Podgorski - Pharmacokinetics II Flashcards
How does decreased cardiac flow affect metabolism rate?
With what drugs is it more pronounced?
Decreased cardiac output will decrease hepatic blood flow and can affect drug metabolism rates. This is more pronounced with drugs showing large 1st pass effects since drug delivery via hepatic blood flow rather than enzymatic activity is rate-‐limiting for clearance.
What is notable about phenobarbital metabolism?
The ability of phenobarbital to increase its own P450 metabolism
What can happen when the rate of metabolism changes with aminoglycosides?
A serious problem can occur with the aminoglycoside class of antibiotics. Amikacin, for example, produces nephrotoxicity when present at toxic levels. Since amikacin is eliminated by the kidney, toxic accumulation leads to a vicious cycle of kidney damage.
What affects codeine metabolism?
Decreased CYP2D6 activity prevents analgesia by codeine
Potent CYP2D6 inhibitors
fluoxetine, paroxetine, and quinidine – potent CYP2D6 inhibitors
What reduces the antiplatelet effects of clopidogrel?
Decreased CYP2C19 activity reduces the antiplatelet effects of clopidogrel
What are potent CYP2C19 inhibitors?
Chloramphenicol, fluvoxamine
All drugs have two effects:
A therapeutic effect and a toxic effect.
How is parkinson’s disease brought on in a patient taking fluoxetine?
Parkinson’s disease brought on by inhibition of CYP3A4 by cimetidine (Tagamet®) in a patient taking fluoxetine (Prozac® )
What 2 medications can cause hypertension?
Hypertension in a patient taking an antihypertensive medication and self-‐treating a cold with a vasoconstrictor decongestant such as pseudoephedrine (Sudafed®).
What does phenytoin inhibit?
CYP2C9 metabolism of losartan to its active metabolite is inhibited by phenytoin, with potential loss of antihypertensive effect.
What does grapefruit juice inhibit? What are the adverse effects to?
Grapefruit juice inhibits CYP3A
Adverse effects of cyclosporine and some HMG-‐CoA reductase inhibitors
What is CYP2D6 is markedly inhibited by? (3)
CYP2D6 is markedly inhibited by:
- quinidine
- a number of neuroleptic drugs (chlorpromazine and haloperidol)
- the SSRIs fluoxetine and paroxetine.
How does rifampin affect oral contraceptives?
Rifampin (synthetic antibiotic) -‐ CYP3A4 inducer – 20 to 40 fold reduction in oral contraceptive levels.
How does Ritonavir affect HIV regimens?
Ritonavir is a very potent CYP3A4 inhibitor that is sometimes added to anti-‐HIV regimens decreases clearance, and hence increases efficacy, of other anti-‐HIV agents
What have calcium channel blockers been co-administered with? Why?
Calcium channel blockers have been deliberately co-‐administered with cyclosporine to reduce its clearance and thus its maintenance dosage and cost
What combination increases risk of bleeding?
Increased risk of bleeding as a result of combining antiplatelet agents (glycoprotein IIb/IIIa inhibitors, aspirin, clopidogrel) and anticoagulants (warfarin, heparins)
What increases risk of bleeding from peptic ulcer?
Risk of bleeding from peptic ulcer due to nonsteroidal anti-‐inflammatory drugs (NSAIDs) in patients treated with warfarin
Why shouldn’t you use NSAIDs with antihypertensives?
Elevated blood pressure in patients taking NSAIDs (Indomethacin, piroxicam) that antagonize the antihypertensive effects of -‐adrenergic receptor blockers, diuretics, ACE inhibitors, and other drugs.
How do nitrates interact with sildenafil?
Profound hypotension upon co-‐administration of nitrates (such as nitroglycerin) with sildenafil.
Synergism:
Synergism – relates to both, additive and supra-‐additive effect.
Potentiation:
One drug shows no appreciable effect alone but causes an increased response from the second drug
Phase I Trials:
Phase I Trials: use matched groups of animals or humans to study responses at various dose levels to determine tolerated doses and toxic doses.
Phase II and Phase III double-‐blinded clinical trials:
Phase II and Phase III double-‐blinded clinical trials measure effective and lethal doses (in animals) and efficacy (in humans). Responses are typically measured using a quantal response.
