Antipsychotics Flashcards
Paranoid schizophrenia
one or more delusions or frequent auditory hallucinations, someone is trying to “get them” hurt them, steal from them
Disorganized schizophrenia
speech and behavior oriented
Catatonic schizophrenia
stupor, posturing, mutism, fetal position
Residual
absence of prominent sx but evidence of illness and functional impairment
Epidemiology of schizophrenia
prevalence remarkably similar among most cultures, most common in late adolescence or early adulthood, prevalence in males and females, lifetime prevalence of .6-1.9%
Etiology of schizophrenia
abnormalities in brain structure an dysfunction, changes not consistent among all individuals, multifactorial causes, neurodevelopmental model, utero disturbance, schizophrenic lesions, genetics
Positive symptoms
hallucinations, delusions, false beliefs, disorganized speech, cannot follow train of thought, psychomotor agitation, bizarre behavior
Negative symptoms
alogia-poverty of speech, brief responses, lack of thought; flattened affect, avolition- lack in self initiated goal-directed activity, socially isolated; anhedonia- lack of interest and motivation in other people/activities, attentional impairment- psychomotor slowing
Clinical course
onset (acute/gradual), acute stabilization, stabilization, maintenance
approaches to therapy
individual- supportive/ counseling, personal therapy, social skills therapies, rehab; group- interactive/ social, cognitive behavioral- cog behavior therapy, compliance therapy
MOA of treating schizo
blockade of DA receptors in mesolimbic area, D2 blockade- affinity for this receptor accounts for antipsychotic activity, D1 blockade- partially responsible for antipsychotic activity, responsible for EPS sx, 5HT blockade- improve neg sx and motor ADRs
Receptor activity
D1-D5: relief of psychosis, EPS; 5HT2: helps suppress DA activity, protect from EPS, wt gain; a1: orhto hypo, dizziness, M1: ACh ADRs, may protect against EPS, drowsiness, dry mouth, blurred vision, constipation, H1: wt gain, drowsiness
Popular atypical antipsychotics
Quetiapine (Seroquel), Risperidone (Risperdal), ziprasidone (Geodon), Olanzapine (Zyprexa), Aripiprazole (Abilify)
Nausea and vomiting typical antipsychotics
Prochlorperazine (Compazine), Chlopromazine (Thorazine), Droperidol (Inapsine)
Antipsychotics typical
Haloperidol (Haldol), Thioridazine (Mellaril), Thiothixene (Navane), Loxapine (Loxitane), Perphenazine (Trilafon), Fluphenazine (Prolixin), Trifluoperazine (Stelazine)
Typical antipsychotic pearls
all have equal efficacy, MOA- non-selective blockade of D2 receptors, effective at treating positive sx, major concern is EPS
Haloperidol (Haldol) dosing forms
Available IM or PO, IM-fast acting, also available as Depot shot, given once monthly, IVP is linked to increased risk of arrythmias
Haloperidol (Haldol) Pearls
drug of choice for ICU psychosis, used occasionally for CI for EtOH withdrawals, watch for QTc prolongation, higher potensity for EPS and anticholinergic ADRs, many DI
Chlorpromazine (Thorazine)
available PO or IM (IM used in peds for acute mania), off label- retractable hiccups (DOC), migraines, also used for N/V
Droperidol (Inapsine)
N/V migraines, major concern being proarrhythmic
ADRs or antipsychotics
sedation, ACh- dry mouth, constipation, blurry vision, antiadrenergic- orthstatic hypotension, wt gain, prolongation of QT interval, inc prolactin secretion (menstrual changes)
EPS
related to blockade of D1 receptor in substantia nigra, reversible if discovered early, associated w/ all typicals and some atypicals, includes- dystonia, pseudoparkinsonism, akathisia
Prolonged QT
typicals increase Qt interval, inc risk of torsades/ ventricular arrythmia, medications- typical antipsychotics, antibiotics, antifungals, low mag/K, CHF, renal/ hepatic d, CVA
Treatment of Acute dystonia
diphenhydramine (Benadryl), benztropine (Cogentin), must be given right away for quick reversal, usually IV, follow w/ PO agent x 1-2 wks to prevent recurrence, will worsen tardive dyskinsias
EPS- pseudoparkinsonism
20-40%, happens within several months, because of DA blockade causing relative imbalance of DA and ACh, increased risk w/ use of typicals and high risperidone high dose
Treatment ppseuodparkinsonism
decrease dose, change med, anticholinergics, amantadine to block DA
Tardive dyskinesia
occurs in 10-20% of pts, not EPS, associated w/ chronic use, often irreversible, high risk w/ typicals, elderly and women
Tardive dyskinesia presentation
largely orofacial, involuntary movements of face, neck, back, trunk and extremities, blinking, lip smacking, starts as tongue protrusion w/ appearance of lip smacking and difficulty speaking, chewing and swollowing
Tardive dyskinesia treatment
can be controlled if pt concentrates, limited to duration and dose of drug, often occurs when drug is decreased, no effective drug therapy, inc dose back to where it was, ACh make worse
Neuroleptic malignant syndrome
