Drug Toxicity

Front 1

Determination of toxicity

Back 1

Test on animal level before human trials

Front 2

Acute Toxicity

Back 2

Standard measure is Median Lethal Dose (MLD): Defined as dose that kills 50% of animal population within specific time
Found by interpolation

Front 3

Therapeutic Index

Back 3

Ratio between the MLD and MED
LD50/ED50
Provides intial estimation of relative safety of drug to be used in humans
General larger the ratio GREATER the margin of safety

Front 4

What Therapeutic Index does not do

Back 4

No value in predicting occassional hypersensitive
Not useful for evaluation of therapeutic index

Front 5

Chronic Toxicity

Back 5

Toxic effects which develop only after repeated exposure to a drug for long period of time
Can be estimated in animals with short lives

Front 6

Other Animal Toxicity Tests

Back 6

Irritation, sensitization
Neonatal
Teratogenicity
Carcinogenicity

Front 7

ADR's: Mild

Back 7

Consideredto be non-threatening to life
Annoying, however something like drowiness could be strong enough to reduce ability to drive

Front 8

ADR's: Toxic

Back 8

Undesired effects which can produce seeer effects and potentially fatal
Change in liver function = stop

Front 9

Predictable vs. Unpredictable Toxicity

Back 9

Some ADR are predictable e.g. electrolyte and water depletion during diuretic
Other ADR are largely unpredictable e.g. headache, skin rash
Proper DRUG and DOSAGE necessart to obtain optimum respnse with minimum ADR

Front 10

Relative Risk

Back 10

All drugs are potentially dangerous

Front 11

Benefit to Risk Ratio

Back 11

Potential benefit vs. Possible toxicit is a judgement made by the Physician AND the patient (ultimate decision)
What does the Patient Want?

Front 12

Drug Allergy (Hypersensitivity)

Back 12

Allergic rxn to a drug occur because patient has been exposed previously AND the drug has functioned as an antigen
Appears to be a genetically-determined predisposition regarding development of allergenic rxn to a drug

Front 13

In CONTRAST to toxic rxn an Alergic Rxn

Back 13

Unrelated to dose
Occur only in susceptible pt.
Are the same (NOT related to the pharmacologic classification of drug)

Front 14

Iatrogenic (Physician-induced) Disorders

Back 14

ANY drug prescribed the physician must know AND understand its pharmacology and potential toxicity
Failure can result in pt. needlessly suffering