Chapter 3 CNS - antipsychotic drugs Flashcards
Psychotic disorders
clinical manifestations
* impaired sense of reality
* thought and emotional disturbances
* hallucinations (often auditory)
* delusions (I possess the power to…)
* confusion
schizophrenia
* exhibit sx’s above for at least 6 months l/t impaired ability to maintain interpersonal relationships, a job or daily activity skills
* active psychosis often happens only during a small portion of a pt’s life
* BETWEEN psychotic episodes, pt often withdrawn and perhaps antisocial
- theory – excessive dopamine neurotransmission
- based on the thought that all antipsychotic drugs blocked D2
- high affinity for d2 receptors
chlorpromazine (thorazine)
thoiordazine (mellaril)
mesoridazine
fluphenazine (prolixin)
perphenazine
prochlorperazine (compazine)
trifluoperazine (stelazine)
phenothiazines
- block D2 dopamine receptors (studies shown that doapmine synthesis and metabolism inc w/ acute tx and receptor upregulation occurs after few weeks of use)
- these response happens d/t drug-induced decrease in doapminergic transmission
Potency w/ examples ////////////////////////////////////////////////////////////////////// Adverse effect profile
high
fluphenazine and haloperidol more extrapyramidal side effects (EPS) and less antihistaminic effects (e.g. sedation), alpha adrenergic antagonism (e.g. orthostatic hypotension), and anticholinergic effects (e.g. dry mouth)
middle
perphenazine and loxapine intermediate D2 affinity, with more off-target effects than high-potency agents
low
chlorpromazine less risk of EPS but more antihistaminic effects, alpha adrenergic antagonism, and anticholinergic effects
Cariprazine (vraylar)
atypical antipsychotic (less EPS, more effective for neg sx of schizo)
- partial agonist at D2 and D3
indication
* schizo
effects
1) cerebrovascular events,
2) tardive dyskinesia
3) elderly w/ demenetia at risk
PO, many drug interactions
Asenapine (saphris)
Lurasidone (latuda)
atypical antipsychotic (less EPS, more effective for neg sx of schizo)
- unknown
indication
* psychosis
* bipolar mania
effects:
* somnolence (drowsiness or strong desire to sleep)
* insomnia
* extrapyramidal d/o
- Akathisia: Feeling restless like you can’t sit still. You may have the urge to tap your fingers, fidget, or jiggle your legs.
- Dystonia: When your muscles contract involuntarily. It can be painful.
- Parkinsonism: Symptoms are similar to Parkinson’s disease. You may have a tremor, difficulty finishing thoughts or speaking, and stiff facial muscles. But while a loss of
nerve cells causes Parkinson’s disease, the medication causes Parkinsonism (refer to phenothiazines card) - Tardive dyskinesia: Facial movements happen involuntarily. You may make a sucking or chewing motion with your mouth, stick out your tongue, or blink your eyes a lot.
- elderly w/ dementia related psychosis at risk
PO, rapidly absorbed
Ziprasidone (geodon)
atypical antipsychotic (less EPS, more effective for neg sx of schizo)
- possible dopamine D2 and sertonin 5H2 antagonist
indication
* schizophrenia
effects
1) prlonged QT/QTc interval (Risk for arrhythmia and sudden death)
2) tardive dyskinesia (Facial movements happen involuntarily. You may make a sucking or chewing motion with your mouth, stick out your tongue, or blink your eyes a lot)
3) somnolence
4) Eldery with dementia related psychosis increased risk of death
PO
low risk of abuse
inhibit CYP3A$ activity
pimavanserin (nuplazid)
atypical antipsychotic (less EPS, more effective for neg sx of schizo)
- serotonin 5h2 antagonist
indication:
* psychoses associated with parkinson’s disease
effects
1) elderly with dementia related psychosis increased risk of death
PO
lower risk of abuse
Molindone (moban)
miscellaneous
- chemically unrelated to classes listed (typical + atypical antipsychotic), but similar actions
indication
* psychosis
effects
* few sedative or EPS
* no hypotensive effects
* some anticholinergic effects
PO
loxapine (loxitane)
miscellaneous
- chemically unrelated to classes listed (typical + atypical antipsychotic), but similar actions
indication
* psychosis
effects
1) less sedative and hypotensive effects than chlorpromazine
2) similar EPS
3) sedation lasts up for 12 hours
PO/IM, complete absoprtion, extensive metabolism
cloazpine (clozaril)
miscellaneous
- blocks dopamine receptors as well as cholinergic, adrenergic, serotonergic & histaminergic neurotransmission
- unclear mechanism
indication
* schizophrenia (those failed to use traditional antipsychotics or produced intolerable effects)
effects
1) few EPS
2) potent antimuscarinic effects
3) agranulocytosis in 2% (severe form of neutropenia.)
