Lecture 4: Antipsychotics Flashcards
Positive Symptoms Schizophrenia (7)
- hallucinations
- hostility
- excitability
- delusions
- suspiciousness/persecution
- conceptual disorganization
- grandiosity
Negative symptoms schizophrenia (5)
lessening or absence of normal behaviors and functions related to motivation and interest or verbal/emotional expression
- Blunted effect
- Alogia
- Avolition
- Asociality
- Adnhedonia
Blunted effect
negative symptom shcizophrenia
- diminished facial and vocal
- poor eye contact
- minimal use gestures
Alogia
Negative sx schizophrenia
- short to monosyllable answers to questions
- avoids communication
- uses few words
Avolition
negative sx schizophrenia
- emotional withdrawal
- apathy
- poor grooming/hygiene
- decreased involvement with work or school
Asociality
Negative sx schizophrenia
- few friends/poor relationships
- lack of motivation for relationships
- reduced social interaction
Anhedonia
negative sx schizophrenia
- difficulty or inability to anticipate future pleasure
- few leisure activities
- lack of interest in sexual activity
Goals of therapy (4)
- efficacy: reduction in threat/harm, improvement in acute psychosis
- stabilization: reduce postitive, negative, cognitive sx, medication adherance
- Maintenance: control/remission sx, baseline return, relapse prevention
- Adverse effects: adherence to medication, management ADRS
American Psychiatric Association Guidelines
tx recommentations (4 steps)
- tx with antipsychotic
- monitor for effectivement and side effects
- continue antipsychotics if symptoms improve - Clozapine
- tx resistant schizophrenia
- suicidality remains desire other tx - Tx acute dystonia (involuntary muscle movements) with an anticholinergic rx
- Treat moderate to severe tardive dyskinesia with VMAT2 inhibitor
Tx recommendations (4)
- any antipsychotics could be considered for 1st line
- EXCP: clozapine & lumateperone
- Adequate trial=apropriate dosing for 2-6 weeks - After failure: switch one of the above
- third line: clozapine
- adequate trial: appropriate dosing for 12 + weeks - beyond: augmenting clozapine, multiple agents, ECT
Adequate trial for antipsychotics
appropriate dosing for 2-6 weeks
Exceptions to the antipsychotics 1st line of defense rule
- clozapine
2. lumateperone
Clozapine as third line
adequate dosing for 12+ weeks
1st Generation/ typical antipsychotics
Mechanism (4)
M: 1) dopamines- (DA)D2 receptor blockade
-therapeutic effect, EPS
- muscarinic- M1 receptor blockade
- histaminic- H1 receptor blockade
- Alpha- Aa1 receptor blockade
* agents differ in potency and receptor affinity
Second generation/atypical antipsychotics
MOA
EXCP
M: 1) similar to 1st generation antipsychotics
- increase D2 receptor dissociation
- additional serotonin 5HT2a antagonism
EXCP: aripiprazole, brexiprazole, and caripraszine- partial agonists at D2 receptors
D-HAMS receptors assoc. with antipsychotic therapy
- Dopaminergic
- Histamanic
- Adrenergic
- Muscarinic
- Serotonergic
Dopaminergic receptor (3)
therapeutic effects
extrapyramidal side effects
hyperprolactinemia
Histaminic receptor (2)
sedation and wight gain
Adrenergic receptor (2)
postural hypotension and reflex
tachycardia
Muscarinic receptors (6)
anticholinergic-dry mouth, contipation, urinary retention, blurred vision, decreased cognition
ALL ANTIPSYCHOTIC AE (4)
- mortality and dementia
- FDA boxed warning
- elderly: dementia, related psychosis
- meta-analysis of 17 placebo-controlled trias: 1.6 x more likely to dies compared to placebo
CAUSE: varied, but included cardiovascular and infectious
Precautions for all/most FGAs (first generation antipsychotics) (8)
- seizure disorders
- neuroleptic malignant syndrome
- movement disorders
- blood dycrasias
- inability to adjust to extreme heat
- cardiovascular disease
- hyperprolactinemia
- dysphagia
AE inhaled loxapine
Indication box warning (3)
I: ACUTE tx agitation in schizophrenia/bipolar disorder in adults
W: 1. potential cause respiratory distress and arrest
- can only be used in an enrolled facility that can intubate/ventilate patients
- do not use in patients with asthma, COPD, lung disease or physical exam positive for respiratory problems
Precautions for all/most SGAs (9)
- seizures
- neuroleptic malignant synfrome
- metabolic abnormalities the can increase cardiovascular rx
- hyperprolactinemia
- blood dyscrasia
- orthostasis and syncope
- Suicidality
- Dysphagia
- inability to adjust to extreme heat
Extrapyramidal SE (4)
*more commonly seen with typical antipsychotic
- acute dystonia
- pseudoparkinsonism
- akathisia
- tardive dyskinesia
Acute dystonia (extrapyramidal side effect)
- occurs within 1-3 days
- spastic muscle contraction, usually head & neck
