Drug-Drug Interactions Flashcards
Drug interaction
the modification of a drugs effect by prior or concomitant administration of another drug, herb, foodstuff or drink.
What type of drug interactions are there?
- food
- drink
- pharmacogenetic
- herbal
- drug
Object drug
the drug whose activity is effected by and interaction
Precipitant
the agent which precipitates such an interaction
What do drugs involved in serious interactions have in common?
- they are all potent with a narrow therapeutic index
- this means that a small change in blood levels can induce profound toxicity
Who is susceptible to drug-drug interactions?
- multiple medications
- elderly
- young
- critically ill
- surgical patients
What conditions can increase the likelihood of having a drug-drug interaction?
- liver disease
- renal impairment
- diabetes mellitus
- epilepsy
- asthma
What are the 3 mechanism of drug-drug interactions?
- Pharmaceutical
- Pharmacokinetic (absorption, distribution, metabolism, elimination)
- Pharmacodynamic
What kind of pharmacodynamics interactions can take place?
- antagonistic interactions
- additive or synergistic interactions
- interactions de to changes in drug transport
- interactions due to fluid and electrolyte disturbances
- indirect pharmacodynamics interactions
What are the mechanisms of absorption reactions?
- formation of insoluble complexes
- altered pH
- altered bacterial flora
- altered GIT motility
What do most interactions of drugs in the GIT result in?
changes in absorption rather than the extent of absorption
When is delayed absorption important?
when a drug has a short half life or when we want high plasma levels rapidly
What drugs bind together in the GIT??
- tetracycline and erythromycin complex with Fe, Ca and Mg
- cholestyramine resin can bind to warfarin and digoxin
How does pH affect absorption?
- absorption is affected by the degree of ionisation which is dependent on pH
- H2 antagonists, proton pum blockers and antacids reduce H+ and so increase the pH
What may lead to the failure of the OCP or digoxin toxicity?
-broad spectrum antibiotics destroy normal gut flora
Where are most oral medicines absorbed?
small intestine
What is the rate limiting step in drug absorption?
gastric emptying
What drugs increase/decrease gastric emptying?
- decrease: anticholinergics, tricyclic anti-depressants, opiates
- increase (domperidone, metoclopramide)
When does protein-binding displacement occur?
when there is a reduction in the extent of plasma protein binding of a drug caused by the presence of another drug.
What is the result of displacement of a drug from plasma protein?
increased bioavailability as only the unbound drug is pharmacologically active
What are the 2 most important proteins in protein binding?
- albumin
- a1-glycoprotein
How are some patients protected by interactions?
increased metabolism and excretion
When do drug interactions involving metabolism occur?
when one drug induces or inhibits the metabolism of another
Where does metabolism commonly occur?
in the liver via the cytochrome P450 system
What drugs inhibit the cytochrome system?
- clarithromycin
- erythromycin
- CCBs
- omeprazole
- ketoconazole
What are potent induced of cytochrome P450?
- barbiturates
- carbamazepine
- phenytoin
- rifampicin
- tobacco
How can the metabolism of ciclosporin be increased?
- rifampicin induces CYP3A4
- St John’s Wort induces CYP3A4
How are most drugs excreted?
in urine or bile
How are digoxin and lithium eliminated?
by the kidney
What drugs inhibit excretion?
verapamil/diltiazem and digoxin
What drugs increase tubular reabsorption?
loop diuretics and lithium
When do pharmacodynamics interactions occur?
when the pharmacodynamics actions of a drug either acting directly on the same receptor or indirectly on different receptors
How can pharmacodynamics interactions be described?
- direct
- indirect
- antagonistic
- synergistic/agonistic
Pharmacodynamic interactions: direct antagonism
beta blockers such as atenolol will block the actions of agonist e.g bronchodilators (salbutamol)
Pharmacodynamic interactions: synergistic interaction
when two drugs with the sam epharmacological effect acting on the same receptor are given concurrently
Pharmacodynamic interactions: indirect agonism
-CNS depression
benzodiazepines and tricyclics or alcohol
-warfarin and NSAIDs
-atenolol and verapamil
Pharmacodynamic interactions:
- NSAIDs and antihypertensive medication
- NSAIDs and treatment for heart failure
How to deal with an interaction
If the altering dose timing or no alternative doesn’t solve the issue adjust drug dosage +/- monitor drug level (TDM) and physiological functions
