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Allergy versus side effects: The Confusion Must Stop

1 Contact Hour including 1 Advanced Pharmacology Hour
This peer reviewed course is applicable for the following professions:
Advanced Registered Nurse Practitioner (ARNP), Certified Nurse Midwife, Certified Nurse Practitioner, 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 Sunday, September 17, 2023

Nationally Accredited

CEUFast, Inc. is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation. ANCC Provider number #P0274.


≥92% of participants will know how to prevent and manage allergic reactions and side effects.


After completing this course, the learner will be able to:

  1. Identify the types of adverse drug reactions.
  2. Describe how drugs and their metabolites become active allergens.
  3. Examine type A and type B adverse drug reactions.
  4. Differentiate between anaphylactic and anaphylactoid reactions.
  5. Compare and contrast allergic reactions and side effects.
  6. Explain the management and prevention strategies for allergic reactions and side effects.
  7. Develop a plan of action for patients presenting with symptoms of a medical emergency.
CEUFast Inc. and the course planners for this educational activity do not have any relevant financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

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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:    Berthina Coleman (MD, BSN,RN)

Definition of Terms

Side Effects

Side effects are the secondary and undesired effects of a drug (Sandritter et al., 2020). These are expected reactions that occur with administering a drug and every patient receiving that drug is at risk for experiencing side effects. Examples of side effects include drowsiness with the administration of diphenhydramine and nausea with chemotherapeutic drugs (Sandritter et al., 2020).

Adverse Drug Reactions

An adverse drug reaction is the response to a medication, when given in the prescribed dosages, that is unpleasant and unintended (Shamim, 2016).

Type A Adverse Drug Reactions

Typically, adverse drug reactions are classified into two subtypes: Type A and Type B (Sandritter et al., 2020). Type A refers to dose-dependent reactions, typically predictable reactions, making up approximately 85 to 90% of all adverse drug reactions.

Type B Adverse Drug Reactions

Type B reactions are also called idiosyncratic reactions, which are not dose-dependent and are unpredictable. They account for approximately 10-15% of all adverse reactions. Occasionally, patients may mistake side effects for allergies. For example, drowsiness with Diphenhydramine.

Allergic Reactions

Allergic reactions are aberrant immune responses to an antigen or an allergen (Sandritter et al., 2020). An antigen is defined as a toxin or substance that incites an allergic reaction in the body, especially one that leads to the production of antibodies. An allergen is defined as a substance that incites an allergic reaction in a patient.

It has been previously reported that true hypersensitivity reactions to drugs probably account for less than 10% of all adverse drug reactions. In general, most drugs are small organic molecules incapable of stimulating a full immune response independently. However, when these drug molecules or their metabolites become bound to proteins, they form drug-protein complexes, acting as allergens and stimulating an immune system response. The ability of a drug or a metabolite to sensitize the immune system depends on its ability to bind tissue proteins and become an allergen (Sandritter et al., 2020).


The term allergy implies an immediate hypersensitivity reaction mediated by the immunoglobulin E (IgE) antibody (Sandritter et al., 2020). However, many allergic reactions are not IgE-mediated. The subsequent reaction produces a wide range of clinical symptoms ranging from itching to anaphylaxis.


Anaphylaxis is the most severe form of an allergic reaction, and it can occur suddenly and may, eventually, lead to death.

Anaphylaxis occurs when the body’s immune system produces immunoglobin E. This substance binds to cells in the body called mast cells that then release chemicals that cause an allergic reaction, such as redness, swelling, or hives. After this process occurs once, it is likely to get more severe with each additional exposure (Justiz Vaillant et al., 2021; Rowe & Gaeta, 2016).

Allergic reactions after the oral administration of drugs tend to occur at unpredictable times. The anaphylactic reaction may occur within a few seconds to a few minutes. Anaphylaxis often produces signs and symptoms within 5 to 30 minutes, but reactions sometimes do not develop for several hours (Justiz Vaillant et al., 2021; Rowe & Gaeta, 2016).

Anaphylactic reactions currently account for 1 out of every 2000 ambulance requests and are reported to be fatal in as many as 2% of all cases. Some epidemiologic studies have shown that up to 5,100 hospitalizations have been linked to anaphylactic reactions (Cosco et al., 2017).

Anaphylactic Versus Anaphylactoid Reactions

Anaphylactic Reactions are immunologically-mediated instead of reactions secondary to drug interactions, drug overdose, direct toxicity, or pharmacologic idiosyncrasies (Cosco et al., 2017). Anaphylaxis is a type 1 immediate hypersensitivity reaction. Type 1 reactions are IgE-mediated and produce responses in end organs such as urticaria in the skin, angioedema and bronchospasm in the respiratory system, vasodilation, and increased capillary permeability in the cardiovascular system (Cosco et al., 2017).

