1.0 ADVERSE DRUG REACTIONS (ADR)
1.1 HISTORICAL BACKGROUND
ADR has a long history. In 1831 sudden death due to chloroform was described. Agranulocytosis due to amidopyrine
was described in 1933. Smallpox vaccination was found associated with jaundice in 1883 and it was not until later that the
real cause was identified as viral hapatitis. In 1937 a mistake in mixing reagents led to death of 107 persons because diethylene
glycol was used by mistake as a solvent for sulfonamide. Tin used in a skin preparation by mistake killed 100 people in Paris in 1954.
These disasters were not taken seriously until the thalidomide disaster of 1961. It stimulated interest in ADR due to many
abnormal babies born: 6000 in Germany, 500 in UK.
It was after this disaster that countries set up mechanisms for monitoring ADR. Long-term monitoring is necessary because
the adverse effects of drugs are delayed.
1.2 DRUGS ASSOCIATED WITH ADR
There has been a dramatic increase in synthetic drugs. In 1936 the British Pharmacopeia listed only 36 drugs. Today
it lists thousands. As more drugs are available for use, toxicity incidents also increase. Any drug can cause ARD. The commonest ADRs are due to: anti-HTsives, anti-coagulants, cytotoxics, corticisteroids,
and digoxin. Risk of ADR: The young children and the elderly are at higher risk for ADR. Women are at higher risk than men.
1.3 TYPES OF ADR
Adverse drug reactions (ADR) are classified as type A and type B. Type A reactions are due to the known pharmacological
effects of the drug. They are dose dependent, predictable, and not so severe). Type B reactions are rare idiosyncratic reactions
of the drug. They are non-dose dependent, unpredictable and have more mortality.
1.4 INCIDENCE OF ADR
In the UK, 5% of all hospital admissions are due
to ADR. 1 in 10 admitted for other reasons develop ADR. 1 in 1000 of hospital deaths are due to ADR.
1.5 PREVENTION and SURVEILLANCE
Prevention of ADR: (a) Primary prevention: control of prescription,
know allergy, avoid polypharmacy, rational drug use (b) Secondary: stop drug, antidote, monitoring for further side-effects
Post-marketing surveillance: The process of drug development
takes over 10 years. The initial animal studies may fail to detect adverse effects.
Clinical trials reveal only the common side effects because they involve only a few patients, they are of limited duration,
and exclude some types of patients like pregnant women. Post-marketing surveillance becomes necessary to be able to pick up
more ADRs. The following methods are used: (a) non-systematic reporting of anecdotal case history information in medical journals
(b) spontaneous reporting of any observed reactions to ADR registers. These registers may be regional or national. Drug manufacturers
also maintain registers. The ADR profile of a drug is constructed from studying all these reports. (c) case control studies
that retrospectively study the causes of reported reactions. Cases are essentially
persons with the observed reaction. They are compared to normal controls regarding use of drugs. (d) prospective studies.
2.0 DRUG INTERACTIONS:
According to UK data is 10-20% of all ADR are due
to drug interactions. Primary prevention is by recording of all drugs the patient is taking and making sure no drugs known
to interact are given. Secondary prevention is by stopping / substituting one of the pair of interacting drugs. Tertiary prevention
is by treating any complications.
3.0 DRUG POISONING
Drug Poisoning: can be accidental & deliberate (accidental and deliberate). Drug poisoning is on the increase.
According to UK data 10% of acute hospital admissions are
due to drug interactions. The medicinal agents involved (UK data): CO 23%, barbiturates 21%, analgesics 17%, anti-depressants
7%, tranquilizers 7%, and Others 25% (household solvents, corrosives, and caustics are common causes of child poisoning).
3.2 PREVENTIONPrimary prevention:
keep out of access espp children and the elderly. Child-resistant or child-proof container caps are recommended. Education
can be carried out through community outreach seminars, including drug information in school curricula, information at retail
outlets, and information through the mass media. Secondary prevention: Remove poison (gastric lavage, induce emesis, adsorbents),
anti-dotes, and elimination (forced diuresis, hemoperfusion), support: cardio-vascular, respiratory. Tertiary prevention:
prevent complications: skin care, bladder care, anti-convulsants.