Anti-Psychotic, Mood Stabilizer Flashcards
Valproic Acid (Depakene, Depakote)
Class: anti-convulsant, partial and absence seizures, mood stabilizer, h/a prophylaxis
PD: MOA is still unknown, increases GABA effects, may inhibit glutamate/NMDA receptor-mediated neuronal excitation, can block the voltage-gated sodium channels and T-type calcium channels, is an inhibitor of the enzyme histone deacetylase 1 (HDAC1)
PK: metabolism is 50% UGT, 40% beta-oxidation, 10% CYP450, dissociates to valproate ion in GI tract, urine (<3% unchanged), half-life ~16h
Toxicity: potential for severe impact on liver, hematopoietic and/or pancreatic function, dyspepsia, weight gain, polycystic ovarian syndrome, hair loss
Interaction: pregnancy risk factor D, reduces clearance of carbamazepine and lamotrigine
Monitor: obtain baseline CBC with differential, LFT, and pregnancy test for females. Monitor levels, LFT, and CBC with diff every 3-6mnths, monitor for development of polycystic ovary disease in females
Black Box: hepatotoxicity, teratogenic, pancreatitis
Lithium Carbonate
Class: anti-mania, mood stabilizer, h/a prophylaxis esp cluster h/a
PD: MOA is still unknown, it may alter sodium transport in nerve and muscle cells or inhibit the recycling of neuronal membrane phosphoinositides involved in generation of second messengers, or inhibition of glycogen synthase kinase 3, inositol phosphatase, or modulating glutamate receptors
PK: urine 95% (100% unchanged), feces 1.5mEq/L (adult/child), >.8mEq/L (elderly)
Black Box: lithium toxicity closely related to serum lithium levels and can occur at doses close to therapeutic levels, start tx only if facility available for prompt accurate serum lithium determinations
Carbamazepine (Carbatrol, Tegretol)
Class: pharmacologic class-focal and secondarily generalized seizures, less effective for primary generalized seizures, mood stabilizer for bipolar disorder, works well also for neuropathic pain and trigeminal neuralgia
PD: sodium channel blocker in neuronal membranes, slows repetitive firing and stops seizures
PK: only po, half life 12h, hepatic metabolism, hepatic enzyme inducer P450, levels increased by calcium channel blockers and macrolide abx
Toxicity: drowsiness, h/a, migraines, motor coordination impairment, and/or upset stomach, decreased etoh tolerance, weight gain, aplastic anemia
Interaction: diruetics, NSAID, ACE inhibitor, calcium channel blocker
Special: pregnancy risk factor D, caution for hypersensitivity to drug, brugada syndrome, elderly pts, renal impairment, volume depletion, cvd, thyroid disorder, concurrent CNS depressant, etoh use
Monitor: perform baseline and periodic hematological testing, if low or decr. WBC or platelet counts monitor closely, D/C tx if evidence of significant bone marrow depression
Black Box: appropriate use: can increase toxic potential or decrease activity of other drugs, serious dermatologic rxns and HLA-B*1502 allele: allele most common in asian communities, aplastic anemia/agranulocytosis risk 5-8x greater than that of general public
Lamotrigine (Lamictal)
Class: anticonvulsant, mood stabilizer
PD: unclear, blocks sodium channel and blocks release of glutamate, same class as carbamazepine but unlike other sodium channel blocking anticonvulsants it is also effective in tx of depressed phase of bipolar disorder
PK: po, metabolized by glucuronidation, half-life 13.5h, and Vd=1.36L/kg
Toxicity: rash, fever, and fatigue can be serious, as they may indicate incipient Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS syndrome or aseptic meningitis, 5-10% get a rash but in only .1% will develop a serious rash, nausea/vomiting, dizziness, vertigo, visual disturbance, somnolence, ataxia, pruritus/rash, h/a
Interaction: fewer interactions than many anticonvulsants, other antiepileptic drugs that induce hepatic drug-metabolizing enzymes reduce effect
Special: pregnancy risk factor C
Monitor: Creatinine at baseline, opthal exams if prolonged tx, sx suicidality, clinical worsening if bipolar disorder, and/or unusual behavior changes
Black Box: serious skin rashes, requiring hospitalization and D/C tx included, stevens-Johns syndrome, rare cases of toxic epidermal necrolysis, and rash-related deaths
Oxcarbazepine (Trileptal)
Class: anticonvulsant, mood stabilizer
PD: exact MOA unknown, blocks voltage-sensitive Na channels, like carbamazepine with fewer side effects, stabilizes neural membranes, inhibits repetitive firing, and decreased synaptic impulse propagation
PK: p.o. Urine 95% (<4%, half-life 1-5h, active metabolite
Toxicity: dizziness, drowsiness, blurred or double vision, fatigue, h/a, nausea/vomiting, cognitive impairment, hyponatremia (2.7% of pts), test blood sodium levels if severe fatigue
Interaction: has fewer interaction than many anticonvulsants
Special: pregnancy risk factor C
Monitor: cr at baseline, na, s/sx depression, behavior changes, suicidality
Black Box: Oxcarbazepine is a structural derivative of carbamazepine, it has a reduced effect on inducing liver metabolizing enzymes, which means less dose modifications, more expensive than carbamazepine currently.
Olanzapine (Zyprexa)
Class: atypical anti-psychotic, mood stabilizer
PD: blocks 5HT2A and D2 receptors similar to clozapine
PK: liver extensively, CYP450, urine 57% (7% unchanged), feces 30%, half-life 21-54h
Toxicity: drowsiness, flu syndrome, weight gain, salivation, tardive dyskinesia (e.g. Lip smacking), QTc prolongation (all anti-psychotics), and rarely neuroleptic malignant syndrome
Special: pregnancy risk factor C (preferred bipolar med for pregnancy), p450 inducers
Indications and dose/route: p.o., i.m.
Monitor: fasting glucose and lipid panel at baseline, then periodically, AST/ALT if significant hepatic dz, CBC frequently during initial tx if pre-existing leukopenia or if drug-induced leukopenia/neutropenia hx, wt, s/sx orthosatic hypotension (for i.m. use)
Dementia-related psychosis: not approved for dementia-related psychosis, increased mortality risk in elderly dementia pts in conventional or atypical antipsychotics, most deaths due to cardiovascular or infectious events, extent to which incr. mortality attributed to antipsychotic v. Some pt. characteristic not clear.
Chlorpromazine (Thorazine), Perphenazine (Trilafon), Halopiredol (Haldol), Fluphenazine (Prolixin)
Class: Typical anti-psychotic (Neuroleptics)
Indication: Schizophrenia, Delirium
MOA: D2 Antagonist
Side effects: all first generation antipsychotics cause extrapyramidal symptoms (EPS), limited clinical efficacy, relapses common, cognitive deficits continue, substance use common, neurological side effects
-Low potency (Thorazine): anti-cholinergic sx, e.g. Dry mouth, blurred vision, constipation, urinary retention, hypotension, weight gain, sedation, less acute dystonia, parkinsonism, tardive dyskinesia, akathesia, prolactin elevation
-High potency (Haldol, Prolixin): more acute dystonia, NMS, parkinsonism, prolactin elevation
Clozapine, Risperidone
Class: atypical anti-psychotic
MOA: weak D2 antagonist, potent antagonist at 5HT2 and NE a2. Increased NE increase efficiency of firing patterns of in DA neurons in mesocorticolimbic circuits.
Indication: dramatically effective for positive and negative sx of schizophrenia. Proven useful for alcohol remission and management of suicidal ideation
Side effects: minimal EPS, minimal prolactin elevation, agranulocytosis (isolated neutropenia), seizures, myocarditis, weight gain, tachycardia, hypotension, drooling, sedation, liver function changes
C.f. Risperidone: 5HT2/D2 ratio similar to clozapine, fewer relapses than haldol, but EPS and elevated prolactin, proven effective for reducing irritability in Autism Spectrum Disorder.
Aripriprazol
Class: atypical antipsychotic
MOA: partial dopamine 2 agonist, functional antagonist in condition of hyperactive dopamine, functional agonist in condition of hypoactive dopamine, indicated in both positive and negative sx.
Side effects: minimal EPS, no prolactin elevation, weight gain
Early activation, insomnia
Special: FDA approved for tx of irritability in autistic children and adolescents.
D-Cycloserine
Class: partial agonist at glycine modulatory site
Exp: when added to typical antipsychotic, modest decrease in negative sx. Involves glutamatergic system, when added to clozapine, no effect or increased sx.
