Pharm - from Toronto Notes Flashcards
antipsychotic MOA
block dopamine activity in target brain pathways
neuroleptic
old name for antipsychotic
antipsychotics indicated for
psychotic symptoms!
- schizophrenia & related
- manic or depressive episodes
- substance use
- medical condition (eg neoplasm)
non-psychosis uses of antipsychotics - conditions
- treatment-resistant MDD
- severe GAD
- complex PTSD
- severe OCD
- borderline PD
- behavioural Sx of dementia
- delirium
- tic disorder
- substance abuse in dual Dx
- Huntington’s disease
- pervasive developmental disorders
- impulse control disorders
non-psychosis uses of antipsychotics - symptoms
adjunctive for:
- agitation
- aggression
- severe anxiety
- sleep difficulties when sedative-hypnotics are contraindicated
onset of antipsychotics
- immediate decrease in agitation, calming effect
- 1-4w for thought disorder response
choosing an antipsychotic
- no reason to combine
- all comparably effective (except: clozapine most effective in treatment-refractory psychosis)
- 2nd gen antipsychotics as effective as 1st gen, but different a/e profile: mainly lower risk of EPS and TD
- choose a drug pt or family member has responded to 1st
when to switch antipsychotics
if no response in 4-6w, switch drugs
Emergency Treatment of Acute Psychosis - drugs & dosing
- haloperidol 5mg IM ± lorazepam 2mg IM
- loxapine 25mg ± lorazepam 2mg IM
- olanzapine 2.5-10 mg PO/IM/quick dissolve
- risperidone 2mg (M-tab, liquid)
Dopamine pathways affected by antipsychotics
Mesolimbic, mesocortical, nigrostriatal, tuberoinfundibular
Mesolimbic pathway
dopamine pathway; involved in emotion origination, reward; high dopamine causes delusions, hallucinations (+ sx of schizophrenia)
Mesocortical pathway
Dopamine pathway; involved in cognition, executive function; low dopamine causes negative Sx of schizophrenia
Nigrostriatal pathway
Dopamine pathway; involved in movement; low dopamine causes EPS (think Parkinson)
Tuberoinfundibular
Dopamine pathway; involved in prolactin hormone release; low dopamine causes hyperprolactinemia (–> gynecomastia, galactorrhea)
1st Gen Antipsychotics: MOA, Pros, Cons
MOA: Block postsynaptic D2 receptors
Pros: Inexpensive, many injectables available
Cons: EPS, tardive syndromes, not mood stabilizing
2nd Gen Antipsychotics: MOA, Pros, Cons
MOA:
- block postsynaptic D2 receptors
- Block serotonin (5-HT2) receptors on presynaptic dopaminergic terminals –> dopamine release; also –> reverses dopamine blockade in some pathways
Pros: Fewer EPS, low risk of tardive syndromes, mood stabilizing effects
Cons: Expensive. Few injectables. Metabolic side effects. Exacerbation (or onset) of obsessive behaviour.
Risperidone pros/cons
Pros: Lower EPS compared to 1st gen; less wt gain than clozapine, olanzepine
Cons: Highest risk of EPS/TD among 2nd Gen - avoid if high risk for movement disorder or elderly. Elevated prolactin - sexual dysfunction, galactorrhea, gynecomastia, menstrual disturbance, infertility
Olanzepine pros/cons
Pros: Better overall efficacy compared to haloperidol. Well tolerated. Low incidence of EPS & TD.
Cons: Wt gain & metabolic effects - avoid in DM. Sedating - avoid if high risk for falls or #.
Quetiapine pros/cons
Pros: Less wt gain than clozapine & olanzepine. Mood stabilizing.
Cons: Sedating. Orthostatic hypotension - avoid is high risk for falls or #. QT prolongation in high doses.
Clozapine pros/cons
Pros: Most effective for treatment-resistant schizophrenia. Does not worsen tardive Sx, & may treat them.
