Dr Armini Rostanim
University of Sheffield

At the beginning of an excellent and clear presentation, and discussion, on what could have been of an overwhelmingly technical nature, Dr Rostami described the meaning of an adverse drug reaction (ADR). An ADR is 'the effect of a drug beyond their anticipated therapeutic effect during clinical use'.

In a 1994 study in the USA the following results were recorded for ADRs:

• 2-6% of hospital admissions were caused by ADRs;
• ADRs was the fourth commonest cause of death;
• Of 2,216,000 cases, 6.7% were serious ADRs; and
• Of 106,000 deaths, 0.32% were caused by ADRs.

There are two types of ADR - Type A and Type B. Type A reactions are the augmentation of the pharmaceutical action of a drug and are dose dependant (the reaction is more than expected). Type B reactions can be described as bizarre idiosyncratic reactions that cannot be predicted from the dose given (the reaction is made up of two aspects, one expected and one unexpected).

The working of a drug varies with the dose (or size of the active ingredient(s)). The safe range of a dose that produces a beneficial result is called the 'therapeutic window'. The wider this window, the easier it is to prescribe the drug, predict the result and manage the effects on individual patients. The lower boundary of its optimal effective range is the 'minimum effect concentration' (MEC) and the upper one is the 'minimum toxic concentration' (MTC).

If the therapeutic window of a drug is narrow it is hard to prescribe, predict and manage the effects on a particular patient. Drugs can be under-prescribed and achieve no effects, or over-prescribed and cause Type A ADR. Type B or unexpected ADR is by definition hard to prescribe and predict the effect on a patient. The 'concentration effect' of a drug is the relationship or ratio of the concentration of a drug that causes a toxic ADR to the therapeutic effect.

Drugs are administered in different ways. The active ingredient is often very small and to make it manageable, often as tablets, it has to be mixed with other ingredients that have no pharmacological effect. The tablet has to break down in the gut so the drug is released and absorbed into the blood stream. After reaching the target organs the drug is eliminated via the kidneys or metabolised to by-products, which are excreted from the body.

Efficacy variations

Drug efficacy may be affected by the following factors:

• Drugs may affect ethnic or racial groups in different ways;
• Contra-reaction - caused by polypharmacy (the dispensing of more than one drug): taking two drugs affect 30% of hospital patients; taking nine drugs affect 70% of ambulatory patients and taking 24 drugs affect 49% of nursing home patients. However, drug interactions are responsible for no more than 1-2% of all clinically relevant ADRs;
• Some drugs (e.g. metoprolol, a hypertension drug) may show differing concentrations in the blood of up to 1000 fold for the same dosage;
• Alcohol may affect how the patient handles or is influenced by the drug;
• Genetic differences can cause differing reactions, e.g. with antidepressants;
• Older patients may seem to have a higher rate of ADR. This is partly a result of polypharmacy, which leads to a higher level of contra-reactions; and
• Patients' life styles. Besides sex, race, age etc., patients' reactions to drugs can be analysed by occupation, location, smoking and eating habits.

Dr Rostami ended with the salient point that in the last 20 years no new drugs have been introduced to assist in 'childhood leukaemia' but the survival rate has increased from 20% to 80%. The expertise of the doctors in using the drugs has led to these improvements.