Drug interactions Flashcards
5 general types of drug interactions
- pharmacodynamic
- combined products/duplications
- combined toxicities
- pharmacokinetics
- direct vs. indirect
4 types of pharmadynamic interactions
- duplications (tylenol and neocitran)
- additive (2 B blokers)
- synergystic (1+1=3)
- antagonistic
4 types of pharmacokinteic interactions
- absobtion
- distribution
- metabolizm
- excretion
7 interactions involving absorbtion
- absorbtion (into circ) vs. adsorption (stuck in bag)
- physiochem interactions (drug sticks together)
- GI motility
- changes in flora
- mucosal damage
- gastric pH
- drug transporters
what happens to acidic drug when increase the pH
more go into charged form (less absorption)
what happens to basic drug when increase the pH
more go into uncharged form (more absorption)
what are 2 main types of drug transporters
- uptake transporter (solute carrier linked SLC superfamily)
- efflux transporters (ABC superfamily)
what happens with fenofexadine and juices
inhibits the OATP transporter and lower absorption
what happens with digoxin and p-glycoprotein inhibitor
pgp is efflux tranporter, so inhibition means too much digoxin
5 factors influencing distribution
- displacement from plasma proteins
- displacement from tissue binding sites
- changes in blood flow
- alterations in local tissue barriers
- interactions at drug transporters
what is p-glycoprotein
efflux tranporter (also in brain)
what happens if inhibit an efflux transporter in placenta (BCRP)
fetus gets more of the drug
3 examples of changes in metabolism
- combined toxity
- inhibition of metabolizing enzymes (within hours)
- induction of metabolizing enzymes ( may take days)
what happens in we don’t metabolize terfenadine
don’t degrade and can cause long Q-T interval
what does grapefruit juice do
inhibits CYP3A4, which metabolizes 50% of drugs
why might a birth control fail
induction of a metabolozer of est and prog from antibiotics
4 interactions involving excretion
- combined toxicity - one drug knocks out kidney
- inhibition of transporters
- induction of transporter
- pH (uncharged drugs can be reabsorbed)
what are OATs (organic anion transporters)
- usually uptake transporters
2. substrates usually organic anions
what 2 things does st. johns wort do to digoxin
- induces CYP3A4
- induces pgp
lowers digoxin [c]
3 methods of investigating interactions
- in silico
- in vivo - in humans
- in vitro - in organs or cells
4 reasons to know interactions
- understand plasma [c]
- predict plasma [c]
- avoid adverse interaction
- create beneficial interactions
4 ways to avoid interactions
- ask PT the right questions
- examine ingredients and properties of drugs
- decide if interaction in clinically relevant
- decide if you can prevent by adjusting the dose
