Antipyschotics Flashcards
What are positive symptoms, give 5 examples?
• Positive symptoms: reflect an excess of normal functions. • Hallucinations and delusions • Thought disorder • Perceptual disturbances • Incongruous mood • Increased motor function
What are negative symptoms, give 4 examples?
• Negative symptoms: reflect diminution or loss of normal functions. • Blunted affect • Poverty of speech • Diminished motivation • Social withdrawal
What are cognitive symptoms?
• Cognitive symptoms: Deficits in memory
and cognitive control of behaviour.
Biological basis for symptoms in schizophrenia?
• Positive symptoms are believed to be linked to
overactivity of the mesolimbic pathway.
• Negative and cognitive symptoms may be due to
hypoactivity of the mesocortical pathway.
• There are 4 well-defined dopamine
pathways in the brain: what are they?
- MESOLIMBIC PATHWAY
- NIGROSTRIATAL PATHWAY
- MESOCORTICAL PATHWAY
- TUBEROINFUNDIBULAR PATHWAY
MESOLIMBIC PATHWAY projects from, role, and symptoms involvement?
• Projects from midbrain to limbic system.
• Important role in emotional behaviours.
• Hyperactivity of this pathway is thought to cause
positive psychotic symptoms.
• Blockade of D2 receptors in this pathway
decreases positive symptoms.
MESOCORTICAL PATHWAY projects from and symptoms involvement?
• Projects from midbrain to prefrontal cortex.
• Negative and cognitive symptoms may be due to
reduced activity of this pathway.
• Blockade of D2 receptors in this pathway
may cause or worsen negative and cognitive
symptoms.
NIGROSTRIATAL PATHWAY projects to, role, receptors and ae related to this pathway?
• Projects from substantia nigra to basal ganglia.
• It controls motor movements.
• Blockade of D2 receptors in this system may
lead to disorders of movement.
• This pathway is part of the extrapyramidal
nervous system.
• Motor adverse effects associated with blockade
of dopamine receptors in this system are called
extrapyramidal reactions (EPR).
TUBEROINFUNDIBULAR PATHWAY projection and role?
• Projects from hypothalamus to anterior pituitary.
• Dopamine released from these neurons inhibits
prolactin secretion.
• Blockade of dopamine receptors in this
system will increase prolactin levels.
• This may cause galactorrhea.
List 4 CLASSICAL antipsychotics drugs?
- Chlorpromazine
- Fluphenazine
- Haloperidol
- Thioridazine
List 5 atypical antipsychotic drugs?
- Clozapine
- Risperidone
- Olanzapine
- Quetiapine
- Aripiprazole
Classical antipsychotics are subclassified
according to their potency:
• High-potency drugs: Fluphenazine and
haloperidol. More likely to produce EPRs.
• Low-potency drugs: Chlorpromazine and
thioridazine. Less likely to produce EPRs and
more likely to produce sedation and postural
hypotension.
MOA of CLASSICAL ANTIPSYCHOTIC DRUGS?
CLASSICAL ANTIPSYCHOTIC DRUGS
• The efficacy of the traditional neuroleptic drugs
correlates closely with their ability to block D2
receptors in the mesolimbic pathway.
MECHANISM OF ACTION OF
ANTIPSYCHOTICS atypical
ATYPICAL ANTIPSYCHOTIC DRUGS
• Atypical antipsychotic drugs have higher
affinities for other receptors than for the D2
receptor. For example:
• Clozapine has high affinity for D1, D4, 5HT2,
muscarinic and alpha-adrenergic receptor, but it is
also a D2 blocker.
• Risperidone blocks 5HT2 to a greater extent
than it does D2.
COMMON PROPERTIES OF ATYPICAL ANTIPSYCHOTICS
• Dual antagonism at 5-HT2A and D2 receptors.
• Part of their action is due to 5HT receptor
blockade.
• Less likely to cause EPRs than classical agents.
• Less likely to cause tardive dyskinesia
• Less likely to cause increases in prolactin
• More effective at treating negative symptoms.
• Effective in refractory populations.
PROPERTIES OF SOME ATYPICAL ANTIPSYCHOTIC AGENTS?
• Clozapine is the prototype of the atypical agents.
• Risperidone causes EPR. Rare at therapeutic doses.
• Clozapine and quetiapine are the agents least
likely to induce EPR.
• Aripiprazole is a partial agonist at D2 and 5HT1A
receptors and an antagonist at 5HT2A receptors.
ACTIONS OF ANTIPSYCHOTIC DRUGS
- ANTIPSYCHOTIC
* ANTIEMETIC
ANTIPSYCHOTIC ACTIONS of antipsychotic drugs?
- Reduce hallucinations and agitation.
- Have a calming effect.
- Do not depress intellectual function.
- Motor incoordination is minimal.
- Onset of antipsychotic action is ≤ 24 h.
ANTIEMETIC EFFECTS of antipsychotic drugs?
• With the exception of aripiprazole and
thioridazine, most antipsychotics have
antiemetic effects.
• Mediated by blockade of D2 receptors of the
chemoreceptor trigger zone of the medulla.
METABOLISM of antipsychotic drugs?
• Most antipsychotic drugs are almost completely
metabolized, mainly by CYP2D6, CYP1A2 and
CYP3A4.
