Pharmacology Current Practice

1. Right Patient: Use two identifiers. The room number is not an identifier. Ask the patient to identify themself, and check the name on the order and the patient. If available, use technology such as barcoding. For patients not wearing ID bands or those who 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. Verify drugs at the patient’s bedside with the MAR and two identifiers (Potter et al., 2017).
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 pharmacists can safely split any required pills (Potter et al., 2017). If drugs need to be crushed, 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 about the dose on the MAR or 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. 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 judgment on when to administer, such as an as-needed sleeping drug, other drugs are considered time-critical (Vaismoradi et al., 2018). Studies show that giving drugs at incorrect times results in 30-40% of all drug errors (Tariq & Scherbak, 2018). 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.

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

Due to physiological changes, particularly in hepatic metabolism and renal elimination, dosing in the elderly population can be challenging. Older people 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 body weight but must include physiological differences (Germovsek et al., 2018). 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 function. Therefore, developmental growth must also be considered when administering drugs to this population (Germovsek et al., 2018). 

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.

Antibiotics are a diverse group that fights infection. They are classified by action as bacteriostatic or bactericidal. Bacteriostatic action inhibits growth and bactericidal kills bacteria. These actions are accomplished through 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 (Edmunds & Mayhew, 2013).

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 how 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 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 ensure that the antibiotic will eradicate the organism. It is also essential to assess the severity of the illness (Edmunds & Mayhew, 2013). This assessment will determine how aggressively and how long to treat.

Allergic reactions can occur even in patients who have not previously shown sensitivity to the drug. Observing the patient closely while the drug is being administered is important. 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. The intestinal flora is disrupted when antibiotic therapy is initiated, 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 the 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 the antibiotics' adverse effects and contraindications.

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 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. Antiviral drugs' most common side effects are diarrhea, nausea, vomiting, dizziness, sleep issues, and headaches (Nursing 2016 Drug Handbook). However, each type of antiviral classification has additional side effects and serious reactions.

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 evidenced 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.

The 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.

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 (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 (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 has 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

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 for managing 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 using a neuraminidase inhibitor to manage influenza (CDC, 2020b). Individuals prioritized for treatment include those with severe disease or 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 those at high risk or those requiring hospitalization should receive therapy as soon as possible, even after 48 hours.

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

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 increase to 80 mg daily. 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 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 daily, and the dose can be increased gradually to a maximum of 200 mg daily. 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 missed doses. 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 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 (Williams & Nieuwsma, 2020).

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 daily and may increase 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) can potentially prolong the QT interval and may be fatal. They should be used cautiously in those with underlying heart disease and those prone to becoming hypokalemic.

Serotonin and norepinephrine reuptake inhibitors:

Serotonin and norepinephrine reuptake inhibitors (SNRIs) are newer drugs to treat depression and anxiety. Drugs in this class include venlafaxine (Effexor), duloxetine (Cymbalta), desvenlafaxine (Pristiq), milnacipran (Savella), levomilnacipran (Fetzima). This class has a similar safety profile to SSRIs, but occasionally they may be associated with increased 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 pain and other somatic complaints in depression when compared to other antidepressants (Thase, 2011).

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 daily. 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 daily, it mainly affects serotonin levels, but higher doses affect dopamine and norepinephrine levels. Discontinuation syndrome is high with this drug.

Desvenlafaxine:

Desvenlafaxine (Pristiq) is dosed at 50 mg daily 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 daily on the first day and titrated upwards to a maximum of 200 mg daily divided every 12 hours. It should be used cautiously in those with moderate to severe renal and 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 at 20 mg twice a day to start and may be increased to 30 mg twice daily 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 treating depression in addition to diabetic peripheral neuropathy, chronic musculoskeletal pain, fibromyalgia, and generalized anxiety disorder. This drug is often used by those with 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, Aplenzin, and Forfivo XL. It increases the risk of seizures 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 at 15 mg at bedtime and may be increased every 1-2 weeks up to 45 mg daily in adults. It is given at bedtime because sedation is a significant side effect. Another common side effect is weight gain. Other side effects include dry mouth, constipation, and dizziness.
• Vortioxetine (Brintellix) starting dose is 10 mg daily and may be increased to 20 mg daily. The dose may be lowered to 5 mg a day for those who do not tolerate the higher dose. It works on multiple receptors and increases noradrenaline, dopamine, and glutamatergic transmission. The drug's half-life 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 (Citrome, 2014).
• 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 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. Increased agitation, irritability, or other behavior changes 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 have existed since the 1950s and include 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.

Recognizing and treating side effects is a key component of pharmacotherapy with antipsychotics. Those 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 a 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 (Jibson, 2020). 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 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 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, 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 dementia, the 23 mg dose was associated with improved cognition but no difference in overall functioning and more side effects (Farlow et al., 2010).