On the other hand, anaphylactoid reactions can have an identical clinical response, but they are not mediated by IgE or an antigen-antibody process (Cosco et al., 2017). Examples of anaphylactoid reactions include hypersensitivity to radiocontrast dye and angiotensin-converting enzyme inhibitors. Anaphylactoid reactions tend to activate the complement system. The complement system is usually activated in one of two pathways, the classical pathway or the alternative pathway. The classical pathway is initiated through IgG or IgM. The alternative pathway is mediated by endotoxins or directly by the allergen, such as the drug in question. Anaphylactoid reactions cannot be predicted with pretesting; Only IgE-mediated reactions can be predicted with pretesting (Cosco et al., 2017).

Patients with a past medical history of atopic conditions such as eczema, asthma, and seasonal allergies do not have an increased risk of anaphylactic reactions. However, they have an increased risk of having more severe reactions.

How are Allergic Reactions Mediated?

When an allergen binds IgE antibodies on the surface of basophils and mast cells, eosinophilic chemotactic factors and histamine are released from storage granules in the cell (Cosco et al., 2017). Once this happens, other chemical mediators are rapidly synthesized and released, such as kinins, platelet-activating factors, adenosine, and leukotrienes, which are slow-acting reactants involved in anaphylaxis (Cosco et al., 2017). Clinically, the patient experiences the first wave of symptoms, usually vasodilation and a sense of imminent doom (Cosco et al., 2017).

In a sensitized patient, the onset of signs and symptoms can be experienced almost immediately, but it may be delayed by 2 to 15 minutes (Cosco et al., 2017). Occasionally the allergic reactions can be delayed by up to two and a half hours after exposure to the allergen. Mast cell activation and proliferation promote the production of cytokines which perpetuate the allergic reaction even after the allergen is no longer present, lasting up to 6 to 8 hours. The clinical symptoms of an allergic reaction to a drug may vary widely. A generalized allergic reaction may appear similar to serum sickness reactions or immune-complex reactions.

Serum Sickness

Serum sickness and serum sickness-like reactions occur approximately 7-10 days after the primary exposure to an allergen, in this case, the drug, and are characterized by urticaria (hives), polyarthralgia (joint pain involving multiple joints), fever, and lymphadenopathy (swollen lymph nodes) (Rowe & Gaeta, 2016). Occasionally the patients may have systemic venalities’ (inflammation of the veins during intravenous drug administration), which may progress into a full-blown systemic vasculitis.

Serum sickness and serum sickness-like reactions can also occur after secondary exposure to heterologous proteins (classic serum sickness) or after secondary exposure to non-protein drugs such as sulfa-based drugs or penicillin-based antibiotics (serum sickness-like reactions) (Rowe & Gaeta, 2016).

Most transfusion reactions occur due to the formation of immune complexes, which usually result in serum sickness. Transfusion-based allergic reactions usually occur secondary to IgE and IgG antibodies against IgA and mast cell-mediated reactions. Angioedema is initiated by histamine release, but its effects are sustained by peptide kinins unaffected by antihistamines (Katzung, 2015).

Some patients are more susceptible to the release of histamines and other immunologic mediators with the administration of certain drugs. Some believe that there are environmental and hereditary factors that contribute to this predisposition to allergic reactions (Cosco et al., 2017).

Management of Allergic Reactions

First-generation antihistamines are commonly used over-the-counter drugs for the management of allergic conditions. However, they commonly have sedative effects and, as such, second-generation antihistamines (H1 antagonists) are increasingly more frequently used.

Antihistamines are often the first drugs used to prevent or treat allergic reactions. In allergic rhinitis, the H1 antagonists are used after the administration of intranasal steroids. In urticaria, histamines are responsible for mediating the allergic response. For that reason, antihistamines are the drug of choice. In urticaria, antihistamines tend to be more effective if they are administered before exposure to the allergen (Katzung, 2015).

In asthma, there are multiple mediators of allergic reactions; therefore, antihistamines are mostly ineffective (Katzung, 2015). In patients with atopic dermatitis, antihistamines are usually administered for their sedative effects to reduce the patient’s awareness of itching.

In some cases, such as anaphylactoid reactions to intravenous contrast agents, pretreatment with antihistamines (diphenhydramine) has been shown to prevent or ameliorate the reaction (Katzung, 2015).

How to Minimize a Patient’s Risk of Anaphylactic Reactions

  • Obtain a thorough medical history, including an updated allergies list with the reported reaction
  • Premedicate patients with any risk of an anaphylactoid reaction (antihistamines, steroids, and iv fluids)
  • In cases when the diagnosis is unclear, blood levels of chemical mediators, especially tryptase, can be used to clarify the diagnosis

Factors that affect the extent to which an allergic reaction manifests include the following: the amount of the allergen, the route of entry (oral versus dermic versus intravenous), the persistence of the antigen, and the end-organ response to vasoactive mediators.

