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HIV and Psychiatric Medication Interactions. Karina K. Uldall, MD, MPH. HIV/AIDS Research Program. Department of Psychiatry UW School of Medicine Seattle, WA. ANTIRETROVIRALS. Non-Nucleoside Reverse Transcriptase Inhibitors Nevirapine, Efavirenz, Delavirdine Nucleoside Analogues
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HIV and Psychiatric Medication Interactions Karina K. Uldall, MD, MPH
HIV/AIDS Research Program Department of Psychiatry UW School of Medicine Seattle, WA
ANTIRETROVIRALS • Non-Nucleoside Reverse Transcriptase Inhibitors • Nevirapine, Efavirenz, Delavirdine • Nucleoside Analogues • Tenofovir, Abacavir, Lamivudine, Zidovudine, Stavudine, Zalcitabine, Didanosine • Protease Inhibitors • Lopinavir, Ritonavir, Indinavir, Saquinavir, Nelfinavir, Amprenavir • Fusion Inhibitors • T-20, T-1249
LIVER • weakens substances that could be harmful to the body via oxidation; substances are then excreted through the kidneys • attaches substances to proteins via conjugation; substances are then eliminated through the bowels or kidneys
DRUG METABOLISM • Cytochrome P450 system • Affected by • age - hormones • nutrition - drug half life • stress - drug dosages • hepatic blood flow • liver disease
CYTOCHROME P450 • Collection of liver enzymes • Classified into families (isoenzymes) • Further classified into subfamilies and genes • For example, P450 2D6 or CYP 2D6 • CYP root or super family • 2 family - D subfamily - 6 gene
CYTOCHROME P450 • Substrate • any drug metabolized by P450 enzymes • Inhibitor • any drug that inhibits the metabolism of a P450 substrate (strong, moderate, weak) • Inducer • anything that increases the amount of P450 enzymes (strong, moderate, weak)
P450 COMBINATIONS • Inhibitor + Substrate • higher levels of substrate • Inducer + Substrate • lower levels of substrate • Inhibitor + Inducer • normal, higher or lower levels of each • Inhibitor + Inhibitor • high levels of one or both
P450 VARIATIONS • Some people have more than normal amounts of certain P450 enzymes (ultra-rapid metabolizers) • Some people have normal amounts (extensive metabolizers) • Some people have less than normal amounts (poor metabolizers)
Substrates alprazolam midazolam carbamazepine sertraline haloperidol TCAs thiothixene zolpidem trazadone heroin morphine triazolam diazepam ritonavir Efavirenz methadone CYP 3A
Inhibitors potent nefazadone fluvoxamine cannabis grapefruit juice ritonavir/saquinavir moderate fluoxetine paroxetine sertraline TCAs indinavir/nelfinavir efavirenz amprenavir weak venlafaxine mirtazapine CYP 3A
Inducers phenobarbital carbamazepine alcohol efavirenz CYP 3A
Substrates carbamazepine mirtazapine codeine risperidone fluoxetine TCAs trazadone haloperidol morphine amphetamine ecstasy meperidine droperidol phenothiazines cannabis paroxetine venlafaxine nicotine CYP 2D6
Inhibitors potent fluoxetine paroxetine methadone ritonavir moderate desipramine nortriptyline bupropion sertraline weak efavirenz Inducers phenobarbital carbamazepine CYP 2D6
Substrates caffeine mirtazapine clozapine haloperidol phenothiazines imipramine amitriptyline clomipramine doxepin benzodiazepines olanzapine thiothixene CYP 1A2
Inhibitors potent fluvoxamine ritonavir moderate grapefruit juice TCAs weak nefazadone mirtazapine olanzapine fluoxetine Inducers cigarette smoke cabbage charcoal grilled foods CYP 1A2
Substrates bupropion diazepam temazepam nicotine Inducers carbamazepine phenobarbital CYP 2B6
Substrates diazepam amitriptyline clomipramine doxepin imipramine cannabis PCP efavirenz Inhibitors potent fluvoxamine (9.19) fluoxetine (9) ritonavir moderate paroxetine sertraline (19) fluoxetine (19) efavirenz CYP 2C
Inhibitors weak venlafaxine nefazodone Inducers rifampin rifabutin CYP 2C
DRUG INTERACTIONS • Many drug interactions with ARVs (especially with protease inhibitors) • Cytochrome P450 mechanism • metabolism through liver pathway • some drugs inhibit and some stimulate enzyme production • the effect of some drugs is increased, for others is decreased
ANTIRETROVIRALS • P450 Substrates • all protease inhibitors • indinavir, squinavir, ritonavir, nelfinavir, amprenavir • P450 Inhibitors - reversible • strong - ritonavir • moderate - indinavir, nelfinavir • weak - saquinavir
ANTIRETROVIRALS • P450 Inducers - lasts for several days • moderate - ritonavir, nelfinavir, nevirapine
PSYCHIATRIC MEDICATIONS • P450 Substrates • many psychiatric medications are metabolized through the liver • P450 Inhibitors • strong - fluoxetine, fluvoxamine • moderate - paroxetine, sertraline, TCAs • weak - venlafaxine, mirtazapine
PSYCHIATRIC MEDICATIONS • p450 Inducers • nicotine/cigarette smoke • carbamazepine • alcohol
SUMMARY • Fewer medications and lower doses are worthy goals • If someone has symptoms, always think of drug interactions • Keep up to date on each client’s med list (and substance use) • Consider diet/lifestyle and medication interactions
SUMMARY • Consult with a local pharmacist • Call the AETC/HRSA warmline: • (800) 933-3413 • Use the Internet: • www.aidsmeds.com • www.hivinsite.ucsf.edu/InSite.jsp?page=ar-00-00 • www.medscape.com/druginfo