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HIV and Psychiatric Medication Interactions

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... 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 ... – PowerPoint PPT presentation

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Title: HIV and Psychiatric Medication Interactions


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

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

12
CYP 3A
  • Inducers
  • phenobarbital
  • carbamazepine
  • alcohol
  • efavirenz

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

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

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

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

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

18
CYP 2C
  • Substrates
  • diazepam
  • amitriptyline
  • clomipramine
  • doxepin
  • imipramine
  • cannabis
  • PCP
  • efavirenz
  • Inhibitors
  • potent
  • fluvoxamine (9.19)
  • fluoxetine (9)
  • ritonavir
  • moderate
  • paroxetine
  • sertraline (19)
  • fluoxetine (19)
  • efavirenz

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

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 clients 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?pagear-00-00
  • www.medscape.com/druginfo
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