• Antipsychotics do not interfere with the
metabolism of other drugs
EXTRAPYRAMIDAL REACTIONS with antipsychotics?
• Associated with high D2 potency.
• Most likely to occur with high-potency conventional antipsychotics, such as haloperidol and fluphenazine, that have a high affinity for
D2-receptors.
• Less likely with low-potency conventional
antipsychotic drugs such as chlorpromazine or
thioridazine.
• EPRs are also less likely to occur with conventional agents with strong anticholinergic activity, such as thioridazine and
chlorpromazine.
• Atypical antipsychotic drugs have low potential
for causing EPRs.
EPRs include:
- Parkinsonism
- Dystonia
- Akathisia
- Tardive Diskynesia
NEUROLOGIC EFFECTS
PARKINSONISM:?
• Parkinsonism can be treated with antimuscarinic
drugs like benztropine or trihexyphenidyl, with
diphenhydramine, or with amantadine.
• Levodopa should never be used in these
patients.
Dystonia and akathisia with antipsychotic use?
DYSTONIA
• Dystonia can be controlled with benztropine,
trihexyphenidyl, or diphenhydramine.
AKATHISIA • Management requires reduction of dosage or a change of the antipsychotic drug. • The drugs most commonly used to manage akathisia are clonazepam or propranolol.
Tardive dyskinese with antipsychotic use?
TARDIVE DYSKINESIA • Late-occurring syndrome of abnormal choreoathetoid movements. • Most important unwanted effect of antipsychotics. • Potentially irreversible. • May be due to dopamine receptor upregulation.
Tardive dyskinese management with antipsychotic use?
TARDIVE DYSKINESIA: MANAGEMENT
• Discontinue antipsychotic drug or reduce dose.
• Eliminate all drugs with central anticholinergic
action.
• The VMAT inhibitors tetrabenazine or
valbenazine can be used to treat tardive
dyskinesia.
• Administration of a benzodiazepine may help.
• Clozapine is recommended for patients with
tardive dyskinesia who require antipsychotics.
Describe neuroleptic malignant syndrome
NEUROLEPTIC MALIGNANT SYNDROME • Rare and life-threatening disorder. • Rigidity, tremor, hyperthermia • Altered mental status • Autonomic instability • Elevated WBC, elevated CK • Myoglobinemia, with potential nephrotoxicity. • Dantrolene or bromocriptine may be helpful.
Sedation with antipsychotic use?
SEDATION
• More likely with low-potency antipsychotics and
with the atypical agents.
• Due to blockade of central H1 receptors.
Describe blockade actions of antipsychtoics in regards to AE?
• Blockade of alpha1 receptors causes orthostatic
hypotension and impaired ejaculation.
• Some antipsychotics block muscarinic receptors,
producing anticholinergic effects.
• Antimuscarinic effects are beneficial in relation to EPRs.
TOXIC OR ALLERGIC REACTIONS with antipyschotics?
• Clozapine causes agranulocytosis in 1-2% of
patients.
• Regular blood cell counts are mandatory.
ENDOCRINE & METABOLIC EFFECTS with antipsychotics?
PROLACTIN SECRETION
• Blockade of D2 receptors in the pituitary leads to
increase in prolactin secretion.
• In women: amenorrhea-galactorrhea syndrome
and infertility.
• In men: loss of libido, infertility and impotence.
• Atypical antipsychotics are less likely to produce
prolactin elevations
WEIGHT GAIN
• Some atypical antipsychotics produce more weight gain and increases in lipids than some typical agents.
• Adverse effects of weight gain include type 2
DM, hypertension and hyperlipidemia.
CARDIAC TOXICITY with antipsychotics?
• Thioridazine causes a high incidence of QTcand T-wave changes and may rarely produce ventricular arrhythmias and sudden death.
OCULAR COMPLICATIONS with antipsychotics?
• Chlorpromazine causes deposits in the cornea
and lens.
• Thioridazine causes retinal deposits.
ANTIPSYCHOTICS: USES?
PSYCHIATRIC INDICATIONS
• Schizophrenia.
• Bipolar disorder.
• Suppression of tics in Tourette’s disorder.
• Control of disturbed behavior in Alzheimer’s
disease.
• Adjuncts to antidepressants in treatmentresistant major depression.
• In combination with antidepressants in psychotic
depression.
• Irritability associated with autistic disorder.
NON-PSYCHIATRIC INDICATIONS of antipsychotics?
• Nausea and vomiting.
• Droperidol is used in combination with fentanyl
in neurolept-anesthesia.
ANTIPSYCHOTICS IN PREGNANCY
• Antipsychotic drugs are category C.
• Only clozapine is category B.
• The risk of hyperglycemia and weight gain,
which may be problematic in pregnancy, is
greater with atypical antipsychotics.
DRUG CHOICE with antipsychotics drugs?
• Atypical drugs are preferred due to:
• Benefit for negative symptoms and cognition
• Diminished risk of EPRs and tardive dyskinesia
• Lesser increases in prolactin levels
• Aripiprazole is currently the most prescribed
antipsychotic in the US.
• Clozapine, because of its potential for
agranulocytosis is reserved for refractory patients.
