Drug-Drug Interactions Flashcards
define drug interaction
drug interaction has occurred when the pharmacological effect of two or more drugs give together is not just a direct function of their individual effect
what are 5 types of drug interactions?
- drug-drug interaction
- herbal-drug interaction
- food-drug interaction
- drink-drug interaction
- pharmacogenetic interaction
what is the name of the drug whose activity is effected by such drug interaction?
object drug
what is the name of the agent which precipitates such as interaction (drug-drug)?
precipitant
what are 4 common factors which modify drug action?
- food
- smoking
- alcohol
- herbs
What percentage of all ADRs are drug-drug interactions?
7%
give an example of when drug interactions are beneficial to a patient’s health
chemotherapy
what are 5 main patient specific factors which puts them at risk of having a drug-drug interaction (DDI)?
- advanced or young age
- genetic polymorphisms
- concomitant disease (critically ill patients)
- number of medicaments
- surgical patients
what are the drugs which are most likely to cause a DDI? (5)
- steep dose response curve
- narrow therapeutic index
- high protein binding
- those with hepatic enzyme inducers or inhibitors
- those with altered renal clearance
what are other “hospital” factors increasing chances of DDIs? (3)
- multiple prescribing physicians
- self-prescription
- prolonged length of stay
why are drugs with a narrow therapeutic index more likely to cause DDIs?
because small change in blood levels can induce profound toxicity
what foods often interact with drugs like Warfarin?
- vegetables
- herbals
- avocado
- fish oils
- liver
- soya beans
- papain
what chronic diseases put patients at risk of a DDI?
- liver disease
- renal impairment
- diabetes mellitus (often have vascular disease which affects kidneys)
- epilepsy
- asthma
what are the 3 pharmaco- related drug factors which lead to DDIs?
- pharmokinetic
- pharmacodynamic
- pharmaceutical
what are pharmaceutical interactions?
mixing two drugs together in the same solution
what are pharmacokinetic interactions?
occur when absorption, distribution, metabolism and elimination of a drug is altered by another drug
what are pharmacodynamic interactions?
where one drug alters the effect of another drug at its site of action (can be direct or indirect)
what are some examples of pharmacodynamic interactions? (5)
- antagonistic interactions
- additive/synergistic interactions
- interactions due to changes in drug transport
- interactions due to fluid and electrolyte disturbances
- indirect pharmacodynamic interactions
what 4 mechanisms alter drug absorption?
- formation of insoluble complexes
- altered pH (degree of ionisation)
- altered bacterial flora
- altered GI motility
Some drugs bind to each other in the GI tract. what 2 drugs complex with iron, calcium and magnesium?
tetracycline and erythromycin
what other drugs does cholesteramine resin (used to be bind cholesterol in GI tract) bind to? (2)
warfarin and digotoxin
what 3 substances reduce H+, therefore increase pH in the gut? (affecting drug absorption)?
- H2 antagonists
- proton pump blockers
- antacids
where is the bacterial flora usually found?
large bowel/intestine
where are most oral medicines absorbed?
in small intestine
What is the rate-limiting step in GI motility factor that affects drug absorption?
gastric emptying (some drugs can increase and some can decrease it)
what are some drugs which delay gastric emptying?(3)
- anticholinergics
- tricyclic antidepressants
- opiates
what are some drugs which increase gastric emptying and increase absorption of paracetamol? (2)
- 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
- displacement of a drug from a plasma protein results in increased bioavailability of the displaced drug
- only unbound drug is pharmacologically active (exaggerated drug response occurs since more drug is active)
what are the 2 most common proteins that drugs bind to in the blood?
- albumin
- alpha-1 glycoprotein
how is metabolism affected by drug interactions?
one drug can induce OR inhibit the metabolism of another drug
which system does drug metabolism go through in the liver?
via cytochrome P450 system
what drugs inhibit the cytochrome P450 system in the liver? (6) (inhibit enzyme secretion which can lead to toxicity)
- clarithromycin
- erythromycin
- cimetidine
- ketoconazole
- omeprazole
- CCBs (diltiazem)
what drugs does cimetidine inhibit metabolism of? (2)
- warfarin
2. diazepam
what drugs does metronidazole inhibit metabolism of? (2)
- warfarin
2. alcohol
what drugs does omeprazole inhibit the metabolism of? (2)
- phenytoin
2. warfarin
what drugs are potent INDUCERS of cytochrome P450 system? (increase metabolism)
- barbiturates
- carbamazepine
- phenytoin
- rifampacin
- tobacco
what does phenyton increase the metabolism for?
- warfarin
- steroids
- Oral contraceptive
what does rifampacin increase the metabolism for?
- warfarin
- Oral contraceptive
- ciclosporins
where are most drugs excreted in? (2)
urine or bile
what patients are particularly susceptible to renal disorders?
elderly patients
what 2 drugs inhibit excretion of drugs?
- verapamil/ diltiazem
- digotoxin
what 2 drugs increase tubular reabsorption?
- loop diuretics
- lithium
what are 4 kinds of pharmacodynamic reactions?
- direct
- indirect
- antagonistic
- synergistic/ agonistic
when are pharmacodynamic actions of a drug changed?
when another drug acts directly on the same receptor or indirectly by binding to different receptors
what is used to monitor plasma drug levels which can be toxic?
TDM; therapeutic drug monitoring
what drugs is TDM most commonly used for?
- aminoglycoside antibiotics
- lithium
- digoxin
- phenytoin
- warfarin
- paracetamol in overdose
what is an example of direct antagonism?
beta blockers (eg. atenolol) blocks actions of agonists (e.g. bronchodilators such has salbutamol)
what are common pharmacodynamic interactions of indirect agonism between drugs? ( disease affects one organ and other drug enhances response elsewhere in the body)
- CNS depression
- benzodiazepines and tricyclins or alcohol
- warfarin and NSAIDs (indomethacin)
- atenolol and varepamil
what two substances can NSAIDs (non-steroidalanti-inflammatorydrugs) react with to from an indirect antagonistic pharmacodynamic interaction?
- antihypersensitive medication
2. heart failure
what to do of altering dose timing of drug and no alternative helps a DDI?
- adjust drug dosage
- monitor drug level (TDM) and physiological function
when is drug absorption in a DDI important?
when a drug has a short half life or rapid results are needed
what 3 things cause a delay in drug absorption?
- drugs bind to each other in GI tract
- drugs can alter pH (e.g. antacids) varying degree of ionisation
- broad spectrum of antibiotics kills normal gut flora (digoxin toxicity)