4) no tardive dyskinesia or increased prolactin release
PO
Tolerance
* abrupt withdrawal may induce psychosis
drug interaction
* potentiates antihypertensive and anticholinergic agenets
* displaces plasma proteins
THERAPY held if granulocyte count < 1500/mm3
olanzapine (zyprexa)
miscellaneous
- blocks dopamine receptors as well as cholinergic, adrenergic, serotonergic & histaminergic neurotransmission
- unclear mechanism
indication
* psychosis
effects
1) few EPS
2) potent antimuscarinic effects
4) no tardive dyskinesia or increased prolactin release
PO
abrupt withdrawal may induce psychosis
quetiapine (seroquel)
miscellaneous
- similar to phenothiazines (chlorpromazine for e.g)
indication
* psychosis
effects
1) no anticholinergic effets
2) orthostatic hypotension
3) sedation
4) less EPS
**PO, extensively metabolized by liver
Hepatic enzyme inducer and inducer of P450 3A
haloperidol (haldol)
miscellaneous
- similar to phenothiazines
indication:
* psychosis
* tourette’s syndrome
* severe BH problem in children
* hyperactive children (short term)
* huntington’s disease
The hallmark symptom of Huntington’s disease is uncontrolled movement of the arms, legs, head, face and upper body. Huntington’s disease also causes a decline in thinking and reasoning skills, including memory, concentration, judgment, and ability to plan and organize.
Huntington’s disease brain changes lead to alterations in mood, especially depression, anxiety, and uncharacteristic anger and irritability. Another common symptom is obsessive-compulsive behavior, leading a person to repeat the same question or activity over and over.
effects
1) less sedation, anticholinergic effects and alpha-adrenergic blocking than chlorpromazine
2) rarely hypotension
3) EPS effects may be dramatic
PO/IM/IV
* begin tx with low dose
* individualize dose
Transient dyskinesias may be d/t abrupt withdrawal
Interaction
* enchances CNS depressants, alcohol + anticonvulsants
* decreases actions of amphetamines
* severe hypotension with alcohol, epinephrine, antihypertensives
* w/ antimuscarinics – inc. intraocular pressure and reduce haloperidol effects
* w/ lithium – encephalopathic syndrome
pimozide (orap)
miscellaneous
- blocks dopamine receptors
indication:
* tourette’s syndrome (Tics are sudden twitches, movements, or sounds that people do repeatedly. People who have tics cannot stop their body from doing these things. For example, a person might keep blinking over and over)
effects
* extrapyramidal disorder
&&&
* Akathisia: Feeling restless like you can’t sit still. You may have the urge to tap your fingers, fidget, or jiggle your legs.
* Dystonia: When your muscles contract involuntarily. It can be painful.
* Parkinsonism: Symptoms are similar to Parkinson’s disease. You may have a tremor, difficulty finishing thoughts or speaking, and stiff facial muscles. But while a loss of
nerve cells causes Parkinson’s disease, the medication causes Parkinsonism (refer to phenothiazines card)
* Tardive dyskinesia: Facial movements happen involuntarily. You may make a sucking or chewing motion with your mouth, stick out your tongue, or blink your eyes a lot.
&&&
* sedation
* headache
* sensory changes
* hypotension
PO, serum level
withdraw slowly, dyskinesia may develop after abrupt withdrawal
LOWER SZ threshold in pt’s taking seizure meds
potentiate CNS depressants
risperidone (risperdal)
miscellaneous
- mechanism unknown
- binds as antagonists at serotonin, dopamine, alpha adrenergic and H1 receptors
indication
* psychosis
effects
* extrapyramidal d/o
&&&&&
* Akathisia: Feeling restless like you can’t sit still. You may have the urge to tap your fingers, fidget, or jiggle your legs.
* Dystonia: When your muscles contract involuntarily. It can be painful.
* Parkinsonism: Symptoms are similar to Parkinson’s disease. You may have a tremor, difficulty finishing thoughts or speaking, and stiff facial muscles. But while a loss of
nerve cells causes Parkinson’s disease, the medication causes Parkinsonism (refer to phenothiazines card)
* Tardive dyskinesia: Facial movements happen involuntarily. You may make a sucking or chewing motion with your mouth, stick out your tongue, or blink your eyes a lot.
&&&&&
- sedation
- hyperkinesia
- somnolence
- constipation
PO; reduce dose with liver or kidney dysfunction and elderly folks
* withdraw slowly
* metabolism (varies genetically among patients)
paliperidone (invega sustenna)
Iloperidone (fanapt)
miscellaneous
- unknown
- possible D2 dopamine and serotonin 5h2 antagonist
indication
* schizo
effect
* prolonged QT/qtc interval
* elderly w/ dementia related psychosis face inc risk of death
* dizziness
* somnolence
* tachycardia
* orthostatic hypotension
PO
low risk of abuse
drug interaction
* QT interval-prolonging drugs
* abiraterone (It can treat prostate cancer. It’s given with prednisone.)
* antihypertensives
