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60 Cards in this Set
- Front
- Back
T/F:
ADR are estimated as the 4th leading cause of death |
True
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As Rx filled per pt are increased, ADR are _____
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As Rx filled per pt are increased, ADR are _increased_
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What is a unidirectional drug interaction?
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When a drug is taken that effects other drugs but not itself
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What is a bidirectional DDI?
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When a drug is give together and effects eachother
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What is the difference between an object and a precipitant drug?
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An object drug is affected by the interaction while a precipitant drug is what causes the interaction
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What are some PK that affect absorption? (3)
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Complexion/chealation/binding
Altered GI transit/emptying Altered gastric pH |
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What are 2 examples of Complexion/chelation/binding PK interactions affecting absorption?
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Antacids+fluroquinolones
(form insoluble compounds) Statins+cholestyramine (decrease of statin bioavail.) |
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T/F:
Altered gastric emptying/GI transit effects the extent not the rate |
False:
Effects the RATE not the extent |
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Anticholinergic+tylenol is an example of what PK interaction? What affect does the anticholinergic have on tylenol?
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Altered gastric emptying/GI transit
anticholinergic delays the absorption of tylenol by decreasing motility (narcotics also decrease motility) |
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Metoclopramide and erythromycin do what to motility?
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Increase
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Altered gastric pH is caused by what example given in the lectures?
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H2 blockers (ranitidine) and ketoconazole
(dissolution of ketoconazole is decreased resulting in reduced absorption) Ketoconazole is not soluble at neutral pH |
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T/F:
Changes in protein binding cause PK interactions in distribution |
True that
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What is phase 1 of the drug disposition process?
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functionalization:
oxidation/reduction CYP450* (bolded)/Flavin monooxygenases |
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What is phase 2 of drug disposition?
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Conjugation:
Glucuronidation/sulfation UGT/ST |
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What is the 3rd phase of drug disposition?
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Transport:
biliary/renal ABC fam/MDR fam |
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What is the predominate route of elimination of the top 50 drugs in 2002?
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Metabolic-58%
renal- 28% biliary- 4% 54% of drugs metabolized by CYP450 |
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What is the labeling for the 2 in CYP2D6? What about the D? And the 6?
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2- family
D- subfamily 6- individual enzyme (unique) |
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Which enzyme is the major metabolizer for the CYP450 enzymes? Which 2 follow?
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CYP3A
followed by CYP2D6 followed by CYP2C9/2C19 |
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Induction ________ metabolism while inhibition __________ metabolism
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Induction _increases_ metabolism while inhibition _decreases_ metabolism
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Which drug is given as example that is a substrate, inhibitor, and inducer?
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Ritonavir
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What enzyme does smoking induce?
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CYP1A2
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What is autoinduction?
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When a drug induces the enzyme responsible for its metabolism (carbamazepine, ritonavir)
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What occurs when exposed to a xenobiotic in the environment (foreign chemicals including drugs)?
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Enzyme induction
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By inducing a P450 enzyme, one drug can _____ the metabolism of another resulting in _____ blood levels and _______ response
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By inducing a P450 enzyme, one drug can _stimulate_ the metabolism of another resulting in _decreased_ blood levels and _decreased_ response
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What happens to the parent and metabolite drugs in enzyme induction?
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the blood levels of the parent drug decrease while the metabolite levels increase
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Why is there a lag in seeing the effects of enzyme induction?
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It takes time to synthesize new enzymes
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What happens to half life, clearance, and AUC in regards to enzyme induction?
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half life decreases
clearence increases and AUC decreases |
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What causing the gradual onset of enzyme induction?
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accumulation of inducing agents and buildup of enzyme stores
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What causing the gradual offset of enzyme induction?
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elimination of inducing agent and decay of enzyme stores
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What 2 drugs are important to know for this exam that cause CYP enzyme induction?
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Rifampin and St Johns Wort
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What 4 things are considered environmental factors that can lead to induced CYP enzymes?
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Drugs
Foods (cruiciferous veggies, char broiled beef) Social habits (alcy smoking) Disease states (DM,viral,hyperthyroid) |
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What nuclear receptor activates CYP3?
