Antipsychotic Agents/Schizophrenia
Anti-psychotic agents
Used for a diverse spectrum of psychotic disorders: schizophrenia, delusional disorders,
bipolar disorder, depressive psychosis, and drug induced psychosis.
- Also used to suppress emesis, treat Tourette syndrome and Huntington chorea.
The first generation (FGAs)
Also known as conventional anti-psychotics.
- Produce a strong blockade of receptors for dopamine in the CNS.
can cause serious movement disorders known as extra pyramidal symptoms
(EPS).
Second generation (SGAs)
Work by producing only moderate blockade of dopamine receptors and a stronger
blockade of serotonin receptors.
- since dopamine blockage is moderateless risk for EPSs
Schizophrenia
A chronic psychotic illness characterized by disordered thinking and reduced ability to
comprehend reality.
3 groups of symptoms:
- Positive symptoms: an exaggeration or distortion of normal function
hallucinations, delusions, agitation, tension and paranoia
- Negative symptoms: a loss or diminution of normal function
No motivation, poverty of speech, blunted affect, poor self-care, and social
withdrawal
- Cognitive symptoms:
Disordered thinking, reduced ability to focus attention, and prominent
learning and memory difficulties.
Positive, negative, and cognitive symptoms respond equally to FGAs and SAs
Subtle changes may appear years before symptoms become florid, when thinking and
speech may be completely incomprehensible to others.
Acute schizophrenic episode: delusions (fixed false beliefs) and hallucinations are
frequently prominent.
Delusions: typically religious, grandiose, or persecutory.
Auditory hallucinations: voices arguing or commenting on one’s behavior.
- Affect may be blunted or labile, lack self-care skills and sleeping/eating are
disrupted.
- Patients have difficulty with relationships, employment and functioning
independently in society.
- Residual s/s (post-acute episode):
suspiciousness, poor anxiety management, and diminished judgement,
insight, motivation, and capacity for self-care.
The long-term course of schizophrenia
Characterized by episodic acute exacerbations separated by intervals of partial
remission. The etiology of this is unknown.
, First-Generation Anti-Psychotics
Classified by potency (refers to the size of dose needed to elicit a given response:
potency implies nothing about the maximal effect a drug can produce)
- low, medium, and high potency.
- High potency produce fewer side effects than the low potency agents, they cause
more early EPSs but less sedation, orthostatic hypotension, and anticholinergic
effects
Classified by chemical structure:
4 major chemical categories: Phenothiazines, Thioxanthene, Butyrophenone, and
dibenzoxazepine.
- Phenothiazines have 3 subgroups.
- Drugs in all groups are equivalent with respect to antipsychotic actions, and hence
chemical classification is not emphasized.
Major Adverse Effects
Extrapyramidal Symptoms:
- Acute dystonia(contraction of muscles, twisting, distorted posture), oculogyric
crisis (upward deviation of the eyes), opisthotonos (tetanic spasm of the back
muscles), joint dislocation, impaired respirations
- Treatment: Anticholinergic meds (benztropine and diphenhydramine)
- Some EPS SE are irreversible
Parkinsonism:
- Bradykinesia, mask-like faces, drooling, tremor, rigidity, shuffling gait,
cogwheeling and stooped posture (within the first month)
- Treatment: with centrally acting anticholinergic drugs such as benztropine and
diphenhydramine. Amantadine may also be given
Akathisia: pacing and squirming brought on by uncontrollable need to be in motion
(within the first 2 months-high potency)
- 3 types of drugs can suppress: anticholinergic drugs, benzodiazepines, and beta
blockers.
Tardive dyskinesia: (w/ long-term) involuntary choreoathetoid movements of the tongue
and face (like lip smacking, tongue flicks) and involuntary movements of limbs, toes,
fingers and trunk can develop later
- Treatment: Valbenazine followed by deutetrabenazine.
These are vesicular monoamine transporter 2 (VMAT2) inhibitors.
SE: QT prolongation and somnolence.
gradually withdrawing anticholinergic drugs, giving benzodiazepines, and
reducing the dosage of the offending FGA can reduce symptoms
Neuroleptic malignant syndrome: Rare but serious
- lead pipe rigidity, a sudden high fever, sweating, autonomic instability,
dysrhythmic, fluctuations in the blood pressure, altered level of consciousness and
seizures or coma can develop.
