors.

Recommendations to Reduce Errors

Reducing drug errors may include the following:71,78

  • Routinely reconcile drug at admission, discharge, or patient transfer
  • Avoid verbal orders except in emergencies
  • Assess all drugs the patient is currently using
  • Keep drug record accurate and up-to-date
  • Assess for allergic reactions
  • Educate patients in all drugs prescribed
  • Assess refill history and compliance
  • Review all side effects
  • Prescribe electronically when possible
  • Use read back with any orders
  • Avoid abbreviations
  • State patient age and weight if required for dosing
  • Nurses, pharmacists, and prescribers should work as a team
  • Adhere to formularies and clinical guidelines
  • Use precautions as indicated with high-risk drugs
  • Consult electronic reference for the most up-to-date evidence-based practices
  • Standardize patient transfers between units and facilities
  • Monitor patient for responses to drug changes
  • Minimize the use of samples

High-Alert Drugs

A meta-analysis on high-risk drugs revealed that seven drugs or classes caused approximately 47% of all serious drug errors. These drugs are methotrexate, warfarin, nonsteroidal anti-inflammatory drugs (NSAIDs), digoxin, opioids, acetylic salicylic acid, and beta-blockers. It is estimated that over 70% of all drugs identified were involved in fatal events.79

Among Medicare patients, four drugs, antidiabetic drugs, oral anticoagulants, antiplatelet drugs, and opioids, account for over half emergency room visits for adverse drug events.71

The Institute for Safe Drug Practices reports the drugs that are considered Look-Alike-Sound-Alike as well as high-risk drugs. The list is extensive and should be reviewed periodically. The Institute recommends that the review included storage and dispensing procedures to help in decreasing sentinel events that involve drug errors (Institutional high alert meds). The entire list can be found at www.ismp.org/tools/institutionalhighAlert.asp

Computerization of the Drug Administration Process

Automation in pharmacy and nursing unit drug dispensing appears to decrease the number of drug errors. The evidence to support a computerized entry system as the ideal way to decrease drug error is marginal at best.72 Nevertheless, health care systems have moved to a more automated method of patient care, including computerized order entry, automated clinical decision support systems, and electronic health records.80 Barcoding systems for drug administration help to identify the right patient, drug, dose, route, and time. This system has lowered the errors that occur in the administration phase.81 However, the transcription phase must be correct for the bar code to be effective.

Some physicians' orders are still handwritten and then manually transcribed to a drug administration record. This handwriting transcription leaves a lot of opportunity for errors. A computerized physician order entry, in which the physician must enter all orders by computer, eliminates handwriting and transcription errors but still may not reduce administration error.72, 80 It also makes it possible to automatically check doses, drug-drug interactions, allergies, and significant patient data, like impaired renal function. Automation is very dependent upon each phase being correct. If one step is missed or is incorrect due to human inaccuracy, the risk of an adverse effect due to a drug error is significantly increased.

Automated systems can present several problems. There is a significant expense that smaller facilities may not be able to afford. Cost prohibitions or lack of space may limit the number of PCs to the point that practitioners have long wait times for computer access. It also seems slow and inconvenient at times. Also, physicians who are less computer-savvy may be resistant to implement the system fully. Human error is also a factor. Education and communication are again the keys to decreasing drug errors.

Case Study

Ms. Smith is a 72-year-old woman with a history of chronic obstructive pulmonary disease, coronary artery disease, hypertension, hyperlipidemia, chronic renal insufficiency, and depression. She was admitted to a post-operative unit after receiving a total hip arthroplasty after a femoral neck fracture from a fall. When she awoke from surgery, she complained hip pain.

She has an order for IV morphine 2 to 4 mg every 2 to 4 hours as needed. When the nurse did the initial assessment, the patient reported the pain to be 10/10. She reviewed the order, and the nurse drew up 3 mg of hydromorphone instead of morphine. After she gave the drug, she left the room and came back 20 minutes later and found the patient cyanotic and not breathing. A code was called, and aggressive measures were undertaken, including intubation and ventilation. An assessment of brain activity revealed no brain activity, and the family decided to take the patient off life support, and the patient died after twenty minutes off the ventilator.

A lawsuit was filed, and the verdict found against the nurse for 3 million dollars.

Why the patient died? The nurse gave the incorrect drug, and consequently, the patient received a 7 to 10 -fold increase in intended pain drug dose leading to respiratory arrest, intubation, brain death, and death. The typical dose of hydromorphone IV would be 0.2 to 0.6 mg, and when she received 3 mg, this is about a seven to10 times increase in the appropriate dose. In an opiate naïve patient, this led to respiratory arrest.

What lessons can be gleaned from the above study?

Follow the ten rights every time.

Know common errors. In this case, the wrong drug was administered. Even though it was the wrong drug, the nurse should have realized that using two bottles of hydromorphone (1 mg/mL and 2 mg/mL) was incorrect. Older patients typically require small doses of drugs, and when two bottles were needed, the nurse should have been suspicious, something was amiss.

Review and verify the drug administration record (MAR). Errors can occur if the MAR is not reviewed. It should be compared with any subsequently ordered drugs and reviewed for any contraindications or discrepancies. In this case, if the nurse carefully looked at the MAR, she would have realized which drug was ordered.

Perform your duty. The nurse must administer the drug safely and correctly.

Know commonly prescribed drugs for your unit. In this unit, hydromorphone is not a standard drug that is used. If the nurse would have considered this before drawing up or administering the drug, the nurse may have been more cautious in giving this drug. Also, be familiar with typical doses, possible side effects, and contraindications to commonly used drugs. If the nurse were familiar with the typical dose of hydromorphone, she would have realized that this was too high.

Conclusion

This course provided an overview of pharmacology. Starting with the basic duties of the nurse, a brief discussion of pharmacokinetics, and how to use drugs, then discussing basic pharmacology of multiple drug classes and finishing with drug administration and drug errors. This course has the goal of improving the knowledge of the nurse to administer drugs safely and effectively.

Select one of the following methods to complete this course.

Take TestPass an exam testing your knowledge of the course material.
OR
Reflect on Practice ImpactDescribe how this course will impact your practice.   (No Test)

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