Toxicology and Drug safety

Question 1

the wider apart the safety window on an effect/exposure graph means….

Answer 1

the wider apart the window, the safe the drug

Question 2

how do drugs elicit adverse drug reactions/effects?

Answer 2

Question 3

what is meant by intended target? give an example.

Answer 3

the drug has on target effects

e.g. propanolol binds to b1 adrenoreceptors in the heart to reduce heart rate for anxiety

Question 4

what is meant by unintended target? give an example.

Answer 4

the drug has off target effects

e.g. propanolol also binds to b2 adrenoreceptors in the lungs, narrow airways and cause difficulty breathing

Question 5

how do pharmacologists deal with unintended targets (off target effects)?

Answer 5

Many drugs can bind to other proteins so trick is to make sure they bind with less affinity to unintended proteins

All about the right dose in the right tissue → too high and the drug can bind more to the unintended protein → ADR (adverse drug reaction)

Question 6

in what 3 ways can a drug go from being therapeutic to eliciting an ADR?

Answer 6

Drug overdose

Drug adverse/side effect

Drug interaction

Question 7

what is drug overdose

Answer 7

Drug overdose—Toxic reactions linked to excess dose or impaired excretion, or to both (intended – suicidal or unintended-renal dysfunction)

Question 8

what is drug adverse/ side effect

Answer 8

Drug adverse/side effect—Undesirable pharmacological effect at recommended doses (often hyperpharmacology)

Question 9

what is drug interaction

Answer 9

Drug interaction—Action of a drug on the effectiveness or toxicity of another drug (also could be e.g. drug-diet interaction)

Question 10

What can influence the expression of adverse drug reactions?

Answer 10

age

underlying disease

pregnancy

polymorphisms in target/off target proteins

Diet e.g. altered metabolism

Occupation e.g. exposure to other agents

Drug-drug interactions (if person on another medication can alter ADME of another compound)

Question 11

what is involved in the discovery part of the drug discovery and development pathway

Question 12

the acceptable margin for a new drug will depend on what 2 things

Answer 12

Risk:benefit (Safety vs Efficacy)

The Therapeutic Area (e.g. oncology vs hayfever)

Question 12

what is involved in the development part of the drug discovery and development pathway

Question 13

What 3 things is benefit to risk ratio determined by?

Answer 13

efficacy
toxicity
disease