Common side effects of donepezil include nausea, vomiting, and diarrhea. Bradycardia can arise and may slow the heart rate to a point 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 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 or high dose patch (Birks et al., 2015).

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 (Ford & Almeida, 2017). Combining memantine and a cholinesterase inhibitor may have extra benefits when combined.

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 disorder in childhood and adolescence, and many of these cases persist into adulthood (CDC, 2020c). The pathology of ADHD is unknown, but it is theorized that certain brain parts are linked to attention lack in neural transmission. 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% (Sofeff, 2020).

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 (CDC, 2020c). 

There are three types of ADHD:

• Predominantly hyperactive
• Predominantly inattentive
• Combined

The inattention type must have at least six symptoms (at least five symptoms if an adolescent is 17 years old or older) of inattention persisting for at least six months to the point it is maladaptive and not consistent with the developmental level (APA, 2013). These include difficulty maintaining attention in play or tasks, forgetful in daily activities, avoiding tasks/strongly disliking tasks that require mental effort, being easily distracted, losing items necessary for tasks or activities, not seeming to listen, having difficulty organizing tasks and activities, failing to pay close attention to details or makes careless mistakes and does not follow through on instructions.

The hyperactive/impulsive type must have at least six of the following symptoms (at least five symptoms if an adolescent is 17 years old or older) for at least six months to the point it is maladaptive and not consistent with the developmental level (APA, 2013).  These include hyperactivity 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 include being 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 (APA, 2013). 

Before prescribing drugs for ADHD, the clinician must ensure 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 with the patient (particularly with immediate-release 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 an MAO inhibitor. It should be used carefully in those with hypertension, bipolar disease, psychosis, and seizures.

Potential side effects include headaches, nausea, seizures, increased blood pressure, 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; therefore, long-acting (once a day) drug is better at improving compliance.

This drug's exact mechanism of action 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 with 2.5 mg twice daily and increased every week by 2.5 to 5 mg increments with a maximum dose of 20 mg daily. The extended-release formulation is dosed 5-10 mg a day and increased to 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 with hypersensitivity to dexmethylphenidate, those with Tourette syndrome, motor tics, significant agitation, glaucoma, or anxiety. It should not be used within 14 days of taking an 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 that are effective for ADHD but not as effective as stimulants include atomoxetine, extended-release guanfacine (Intuniv), and extended-release clonidine (Kapvay) (Wolraich et al., 2020).

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 effect fully. It is FDA approved for children and adults and is often used by those with a history of substance abuse (Cunill et al., 2015).

Atomoxetine is well tolerated, and side effects may include slight heart-rate/blood pressure increases. 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 using stimulants, or atomoxetine is not effective, have significant side effects or co-morbid conditions exist. Guanfacine or clonidine is sometimes used with stimulants as adjunctive therapy (Wolraich et al., 2020).

Research has shown effectiveness in these agents, but the effectiveness is not as robust as those with stimulants. These agents are not approved in adults. Some argue that the effectiveness of clonidine is due to its sedating effects, which reduce agitation (Pliszka, 2003).

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.

Antihypertensive Drugs:

Globally, approximately one billion individuals have hypertension, which makes up about 25% of the adult population (CDC, 2020d). 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 treating high blood pressure (ALLHAT, 2004). 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 preventing 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 and part of the combination in controlling those with more than 20/10 mm Hg over the goal (Chobanian et al., 2003). Diuretics should also be considered in those with a stroke, heart disease, heart failure, and diabetes history.

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 (ALLHAT, 2004).

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 gout (Bardin & Richette, 2017)
• 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 raises blood pressure. Angiotensin-converting enzyme inhibitors prevent the conversion of angiotensin I to angiotensin II and, in so doing, drop blood pressure. Angiotensin II also elevates blood pressure by contributing to water and sodium retention.

ACE-I can be used as a first-line agent, 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 angioedema happens, but this can be severe, so monitor patients carefully during the first few doses. ACE-I can result in worsening 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 cannot tolerate 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 it 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 make up 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 beta-blockers. The dihydropyridines may result in vasodilatation and may lead to reflex tachycardia.

CCB is used in those with uncomplicated hypertension, those with hypertension and comorbid diabetes, and 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 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 (Woo & Wynne, 2011).

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, reducing heart rate and cardiac output and lowering blood pressure. Also, beta-blockers lower renin release and tend to be most effective in lowering blood pressure in those with elevated renin levels, including 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 (Nursing 2016 Drug Handbook).

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 can potentially 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 thrice daily.

In the United States, heartburn affects approximately 7% of the population daily, and up to 25-40% experience symptomatic gastroesophageal reflux disease (GERD) (Patti, 2019). 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 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). Adding alginic acid to an antacid is more effective than an antacid alone but is more expensive. A stronger drug is needed if lifestyle changes and antacids do not help symptoms.

