Dii / 21B15 / 17A03 / 15A09: Classify and describe mechanisms of drug interactions with examples

21B15: Exam Report

Classify and describe the mechanisms of drug interactions with examples.

54% of candidates passed this question.

This question has been asked previously, the answer template expected some description rather than a list of drug interactions. Generally, examples were provided for each type of interaction. The examiners reported too many vague, factually incorrect descriptions of the mechanisms and in some cases a very limited classification.

17A03: Exam Report

Classify and describe the mechanisms of drug interactions with examples.

44% of candidates passed this question.

Candidates with a well organised answer scored highly. A list of drug interactions was not sufficient to pass, as the question asked to ‘describe’ the mechanism of drug interactions. Some candidates described the interaction but did not give examples. Common mistakes included using incorrect examples for a particular mechanism and describing the mechanism of action of drugs instead of drug interactions.

15A09: Exam Report

Classify and describe mechanisms of drug interactions with examples.

33% of candidates passed this question.

This question was best approached by classifying drug interactions as physicochemical or pharmaceutical, then pharmacokinetic and finally pharmacodynamic. Pharmacokinetic drug interactions could then be further sub classified into those affecting the rate and extent of absorption of other drugs by mechanisms such as surface adsorption, chelation, altering
gastric pH and altering gastrointestinal motility. Drug interactions affecting the distribution of drugs mainly involve competition for protein binding and the displacement of highly protein bound drugs. Drug metabolism interactions usually involve drug induction or inhibition of hepatic microsomal enzymes either increasing or decreasing the metabolism of other drugs.

Examples of drug interactions affecting drug excretion include drugs altering urinary pH or drugs altering the tubular rate of secretion of other drugs. Pharmacodynamic drug interactions include potentiation of one drug by another, antagonism and combined toxicity at the tissue level. Combined toxicity can be due to the potentiation of adverse effects of two drugs.This is a broad question with plenty of opportunity to score marks. A structured approach such as that described above and providing an example for each mechanism was important.

Dii / 21B15 / 17A03 / 15A09: Classify and describe mechanisms of drug interactions with examples

Pharmacokinetic Interactions

Classification

Mechanism

Example

Classification

A

Mechanism

Formation of insoluble complexes

Inhibition active transporters

Inhibition of efflux transporters

Example

↓OBA bisphosphonates when Ca co-administered

Inhibition metformin uptake by repaglinide interfering w organic cation transporter OCT1

Verapamil on P-glycoprotein efflux pump → reduces Digoxin efflux → [Digoxin] ­

Classification

D

Mechanism

Competition for PPB

Example

Phenytoin & Valproate → displacing phenytoin

Classification

M

Mechanism

Competition for CYP450

Inhibition/Induction metabolic enzymes

Example

Macrolides inhibiting warfarin metabolism

Carbamazepine↑ ­warfarin & OCP metabolism

Classification

E

Mechanism

Competition for active transport

Solubility interference

Example

Probenecid ↓active secretion of b lactams

Alkalanisation of urine w acetazolamide to ion trap salicylates

Pharmacodynamic Interactions:  when one drug modifies the pharmacodynamics response to the same concentration of another

Classification

Homodynamic

Mechanism

Bind to same receptor

Example

Opioids & naloxone

Classification

Allosteric

Mechanism

Bind to same receptor but different sites

Example

Barbituates (GABA agonist) & BZD (positive modulators of GABA Receptor)

Classification

Heterodynamic

Mechanism

Bind different receptor but affect same secondary messenger system

Example

Antagonist effect of glucagon on cAMP effects of b-blockers

Classification

Second Messenger Effects

Mechanism

Binding to different receptor/messenger systems but having same effect on physiology

Example

Synergistic sedatives

eg PPF & BZD

Classification

Additive or Opposing Physiological Effects

Mechanism

Different receptor systems with the same/opposing clinical effect

Example

GTN & NA post CAGS

Classification

Interference w Control Mechanism

Mechanism

Control of physiological process is

Example

NSAIDs inhibit local PE2 synthesis

Decreases RBF & GFR

Increases RENIN

Antagonising antihypertensive effects of ACEI

Author: Krisoula Zahariou