Drug-drug interactions Flashcards
Define drug interaction.
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)
Object drug
drug whose activity is effected by such an interaction
Precipitant-
the agent which precipitates such an interaction
When are drug interactions not detrimental?
treatment of hypertension or Parkinsonism
Two main risk factors for drug-drug interaction?
Patient specific factors
Drug specific factor
What are the risk factors for patients?
- 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
What are the drug risk factors?
- polypharmancy i.e. o multiple medication
- narrow therapeutic range/index so a small change in blood levels can induce profound toxicity
- dose of drug
Examples of drugs with narrow therapeutic index?
- lithium
- digoxin
- warfarin
- theopyhylline
What are foods interacting with warfarin?
vegetables e.g. alfafa, asparagus, broccoli
herbals e.g. green teas, ginseng
miscellaneous eg. fish oils, soybean, avocado
What are the Mechanism of drug interactions?
- Pharmaceutical
- Pharmacokinetic It is possible for one drug to alter the o Absorption o Distribution o Metabolism o Elimination of another drug
Mechanisms of Absorption interaction
- Formation of insoluble complexes
- Altered pH
- Altered bacterial flora
- Altered GIT motility
Mechanisms of Absorption interaction: - Altered pH
- 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
Mechanisms of Absorption interaction:
Changes in GI bacterial flora.
- 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
Mechanisms of Absorption interaction:
Altered GIT motility
- 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
How does drug-drug interactions affect distribution?
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
How does drug-drug interaction affect metabolism?
when one drug induces or inhibits the metabolism of another drug.
Drug inhibition in drug metabolism.
- 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
Drug induction in drug metabolism.
- 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
How do drug-drug interactions affect elimination/excretion?
- 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
Define DDI and pharmacodynamic interactions?
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
DDI and pharmacodynamic interactions - effects
- Antagonistic interactions
- Additive or synergistic interactions
Example of direct pharmacodynamic interaction.
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.
Example of indirect pharmacodynamic interactions.
o Central Nervous System Depression
o Benzodiazepines and tricyclics or alcohol
o Warfarin and NSAIDs (Indomethacin)
o Atenolol and verapamil
How to deal with drug interactions.
Alter dose timing
Adjust drug dosage
Monitor drug level (TDM)
Monitor physiological functions
