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Appendix 1: Drug Allergy

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TABLE A1–1: Classification of Allergic Drug Reactions

Type

Descriptor

Characteristics

Typical Onset

Drug Causes

Immediate (IgE mediated)

Allergen binds to IgE on basophils or mast cells, resulting in release of inflammatory mediators

Within 1 hour (may be within 1–6 hours)

Penicillin anaphylaxis, angioedema

Blood products

Polypeptide hormones

Vaccines

Dextran

Delayed; Cytotoxic

Cell destruction occurs because of cell-associated antigen that initiates cytolysis by antigen-specific antibody (IgG) and complement. Most often involves blood elements.

Typically >72 hours to weeks

Penicillin, quinidine, quinine, heparin, thiouracils, sulfonamides, methyldopa

III

Delayed; Immune complex

Antigen–antibody (IgG or IgM) complexes form and deposit on blood vessel walls and activate complement. Result is a serum sickness-like syndrome or vasculitis.

>72 hours to weeks

May be caused by penicillins, sulfonamides, minocycline, hydantoins

Delayed; T Cell-mediated

Antigens cause activation of T lymphocytes, which release cytokines and recruit effector cells

>72 hours

IVa

Th1 cells and interferon-γ, monocytes and eosinophils respond to the antigen

1–21 days

Tuberculin reaction, contact dermatitis

IVb

Th2 cells, interleukin-4 and interleukin-5 respond to the antigen

1–6 weeks

Maculopapular rashes with eosinophilia

IVc

Cytotoxic T cells, perforin, granzyme B, FasL respond to the antigen

4–28 days

Bullous exanthems; fixed drug eruptions

IVd

T cells and interleukin-8 respond to the antigen

>72 hours

Acute generalized exanthematous pustulosis

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TABLE A1–2: Top 10 Drugs and Agents Reported to Cause Skin Reactions

Reactions per 1000 Recipients

Amoxicillin

51.4

Trimethoprim–sulfamethoxazole

33.8

Ampicillin

33.2

Iopodate

27.8

Blood

21.6

Cephalosporins

21.1

Erythromycin

20.4

Dihydralazine hydrochloride

19.1

Penicillin G

18.5

Cyanocobalamin

17.9

Data from Roujeau JC, Stern RS. Severe adverse cutaneous reactions to drugs. N Engl J Med 1994;331:1272-1285.

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TABLE A1–3: Treatment of Anaphylaxis

Remove the inciting allergen, if possible.
Assess airway, breathing, circulation, and orientation. Support the airway.
Cardiopulmonary resuscitation: Start chest compressions (100/min) if cardiovascular arrest occurs at any time.
Administer epinephrine 1:1000 (adults: 0.3–0.5 mg; children: 0.01 mg/kg) IM in the lateral aspect of the thigh.
Place patient in recumbent position.
Administer oxygen 8–10 L/min through facemask or up to 100% oxygen as needed; monitor by pulse oximetry, if available.
Repeat IM epinephrine every 5–15 minutes for up to 3 injections if the patient is not responding.
Establish IV line for venous access. Keep line open with 0.9% saline solution. For hypotension or failure to respond to epinephrine, administer 1–2 L at a rate of 5–10 mL/kg in the first 5–10 minutes. Children should receive up to 30 mL/kg in the first hour.
Consider nebulized albuterol 2.5–5 mg in 3 mL of saline for lower airway obstruction; repeat as necessary.
In cases of refractory bronchospasm or hypotension not responding to epinephrine because a β-adrenergic blocker is complicating management, glucagon 1–5 mg IV (20–30 mcg/kg; maximum, 1 mg in children) given IV over 5 minutes.
Give epinephrine by ...