GAUTHAM COLLEGE OF PHARMACY

The study of ADRs is the concern of the field known as pharmacovigilance. An adverse drug event (ADE) refers to any injury occurring at the time a drug is used, whether or not it is identified as a cause of the injury. An ADR is a special type of ADE in which a causative relationship can be shown.

 

Classification: ADRs may be classified by e.g. cause and severity

 

Cause

 

Type A: Augmented pharmacologic effects - dose dependent and predictable

Type A reactions, which constitute approximately 80% of adverse drug reactions, are usually a consequence of the drug’s primary pharmacological effect (e.g. bleeding when using the anticoagulant warfarin) or a low therapeutic index of the drug (e.g. nausea from digoxin), and they are therefore predictable. They are dose-related and usually mild, although they may be serious or even fatal (e.g. intracranial bleeding from warfarin). Such reactions are usually due to inappropriate dosage, especially when drug elimination is impaired. The term ‘side effects’ is often applied to minor type A reactions.

 

Type B: Idiosyncratic

Types A and B were proposed in the 1970s, and the other types were proposed subsequently when the first two proved insufficient to classify ADRs.

 

Seriousness and severity

The American Food and Drug Administration defines a serious adverse event as one when the patient outcome is one of the following:

 

• Death

• Life-threatening

• Hospitalization (initial or prolonged)

• Disability - significant, persistent, or permanent change, impairment, damage or disruption in the patient's body function/structure, physical activities or quality of life.

• Congenital anomaly

• Requires intervention to prevent permanent impairment or damage

 

Severity is a point on an arbitrary scale of intensity of the adverse event in question. The terms "severe" and "serious" when applied to adverse events are technically very different. They are easily confused but can not be used interchangeably, requiring care in usage.

 

Assessing causality

Causality assessment is used to determine the likelihood that a drug caused a suspected ADR. There are a number of different methods used to judge causation, including theNaranjo algorithm, the Venulet algorithm and the WHO causality term assessment criteria. Each have pros and cons associated with their use and most require some level of expert judgement to apply. An ADR should not be labeled as 'certain' unless the ADR abates with a challenge-dechallenge-rechallenge protocol (stopping and starting the agent in question). The chronology of the onset of the suspected ADR is important, as another substance or factor may be implicated as a cause; co-prescribed medications and underlying psychiatric conditions may be factors in the ADR. A simple scale is available at http://annals.org/cgi/content/full/140/10/795.

 

Assigning causality to a specific agent often proves difficult, unless the event is found during a clinical study or large databases are used. Both methods have difficulties and can be fraught with error. Even in clinical studies some ADRs may be missed as large numbers of test individuals are required to find that adverse drug reaction. Psychiatric ADRs are often missed as they are grouped together in the questionnaires used to assess the population.