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HIV and Psychiatric Medication Interactions

Learn about the potential interactions between antiretrovirals and psychiatric medications metabolized by the liver's cytochrome P450 system. Understand how drug metabolism can be affected and the impact on medication effectiveness and safety.

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HIV and Psychiatric Medication Interactions

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  1. HIV and Psychiatric Medication Interactions Karina K. Uldall, MD, MPH

  2. HIV/AIDS Research Program Department of Psychiatry UW School of Medicine Seattle, WA

  3. 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

  4. 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

  5. DRUG METABOLISM • Cytochrome P450 system • Affected by • age - hormones • nutrition - drug half life • stress - drug dosages • hepatic blood flow • liver disease

  6. 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

  7. 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)

  8. 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

  9. 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)

  10. Substrates alprazolam midazolam carbamazepine sertraline haloperidol TCAs thiothixene zolpidem trazadone heroin morphine triazolam diazepam ritonavir Efavirenz methadone CYP 3A

  11. Inhibitors potent nefazadone fluvoxamine cannabis grapefruit juice ritonavir/saquinavir moderate fluoxetine paroxetine sertraline TCAs indinavir/nelfinavir efavirenz amprenavir weak venlafaxine mirtazapine CYP 3A

  12. Inducers phenobarbital carbamazepine alcohol efavirenz CYP 3A

  13. Substrates carbamazepine mirtazapine codeine risperidone fluoxetine TCAs trazadone haloperidol morphine amphetamine ecstasy meperidine droperidol phenothiazines cannabis paroxetine venlafaxine nicotine CYP 2D6

  14. Inhibitors potent fluoxetine paroxetine methadone ritonavir moderate desipramine nortriptyline bupropion sertraline weak efavirenz Inducers phenobarbital carbamazepine CYP 2D6

  15. Substrates caffeine mirtazapine clozapine haloperidol phenothiazines imipramine amitriptyline clomipramine doxepin benzodiazepines olanzapine thiothixene CYP 1A2

  16. Inhibitors potent fluvoxamine ritonavir moderate grapefruit juice TCAs weak nefazadone mirtazapine olanzapine fluoxetine Inducers cigarette smoke cabbage charcoal grilled foods CYP 1A2

  17. Substrates bupropion diazepam temazepam nicotine Inducers carbamazepine phenobarbital CYP 2B6

  18. 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

  19. Inhibitors weak venlafaxine nefazodone Inducers rifampin rifabutin CYP 2C

  20. 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

  21. ANTIRETROVIRALS • P450 Substrates • all protease inhibitors • indinavir, squinavir, ritonavir, nelfinavir, amprenavir • P450 Inhibitors - reversible • strong - ritonavir • moderate - indinavir, nelfinavir • weak - saquinavir

  22. ANTIRETROVIRALS • P450 Inducers - lasts for several days • moderate - ritonavir, nelfinavir, nevirapine

  23. PSYCHIATRIC MEDICATIONS • P450 Substrates • many psychiatric medications are metabolized through the liver • P450 Inhibitors • strong - fluoxetine, fluvoxamine • moderate - paroxetine, sertraline, TCAs • weak - venlafaxine, mirtazapine

  24. PSYCHIATRIC MEDICATIONS • p450 Inducers • nicotine/cigarette smoke • carbamazepine • alcohol

  25. 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

  26. 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

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