Lec 17: drug interactions

Question 1

what is the polypharmacy problem?

Answer 1

when ppl take a lot of drugs at sam etime, higher chance of drug drug ints

Question 2

what types of drugs are there?

Answer 2

therapeutics, nontherapeutics, supplements, nhps, enviro chems

Question 3

what are the three ways to categorize drug interactions?

Answer 3

pharmacodynamic (drug action, what drug does to body) and pl (what body does to drug) and unintentional vs intentional

Question 4

what are each of the types of drug ints?

Answer 4

can be pd, pk, duplicative, direct or indirect

Question 5

what are the types of pharmacodynamic drug interactions? which have a greater vs lesser effect?

Answer 5

dups, adds, syns (greater), antag (lesser)

Question 6

what are duplications drug ints? additive? synergistic?

Answer 6

duplications (greater): same drug in two dif products (ie tylenol and neocitran both are acetaminphen)

additive (greater): both with same action mech and cause drastic effects (propanolol, timolol)

synergistic effects (greater): super additive, where 1+1&raquo_space;2: drugs have the same effect (ethanol and diazepam)

Question 7

example of pd interaction? what do they do>

Answer 7

opioids (morphine, codeine, fentanyl) bind and activate mu opioid receptors

Question 8

what are antagonistic drug ints? example?

Answer 8

when one drug prevents the binding and action of the other drug. fentanyl and naloxone

Question 9

antagonistic vs partial agonistic effect?

Answer 9

antag: one blocks the other
partial ag: also competes for the recep, so does reduce effect of the full ag

Question 10

what is an inverse agonist?

Answer 10

antagonistic to the full agonist – has the opp effect of the agonist (favours inactive. ie: doesnt just block, but favours this)

Question 11

how do drug ints occur through non comp binding?

Answer 11

theyre not binding at the same site, but binding at dif site on same receptor, or at dif spots in the body

Question 12

what are the pharmacodynamic drug ints?

Answer 12

combined toxicities
duplications (tylenol and neocitran –> acetominophen)
additive (propanolol and metroprolol –> both lower bp)
synergistic (ethanol and diazepam –> CNS depressants)
antagonistic (morphine and naloxone –> upioid receptors)

Question 13

when are pd drug ints increased?

Answer 13

you activate the same recep by two or more drugs binding at same site
drug binds to recep, conf change allowing another drug to bind on same receptor (pos allo mod)
2+ drugs have same clinical effect, different mech

Question 14

when are pd drug ints decreased?

Answer 14

agonist and antagonist given together

negative allosteric modulation

2+ drugs with opposing clinical effects

Question 15

what are the pharmacokinestic drug interactions?

Answer 15

abs
dist
bitrans
excretion

Question 16

what interactions affect absorption ?

Answer 16

physiochem
gi motility
changes in bacterial flora
gastric ph
mucosal damage
drug transporters

Question 17

what are physiochemical interactions?

Answer 17

things that make drugs stick together

ion exchange binding
chelation dissolution
gastric ph

Question 18

what is ion exchange binding? example?

Answer 18

drugs with opp charges attracted to eo

heparin (-) and protamine sulfate (+)
when bound, heparin is neutralized, lose anticoag effect

Question 19

what is chelation? example?

Answer 19

molecules of chelating agent form bonds iwth metal ion

lead and edta
iron and deferoxamine

you want to give a drug to get rid of the high metal levels so that the drug u want isnt chelated

Question 20

what is dissolution? example?

Answer 20

drug dissolves in material that isnt absorbed

fat sol vitamines dissolving in mineral oil, dont actually get absorbed, pass through

Question 21

how do gastic ph changes affect drug absorption? example?

Answer 21

ph alterations effect how well some drugs get absorbed

ph raised by antacids, recep antagonists, proton pump inhibs

Question 22

when do drugs get ionized (acidic vs basic)

Answer 22

when pka > ph, protonation

for acids: when pka > ph, acid is protonated, not ionized

for bases: when pka > ph, base is protonated, ionized

Question 23

henderson hassel bach equation:

Answer 23

pka - ph = log [prot]/[deprot]

Question 24

when are acidic drugs in their uncharged form? basic drugs?

Answer 24

acids are uncharged when pka > ph
based are uncharged when pka < ph

remember only uncharged drugs can pass the membranes !!

Question 25

how do changes in bacterial flora affect drug absorption?

Answer 25

if antibiotics kill natural bacteria in gut, biotrans of certain drugs can get reduced (like dogoxin)

Question 26

how does gastro intestinal motility affect drug absorption?