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PXR
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What is the term for CYP enzyme supression due to environmental or xenobiotic factors?
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Enzyme Inhibition
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By inhibiting a P450 enzyme one drug can ___ the metabolism of another drug leading to a ____ in blood concentartions and a ______ in response/toxicity
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By inhibiting a P450 enzyme one drug can _impair_ the metabolism of another drug leading to a _increase_ in blood concentartions and a _increase_ in response/toxicity
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Usually enzyme inhibition is by _______ binding to the enzyme site
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Usually enzyme inhibition is by _competitive_ binding to the enzyme site
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The onset and offset of enzyme inhibition depends on what 2 things?
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The half life and time to steady state of the inhibitor
(i.e. amiodarone takes longer to see inhibition than cimetidine because amiodarone has a longer half life) |
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What is meant by competitive inhibition?
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One substrate (or nonsubstrate) competing with another for metabolism by a CYP
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What is meant by a noncompetitive inhibition?
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An inhibitor tightly or irreversibly binds to the CYP enzyme inhibiting the enzymes activity
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In enzyme inhibition, decreased metabolism results in _____ blood levels of parent drug and ____ levels of metabolite
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In enzyme inhibition, decreased metabolism results in _increased_ blood levels of parent drug and _decreased_ levels of metabolite
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What is the one drug that we need to know for the exam that is an enzyme INHIBITOR?
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Ketoconazole
CYP3A Used by FDA to determine what level an enzyme inhibiting drug is |
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With ezyme inhibition, what happens to half life, AUC, and Cl of a drug?
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The halflife increase
AUC increases Cl decreases |
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Does grapefruit effect the halflife of felodipine drug? What does it effect?
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No,
Increases Cmax and AUC |
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Does grape fruit juice effect the p-glycoprotein or the CYP3A4 enzyme in the intestines?
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CYP3A4
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Are IV pharmacokinetics affected by grape fruit juice?
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Nope, liver is not effected by GFJ, only intestine
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What situations would cause GFJ to have a rare clinical synthesis?
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Pt requires high than usual dose of "susceptible" drug and begins drinking GFJ for the 1st time
Pt has sever liver disease PT has an unusualy susceptibility to an adverse effect |
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What is the classification established by the FDA in regards to Enzyme inhibitors?
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Strong >5 fold increase in AUC
Moderate >2-5 fold increase Weak <2 fold increase (in regards to oral admin) |
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What does CAM stand for in regards to DDI?
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Complementary and alternative medicines
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Hyperforin, a PXR (pregnane xenobiotic receptor) ligand affecting CYP3A4 p- glycoproteins, is found in this herbal
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What is St John Wort
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What is a probe drug?
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A drug predominantly metabolized by an individual enzyme
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St John wort had a greater effect on CYP3A- mtabolized drugs that underwent?
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first pass (intestinal) metabolism
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What herbal has an induction effect on the hepatic CYP3A enzyme but an inhibitory effect on the intestine CYP3 enzyme?
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Echinacea
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What enzyme metabolizes warfarin?
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CYP2C9
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T/F:
Herbal products, aka CAM, are regulated in Europe |
True
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Pharmacokinetic "boosting" is also known as?
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Pharmacoenhancement
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What does ritonavir do thats considered PK boosting?
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Increase bioavailability of other protease inhibitors
Decreases dosing and frequency |
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What are 2 examples of drug classes that have beneficial drug interactions?
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Antihypertensives
Combo antiretroviral tx |
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What are pharmacodynamic interactions?
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Interactions that occur at the receptor or site of action level
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There is always a change in _____ which is not seen w/ pure PK interactions
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There is always a change in _concentration-effect profile_ which is not seen w/ pure PK interactions
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Quinidine or paroxetine will inhibit the mtabolism of any drug that is metabolized by ____
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Quinidine or paroxetine will inhibit the mtabolism of any drug that is metabolized by _CYP2D6_
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Ketoconazole will inhibit the metabolism of any drug metabolized by _____
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Ketoconazole will inhibit the metabolism of any drug metabolized by _CYP3A4_
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