Other signs and symptoms of allergic reactions are nausea, vomiting, diarrhea, and colicky abdominal pain (gastrointestinal manifestations), dyspnea, wheezing and chest tightness (respiratory manifestations), and peripheral vasodilation, hypotension, and tachycardia (cardiovascular manifestations) (Cosco et al., 2017).

When the Reaction is a Medical Emergency

Patients who present with severe wheezing, hypotension, stridor, hoarseness of voice, and shortness of breath should be treated as a medical emergency (Cosco et al., 2017). The primary focus is to secure the airway and cardiopulmonary resuscitation. Patients who respond to treatment immediately should be observed as inpatients for 24 hours. Those who respond to therapy more slowly or inadequately should be observed in an intensive care unit, where they are generally intubated for any severe laryngeal edema. Occasionally, the patients may have severe hypotension refractory to the treatment, thereby warranting intensive care monitoring (Cosco et al., 2017).

Although the mechanism of allergic reactions remains the same in outpatient and inpatient settings, certain triggers are specific to a hospital setting, such as latex. Additionally, in the hospital setting, intravenous medications are more frequently administered, and they have been linked to more service allergic reactions compared to oral ingestions.

Case Study

Mrs. Tabe is admitted to a medical/surgical unit with Congestive Heart Failure (CHF) and pneumonia. You are the nurse completing the admission and initial assessment. Upon reviewing her medical record, you note that she has an allergy to sulfa drugs and morphine. What are the missing components of her allergy history? How would you proceed to clarify her allergy history?


When obtaining an allergy history, it is important to obtain the specific allergen, the specific allergic reaction, and the last time the allergic reaction occurred. In addition, the nurse obtaining the history should clarify allergies to broad drug categories and aim to characterize them as specifically as possible.

In Mrs. Tabe’s case, we should first focus on the sulfa drug which caused the allergy. In her case, she had an allergy to Trimethoprim/Sulfamethoxazole (Bactrim), which caused a mild rash on her hands that resolved three days later spontaneously. Since then, she has received other sulfa-based non-antibiotics, which did not elicit a response. The allergic response happened once six years prior.

Upon clarification of her allergies, the clinical providers were able to order Lasix intravenously to manage her CHF. Even though Lasix is a sulfa-containing drug, the clinicians felt comfortable administering it given that she only showed a mild reaction to a sulfa-based antibiotic.

The documented reaction to morphine was somnolence which occurred after administering 10 mg of morphine while she had on a fentanyl patch. The patient was educated about the difference between allergic reactions and side effects, and the allergy to morphine was removed from her records.


Nurses play a critical role in obtaining and verifying allergy histories. As such, a thorough and detailed approach is necessary. In some cases, the patient may need to be educated about the difference between side effects and allergies, as detailed in the case above. It is important to enter a note in the medical record explaining details in the allergy history before updating the clinical record.

Select one of the following methods to complete this course.

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  • Cosco, D., Winawer, N., & Murali, M. (2017). Allergy and Anaphylaxis. In S. McKean, J. Ross, D. Dressler, D. Scheurer, Principles and Practice of Hospital Medicine, (2nd Ed). New York, NY: McGraw-Hill. Visit Source.
  • Justiz Vaillant, A., Vashisht, R., & Zito, P. (2021). Immediate Hypersensitivity Reactions. StatPearls Publishing. Retrieved September 2nd, 2021. Visit Source.
  • Katzung, B. (2015). Histamine, Serotonin, & the Ergot Alkaloids. In B. Katzung & A. Trevor, Basic & Clinical Pharmacology, (13th Ed). New York, NY: McGraw-Hill. Visit Source.
  • Rowe, B. & Gaeta, T. (2016). Anaphylaxis, allergies, and angioedema. In J. Tintinalli, J. Stapczynski, O. Ma, D. Yealy, G. Meckler, D. Cline, Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, (8th Ed). New York, NY: McGraw-Hill. Visit Source.
  • Sandritter, T., Lowry, J., Jones, B., Liewer, S., & Kearns, G. (2020). Principles of drug therapy In R. Kliegman, J. St Geme III, N. Blum, S. Shah, R. Tasker, & K. Wilson, Nelson Textbook of Pediatrics, (21st Ed)., Elsevier Inc. Visit Source.
  • Shamim, S., Sharib, S., Malhi, S., Muntaha, S., Raza, H., Ata, S., Farooq, A., & Hussain, M. (2016). Adverse drug reactions (ADRS) reporting: Awareness and reasons of under-reporting among health care professionals, a challenge for pharmacists. SpringerPlus 5, 1778. Visit Source.