3. Drug interactions

Question 1

What is a drug interaction?

Answer 1

> A drug interaction occurs when the action of one drug is altered by the
concurrent or prior administration of another drug.
It is estimated that one in six drug charts contains a significant drug interactions.

Question 2

How can drug interactions be

classified?

Answer 2

1. Physicochemical
   - physical properties
2. Pharmacokinetic
   one drug alters way in which the body handles another.
3. Pharmacodynamic
   action of one drug is altered administration of another.

Question 3

Give examples of physicochemical
drug interactions you may
encounter.

Answer 3

Some drug interactions are clinically useful:

> Chelation
• Sugammadex and rocuronium

> Neutralisation
• Heparin and protamine

Others occur inadvertently with undesirable effects:

> Precipitation
• Thiopentone (weak acid) and suxamethonium (weak base)

> Adsorption
• Halothane dissolving into rubber

Question 4

Give examples of pharmacokinetic drug interactions.

Answer 4

These drug interactions can affect drug absorption, distribution, metabolism and excretion.

1 > Absorption
• Adrenaline administered with local anaesthetics reduces absorption of the local anaesthetic by causing local vasoconstriction

2 > Distribution
• Aspirin (80% plasma protein bound) displaces warfarin (97% plasma protein bound) from plasma proteins, thereby increasing the unbound fraction of warfarin and increasing the risk of bleeding.

3 > Metabolism
• Phenytoin, carbamazepine, rifampicin and barbiturates induce hepatic enzymes, which results in the accelerated breakdown of drugs metabolised by these enzymes.
• Omeprazole and cimetidine inhibit hepatic enzymes, reducing the breakdown of drugs metabolised by these enzymes.

4 > Excretion
• Alkalinising the urine increases the renal excretion of salicylates.

Question 5

Give examples of pharmacodynamic drug interactions.

Answer 5

1 > Summation occurs when the action of two or more drugs is additive
(i.e. 1 + 1 = 2):
• nitrous oxide and inhalational anaesthetic agents.

2 > Synergism occurs when the combined action of two or more drugs is greater than the sum of their individual effects (i.e. 1 + 1 > 2):
• Propofol and remifentanil

3 > Potentiation occurs when the action of one drug is increased by the administration of another drug:
• probenecid increases the action of penicillin by reducing its renal excretion

4 > Antagonism occurs when the action of one drug is blocked or reversed by another drug (i.e. 1 + 1 = 0):
• morphine and naloxone.