Managing a suspected adverse drug reaction

Oliver Jones explains the different types of adverse drug reactions and what to do about them

The clinical scenario is familiar to many of us. You are asked to see a patient just before midnight. The patient has been in hospital for several days, but started to develop a rash with slight puffiness round the eyes and mouth only in the previous couple of hours. You suspect an adverse drug reaction (ADR). What should you do?

Frequency and types of adverse drug reaction

ADRs are common. In a recent single practice study general practitioners estimated that the presenting symptom of 1.7% of their consultations over a six month period was a manifestation of an ADR.¹ Furthermore, it is likely that 2-6% of hospital admissions are for ADRs.² Both these figures may underestimate the true incidence.

Any drug may cause a reaction. In broad terms, ADRs may be considered in five groups. The two most common are dose related effects (type A: augmented) and effects related to abnormal interaction between patient and drug (type B: bizarre). Postural hypotension in a patient on antihypertensive medication is an example of a type A reaction, reflecting nothing more than the normal pharmacological effect of the drug. Rash associated with penicillin use is an example of a type B reaction. The remaining three types are listed in table 1.³

Assessing likelihood that an ADR has occurred

An ADR should be considered in any patient taking prescribed or over the counter medications. One of the first issues to consider is if the time scale of onset of the adverse reaction fits with the timing of dosage or peak plasma concentration. A similar relation may be seen between withdrawal of the drug and abatement of symptoms. In the case of drug allergic reaction, there is often (though not always) a history of previous exposure to the drug. Finally, there is also the option of reintroducing the suspected drug. This may be of long term benefit to the individual, especially for those in whom alternative pharmacological options are limited. This should not be undertaken without careful consideration and observation.

Management of a suspected ADR

For type A reactions, the management is simply reduction in the dose or withdrawal of the medication altogether. By contrast type E reactions require reintroduction of the drug and more gradual withdrawal. By the time a type C or D reaction occurs, it may be irreversible or at best only partially reversible on drug withdrawal.

Type B reactions are both uncommon, unpredictable, and have high morbidity and mortality. The first step is always the immediate withdrawal of the drug. If the reaction is mild, no further intervention may be necessary. Urticarial rashes, and to a lesser extent non-urticarial rashes, may be treated with antihistamines such as chlorpheniramine and an adrenocortical steroid. In more severe cases, these drugs may be given intravenously or intramuscularly. If angioedema develops with threatened laryngeal oedema, consideration should be given to adrenaline (see below).

Anaphylaxis is a medical emergency. Senior help should be summoned, including an anaesthetist. The patient should be positioned flat, with feet raised and airway secured. Oxygen should be administered. 0.5-1.0mg of adrenaline should be given intramuscularly as first line treatment (equivalent to 0.5-1.0ml of 1:1000 adrenaline). This is repeated every ten minutes according to cardiovascular parameters and clinical improvement. Chlorpheniramine (10-20mg) should also be administered by slow intravenous injection, and hydrocortisone (100-300mg), though the onset of action of the latter may not be for several hours. Further deterioration may necessitate intravenous fluids, nebulised inhalers, and intubation or tracheostomy.

Other ADRs may involve any body system and manifest in several different ways. The correct management of these patients should be considered on an individual basis. Often this is delayed by failure to consider an ADR as the underlying cause of a patient's deterioration.

Summary points

• Always suspect an ADR in the unwell patient taking any medication
• The first step in management is to withhold or withdraw the suspected drug
• Further treatment should be decided on an individual basis
• Although rare, ADRs are a significant cause of morbidity and mortality
• Always tell the patient of a suspected ADR so that they are able to take precautions in the future
• Consider whether the ADR warrants reporting to the Medicines Control Agency

Reporting ADRs

The first person to whom the drug reaction should be reported is the patient. Subsequent re-exposure (especially if a type B reaction) may induce a more severe reaction than the first, and patients should be told of the need to tell all their future doctors.

It is worth remembering that although all drugs are evaluated before marketing (phase I-III trials), ADRs either of low frequency or found only in subgroups of patients, may not be detected until postmarketing surveillance (phase IV). The surveillance system in Britain requires doctors to report to the Medicines Control Agency using the yellow cards available at the back of the British National Formulary (BNF). Serious or unusual adverse events for all drugs should be reported. Recently marketed drugs, identified in the BNF by an inverted black triangle, should have all suspected minor or major ADRs reported. Further postmarketing surveillance is carried out by various agencies who contact doctors directly for information on ADRs (if any) in patients under their care receiving new drugs.

Oliver Jones, research fellow, department of pharmacology, University of Oxford
Email: oliver.jones@pharm.ox.ac.uk


studentBMJ 2001;09:261-304 August ISSN 0966-6494

1. Millar JS. Consultations owing to adverse drug reactions in a single practice. Br J Gen Pract 2001;51:130-1.
2. Pirmohamed M, Breckenridge AM, Kitteringham NR, Park BK. Adverse drug reactions. BMJ 1998;316:1295-8.
3. Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis and management. Lancet 2000;356:1255-9.