Valentovic- Drug Interactions - Leah :) Flashcards
What patients are predisposed to DD interactions? (5)
- multiple meds
- female (OCPs + CYP inducer–> ineffective)
- age extremes
- major organ/metabolic/ endocrine dysfxn
- genetic polymorphisms
3 examples of drugs that effect OCP efficacy?
- Rifampin, St. Johns Wart (CYP inducers–> less effective)
- Abx (alters gut flora)
Define pharmacokinetics + dynamics:
-pharmacokinetics= what body does to drug
-pharmacodynamics= what drug does to body
(Dynamic= D= “D”rug action on body)
Describe the difference between precipitant and object drugs:
- precipitant: effects body
(i. e. alcohol = more NAPQI production) - object drug: drug effected by initial modification
(i. e. acetaminophen)
What are three types of pharmacodynamic interactions?
- additive (alcohol + BDZ = ^^ resp depression)
- antagonistic (BDZ + flumazenil)
- synergistic (aminoglycoside + succinylcholine = ^^ resp depression during surgery)
How do aminoglycosides interact with succinylcholine in surgery?
How do you reverse these effects?
What kind of interaction is this?
This is an example of synergistic pharmacodynamic interaction:
-further increase respiratory depression
(presynaptic acetylcholine synthesis decreased by AGs)
-neostigmine can reverse these effects
-pharmacodynamic interaction
(precipitant = AG; object drug= succinylcholine)
What two types of interactions effect the absorption of a drug? How do we work around this?
-drug-drug
-drug-food
(altered pH, chelation, transport, metabolism)
-should stagger drugs or drugs/ meals
Ex: cholestyramine should be staggered with food
Antacids:
What can they contain?
What drug can they prevent from being absorbed?
- Ca, Mg, Al
- Complex with TCN –> tetracycline excreted in feces
Cholestyramine effects the absorption of what two drugs? Via what mechanism?
-digoxin
-warfarin
(forms complex)
Mycophenolate mofteil:
- MOA
- COMPLEXES with what drugs? (2)
-Immunosuppressant: Inosine monophosphate dehydrogenase (IMPDH) inhibitor
- ferrous sulfate/ iron 2+ containing vitamins and Ca, Mg, Al (antacids)
- NOT influenced by pH; don’t interact w/ bicarb*
How do drugs that decrease GI motility affect absorption? What drugs slow motility? (2)
- slow peak time, but not extent of absorption (bioavailability)
- morphine/ amitryptilline + other tricyclics
How do drugs that increase GI motility affect absorption?
What drug increases GI motility?***
- shorter peak time, but no change in extent of absorption
- metaclopromide
How do H2 antagonists (–idines) and PPis (–prazole) effect ketaconazole/ itraconazole absorption?
- INCREASE stomach pH –> decreased absorption and levels of ketaconazle/ itraconazole
In addition to azoles, what drug also has decreased bioavailability when taken with PPis?
-atazanavir (HIV protease inhibitor)
- ATP dependent transporters known as the “gatekeepers of metabolism” are called___?
- What specifically is their function?
- Where in the intestine are p glycoproteins found?
- P glycoproteins
- transport lipophilic substances out of the brain, liver, etc –> to bile, gut lumen, urine (excrete lipophilic substances)
- Enterocytes of small intestine
What 4 substances are known to inhibit P glycoproteins?
What drugs will be “object” drugs when taking a P glycoprotein inhibitor? What will be the effect?
- ketaconazole
- Erythro, clarithromycin
- Grapefruit juice
(Many CYP3A4 also = P glycoprotein inhibitors; may balance effects…)
-Drugs that are P glycoprotein substrates will be “object” drugs (i.e. cyclosporin) and have ^^^^ absorption
How is the efficacy of:
-OCPs
-digoxin
Changed when taking abx?
- OCP efficacy decreased
- Digoxin efficacy ^^ (^^^ blood levels due to ^^^ enterohepatic circulation when gut bacteria are killed)
Which drugs have drug-drug binding displacement interactions?
What happens to the “object” drug?
- drugs that are more than 90% protein bound can have drug-drug binding displacement interactions
- one of the two drugs will have a higher free fraction that normal (important when drug normally has a very SMALL free fraction)
***Example of a drug-drug binding displacement interaction
- Warfarin = 99% protein bound
- TMP-SMX displaces warfarin and can ^^ INR to 6 (normal is below 3)
Five drugs known to DECREASE/ INHIBIT
cyp450 activity?
KNOW THESE FOREVER
- ketaconazole (3A4)
- erythromycin (3A4)
- clarithromycin
- grape fruit juice
- cimetidine (ALL CYPs)
(INCREASE availability of drugs that are cyp 450 metabolites, i.e. warfarin)
Four drugs known to INCREASE CYP 450 acitvity?
Which cyps for each drug?
KNOW THESE FOREVER
- St Johns Wart
- Rifampin (3A4, 2C9, 2C19)
- Phenytoin (3A4)
- Carbamazepine (3A4)
(DECREASE availability of drugs that are cyp450 metabolites, i.e. warfarin)
CYP 1A2 is induced by ____/_____ and its substrate is____.
- cigarette smoke, phenobarbital
- theophylline
***You had phenytoin, and that might have been right but I am going off of the chart on slide 19; I might be misreading it or I might have missed this elsewhere in the notes.
How are opioids effected when combined with abs?
Which two antibiotics in particular will affect their metabolism?
Decreased clearance with erythromycin and clarithromycin = ^^ risk of oxycodone OD due to P450 inhibition
Which CYP metabolizes warfarin?
CYP3A4