- increased in males, younger, high doses, high potency
*manage with anticholinergic agent, Diphenhdyramine (benadryl) or Benztopine (cogentin)
Pseudoparkinsonism (extrapyramidal side effect) (4)
- occurs within 1-3 months imitation
- symptoms resemble parkinson’s
- gait disturbances, cogwheel rigifity, bradykinesia, etc. - increased in females, elderly, high doses, high potency
- Manage by decreases dose, anticholinergic agents
- benztropine
- duphenhydramine
- tryhexyphenidyl
Akathisia (extrapyramidal) (4)
- occ. first 3 months
- sx include subjective restlessness, jitteriness, fidgeting, pacing
- increased in high dose, high potency, fast titration, concomitant stimulant use
- Manage by decreasing dose, change agent, pharmacologically
- propranolol
- lorazepam
Tardive Dyskinesia (extrapyramidal)
- 3% per year
typical > atypicals - sx=repetative involunatry movements, generally involving mouth and face
- can be irreversible
- increased in females, elderly, DM, affective disorders, early EPS deeloplemtn, alcohol use
- Manage by decreased minimum effective dose, atypical meds
- valbenazine, deutetrabenazine
Neuroleptic Malignant syndrome
sx(4)
- rare but life threatening, 1% occurance
- sx: fever, lead pipe rigidity, mental status change, autonomic dysfunction
- manage: supportive care, d/c antipsychotic
1. bromocriptine
2. dantrolene
QTC prolongation
caution
leas common rx
most common
- caution in pre-existing abnormalities
- least: ariprazole, lurasidone
- Most: ziprasidone, thioridazine with box warning
Endocrine adverse effects
- hyperprolactinemia from hypothalamic dopamine blockade
- glactorrhea
- gynecomastia
- amenorrhea
- sexual dysfunction
more common with typical antipsychotics
Metabolic Adverse effects
*more common with atypical
- central obesity
- high blood pressure
- high triglycerides
- low HDL-cholesterol
- insulin resistance
TypicalsL Misc. effects
- thioridazine
- low potency agents
- all agents
- thioridazine: pigmentary retinopathy (max dose 800 mg/day)
- low potency agents: skin discoloration with sun exposure
- all agents: transient elevations in LFTS
Atypical drugs and their adverse effects (4)
“apines” (3)
“peridones” (3)
“sidones” (3)
partial agonist
- “apines” sedation, metabolic, anticholinergic
- “peridones” less sedation, some metabolic, more EPS
- Admin: asenapine (TD, SL) Sidones: with food, low metabolic rx, med EPS rx
- Partial agonists: lowest metabolic rx, no prolactin increase, more akathisia
Clozapine rxns (4)
- seizures: dose dependent
- orthostatic, syncope, cradycardia, cardiac arrest: avoid combination with benzodiazepines, rx greatest during titration periods
- myocarditis and cardiomyopathy: baseline ECG recommended, eosinophilia may be early indicator
- agranulocytosis: CBC monitoring **, enrollment in clozapine REMS program
Pregnancy rx
- concern: movement disorders, withdrawal following birth
- data lacking in general, mostly historical
- clozapine and lurasidone may have less rx
Lactation rx
should be avoided
loses doeses and close monitoring
Pediatrics rx
- ped and adolescents more susceptible to metabolic changes (wt gain)
- schizophrenia in pets is rare
- psychotherapeutic interventions should b used in combination
- antipsychotics approved for autism: aripiprazole and risperidone
Elderly antipsychotics
- behavioral and psychological symptoms of dementia (BPSD)
- anxiety, agitation, hypnosis
- rationale: reduce use of benzodiazepines
- depression augmentation - less common: Parkinson’s assoc. psychosis
Parkinson’s disease psychosis
mOA
indication
dose
AE
Pimavancerin/nuplazid
MOA: inverse agonist of 5-HT2a
indicated only for PD related psychosis
Dosing: 24 mg PO once daily
-strong CYP3A4 inhibitors (i.e. ketoconazole) 10 mf daily
- AE: peripheral edema, confusion, hallucinations, nausea, orthostasis, QTc prolongation
- same boxed warning for death in dementia
How to choose medications?
- what has pt. responded to in the past?
- What have family members responded to?
- Does the patient have comorbidities to consider when choosing agents?
- rx cost?
How to educate pt?
- tx as chronic disease
- rx of relapse high
- most need lifelong therapy - administration specifics
- agents needing food
- keeping f/u with LAIs, PO overlap
- dissolvine asenapine-no food/water x10 minutes - side effects concern
Summary
- antipsychotics exert their effects through modulation of NTSM recpetors in brain
- block D2, 5HT2a, Etc - both 1st and 2nd generation antipsychotics have considerable, but varying adverser effect profiles
- medication compliance and efficacy may bot differ significantly between most agents
- multiple medication trials may be necessary
