Chapter 64 - Schizophrenia Flashcards
Dystonias:
prolonged contraction of muscles during drug initiation, including painful muscle spasms; life-threatening if airway is compromised.
Higher risk with younger males.
Centrally-acting anticholinergics (diphenhydramine, benztropine) can be used for prophylaxis or treatment.
Akathisia:
restlessness with anxiety and an inability to remain still;
treated with benzodiazepinesor propranolol.
Parkinsonism:
looks similar to Parkinson disease, with tremors, abnormal gait and bradykinesia;
treat with anticholinergics or propranolol if tremor is the main symptom.
Tardive dyskinesias(TD):
abnormal facial movements, primarily in the tongue or mouth;
higher risk with elderly females.
TD can be irreversible.
Must stop the drug and replace with an SGA with low EPSrisk (e.g., quetiapine, clozapine).
Dyskinesias:
abnormal movements;
more common with dopamine replacement for Parkinson disease.
Hallucinations:
sensing something that is not present, such as
imaginary voices.
Delusions:
a belief about something real that is not true, such as imagining that your family (which is real) wishes to hurt you (delusion).
Disorganized thinking/behavior:
inability to focus attention and communicate organized thoughts.
DSM-5 DIAGNOSTIC CRITERIA FOR SCHIZOPHRENIA
Note: delusions, hallucinations or disorganized speech must be present
Negative signs and symptoms
- Loss of interest in everyday activities
- Lack of emotion (apathy)
- Inability to plan or carry out activities
- Poor hygiene
- Social withdrawal
- Loss of motivation (avolition)
- Lack of speech (alogia)
Positive signs and symptoms:
- Hallucinations: can be auditory (hearing voices), visual or somatic
- Delusions: beliefs held by the patient that are without a basis in reality
- Disorganized thinking/behavior, incoherent speech, often on unrelated topics, purposeless behavior, or difficulty speaking and organizing thoughts, such as stopping in mid-sentence or jumbling together meaningless words
- Difficulty paying attention
meds/ illicit drugs that can cause psychosis
1- Anticholinergics (centrally-acting, high doses)
2- Dextromethorphan
3- Dopamine or dopamine agonists (e.g.,Requip, Mirapex, Sinemet)
4- Interferons
5- Stimulants, especially if already at risk (includes amphetamines)
6- Systemic steroids (typically with lack of sleep - ICU psychosis)
Illicit substances
1- Bath salts (synthetic cathinones, MDPV)
2- Cannabis
3- Cocaine, especially “crack” cocaine
4- Lysergic acid diethylamide (LSD, hallucinogenics)
5- Methamphetamine, ice, crystal
6- Phencyclidine (PCP)
FGA or SGA as 1st line?
SGAs are used first-line due to a lower incidence of extrapyramidal symptoms (EPS),
yet there are many patients who are stabilized on FGAs and in some initial cases, they may be preferable.
FGAs have a high incidence of EPS, Sx:
- dystonias (muscle contractions),
- dyskinesias (abnormal movements),
- tardive dyskinesias (repetitive, involuntary movements, such as grimacing and eye blinking) and
- akathisia (restlessness, inability to remain still).
Long-Acting Injections:
eliminate the need for daily oral tablets or capsules. They are given IM.
Orally Disintegrating Tablets (ODTs)
are useful with dysphagia (difficulty swallowing) and prevents cheeking (when tablets are hidden inside the cheek and spit out later).
ODTs dissolve quickly in the mouth.
Oral solutions/suspensions
are useful for children and people with a feeding tube (e.g., PEGtube).
Acute IM Injections
provide “stat” relief to calm down an agitated, psychotic patient for their own safety and the safety of others.
IM antipsychotics are often mixed with other drugs (in “cocktails”), such as:
- benzodiazepines for anxiolytic/sedative effects, and
- anticholinergics to reduce dystonias
(e.g., the “Haldolcocktail” contains haloperidol, lorazepam and diphenhydramine).
Can you give Olanzapine and benzodiazepines together?
olanzapine: BBW for sedation/ coma
should not be given together (i.e., in an injection) due to risk of excessive sedation and breathing difficulty.
BBW for antipsychotics and elderly patients with dementia:
Antipsychotics are not indicated for agitation control in elderly with dementia-related psychosis.
There is an increased risk of MORTALITY when used for this purpose, mostly due to CARDIOVASCULAR conditions (e.g., heart failure, sudden death) and INFECTION.
Several antipsychotics also carry a warning for an increased risk of STROKE in patients with dementia. All antipsychotics carry a warning for FALLS.
First-generation antipsychotics (FGAs) work mainly by
blocking dopamine-2 (D2) receptors, with minimal serotonin (5-HT2A)receptor blockade.
low potency FGA:
- chlorpromazine (pro? ma)
- thioridazine (redda mish awiye)
lower potency drugs have inc sedation and lower EPS
mid potency FGA
- loxapine (Adasuve)
- perphenazine (per phenazine)
high potency FGA
- Haloperidol (halo)
- Fluphenazine (ouf awiyye)
- Thiothixene (thick potent)
- Trifluperazine
higher potency drugs have lower sedation and inc EPS
BBW for elderly with dementia related psychosis:
Elderly patients with dementia-related psychosis: i risk death from antipsychotics
BBW QT prolongation drug?