Answer 26

if u speed up or slow down motility it can affect the rate and extent of absorption of drugs

Question 27

how do cathartics affect gi motility

Answer 27

increase motility, and could increase rate of absorption, but slow extent of absorption

Question 28

how do opioids affect gi motility

Answer 28

opioids decrease motility, decrease rate of emptying and rate of abs, increase extent of abs bc its in body for longer

Question 29

how does mucosal damage impact drug absorption. example?

Answer 29

drugs impact the barrier functions of gi tract nsaids: damage mucosa, easier for drugs to enter

Question 30

how do drug transporters impact absorption

Answer 30

depedning on whether drug is a substrate, inhibitor, activator of certain transporter, can impact what does/doesnt get transported

Question 31

which are the uptake tranporters

Answer 31

slcs: oats oatps octs octns

Question 32

which are the efflux transporters

Answer 32

abcs: mdr mrp bcrp

Question 33

how do non drugs affect drug absorption

Answer 33

can inhibit transporters and thereby decrease absorption and or excretion

Question 34

explain relationship between fexofenadine and grapefruit juice

Answer 34

grapefruit juice: inhibits uptake oatp1a2 reduces amount of fexo (antihistamine) that gets into blood steam cant carry out its function

Question 35

explain relationshio between digoxin and propafenone

Answer 35

propafenone inhibits pgp efflux transporter mdr1 , so helps keep digoxin in body for longer, greater absorption, greater serum conc

Question 36

what kinds of drug interactions affect distribution

Answer 36

being displaced from plasma proteins displaced from tissue bindig sites alterations in blood flow alterations in local tissue barriers interactions at drug transporters

Question 37

explain the protein binding of warfrin

Answer 37

its an anticoag and slows down blood clotting, and most is bound to albumin

Question 38

what happens to warfarin binding when phenytoin is present

Answer 38

phenytoin (antiseizure) has higher albumin affinity, too much free warfarin, more bleeding (too much anticoag effect)

Question 39

explain relationship between loperaminde and quinidine

Answer 39

loperamine = antidiareah drug is an opioid so slows metabolism, but gets kicked out by pgp so doesnt cross bbb but quinidine inhibits pgp, so loperamide gets into brain and you get high

Question 40

what happens to desmethyl loperamide when injected with or without mdr1 inhibitors? what does this show?

Answer 40

when blocked, loperamide enters brain when unblocked, drug doesnt enter brain

Question 41

what happens when you inhibit placental bcrp?

Answer 41

placenta has pgb and bcrp (efflux), nicardipine inhibits efflux, keeps drug in the moms placenta longer.

Question 42

how does drug metabolism get affected by interactions??

Answer 42

inhibit drug metabolising enzymes (hours, days) induce drug metabolising enzymes (weeks) - need to make new proteins

Question 43

how can you inhibit drug metabolism?

Answer 43

terfendine and erythromycin cyp3a4 inhbition by ketoconazole, erythromycine, grapefruit juice

Question 44

how can you induce drug metabolism? examples?

Answer 44

rifampin and carbamazepine induce cyp3a4, metabolise contraceptive med (and estrogen, progestin) too fast phermobarbital induced cyp2c9 which metabolises warfarin

Question 45

how does excretion get impacted by drug interactions?

Answer 45

ph can get altered, making some drugs more ionized so you dont reabsorb them inhibiting drug transporters inducing drug transporters

Question 46

explain relationship between probenecid and peniccilin

Answer 46

penicillin is a subtrate of oats trasnporter oat helps penecillin get into pt to be excreted probenecid blocks oat and prevents excretion of penecillin

Question 47

relationship between cyclosporine and st johns wort> what happened? what does this demostrate?

Answer 47

st johns wort induced cyp3a4, ppgp. more met, more efflux, leads to less cyclosproin didnt have enough immunosuppressant (cyclo) therefore hearts were rejected

Question 48

how can you investigate drug interactions?

Answer 48

in silico in vitro in vivo

Question 49

why is knowledge of drug ints important

Answer 49

lets u understand plasma conc predict plasma drug conc avoid adverse interactions make beneficial interactions

Question 50

why might you create drug ints

Answer 50

to increase plasma levels to reverse resistance to penetrate bbb or maternal fetal barrier to prevent tox to treat overdoses

Question 51

overall impacts of pk drug interactions

Answer 51

abs, dist, biotrans, excretion

Question 52

how to avoid drug ints