drug interactions Flashcards
define drug interaction
modification of a drug’s effect by prior or concomitant administration of another drug/herb/food/drink
occurs when the pharmacological effect of 2 or more drugs given together isnt just a direct function of their individual effects
aren’t always detrimental
type of drug interactions
drug-drug herbal-drug food-drug drink-drug pharmacogenetic interactions
the object drug
the drug whose activity is affected by the interaction
the precipitant
the agent which precipitates such an interaction
factors that can modify drug action
food, smoking, alcohol and herbs as well as other drugs
epidemiology of drug-drug interactions
2.3-3.0% of hospital patients
9.2-70% of GP patients
significant interactions - 1%
drugs involved with serious interactions
potent with a narrow therapeutic index - small change in blood levels can induce profound toxicity
e.g. lithium, digoxin, warfarin, erythromycin
foods that interact with warfarin
vegetables: asparagus, broccoli, cabbage, onions
herbals: ginseng, green tea
misc: avocado, fish oils, liver
susceptible patients to drug-drug interactions (5)
- polypharmacy
- elderly and young
- critically ill
- undergoing complicated surgical procedures
- chronic conditions: liver disease, renal impairment, diabetes, epilepsy, asthma
mechanism of drug interactions (3)
pharmaceutical
pharmacokinetic
pharmacodynamic
pharmacokinetic drug interactions
ADME
one drug can alter the ADME of another drug
there is marked inter-individual variation in these processes - possible to predict potential interactions but not in which patient
types of pharmacodynamic interactions (5)
antagonistic
additive/synergistic
interactions due to changes in drug transport
interactions due to fluid and electrolyte disturbance
indirect interactions
mechanisms of absorption interactions (4)
formation of insoluble complexes
altered pH
altered bacterial flora
altered gut motility
absorption interactions: interaction in the GI tract
- complex
- most interactions result in changes in absorption rate (rather than extent of absorption)
delayed absorption is important when a drug has a short half life or when we want high plasma levels rapidly
moset interactions result in delay in absorption and can be avoided if 2-4 hrs are left between administration of the drugs
absorption interactions: drug binding in the GI tract
some drugs bind to each other in the GI tract
e.g. tetracycline and erythromycin complex bind with Fe, Ca and Mg
cholestyramine resin used to bind cholesterol in the GI tract also binds to a variety of drugs e.g. warfarin
absorption interactions: changes in pH
- absorption is affected by the degree of ionisation which is dependent on pH
H2 agonists, proton pump blockers and antacids reduce H+ and so increase pH
absorption interactions: changes in bacterial flora
usually found in the large bowel
broad spectrum antibiotics destroy normal gut flora
may lead to failure of OCP
absorption interactions: GI motility
most oral medicines are absorbed in the S intestine
gastric emptying is the rate limiting step
many drugs delay gastric emptying (anticholinergics tricyclic anti-depressants, opiates) and some increase it and accelerate absorption of paracetamol
distribution interactions
protein binding displacement occurs when there is a reduction in the extent of plasma protein binding of a drug caused by the presence of another drug
results in increased bioavailability of the displaced drug
only the unbound drug is pharamcologically active
common interaction but patients are protected by increased metabolism and excretion
significant in drugs with >95% plasma protein binding (narrow therapeutic window)
metabolism interactions
occur when one drug induces or inhibits the metabolism of another
drugs (such as erythromycin, clarithromyciin, cimetidine etc) inhibit the cytochrome system
some drugs can also induce the C P450
metabolism commonly occurs in the …
liver via the cytochrome P450 system
metabolism interactions: inhibition of the cytochrome P450 system
these drugs inhibit the metabolism of a small group of drugs metabolism by the C P450 system:
cimetidine = warfarin, diazepam
metronidazole = warfarin, alcohol
omeprazole = phenytoin, warfarin
metabolism interactions: inducers of cytochrome P450 system
- Drugs such as barbiturates, carbamazepine, phenytoin, rifampicin and tobacco smoke are potent inducers of cytochrome P450
- The effects of enzyme induction aren’t seen for 2-3wks
- The effects of induction depend on age, disease, genetics and concurrent drug therapy
metabolism interactions: common examples of inducers of cytochrome P450 system (drugs)
phenytoin: warfarin, steroids, OCP
rifampicin: warfarin, OCP
elimination/excretion interactions
most drugs are excreted in urine/bile
changes in GFR or tubular secretion with effect excretion
elimination/excretion interactions: examples
- Digoxin and lithium are toxic agents that are eliminated by the kidney - Verapamil/diltiazem and digoxin (CCBs inhibit excretion)
- Loop diuretics and lithium (loop diuretics increased tubular reabsorption)
what are pharmacodynamic interactions
occurs when the pharmacodynamic actions of a drug are changes due to presence of another drug acting directly on the same receptor or indirectly on different receptors
types of pharmacodynamic interactions
direct indirect - agonism antagonistic - direct/indirect synergistic additive/multiplicative
pharmacodynamic interactions: indirect agonism
CNS depression, benzodiazepines and tricyclics or alcohol, warfarin and NSAIDs (indomethacin), atenolol and verapamil
pharmacodynamic interactions: direct antagonism
beta blockers such as atenolol will block actions of agonists e.g. bronchodilators such as salbutamol
pharmacodynamic interactions: indirect antagonism
NSAIDs and antihypertensive medication
NSAIDs and treatment for heart failure
pharmacodynamic interactions: synergistic
when 2 drugs with the same pharmacological effect acting on the same receptor are given concurrently
which CP450 is responsible for the genetic variation in the metabolism of warfarin
CYP2C9
rifampicin increases metabolism of ciclosporin by inducing …
CYP3A4
St John’s wort increases metabolism of ciclosporin by induing
CYP3A4