due to blockade of DA receptors, typicals have highest risk, Medical Emergency, 5-20% fatality,, mean age 40, higher risk in pts w/ mood disorders, lithium use, 1/3 cases develop subsequent NMS if re-chanllenged
NMS diagnosis
tx w/ AP w/in 7 days of onset, hyperthermia >100.4, muscle rigidity, 5 of following- changed in mental status, tachy myoglobinuria, inc WBC, tremor, tachypnea, incontinence, CPK inc, metabolic acidosis, labile BP
NMS TX
dec risk factors, early recognition, stop offending agent, supportive care, Dantrolene (Dantrium), amantadine, bromocriptine, lorazepam, may have to sedate, intubate and paralyze
Atypical antipsychotics
Clozapine, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paloperidone, asenapine, iloperidone, lurasidone
Atypical antipsychiotics MOA
D2 and 5HT antagonists, 5HT is an inhibitory neurotransmitter, mesolimbic selectvely for D2 blockage, 5HT has minimal effects on prolactin, dec EPS, beneficial on neg sx
Clozapine (Clozaril)
first atypical, no EPS, TD or effect on prolactin, slow dose titration due to dec BP, strict monitoring for WBS
Clozapine (Clozaril) use
considered to be most efficacious, only for pts who have failed other agents, most potent for tx of pos and neg sx, good for pt w/ hx of suicide, substance abuse, last line, avoid in combo w/ benzos
Clozapine agranulocytosis
occurs in 3%, requires monitoring once weekly for 6 months, biweekly for next 6 months and once a month after, do not initiate if WBC 600 mg/d
Risperidone (Risperdal)
EPS dose related (>6mg/d) low dose good for geriatric agitation, not as effective for treating neg sx
Clozapine ADRs
hypersalivation, wt gain, dec bp, sig sedation, seizures if >600 mg/d
Risperidone dose and ADRs
.5 mg PO BID up to 3 mg PO BID, elevated LFTs, hyperprolactinemia, orthostasis, sexual dysfunction, sedation, wt gain,
Risperdal CONsta
IM injection q 2 weeks, must be overlapped w/ oral therapy upon initiation
Olanzapine (Zyprexa)
similar to Clozaril, no EPS, low TD, also used for acute agitation, bipolar maintenance, acute mania
Olanzapine ADRs and dose
20-60 mg PO QHS, significant sedation, wt gain, diabetes risk, low BP, no agranulocytosis, IM injection- short term treatment of acute agitation, at least as effective as Haldol, w/ quicker onset and lower incidence of dystonia and EPS
Quetiapine (Seroquel)
Low risk EPS, low TD, can see addiction
Quetiapine ADRs and dose
Sedation, mild hypo, wt gain, HA, cataracts in animals, 50-300 mg PO qHS, low doses used for anxiety, insomnia, depression
Ziprasidone (Geodon)
Oral IM, 20-40 mg PO BID, IM favored by many for acute mania, acute agitation IM q 2 hrs prn, ADRs-prolonged QT, mild sedatioin, minimal wt gain, EPS- low, TD low
Aripiprazole (Abilify) MOA
da modulator, only works when needs to, partially blocks D2 receptor when DA is inc, activate D2 receptor when DA is dec, 5HT2 antagonists improves efficacy for neg sx; often used in peds
Aropiprazole Adrs, dose
little wt gain, inc prolactin levels, possible diabetes, anxiety insomnia, HA, nausea, vomiting, low incidence EPS, no TD, no QT, least low BP; 5-15 mg PO Daily
Paliperidone (Invega)
active metabolite of risperidone, once daily, PO, less risk EPS and prolactin inc, niche- pts w/ liver disease, ADR- sedation, low BP
Iloperidone (Fanapt)
schizo only, Qt prolongation, avoid in arrhythmias
Luprasidone (Latuda)
schizo only, no Qt prolongation, $$$, not 1st line
Asenapine (Saphris)
D2 antagonist, 5 HT2A antagonist, SL only
Meatabolic syndrome
consider when starting therapy, do baseline screenings and regular monitoring, get good fam hx
Transitioning
taper over 1-2 weeks to prevent w/ drawal, Risperidone- overlap oral and IM by 3 weeks, haloperidol- overlap oral and IM by 1 month
Augmentation therapy for schizo
Benzos- lorazepam for agitaton and aggression, BB (aggression), mood stabilizers- improves aggitation, lithium, anticonvulsants (carbamazepine, valproate, gabapentin, topiramate), SSRI w/ 1st generation OCD
General principals for APs
therapeutic trial for 6 weeks, (Clozapine needs 12), duration of tx- initial diagnosis (1-2 years) then reassess if relapse treat 5yrs-life, polypharm- consider clozapine before combo, not recommended unless failed others
Compliance
1 reason for relapse, cog fun may be lower, lack of understanding, stigma, cost is little concern
Summary of APs
considered 1st line, effectively treats all psychotic sx, enhanced tolerability, improved cog effects, better outcome in long-term, reduced rate of relapse and hospitalization
Summary of TPs
not usually 1st line, inc risk of EPS/ TD, not as effective in treating neg sx, not likely to improve cog func, no more effective in treating pos sx
Summary of compiance and duration of Tx
chronic disorder requiring life-long tx, tx after 1st episode continued for at least one year, nonadherence to meds is a complicated and signif issue, up to 70% of pts relapse w/in 1st 12 months if not taking maintenance meds
