What is a drug allergy
It is immunological Mediated reaction producing stereotype symptoms which are unrelated to the pharmacodynamic profile of the drug, generally, occur even with much smaller does and have a different time course of the of the onset and duration. This is also called drug hypersensitivity but does not refer to increase response which is called supersensitivity.
Allergic reactions occur only in a small proportion of the population exposed to the drug and cannot be produced in other individuals at any dose. Prior sensitization is needed and a latent period of at least I-2 weeks is required after the first exposure. The drug or its metabolite acts as antigen (AG) or more commonly hapten (incomplete antigen: drugs have small molecules which become antigenic only after binding with n endogenous protein) and induce production f antibody (AB) sensitized lymphocytes. Pre- ence of AB to a drug is not necessarily followed y allergy to it. Chemically related drugs often how cross-sensitivity. One drug can produce different types of allergic reactions in different individuals, while widely different drugs can produce the same reaction. The course of drug allergy is variable: an individual previously sensitive to a drug may subsequently tolerate it without a reaction and vice versa.
Mechanism and types of allergic reactions
Type-1 (anaphylactic) reactions Reaginic antibodies (gE) are produced which get fixed to the mast cells. On exposure to the drug, AG: AB reaction takes place on the mast cell surface releasing mediators like histamine, 5-HT. leukotrienes especially LT-C4 and D4. prostaglandins, PAF, etc. resulting in urticaria, itching, angioedema, bronchospasm, rhinitis or anaphylactic shock. The manifestations occur quickly after challenge and are called immediate hypersensitivity. Antihistaminic drugs are bene. hotel income out feels reactions.
Type-2 (cytolytic) reactions Drug + component of a specific tissue cell act as AG. The resulting antibodies (IgG, IgM) bind to the target cells; on reexposure AG: AB reaction takes place on the surface of these cells, complement is activated and cytolysis occurs, e.g. thrombocytopenia, agranulocytosiS, aplastic anaemia, haemolysis, organ damage (liver, kidney, muscle), systemic lupus erythematosus.
Type-3 (retarded, Arthus) reactions These are mediated by circulating antibodies (predominantly IgG, mopping AB). AG: AB complexes bind complement and precipitate on vascular endothelium giving rise to a destructive inflammatory response. Manifestations are rashes, serum sickness (fever, arthralgia, Iymphadenopathy), polyarteritis nodosa, Stevens-johnson syndrome (erythema multiforme, arthritis, nephritis, my-1 carditis, mental symptoms). The reaction usually subsides in 1-2 weeks.
Type-4 (delayed hypersensitivity) reactions These are mediated through production of sensitized I-lymphocytes carrying receptors for the AG. On contact with the AG, these Tr cells produce lymphokines which attract granulocytes and generate an inflammatory response, Oo e5. contact dermatitis, some rashes, fever, photosensitization. The reaction generally takes 12 hours to develop.
Treatments of drug allergy
The offending drug must be immediate must the offending drug stopped. Most mild reactions (like skin rashes) subside by themselves and do not require specific treatment. Antihistamines (H) are beneficial in some type l reactions (urticaria, rhinitis, swelling of lips, etc.) and some skin rashes. In case of anaphylactic shock or angioedema of larynx the resuscitation council of UK has recommended the following measures:
- Put the patient in reclining position, administer oxygen at a high flow rate and perform cardiopulmonary resuscitation it required.
- Inject adrenaline 0.5 mg (0.5 ml of 1 in 1000 solution) i.m.; repeat every 5-10 min in case patient does not improve or improvement 1s transient. This is the only life-saving measure. Adrenaline should not be injected i.v. (can itself be fatal) unless shock is immediately life-threatening. If adrenaline is to be injected i.v., it should be diluted to 1:10,000 or 1:100,000 and infused slowly with constant monitoring.
- Administer a H1 antihistaminic (chlorpheniramine 10-20 mg) i.m./slow i.v. It may have adjuvant value.
- Intravenous glucocorticoid (hydrocortisone sod. succinate 100-200 mg) should be added in severe/recurrent cases. It acts slowly but is especially valuable for prolonged reactions and in asthmatics.
Adrenaline followed by a short course of glucocorticoids is indicated for bronchospasm attending drug hypersensitivity. Glucocorticoids are the only drug effective in type I, type Ill and type IV reactions.