Acne Vulgaris definition, causes, aggravating factors, pathogenesis, classification, complications, treatment and management.

Overview of adverse drug reactions “ADRs”

Adverse drug reaction (ADR) has been defined as the noxious and unintended response to drug, which occurs at doses that are used for the prophylaxis ,diagnosis or therapy of a disease.

ADRs are more common in women (>60 years), very young children (1-4 years) and patients taking more than one drug.

Difference between adverse drug reactions, side effects and adverse drug events

• Side effect is a term used to describe the beneficial effects of the drug (such as; sedation of antihistamines when used as an OTC sleeping aids) as well as non-beneficial effects of the drug (such as; sedation of antihistamines when used to treat allergy). 
• Adverse drug events (ADE) refers to adverse outcomes that occurs after the use of drug that may or may not be related to the use of drug.Therefore all ADRs are ADEs but not all ADEs are ADRs.

Adverse drug reactions types

Adverse drug reactions are classified into 6 classes according to Rawlins-Thompson classification.

1. Type A reactions “Augmented”.
2. Type B reactions “Bizarre”.
3. Type C reactions “chronic & chemical”.
4. Type D reactions “delayed”.
5. Type F reactions “unexpected failure of therapy”.
6. Type E reactions “withdrawal”.

• Type A reactions “augmented drug reactions”

Which constitute approximately 80% of adverse drug reactions, are usually a consequence of drug’s primary pharmacological effects (e.g. bleeding from warfarin) 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).Other examples of type A reactions include hypotension from antihypertensive drugs, gastrointestinal hemorrhage from naproxen, bradycardia and bronchospasm from beta blockers, flushing from nitrates, constipation from opioids, hypoglycemia from insulin and antimuscrinic effects from tricyclic antidepressants.

• Type B reactions “idiosyncratic reactions”

Also called bizarre, they are not predictable from the drug’s main pharmacological actions, are not dose related and they are severe, with a considerable mortality. The underlying pathophysiology of type B reactions is poorly understood and often has a genetic or immunological basis.Type B reactions occur infrequently (1:1000-1:10,000 treated subjects being typical).Examples of type B reactions include hepatitis from phenytoin, agranulocytosis from naproxen, cholestatic jaundice from chlorpromazine, thrombocytopenia from thiazides, anaphylactic shock from penicillin and breast necrosis from warfarin.

• Type C reactions “time related and dose related”

Continuous reactions due to long term drug use, related to cumulative doses of the drug (e.g. neuroleptic-related tardive dyskinesia, analgesic nephropathy, osteonecrosis of the jaw from bisphosphonates and HPA axis suppression by corticosteroids.

• Type D reactions “time related reactions”

Also called delayed-reactions (e.g. alkylating agents leading to carcinogenesis or retinoid-associated teratogenesis, tardive dyskinesia from antipsychotic drugs and nephropathy from NSAIDs).

• Type E reactions “withdrawal reactions”

Also called end-of-use reactions such as withdrawal symptoms following discontinuation of treatment with benzodiazepines or Beta adrenoreceptor antagonists (rebound angina, MI or hypertension), seizures from withdrawal of phenytoin,

• Type F reactions “unexpected failure of therapy”

They are usually dose related and often caused by drug interactions (e.g. failure of oral contraceptives when used with hepatic microsomal enzyme inducers such as; rifampicin or when used with St Johns Wort, deceased clearance of drugs by dialysis and decreased effect of antibiotic due to resistance.