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. H2RAs block histamine from binding to the histamine two receptors on the parietal cell, leading to a decreased amount of acid production.

H2RA can treat grade 1 and 2 esophagitis and mild to moderate symptoms. Long-term use is not recommended because tolerance can develop.

H2RA has a slower onset of action than antacids but works 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 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.

The PPIs provide a slower onset of relief when compared to the H2RA. It may take 1-4 days to notice complete relief 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.

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 (Williams, 2018). Glucocorticoids decrease inflammation, increase capillary permeability, and modify the body's immune response. Mineralocorticoids increase sodium's reabsorption by increasing the excretion of hydrogen and potassium.

Glucocorticoids are used to treat asthma allergic reactions and 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 for 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

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 (Shamliyan et al., 2012).

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 (Finney et al., 2006). 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 (Lukacz, 2020).

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.

The side effects of antimuscarinics are problematic. Side effects are limited by starting low and going slow. Side effects vary among drugs, but 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.

Anticoagulants 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 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, a lower risk of osteoporosis, and possibly a lower bleeding risk. LMWH drugs include dalteparin (Fragmin®), enoxaparin (Lovenox®), and tinzaparin (Innohep®) (Solari et al., 2019).

Anticoagulant drugs' most common side effect is an increased risk of bleeding. Renal excretion must be considered 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, impacting Factors II, VII, IX, and X. At a therapeutic level, warfarin inhibits the ability of the liver to produce vitamin K, which creates a 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 another new drug (Nursing 2016 Drug Handbook).

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 and complete a full patient assessment. Warfarin also interacts with several other drugs and foods. Check all drugs for interactions, assess the patient’s diet, and ask about any herbals or vitamins taken.

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 to treat 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, pain, and bruising at the injection site. Monitoring aPTT begins 3-4 hours after initiation, and doses are adjusted accordingly.

Nursing Considerations for heparin:

• Inject between iliac crests in the lower abdomen into the fat layer
• Do not massage the 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.

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 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 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 (Nathan et al., 2018). 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 reduce the amount of blood glucose the liver excretes. TZD lowers the HbA1C by 0.4 to 1.4 points when used alone (Nathan et al., 2018). 

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

These agents have been shown to lower triglyceride levels but may increase LDL cholesterol. They can potentially 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 the liver produces and enhances the cell’s ability to use insulin more effectively.

Metformin and lifestyle changes are recommended for the initial treatment of diabetes, assuming there are no contraindications (Nathan et al., 2018).  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 and lowers the risk of death and diabetes-related endpoints (UKPDS, 1998).

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 the 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 cautiously 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, reducing 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 by 0.5 to 0.8 percent (Nathan et al., 2018).  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 by 1.0 to 1.5 percent (Radley et al., 2013).  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 instead of nateglinide, which the kidney metabolizes. 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 daily, 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 cardiovascular benefits (DeSantis, 2019). Other agents in this class include canagliflozin, ertugliflozin, and dapagliflozin. Assessing and monitoring renal function and volume status is important when using these agents. 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. 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 blood glucose control. 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 replaces 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.

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

Ms. Stevenson, 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 ordered diltiazem for ventricular rate control as an intravenous bolus at 0.25 mg/kg over two minutes. 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 of 5 mg/mL. How many mL does she need to push over 2 minutes?

15 mg divided 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?

After taking the order off, the nurse enters the drug room 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....

Reducing drug errors may include the following:

• Routinely reconcile drugs at admission, discharge, or patient transfer
• Avoid verbal orders except in emergencies
• Assess all drugs the patient is currently using
• Keep drug records accurate and up-to-date
• Assess for allergic reactions
• Educate patients on 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 references 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 (Billstein-Leber et al., 2018)

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 (Saedder et al., 2014).

Among Medicare patients, four drugs, antidiabetic drugs, oral anticoagulants, antiplatelet drugs, and opioids, account for over half of emergency room visits for adverse drug events (DHHS, 2020). 

The Institute for Safe Drug Practices reports the drugs 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 include 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

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 (Radley et al., 2013). 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 (Alotaibi & Federico, 2017). Barcoding systems for drug administration help identify the right patient, drug, dose, route, and time. This system has lowered errors in the administration phase (Chen et al., 2019). However, the transcription phase must be correct for the bar code to be effective.

Some physicians' orders are handwritten and manually transcribed to a drug administration record. This handwriting transcription leaves many opportunities 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 errors (Radley et al., 2013).  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, less computer-savvy physicians may be resistant to implementing the system fully. Human error is also a factor. Education and communication are again the keys to decreasing drug errors.

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 of 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 giving 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. The patient died after twenty minutes off the ventilator.

A lawsuit was filed, and the verdict was 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 the 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 from 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 the nurse should have suspected something was amiss when two bottles were needed.

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 contraindications or discrepancies. In this case, if the nurse had carefully examined 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 had 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 this was too high.