Drug Interactions

Question 1

What are phase I trials?

Answer 1

Healthy human subjects (approx 100)
First use in man
Evaluation of safety and toxicity
Pharmacokinetic (and sometimes pharmacodynamic) assessment

Question 2

What are phase II trials?

Answer 2

First assessment in patients (approx 500)
Safety and toxicity evaluated
Dose range identified
Pharmacokinetic and pharmacodynamic monitoring

Question 3

What are phase III trials?

Answer 3

Use in wider patient population (approx 2000), usually multi-centre
Efficacy main objective
Safety and toxicity also carefully monitored

Question 4

What are phase IV trials?

Answer 4

Post-marketing surveillance
All patients prescribed drug monitored
Efficacy, safety and toxicity measured
Quantification of unusual adverse drug events

Question 5

Name some drugs that have potentially serious drug interactions.

Answer 5

Warfarin, digoxin, beta blockers…

Question 6

What is a drug interaction?

Answer 6

a predisposing factor to adverse drug reactions

Question 7

What is a medication error?

Answer 7

Any unintentional error in the prescribing, dispensing, or administration [including preparation for administration] of a medicinal product while in control of the healthcare professional, patient or consumer

Question 8

What is an adverse drug reaction?

Answer 8

A response to a drug which is noxious and unintended and which occurs at doses normally used in man for prophylaxis, diagnosis, or therapy of disease or for the modification of physiologic function

Question 9

What are adverse drug events?

Answer 9

Harm caused by the drug (adverse drug reactions and overdoses) and harm from the use of the drug (including dose reductions and discontinuations of drug therapy)

Question 10

What makes a drug ‘high risk’ in terms of interactions?

Answer 10

– Narrow therapeutic index drugs

– Recognised enzyme inhibitors or inducers

Question 11

What is meant by a narrow/low therapeutic index?

Answer 11

Small range between drug’s risks and benefits

Question 12

Give some examples of drugs with low therapeutic indices.

Answer 12

Lithium
Digoxin
Carbamazepine
Cyclosporin
Phenytoin
Phenobarbitone
Theophylline
Warfarin

Question 13

Types of drug interactions (3)

Answer 13

Pharmaceutical interactions
Pharmacodynamic interaction
Pharmacokinetic interaction

Question 14

What is a pharmaceutical interaction?

Answer 14

An interaction between drugs (outside the body) leading to inactivation of one or both drugs

Question 15

What is a pharmacodynamic interaction?

Answer 15

The pharmacological effect of drug (B) is modified by
another drug (A)
There is no change in tissue concentration of drug B

Question 16

What is a pharmacokinetic interaction?

Answer 16

Delivery of drug to its site of action is altered by another drug
Tissue concentration of drug B increased/decreased

Question 17

The pharmacokinetic behaviour of drugs is determined by what 4 major processes?

Answer 17

Absorption
Distribution
Metabolism
Excretion

Question 18

How might absorption be affected by drugs?

Answer 18

Drugs may slow gastric emptying e.g. opiates, accelerate gastric emptying e.g. anti-emetic metoclopramide, or bind other drugs which prevents their absorption

Question 19

How might distribution be affected by drugs?

Answer 19

A drug (A) may be displaced from binding sites on plasma proteins or tissue by another drug (B). 
Rarely clinically significant due to establishment of new steady state with unaltered concentrations of free (unbound) drug A. May be important if the displacing drug B concomitantly inhibits metabolism or excretion of drug A leading to increased free (unbound) drug A.

Question 20

How are hydrophilic drugs excreted?

Answer 20

Hydrophilic drugs are excreted unchanged in urine

Question 21

How are lipophilic drugs excreted?

Answer 21

Lipophilic drugs require prior metabolism and conversion to polar metabolites in the liver and thereafter are excreted in the urine

Question 22

The main mechanisms by which one drug can affect the rate of renal excretion of another are…?

Answer 22

• by altering protein binding and hence filtration
• by inhibiting tubular secretion
• by altering urine flow / pH