Thioridazine
redda btaamul QT
FGA that cause QT prol
thioridazine, haloperidol, chlorpromazine
FGA that requires REMS and why?
BBW
Adasuve (Loxapine)
causes bronchospasm
Warnings with FGA:
1) Cardiovascular effects:
- QT prolongation (especially with thioridazine, haloperidol, chlorpromazine),
- orthostasis/ falls,
- tachycardia
2) Anticholinergic effects:
- constipation,
- xerostomia,
- blurred vision,
- urinary retention
3) CNS depression
4) Extrapyramidal symptoms (EPS): including
- Parkinsonism,
- dystonic reactions,
- akathisia,
- tardive dyskinesia
(inc EPSwith injections)
- can give anticholinergic (e.g.,benztropine, diphenhydramine) to limit/avoid painful dystonic reactions
5) Hyperprolactinemia:
- infertility,
- oligomenorrhea/amenorrhea (less or no menstrual periods),
- galactorrhea (abnormal breast discharge),
- erectile dysfunction/ dec libido
6) Neuroleptic malignant syndrome (NMS):
- use may be associated with NMS;
- monitor for mental status changes, fever, muscle rigidity, autonomic instability
7) Blood dyscrasias (leukopenia, neutropenia and agranulocytosis),
8) ocular effects
FGA that has metallic taste
Adasuve:dysgeusia(bad,bitter, or metallic taste in mouth)
FGA drugs that can be given as injection? doses?
Haloperidol (Haldol):
- Oral (tablet, solution): start 0.5-2 mg BID-TID,
up to 30 mg/day
- IV: usually 5-lO mg
- Decanoate (monthly): IM only; for conversion from
PO, use 10-20x the PO dose
Fluphenazine:
6 - 12 mg/ day, divided doses
Decanoate: IM every 2 weeks)
Second-generation anti psychotics (SGAs) moa:
block dopamine (D2) and serotonin (5-HT2A) receptors.
…, … and … are unique: they are D2 and 5-HTlA partial agonists, and … is also a 5-HT2A antagonist.
Aripiprazole, brexpiprazole and cariprazine are unique: they are D2 and 5-HTlA partial agonists, and brexpiprazole is also a 5-HT2A antagonist.
Aripiprazole
- brand
- dose
- Abilify
- Abilify Maintena IM suspension
- Aristada injection IM suspension
Tablet, ODT, IM suspension
DOSE:
- 10 - 30 mg PO QAM
- Ability Maintena: lM suspension, give monthly
- Aristada: lM suspension, give every 4-8 weeks
SE:
- Akathisia, activating or sedating,
- headache,
- anxiety,
- constipation
- Lower risk of weight gain,
- some QT prolongation,
- EPS (in children)
1) Drugs that are also used for Tourette syndrome (for tics and vocal outbursts)
2) Drugs that are also approved for irritability associated with autism
- Haloperidol
- Aripiprazole
- Aripiprazole
- Risperidone
What drug do you only give if pt failed to respond to treatment with 2 standard AP treatments, or had significant ADRs?
why?
Clozapine
(must try SGA first)
Clozapine is very effective and has dec risk of EPS/TD, but used no sooner than 3rd line due to severe side effect potential:
- metabolic effects,
- neutropenia
Abrupt D/C of clozapine can cause:
seizure
Clozapine brand names:
Clozapine (Clozaril, Versacloz suspension)
Clozapine dose:
300-900 mg/day, divided
- start at 12.5 mg and titrate;
- titrate off since abrupt discontinuation can cause seizures)
BBW with clozapine:
1) Significant risk of potentially life-threatening neutropenia/agranulocytosis (REMS program)
2) Bradycardia, orthostatic hypotension, syncope and cardiac arrest; risk is highest during the initial titration period especially with rapid dose increases; titrate slowly
3) Myocarditis and cardiomyopathy; discontinue if suspected
4) Seizures, dose related; start at no higher than 12.5 mg once or twice daily, titrate slowly, using divided doses; use with caution in patients at seizure risk (e.g., seizure history, head trauma, alcoholism or taking medications which lower seizure threshold)
SE with clozapine
- Agranulocytosis,
- seizures,
- constipation,
- somnolence,
- metabolic syndrome (inc weight, BG, lipids),
- sialorrhea (hypersalivation),
- hypotension
monitoring with clozapine
- REMS: prescribers and pharmacies must be certified and patients must be enrolled with the Clozapine REMS
- To start treatment, baseline ANC must be
>= 1,500/mm 3 - Check ANC weekly x 6 months,
- then every 2 weeks x 6 months,
- then monthly
- stop therapy if ANC < 1,000/mm 3
patients who smoke can require higher/lower doses of:
- Smoking reduces drug levels
- Clozapine
- Olanzapine
Lurasidone Brand name
Latuda
Lurasidone dose:
40-160 mg/day, divided
Take with food >= 350 kcal
CI with lurasidone
Use with strong CYP450 3A4 inducers and inhibitors is CI
SE with lurasidone
- Somnolence,
- EPS (dystonias),
- nausea,
- risk of metabolic syndrome but nearly weight, lipid and blood glucose neutral
Olanzapine brand name
- Zyprexa,
- Zyprexa Zydis ODT,
- Zyprexa Relprevv injection