Anti-psychotic agents
Used for a diverse spectrum of psychotic disorders: schizophrenia, delusional disorders,
bipolar disorder, depressive psychosis, and drug induced psychosis.
- Also used to suppress emesis, treat Tourette syndrome and Huntington chorea.
The first generation (FGAs)
Also known as conventional anti-psychotics.
- Produce a strong blockade of receptors for dopamine in the CNS.
can cause serious movement disorders known as extra pyramidal symptoms
(EPS).
Second generation (SGAs)
Work by producing only moderate blockade of dopamine receptors and a stronger
blockade of serotonin receptors.
- since dopamine blockage is moderateless risk for EPSs
Schizophrenia
A chronic psychotic illness characterized by disordered thinking and reduced ability to
comprehend reality.
3 groups of symptoms:
- Positive symptoms: an exaggeration or distortion of normal function
hallucinations, delusions, agitation, tension and paranoia
- Negative symptoms: a loss or diminution of normal function
No motivation, poverty of speech, blunted affect, poor self-care, and social
withdrawal
- Cognitive symptoms:
Disordered thinking, reduced ability to focus attention, and prominent
learning and memory difficulties.
Positive, negative, and cognitive symptoms respond equally to FGAs and SAs
Subtle changes may appear years before symptoms become florid, when thinking and
speech may be completely incomprehensible to others.
Acute schizophrenic episode: delusions (fixed false beliefs) and hallucinations are
frequently prominent.
Delusions: typically religious, grandiose, or persecutory.
Auditory hallucinations: voices arguing or commenting on one’s behavior.
- Affect may be blunted or labile, lack self-care skills and sleeping/eating are
disrupted.
- Patients have difficulty with relationships, employment and functioning
independently in society.
- Residual s/s (post-acute episode):
suspiciousness, poor anxiety management, and diminished judgement,
insight, motivation, and capacity for self-care.
The long-term course of schizophrenia
Characterized by episodic acute exacerbations separated by intervals of partial
remission. The etiology of this is unknown.
, First-Generation Anti-Psychotics
Classified by potency (refers to the size of dose needed to elicit a given response:
potency implies nothing about the maximal effect a drug can produce)
- low, medium, and high potency.
- High potency produce fewer side effects than the low potency agents, they cause
more early EPSs but less sedation, orthostatic hypotension, and anticholinergic
effects
Classified by chemical structure:
4 major chemical categories: Phenothiazines, Thioxanthene, Butyrophenone, and
dibenzoxazepine.
- Phenothiazines have 3 subgroups.
- Drugs in all groups are equivalent with respect to antipsychotic actions, and hence
chemical classification is not emphasized.
Major Adverse Effects
Extrapyramidal Symptoms:
- Acute dystonia(contraction of muscles, twisting, distorted posture), oculogyric
crisis (upward deviation of the eyes), opisthotonos (tetanic spasm of the back
muscles), joint dislocation, impaired respirations
- Treatment: Anticholinergic meds (benztropine and diphenhydramine)
- Some EPS SE are irreversible
Parkinsonism:
- Bradykinesia, mask-like faces, drooling, tremor, rigidity, shuffling gait,
cogwheeling and stooped posture (within the first month)
- Treatment: with centrally acting anticholinergic drugs such as benztropine and
diphenhydramine. Amantadine may also be given
Akathisia: pacing and squirming brought on by uncontrollable need to be in motion
(within the first 2 months-high potency)
- 3 types of drugs can suppress: anticholinergic drugs, benzodiazepines, and beta
blockers.
Tardive dyskinesia: (w/ long-term) involuntary choreoathetoid movements of the tongue
and face (like lip smacking, tongue flicks) and involuntary movements of limbs, toes,
fingers and trunk can develop later
- Treatment: Valbenazine followed by deutetrabenazine.
These are vesicular monoamine transporter 2 (VMAT2) inhibitors.
SE: QT prolongation and somnolence.
gradually withdrawing anticholinergic drugs, giving benzodiazepines, and
reducing the dosage of the offending FGA can reduce symptoms
Neuroleptic malignant syndrome: Rare but serious
- lead pipe rigidity, a sudden high fever, sweating, autonomic instability,
dysrhythmic, fluctuations in the blood pressure, altered level of consciousness and
seizures or coma can develop.
