Drug Interactions Flashcards
Drug interactions can affect the rate & extent of systemic drug _____
absorption
Distribution involves what
- Plasma protein binding & displacement
- Tissue binding
How is renal drug clearance work?
Drug elimination can be affected by
changed in GFR, tubular reabsorption, active
drug secretion, and renal blood flow
A drug must pass through _____ to reach the systemic circulation
biological membranes
Factors affecting absorption
Ø Chelation: calcium & tetracyclines
Ø Physical binding: cholestyramine & mycophenolate/Cellcept
Ø Gastric pH: omeprazole & erlotinib/Tarceva
Gastrointestinal motility: diphenhydramine & hydrocodone
Ø Transport proteins (e.g., P-glycoprotein): loperamide & verapamil
T/F If drug A, displaces drug B from its
binding site, this will increase the amount
of drug B that is unbound and free to
exert a pharmacologic effect
T
volume of distribution (Vd) Serves as a
constant to compare ____
relative distribution of drugs
Formula for Vd =
total amount of drug in the body / plasma concentration of drug
Loading dose equation
LD = [Vd x desired plasma concentration]/S x F
S (salt factor) and F (bioavailability) represent the fraction of the dose administered that will reach systemic circulation
FACTORS AFFECTING DRUG DISTRIBUTION
*Drug properties
*Drug solubility – lipophilic vs. hydrophilic
*Tissue binding
*Protein binding
*Compartment properties
*Blood flow
*Blood brain barrier
*Patient factors
*Age
*Gender
*Concurrent disease states
*Body mass (weight, adipose tissue vs. muscle mass)
*Pregnancy
*Other medications
PHASE I & II metabolism goals:
Make drugs more polar (water
soluble) that is more easily eliminated
Phase I metabolism
- Cytochrome P450 enzymes
- Oxidation, reduction, hydrolysis
Phase II
- Conjugation with hydrophilic compounds
- Glucuronide & sulfate
CYP450 enzymes are responsible for ____
phase I (oxidative) metabolism of endogenous or exogenous substrates
____ CYP450 enzymes identified- although only a few are associated with clinically relevant drug interactions
40
Cytochrome P-450 Enzymes are Responsible for the metabolism of ____% of
commonly prescribed drugs
60%
P-450 ENZYME INDUCERS
- Phenobarbital
- Carbamazepine
- Phenytoin
- Rifampin
- Ritonavir
- Isoniazid
- Smoking
- St. John’s wort
P-450 ENZYME INHIBITORS
ØCiprofloxacin
ØSSRIs (fluoxetine, fluvoxamine, sertraline)
ØNefazodone
ØAntifungals (ketoconazole, fluconazole)
ØFluvastatin
ØOmeprazole
ØCimetidine
ØMacrolides (erythromycin, clarithromycin)
ØCCB (verapamil, diltiazem)
Phase II reactions are performed by a family of enzymes called ____
uridine 5′- diphosphate glucuronosyltransferases (UDPGT)
A drug can affect excretion of another drug through ___
ØFiltration—by altering plasma protein binding
ØSecretion—by inhibiting tubular secretion
(probenecid & penicillin)
ØReabsorption—by enhancing reabsorption of cations (lithium & hydrochlorothiazide/Na+)
ØAltering urine pH—by affecting the excretion of weak acids or bases (aspirin &
acetazolamide)
Aspirin inhibits platelet aggregation increasing the risk of bleeding in patients on _____
warfarin
T/F All drug interactions are significant or cause an adverse effect
F
T/F both Rx and OTC drugs can lead to interactions
T
Patient risk factors for drug interactions
Ø Older patients at higher risk
Ø Certain disease states predispose for drug
interactions
Ø Diabetes, asthma, AIDS, alcoholism, renal/liver failure
Provider risks for drug interactions
Multiple prescribers – lack of care coordination
Classification of interactions
ØEstablished – supported by well proven clinical studies
ØProbable – very likely but might not be proven clinically
ØSuspected –might occur
ØPossible –could occur
ØUnlikely –doubtful; no good evidence available
