Drug-Drug Interactions

Question 1

Name 4 mechanisms of Drug-Drug Interactions.

Answer 1

1. Oral Route - altered bioavailability of drugs
2. IV Route - In vitro interaction
3. Plasma - Drug competition for protein binding sites
4. Receptor Site - Drug Agonism or Antagonism
5. Intestine - Drug or food modifies the absorption of another drug (absorption)
6. Liver - Induction or inhibition of Metabolic enzyme systems (metabolism)
7. Kidney - Drug modifies excretory mechanism (excretion)

Question 2

Name 1 example of Pharmacokinetic DDI affecting ABSORPTION.

Answer 2

Antacids.

Antacids with Ca, Fe, Al, Mg bind to drugs and decrease the absorption of antibiotics.

Question 3

Name 1 example of Pharmacokinetic DDI affecting DISTRIBUTION.

Answer 3

Binding to Plasma Protein.

Aspirin is a highly-bound drug that displaces warfarin leading to increased warfarin free drug concentration. This causes an increase in anti-coagulant effect, and causes INR to increase. The patient becomes susceptible to hematoma.

Question 4

Name ALL 4 examples of Pharmacokinetic DDI affecting METABOLISM by CYP Induction.

Answer 4

CYP Inducers:

Anti-epileptics: - Phenobarbitone, Carbamazepine, Phenytoin

Anti-TB: Rifampicin

Question 5

Describe the action of CYP Inducers.

Answer 5

CYP Inducers increase the activity of CYP450 in the liver, increasing the rate of metabolism of drugs. This causes the drugs to persist in the patient’s circulation for a shorter period of time. As such, the half-life of the original drug is reduced.

Question 6

Name ALL 8 examples of Pharmacokinetic DDI affecting METABOLISM by CYP Inhibition.

Answer 6

CYP Inhibitors:

• H2 Blocker: Cimetidine (CYP4 Inhibitor)
• Antimicrobials: Ciprofloxacin, Erythromycin (Anti-bacterial), Isoniazid (Anti-TB), Ketoconazole (Anti-fungal)
• Antidepressants: Selective Serotonin Reuptake Inhibitors (SSRIs) - Fluxotine, Fluvoxamine
• Food: Grapefruit juice

Question 7

Describe the action of CYP Inhibitors.

Answer 7

CYP inhibitors decrease the activity of CYP450 in the liver, increasing the bioavailability of drugs. This causes the drugs to persist for a longer time in the patient’s circulation. As such, the half-life of the original drug is increased.

Question 8

What are 2 examples of Pharmacodynamic DDIs?

Answer 8

(i) Agonist-Antagonist Interactions
(ii) Synergism/ Potentiation

Question 9

What is one example of agonist-antagonist interaction in PD DDI?

Answer 9

Salbutamol and Propanolol.
Salbutamol is a Beta-2 adrenergic agonist.
Propanolol is a Beta-blocker.

Salbutamol causes bronchodilation.
Propanolol causes bronchoconstriction and increase in airway secretion.

Question 10

What is an example of synergism in PD DDI?

Answer 10

Alcohol consumption increases the bioavailability of the original drug.

Other examples: Benzodiazepines, Narcotic analgesics.