Pharmacodynamic
Interactions
P450 Interactions
P450 Interactions+
Case Reports
Potpourri
100
Describe the nature of a pharmacodynamic interaction.
two or more drugs have mechanisms of action that result in the same physiological outcome
100
List at least four Cytochrome P450 enzymes.
1A2, 2C9, 2C19, 2B6, 2D6, 3A4
100
Which benzodiazepines bypass oxidative metabolism?
Lorazepam Oxazepam Temazepam
100
"Surprising Sedation"
Alprazolam=3A4 substrate (triazolobenzodiazepine) Carbamazepine=3A4, 1A2 inducer Discontinuation of carbamazepine led to increased blood levels Alprazolam
100
List two medications that are heavily protein bound.
benzodiazepines (e.g. diazepam bound 98%), warfarin (bound 99%), aspirin, valproic acid (plasma protein binding of valproate is concentration dependent and the free fraction increases from approximately 10% at 40 µg/mL to 18.5% at 130 µg/mL), phenytoin
200
Describe the likely fatal combination of medications involved in the Libby Zion case.
Phenelzine, Meperidine
200
List four antidepressant medications that are relatively free of P450 inhibition qualities.
Escitalopram, Citalopram, Venlafaxine, Mirtazapine
200
Fluvoxamine is an inhibitor of which P450 enzymes?
1A2, 2C9/19, 3A4
200
"Dry Heat"
Desipramine=2D6 substrate Methadone=moderately strong 2D6 inhibitor
200
Which benzodiazepines lack active metabolites:
CLOT
300
What medication is useful in treating benzodiazepine overdose (pharmacodynamic antagonism)?
Flumazenil (competitive inhibitor at GABA-A site)
300
List at least five P450 inducers. List one UGT inducer.
Carbamazepine (3A4, 2C9, 1A2), Oxcarbazepine (3A4), Topiramate (3A4), Ritonavir (3A4), St. John's Wort (3A4), Phenobarbital (pan-inducer), Phenytoin (pan-inducer), cigarettes (1A2); UGT inducer-ethinylestradiol
300
Which P450 enzymes are inhibited by fluoroquinolones? Bonus: Which antipsychotics may be affected by fluoroquinolones?
1A2, 3A4 Bonus: clozapine, olanzapine (1A2 substrates), tertiary TCAs; aripiprazole, haloperidol, ziprasidone (3A4 substrates)
300
"Conspiracy Theory"
Olanzapine=1A2 substrate Carbamazepine=1A2, 3A4 inducer
300
List three medications that are heavily protein bound.
Coumadin, Aspirin, Benzos (e.g. Diazepam), Depakote, Phenytoin
400
List at least six signs or symptoms of anticholinergic toxicity.
dry mouth, blurred vision (mydriasis), flushing, dry skin, tachycardia, constipation, urinary retention, confusion/delirium
400
Addition of carbamazepine to a patient on stable doses of methadone might develop what symptoms? Over what time period do these symptoms develop?
opiate withdrawal symptoms; days to weeks
400
List at least three psychotropic medications that might affect oral contraceptive effectiveness. Bonus: at what primary site is ethinylestradiol a substrate?
Ethinylestradiol-containing oral contraceptives are likely to lose efficacy with 3A4 inducers such as the following: carbamazepine, oxcarbazepine, Topiramate, modafinil, St. John's Wort Bonus: 3A4 substrate
400
"I Get Delirious"
Pharmacokinetic interaction: Tramadol=2D6 substrate Tramadol--->M1 (stronger analgesic properties) Paxil=strong 2D6 inhibitor Pharmacodynamic interaction: synergy between Tramadol serotonergi blockade and Paroxetine causing central serotonin syndrome
400
List two tertiary and two secondary TCAs.
Tertiary: Amitriptyline, Imipramine, Clomipramine Secondary: Nortriptyline, Desipramine
500
Identify at least three drugs (other than antidepressant medications) with serotonergic properties.
LSD, Linezolid, Meperidine, Antiemetics, Tramadol, Triptans
500
Name at least four antidepressant medications that have 2D6 inhibitory effects.
Prozac, Paxil, Zoloft (high doses), Bupropion, Duloxetine
500
List at least one pro-drug and its associated active metabolite. Bonus: list applicable P450 substrate
hydrocodone-->hydromorphone tramadol-->M1 codeine-->morphine Bonus: above pro-drugs all 2D6 substrates
500
"Window"
Nortriptyline=2D6 substrate Ritonavir=2D6 inhibitor (also inhibitor p450 enzymes EXCEPT 1A2, inducer 3A4) Elevated blood level of nortriptyline beyond therapeutic window so less effective antidepressant
500
What metabolite is responsible for the potential neurotoxic effects resultant from the coadministration of Tegretol and Valproic Acid?
Carbamazepine-10,11-Epoxide (ataxia, lethargy, seizures)
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