April 2003 April 2003 HIV and Psychiatric HIV and Psychiatric Medication Medication Interactions Interactions Karina K. Uldall, MD, MPH Karina K. Uldall, MD, MPH
Dec 22, 2015
April 2003April 2003
HIV and Psychiatric HIV and Psychiatric Medication InteractionsMedication Interactions
Karina K. Uldall, MD, MPHKarina K. Uldall, MD, MPH
April 2003April 2003
HIV/AIDS Research HIV/AIDS Research ProgramProgram
Department of PsychiatryDepartment of Psychiatry
UW School of MedicineUW School of Medicine
Seattle, WASeattle, WA
April 2003April 2003
ANTIRETROVIRALSANTIRETROVIRALS
• 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
April 2003April 2003
LIVERLIVER
• 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
April 2003April 2003
DRUG METABOLISMDRUG METABOLISM
• Cytochrome P450 system
• Affected by– age - hormones– nutrition - drug half life– stress - drug dosages– hepatic blood flow – liver disease
April 2003April 2003
CYTOCHROME P450CYTOCHROME 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
April 2003April 2003
CYTOCHROME P450CYTOCHROME 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)
April 2003April 2003
P450 COMBINATIONSP450 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
April 2003April 2003
P450 VARIATIONSP450 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)
April 2003April 2003
CYP 3ACYP 3A
• Substrates– alprazolam– midazolam– carbamazepine– sertraline– haloperidol– TCAs– thiothixene– zolpidem
– trazadone– heroin– morphine– triazolam– diazepam– ritonavir– Efavirenz– methadone
April 2003April 2003
CYP 3ACYP 3A
• Inhibitors– potent
• nefazadone• fluvoxamine• cannabis• grapefruit juice• ritonavir/saquinavir
– moderate• fluoxetine• paroxetine• sertraline• TCAs• indinavir/nelfinavir• efavirenz• amprenavir
– weak• venlafaxine• mirtazapine
April 2003April 2003
CYP 3ACYP 3A
• Inducers– phenobarbital– carbamazepine– alcohol– efavirenz
April 2003April 2003
CYP 2D6CYP 2D6
• Substrates– carbamazepine– mirtazapine– codeine– risperidone– fluoxetine– TCAs– trazadone– haloperidol
– morphine– amphetamine– ecstasy– meperidine– droperidol– phenothiazines– cannabis– paroxetine– venlafaxine– nicotine
April 2003April 2003
CYP 2D6CYP 2D6
• Inhibitors– potent
• fluoxetine• paroxetine• methadone• ritonavir
– moderate• desipramine• nortriptyline• bupropion• sertraline
– weak• efavirenz
• Inducers– phenobarbital– carbamazepine
April 2003April 2003
CYP 1A2CYP 1A2
• Substrates– caffeine– mirtazapine– clozapine– haloperidol– phenothiazines– imipramine– amitriptyline– clomipramine
– doxepin– benzodiazepines– olanzapine– thiothixene
April 2003April 2003
CYP 1A2CYP 1A2
• Inhibitors– potent
• fluvoxamine• ritonavir
– moderate• grapefruit juice• TCAs
– weak• nefazadone• mirtazapine• olanzapine• fluoxetine
• Inducers– cigarette smoke– cabbage– charcoal grilled foods
April 2003April 2003
CYP 2B6CYP 2B6
• Substrates– bupropion– diazepam– temazepam– nicotine
• Inducers– carbamazepine– phenobarbital
April 2003April 2003
CYP 2CCYP 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
April 2003April 2003
CYP 2CCYP 2C
• Inhibitors– weak
• venlafaxine• nefazodone
• Inducers– rifampin– rifabutin
April 2003April 2003
DRUG INTERACTIONSDRUG 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
April 2003April 2003
ANTIRETROVIRALSANTIRETROVIRALS
• P450 Substrates– all protease inhibitors– indinavir, squinavir, ritonavir, nelfinavir,
amprenavir
• P450 Inhibitors - reversible– strong - ritonavir– moderate - indinavir, nelfinavir– weak - saquinavir
April 2003April 2003
ANTIRETROVIRALSANTIRETROVIRALS
• P450 Inducers - lasts for several days– moderate - ritonavir, nelfinavir, nevirapine
April 2003April 2003
PSYCHIATRIC MEDICATIONSPSYCHIATRIC MEDICATIONS
• P450 Substrates– many psychiatric medications are metabolized
through the liver
• P450 Inhibitors– strong - fluoxetine, fluvoxamine– moderate - paroxetine, sertraline, TCAs– weak - venlafaxine, mirtazapine
April 2003April 2003
PSYCHIATRIC MEDICATIONSPSYCHIATRIC MEDICATIONS
• p450 Inducers– nicotine/cigarette smoke– carbamazepine– alcohol
April 2003April 2003
SUMMARYSUMMARY
• 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
April 2003April 2003
SUMMARYSUMMARY
• 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