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