Cons: Wt gain, metabolic effects - avoid in DM. Sedating, orthostatic hypotension - risk fo falls & #. Potential severe constipation. Cardiomyopathy. Sz. Agranulocytosis!!! (1% - avoid if exisiting leukopenia/neutropenia, & get blood counts q1w for 6mo then q2w
Aripiprazole pros/cons
Pros: Less wt gain & metabolic syndrome than olanzapine. Less EPS than haloperidol
Cons: Insomnia
Commonly used 2nd gen antipsychotics
Risperidone Olanzapine Quetiapine Clozapine Aripiprazole
Anticholinergic effects
Red as a Beet, Hot as a Hare, Dry as a Bone, Blind as a Bat, Mad as a Hatter … … …
or, Anticholinergic: dry mouth, urinary retention, constipation, blurred vision, confusional states
How frequently are antipsychotics discontinued?
One trial with daily dosing recorded discontinuation rates from 64% to 82% w/in 6mo. So … a lot.
What are common side effects of antipsychotics?
- anticholinergic
Anticholinergic: dry mouth, urinary retention, constipation, blurred vision, confusional states
What are common side effects of antipsychotics?
- beta-adrenergic
orthostatic hypotension, erectile dysfunction, failure to ejaculate
What are common side effects of antipsychotics?
- dopaminergic blockade
EPS, galactorrhea, amenorrhea, ED, weight gain
What are common side effects of antipsychotics?
- antihistamine
sedation, weight gain
What are common side effects of antipsychotics?
- Hematologic
Agranulocytosis (! severe)
What are common side effects of antipsychotics?
- Hypersensitivity reactions
Liver dysfunction, blood dyscrasias, skin rashes, NMS, altered temp regulation (hypo or hyperthermia)
What are common side effects of antipsychotics?
- Endocrine
Metabolic syndrome
What is neuroleptic malignant syndrome?
Neuroleptic malignant syndrome is a reaction to antipsychotics (= neuroleptics)
characterized by altered mental status, muscle rigidity, hyperthermia, and autonomic hyperactivity.
Clinically, resembles malignant hyperthermia.
Happens due to strong dopamine blockade.
What are common side effects of antipsychotics? (categories)
anticholinergic, beta-adrenergic, dopaminergic blockade, antihistamine, hematologic, hypersensitivity reactions, endocrine
Also, QTc prolongation!
Which antipsychotics merit ECGs?
All antipsychotics can cause QTc prolongation; consider getting ECG prior to initiating any.
Monitor (get baseline and follow up ECGs) in:
1st gen: chlorpromazine, haloperidol
2nd gen: ziprasidone, clozapine
What is the clinical presentation of NMS? (& risk factors)
- mental status changes, fever, autonomic reactivity, rigidity
- develops over 24-72h
- labs: increased CK, leukocytosis, myoglobinuria
Risk factors: sudden dose increase, new drug; illness, dehydration, exhaustion, poor nutrition, external heat load, young, male.
Treatment of NMS
supportive:
- d/c antipsychotic
- hydration, cooling blankets
- dantrolene (muscle relaxant)
- bromocriptine (dopamine agonist)
5% mortality
EPS: Acute vs tardive
Acute: early-onset, reversible
Tardive: late-onset, often irreversible
EPS: Dystonia
Sustained abnormal posture; torsions, twisting, contraction of muscle groups; muscle spasm (eg oculogyric crisis, laryngospasm, torticollis)
Acute: w/in 5d; Tardive: >90d
Risk: Acute: Young Asian and Black males
Treatment: acute: benztropine, diphenhydramine
EPS: Akathisia
Motor restlessness; crawling sensation in legs relieved by walking; very distressing (incr risk of suicide, poor adherence)
Acute: w/in 10d; Tardive >90d
Risk: elderly women
Treatment: Acute: lorazepam, propranolol, diphenhydramine; reduce or switch antipsychotic
EPS: Pseudoparkinsonism
Tremor, Rigidity, Akinesia (bradykinesia, hypokinesia), Postural instability (decr. arm swing, stooped, shuffling gait, difficulty pivoting)
Acute: w/in 30d
Risk: elderly women
Treatment: Acute: benztropine (or benzo); reduce or switch antipsychotic
EPS: Tardive dyskinesia
Purposeless, constant movements, involving facial and mouth musculature; less commonly, limbs; rarely, diaphragm
Tardive: >90d
No specific risk group
No good treatment; may try clozapine (can help with TD); reduce, discontinue, or switch antipsychotic
What medications can be used for EPS, and when would/wouldn’t you use them?
Anticholinergics: benztropine, diphenhydramine
Do not routinely Rx: only give if acute EPS develop, or v high risk. Can worsen tardive Sx (do not Rx).
