Lecture 16: Medicine interactions Flashcards
Define drug interactions: what does it include?
When effects of one drug are changed when administered with another drug, food or another substance.
Drug-drug, food, herb
What is the relevant terminology to drug interactions?
Synergism
Potentiation
Additivity
Antagonism
How are drug interactions classified?
Pharmacokinetic
Pharmacodynamic
Pharmacuetical
Define pharmacokinetic drug interaction classification
Drug interaction due to an effect of one drug on the absorption, distribution, metabolism or elimination of another drug.
Define pharmacodynamic drug interaction classification
Drug interaction due to the effects of two or more drugs on the same receptor or physiological system, without change in drug concentration
Define pharmacuetical drug interaction classification
Drug interaction occurring in syringes or infusion fluids
Describe how drug interactions can result in altered absorption:
- One drug may alter the RATE or DEGREE of absorption of another drug from the gastrointestinal tract.
- Decreased absorption may lead to loss of therapeutic activity
- Increased absorption may lead to exaggerated and/or prolonged activity and/or toxicity
Whats example one drug interactions/altered absorption:
Metal chalate formation:
- B/w metal containing antacids or supplements, decreasing absorption of antibiotics i.e aluminium hydroxide and doxycycline or ciproflaxin
Whats example two drug interactions/altered absorption:
P-glycoprotein inhibition:
- By perpertrator drug increasing the bioavailability of susceptible drug i.e ciclosporin and loperamide respectively
Describe how induced drug metabolism functions as a drug interaction:
- One drug can induced an enzyme altering the metabolism of another drug
- Clinical consequences depends on metabolites
- Occurs over several days or weeks.
NB: Regulated at transcription level, involves P450 frequently
What class of drugs are known to induce metabolising enzymes?
- Anticonvulsants, Antimicrobials for TB and HIV, Natural health products i.e st johns wart
What are two specific examples of drugs that induce enzymes?
- Phenytoin
- Carbamazapine
What are the susceptible drugs to induced metabolic enzymes?
- Ethinyloestradiol/levonorgestrel
- Warfarin
- Gefitinib (anticancer)
Write some notes on drug interactions that inhibit drug metabolism:
- Inhibits other drugs metabolism:
- Frequently involves CYP450
- RAPID onset, within hours of concurrent drug administration
= Can result in exaggerated or prolonged responses or increased toxicity
What are some drug classes that inhibit CYP450 metabolism and what are some drug classes that are susceptible because of this?
Perpetrators: Macrolides, azole antifungals, protease inhibitors, antidepressants, grapefruit juice
Susceptible: Anticoagulants, oral hypoglycaemics, statins
Give two specific examples of drugs that inhibit CYP450:
Erythromycin inhibits simvastatin metabolism (increases toxicity)
Fluconazole inhibits warfarin metabolism (increased effects)
Whats a specific example of a drug that inhibits aldehyde dehydrogenase metabolism:
Metronidazole inhibits alcohol metabolism producing dysphoria
Write some notes on altered elimination:
- One drug can alter the effects of another drug by interfering with renal or biliary elimination
- These drugs may compete for renal TUBULAR secretion
- This altered elimination may slow drug clearance causing:
-> Exaggerated or prolonged activity or increased toxicity
What is example one of specific examples of altered elimination drug interactions:
P-Glycoprotein
-> Inhibition of renal elimination of digoxin by erythromycin (digoxin toxicity)
What is example two of specific examples of atlered elimination drug interactions:
Solute carrier transporters
-> Inhibition of renal elimination of penicillin by probenecid (increased penicillin concentration)
Describe pharmacodynamic drug interactions:
- Drugs may act on same physiological system, without any change in drug concentration (effecting other drug)
- May occur from drug actions on same or different receptors
- May result in potentiation or antagonism of drug effects
Whats an example of pharmacodynamic drug interactions of drugs acting on the same receptor:
Same receptor:
- > Beta-2-adrenoreceptor agonist and antagonist
- > i.e salbutamol and atenalol
Whats an example of pharmacodynamic drug interactions of drugs acting on the same tissue:
Same tissue: -> Multiple CNS depressants i.e - Alcohol + Recreational drugs - Polypharmacy in elderly I.e diazapam and notriptyline
or
- > Blood coagulation
- Warfarin and aspirin
How do you reduce the harm from drug interactions?
- Know the concepts
- Know most common perpertrator drugs
- Know about drugs with low TI
- Know how to recognise high risk pts.
- Know the drugs you frequently prescribe
What are some drugs with low TI?
- Anticoagulants, Anti-arrhythmitics, Anti-epileptics, Aminoglycosides, Anti-neoplastics
What makes a patient high risk?
Extremes of age: Number of medicines, organ impairment
