Drug-drug interactions

Question 1

Define drug interaction.

Answer 1

The modification of a drugs effect by prior or concomitant administration of another drug, herb, food, drink.

or

Drug interaction has occurred when the pharmacological effect of two or more drugs given together is not just a direct function of their individual effects. (Pharmacogenetic interaction)

Question 2

Object drug

Answer 2

drug whose activity is effected by such an interaction

Question 3

Precipitant-

Answer 3

the agent which precipitates such an interaction

Question 4

When are drug interactions not detrimental?

Answer 4

treatment of hypertension or Parkinsonism

Question 5

Two main risk factors for drug-drug interaction?

Answer 5

Patient specific factors

Drug specific factor

Question 6

What are the risk factors for patients?

Answer 6

• advanced age- very young or elderly
• criticaly ill
• chronic conditions such as liver disease, renal impairment, diabetes mellitus, epilepsy, asthma
• unergoing complicated surgical procedures
• genetic polymorphism
• concomitant disease

Question 7

What are the drug risk factors?

Answer 7

• polypharmancy i.e. o multiple medication
• narrow therapeutic range/index so a small change in blood levels can induce profound toxicity
• dose of drug

Question 8

Examples of drugs with narrow therapeutic index?

Answer 8

• lithium
• digoxin
• warfarin
• theopyhylline

Question 9

What are foods interacting with warfarin?

Answer 9

vegetables e.g. alfafa, asparagus, broccoli

herbals e.g. green teas, ginseng

miscellaneous eg. fish oils, soybean, avocado

Question 10

What are the Mechanism of drug interactions?

Answer 10

• Pharmaceutical

-	Pharmacokinetic
It is possible for one drug to alter the 
o	Absorption
o	Distribution
o	Metabolism
o	Elimination        of another drug

Question 11

Mechanisms of Absorption interaction

Answer 11

• Formation of insoluble complexes
• Altered pH
• Altered bacterial flora
• Altered GIT motility

Question 12

Mechanisms of Absorption interaction: - Altered pH

Answer 12

• Absorption is affected by the degree of ionisation which is dependent on pH
• H2 antagonists, proton pump blocks and anatacids reduce H+ and so increase the pH

Question 13

Mechanisms of Absorption interaction:

Changes in GI bacterial flora.

Answer 13

• Bacterial flora are usually found in the large bowel
• Broad spectrum antibiotics destroy normal gut flora
• May lead to failure of oral contraceptive or digoxin toxicity

Question 14

Mechanisms of Absorption interaction:

Altered GIT motility

Answer 14

• Some drugs bind to each other in the GI tracts and most result in changes in absorption rate rather than the extent of absorption
• Tetracycline and erythromycin complex with iron, calcium, magnesium

Question 15

How does drug-drug interactions affect distribution?

Answer 15

Protein-protein displacement:

• Occurs when there is a reduction in the extent of plasma protein binding of a drug caused by the presence of another drug
• displacement of a drug from plasma protein results in increased bioavailability of the displaced drug

Question 16

How does drug-drug interaction affect metabolism?

Answer 16

when one drug induces or inhibits the metabolism of another drug.

Question 17

Drug inhibition in drug metabolism.

Answer 17

• Drugs inhibits the metabolism of a small groups of drugs which are metabolised by cytochrome P450 system
• Cimetidine -> warfarin, diazepam
• Metronidazole -> warfarin alcohol
• Omeprazole -> phenytoin, warfarin

Question 18

Drug induction in drug metabolism.

Answer 18

• Drugs such as barbiturates, carbamazepine, phenytoin, rifampacin and tobacco smoke are potent inducers of cytochrome P450

 Phenytoin -> warfarin, steroids, OC drug
 Rifampacin -> warfarin, OC drug

Question 19

How do drug-drug interactions affect elimination/excretion?

Answer 19

• Most drugs excreted in Urine or bile
• Changes in GFR or tubular secretion
• can reduce the clearance and increase the plasma concentration of many drugs
• Digoxin and lithium are toxic agents that are eliminated by the kidneys

Question 20

Define DDI and pharmacodynamic interactions?

Answer 20

Occurs when the pharmacodynamic actions of a drug are changed due to the presence of another drug either acting directly on the same receptor or indirectly on a different receptors

Question 21

DDI and pharmacodynamic interactions - effects

Answer 21

• Antagonistic interactions

- Additive or synergistic interactions

Question 22

Example of direct pharmacodynamic interaction.

Answer 22

o beta-blockers such as atenolol will block the actions of agonists e.g. bronchodilators such as salbutamol
o Synergistic: When two drugs with the same pharmacological effect acting on the same receptor are given concurrently.

Question 23

Example of indirect pharmacodynamic interactions.

Answer 23

o Central Nervous System Depression
o Benzodiazepines and tricyclics or alcohol
o Warfarin and NSAIDs (Indomethacin)
o Atenolol and verapamil

Question 24

How to deal with drug interactions.

Answer 24

Alter dose timing
Adjust drug dosage
Monitor drug level (TDM)
Monitor physiological functions