6.drug toxicity and safety

drug toxicity

Therapeutic index

Ratio of = Median lethal dose (LD50) Median effective dose (ED50)

Adverse drug reaction (ADR)

Unwanted effect due to drug administration

Classification of ADR:

I. Predictable (Dose related effects):

Side effects, toxic effects

II. Unpredictable (Non-dose related):

Idiosyncrasy, hypersensitivity

III. Others: Iatrogenic effect, photosensitivity,

Teratogenicity, dependence

Side effects:

Unwanted effects of a drug seen with therapeutic doses,

unavoidable.

e.g. Codeine for cough – constipation

Toxic effects :

Unwanted effects either due to over dosage or chronic

use of a drug.

e.g. Streptomycin – Renal damage

Idiosyncrasy :

Genetically determined abnormal reactivity to a drug.

Reaction is restricted to individual with particular

genotype.

e.g. Chloramphenicol causes aplastic anemia,

Succinylcholine apnoea

Hypersensitivity reactions (drug allergy)

An abnormal response to a drug due to Ag:Ab reaction

resulting in the release of various mediators (chemicals)

within the body.

Causes skin allergy, bronchospasm – (anaphylaxis)

Eg: Penicillin, sulphonamides

Teratogenicity :

Capacity of a drug to cause fetal abnormalities when

administered to the pregnant mother

Eg: Tetracycline – discolored and deformed teeth

o Thalidomide:

phocomelia ( seal-like limbs)

o Phenytoin :

cleft lip/ palate

Iatrogenic disease :

Physician induced disease due to drug therapy.

e.g. Aspirin causes peptic ulcer

Photosensitivity reactions :

Drug induced skin reaction after exposure to UV

radiation

e.g. sulfonamides, tetracycline

Drug dependence : A state in which use of drug leads to a

compulsion to take the drug for personal satisfaction

• Psychological dependence

• Physical dependence: presence of drug is necessary to

maintain normal function

• Abrupt stoppage of drug – withdrawal syndrome

• eg: Morphine, alcohol