Adverse Reactions to Drugs: Brief Review

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at NSU

When drug reactions resembling allergy happen, they are called drug hypersensitivity reactions (DHRs). Drug hypersensitivity reactions may be allergic or nonallergic. Drug allergies are drug hypersensitivity reactions caused by the immune system.

Classification of adverse reactions to drugs: "SOAP III" mnemonic (click to enlarge the image):

Adverse drug reactions (ADRs) affect 10–20% of hospitalized patients and 25% of outpatients.

Rule of 10s in ADR

10% of patients develop ADR
10% of these are due to allergy
10% of these lead to anaphylaxis
10% of these lead to death

Figure 1. Mind map diagram of adverse reactions to drugs (click to enlarge the image).

Introduction and Epidemiology (click to read the full article).

Pathophysiology (click to read the full article).

Types of ADRs and Risk Factors (click to read the full article).

Diagnosis of Drug Allergy (click to read the full article).

Management of adverse drug reactions: PAD

Figure 7. Management of adverse drug reactions: PAD (click to enlarge the image).

Premedication with antihistamines and steroids


Desensitization. Used for patients with history of IgE-mediated allergic reactions to PCN who require PCN for serious infections, e.g. bacterial endocarditis or meningitis. Different PO or parenteral protocols have been proposed.

Minimum requirements for rapid desensitization: 1-on-1 RN, CPR/ACLS, crash cart, Epi at bedside, anesthesia/code team, allergist 3 minutes from bedside.

Desensitization protocols for a medication allergy

The patient should be in a monitored environment (at least on telemetry) with IV access, epinephrine, IV diphenhydramine, O2 and resuscitation equipment at the bedside. Obtain informed consent prior to the procedure because an anaphylactic reaction during the protocol administration may result in death.

Desensitization is based on incremental dosing of the antigen q 30 min. Oral or IV regimens can be used; SC or IM regimens are not recommended. A typical desensitization protocol for beta-lactam antibiotics involves starting at a dose which is 6-7 logs below the usual therapeutic dose and increasing the dose by 1 log every 30 minutes.

Dilute drug solution/suspension to 1–3 mg/ml. Prepare three tenfold dilutions.

The success depends on constant presence of drug in the serum and so must not be interrupted; desensitization is immediately followed by full therapeutic doses. Hypersensitivity typically returns 24-48 hours after discontinuation. Minor reactions (eg, itching, rash) are common during desensitization.

Desensitization protocols are considered only for drugs such as penicillin or insulin when the use of the drug could be absolutely life-saving and no alternative exists.

Desensitization should not be attempted in patients who have had Stevens-Johnson syndrome in the past. Serum granulysin (level greater than 10 ng/mL) predicts Stevens-Johnson syndrome and toxic epidermal necrolysis and the test takes just 5 minutes. J Am Acad Dermatol. 2011;65:65-68.


20% of asthmatic adults are sensitive to ASA.

What is the triad of aspirin-exacerbated respiratory disease (AERD)?
Samter's triad include asthma, aspirin sensitivity, and nasal/ethmoidal polyposis:

Sensitivity to aspirin

Associated reactions to other NSAIDs are common and they should be avoided in patients sensitive to ASA.

HIV and Drug Hypersensitivity

Drug hypersensitivity has been reported to occur 100 times more commonly in patients with HIV.


Drug hypersensitivity decreases with time. IgE antibodies are present in 90% of patients 1 year after an allergic reaction but in only about 20-30% after 10 years. Patients who have anaphylactic reactions are more likely to retain antibodies longer.


Clinical review: ABC of allergies. Adverse reactions to drugs. BMJ 1998;316:1511-1514.
Severe Cutaneous Adverse Reactions to Drugs. Current Opinion in Allergy and Clinical Immunology. Faith L. Chia; Khai Pang Leong. Published on Medscape, 08/2007.
Which Cephalosporins to Use in Penicillin Allergy? AllergyNotes, 2007.
Drug Hypersensitivity. Merck Manual, 2005.
Drug hypersensitivity. Francis C K Thien. MJA 2006; 185 (6): 333-338.


Blue Hives. NEJM Images in Clinical Medicine, 02/2008.

Related Reading

Drug Hypersensitivity in HIV. Current Opinion in Allergy and Clinical Immunology. Elizabeth Phillips; Simon Mallal. Published on Medscape, 08/14/2007.
Number of patients with drug allergy before and after allergologic study (figure) and JACI, 2012
Adverse Drug Reactions: Types and Treatment Options. AFP, 2003.
Drug Allergy. Allergy Society of South Africa.
How Can I Recognize an Adverse Drug Event? William N. Kelly, PharmDMedscape Pharmacists, 02/12/2008.
Anticonvulsant Hypersensitivity Syndrome: Implications for Pharmaceutical Care. Medscape, 2007.
Practical Aspects of Choosing an Antibiotic for Patients with a Reported Allergy to an Antibiotic. Joan L. Robinson, Tahir Hameed, and Stuart Carr. Clinical Infectious Diseases 2002;35:26–31.
Seafood Allergy and Radiocontrast Media: Are Physicians Propagating a Myth? Andrew D. Beaty, MD, Philip L. Lieberman, MD, Raymond G. Slavin, MD. American Journal of Medicine,Volume 121, Issue 2, Pages 158.e1-158.e4 (February 2008).

Multiple choice questions

Chapter 57: Drug Allergy. Allergy and Immunology Review Corner: Chapter 57 of Pediatric Allergy: Principles & Practices, edited by Donald Y.M. Leung, et al.

Published: 07/11/2007
Updated: 03/01/2014

No comments: