Antipsychotics Flashcards
Mesolimbic Dopamine Hyperactivity
over activity in nucleus accumbens
Positive Symptoms
Mesocortical Dopamine Underactivity
Negative/Cognitive Symptoms:
negative, cognitive and affective sx of schixo
Dopamine
Serotonin
Dec Postivive sx
Dec post and neg sx
Neuroleptics (Antipsychotics):Dopamine Pathways (MOA)
Mesolimbic:
DA overactivity l/t positive sx for schizophrenia and psychosis with mania, depression and dementia
Mesocortical:
negative sx and cognitive dysfunction (DA underactivity in schizophrenia d/t overactivity of N-methyl-D-aspartate (NMDA) or glutamate system)
Nigrostriatal:
controls motor movements; blockade of dopamine by drugs here causes EPS
Tuberoinfundibular:
hypothalamus to anterior pituitary – DA blockade leads to elevated prolactin levels l/t galactorrhea, amenorrhea, sexual dysfunction
Typical antipsychotics (First generation) FGA
TARGETS POSTIVE SX OF SCHIZO
Blockade of DA2-receptors in mesolimbic dopamine pathway
block in mesocortical, nigrostriatal, and tuberoinfundibular leading to ADE
blockade- histamine, cholinergic , alpha blockade
EFFICACY SAME
Atypical antipsychotics (Second generation)
TARGETS NEG SX OF SCHIZO Block serotonin (5-HT2A) receptors more than DA receptor blockade, mesocortical
less EPS and less TD
Less hyperprolactinemia (except risperidone*)
EFFICACY SAME
Primarily Targets-cognitive deficits, but also can have positive symptom relief
HIGH POTENCY FGA-
-ol, xene, razine, nazine, ide
High EPS
Haloperidol (Haldol)-*has long acting IM form
LESS CV
Fluphenazine (Prolixin)*has long acting IM form
Thiothixene (Navane)- QT
Trifluperazine (Stelazine)
Pimozide (Orap)
LOW POTENCY FGA- AZINE
Have HIGH anticholinergic SE’s
- Orthostatic Hypotension
- Sedation
Chlorpromazine (Thorazine)
Thioridazine (Mellaril)
Mid Potency
Loxapine (Loxitane)
Perphenazine (Trilaphon)
Typical Antipsychotics, FGA Side Effects
Cardiovascular: QTc tosardes de pointes
Anticholinergic
Blurred vision, constipation, dry mouth, urinary retention
Antihistamine effect Sedation
Anti alpha 1 effect Orthostatic hypotension
Endocrine: hyperprolactinemia, osteoporosis, amenorrhea, galactorrhea, gynecomastia, sexual SEs
HIGH Extrapyramidal Symptoms EPS
EPS Extrapyramidal Symptoms EPS
D2 blockage on nigrostriatal pathway
*worse with 1st generation antipsychotics
Tx w/ lower dose or change of antipsychotic or diphenhydramine or benztropine (Cogentin), trihexyphenidyl (Artane)
A.D.A.P.T. EPS SE
ACUTE
DYSTONIA- Hours to days: muscle contraction, commonly affecting facial area
AKATHISIA-Days to weeks: restlessness)
PAKRINSOMISM Weeks to months: Cogwheel rigid
TARDIVE-Months to Years: irreversible
TX CLOZAPINE
Clozapine-SGA
Black box- myocarditis, seizures, agranulocytosis
Plasma monitoring: 300-420 ng/ml best; > 1000 ng/ml = seizure and Ach toxicity
Dose: start 12.5-25mg daily, incr by 25-50mg daily over 2 weeks to minimize low BP, sedation, resp depression, seizure risk
Agranulocytosis
Check WBC/ANC (must be > 3000/1500) qwk x6months, if okay, q2wks x6mon; then q4wks if stable
Concerns if active infectious process, immunosuppressed
Monitor sore throat, fever, cold/flu sx, unhealing sores
Clozapine-SGA ADR
inc salivation sedation tachycardia dizzy DRUG interactions- fluvoxamine, ciprofloxcin, smoking lower levels Carbamezapine_ agranulcyttosis Bupropion- seizures
Risperidone- SGA ADR
priapism, hyperprolactinemia, hypotension
Paliperidone *active metabolite of risperidone
Primarily renal elimination, CRCL
Tachycardia inc.
Olanzapine- SGA ADR
Smoking increases metabolism
FDA report: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
Quetiapine- SGA ADR
titrate due to orthostasis, sedation
Ziprasidone - SGA ADR
take with food, increases absorption
rash and/or urticaria
QTc prolongation
Aripiprazole- SGA ADR
urges for gambling, shopping, binge eating and sexual behavior
Lurasidone- SGA ADR
Newer -once daily dosing bipolar depression
Well tolerated,
does not affect QT, hypotension
somnolence, akathisia, Parkinsonian sx, agitation
Alcohol enhances sedation
Cardiometabolic
Weight gain- higher with low potency
12 month wt gain: Cloz, olanz:
Metabolic syndrome: clozapine and olanzapine worst, least with aripiprazole, ziprasidone
Glucose dysregulation: worst with olanz, cloz;
Monitor w/ SGA
Baselin, 12 wk, annual biometrics
Worse- clozapine, olanzipine, quetiapine
Leaset apriprazole
ALL Neuroleptics
AntiCACh- SE low potent FGA, cloz, olanzo SGA
Sedation- low potency FGA, cloz, olanzo SGA
Seizues- CLOZAPINE, low potent
Higher rate w/ Low potenty FGA vs high
BPH closed anlge AVOID
FGAs
Endocrine Adverse Effects
FGAs-Dopamine inhibits release of prolactin; blocking DA would then Prolactin is increased- reverisle
W- menstrual, infertil
M- dec libido, ED,
LT- osteoporisis,
SGA- Respirodone more than FGA
Neuroleptic Malignant Syndrome (NMS)
Rare, Medical Emergency
Mortality = 10%, if kidney failure = 50%
HIGH potency FGA
Idiosyncratic reaction presenting with confusion, autonomic instability, hyperpyrexia, rhabdomyolysis, renal failure, CV collapse Fever Encephalopathy Vitals unstable Enzyme increase Rigidity of muscles
Treatment: DC neuroleptic, supportive care, can use dantrolene or bromocriptine
Drug interatcion
Smoking decrease serum neuroleptic (esp clozapine, olanzapine)
Antidepressants – increased sx and EPS
Lithium, Carbamazepine – confusion/disorientation, increased EPSE
Antihypertensives – increased hypotensive effects
Ziprasidone – medications that prolong the QT interval
