1. Antipsychotic Agents & Schizophrenia
A chemically diverse group of compounds employed to treat a broad spectrum of psychotic disorders.
Schizophrenia, delusional disorders, acute mania, depressive psychoses, drug induced psychoses.

2. Antipsychotic Agents & Schizophrenia
Two major groups:
Conventional Antipsychotics
Block receptors for dopamine D2in the CNS
Atypical Antipsychotics
Only produce moderate blockage of receptors for dopamine D2 and much stronger blockade of receptors for serotonin

3. Antipsychotic Agents & Schizophrenia
Chronic psychotic illness characterized by disordered thinking and a reduced ability to comprehend reality.
Positive symptoms:
Hallucinations, delusions, disordered thinking, disorganized speech, combativeness, agitation, paranoia
Negative symptoms:
Social/emotional withdrawal, lack of motivation, poverty of speech, blunted affect, poor insight, poor judgment, poor self-care
Etiology is unknown

4. Antipsychotic Agents & Schizophrenia
Conventional Antipsychotic Group Properties:
Because of extrapyramidal side effects (serious movement disorders) they are known as neuroleptics.
Classified by potency (low, high) or by chemical structure.
Mechanism of Action:
Varying degrees these drugs block receptors for dopamine, acetylcholine, histamine, and norepinephrine.
Relief of positive symptoms respond better to conventional antipsychotic drugs; less effect on negative symptoms

5. Extrapyramidal Symptoms
Reaction
Onset
Features
Acute dystonia
Hours to 5 days
Spasm of muscle of tongue, neck, face & back
Parkinsonism
5 – 30 days
Tremor, rigidity, shuffling gait, drooling, stooped posture, instability
Restlessness (Akathesia)
5 – 60 days
Compulsive, repetitive motions; agitation
Tarditive dyskinesia
Months to years
Lip-smacking, worm-like tongue movement, ‘fly-catching’

6. Antipsychotic Agents & Schizophrenia
Conventional Antipsychotics:
Low potency: Prototype = Chlorpromazine (Largactile)
Use: Schizophrenia and other psychotic disorders, manic phase of bipolar disorder, suppression of emesis and relief of intractable hiccups.
High Potency: Prototype = Haloperidol (Haldol)
Can cause more early extrapyramidal symptoms (EPS) but less sedation, orthostatic hypotension. Preferred for initial therapy.
Use: Schizophrenia and acute psychosis,

7. Antipsychotic Agents & Schizophrenia
Atypical Antipsychotic Agents:
Cause few or no EPS, can relieve both positive and negative symptoms of schizophrenia.
Prototype: Clozapine (Clozaril)
Use: Schizophrenia
Blocks receptors for dopamine D4 and serotonin

8. Psychotherapeutic Medications
Dysfunction related to neurotransmitter imbalance.
Norepinephrine.
Dopamine.
Seratonin.
Goal is to regulate excitory/inhibitory neurotransmitters.
Monoamines

9. Anti-Psychotic Drugs (Neuroleptics)
Schizophrenia
Loss of contact with reality & disorganized thoughts
Probable cause: increased dopamine release
Tx. Aimed at decreasing dopamine activity
Two Chemical
Classes:
Phenothiazines
Chlorpromazine
Butyrophenones
haloperidol (Haldol®)

10. Antipsychotic Agents Classic drugs (D2-Affinity)
chlorpromazine (Largactile®)
thioridazine (Mellaril®)
trifluoperazine (Stelazine®)
haloperidol (Haldol®)

11. Antipsychotic Agents Newer drugs (5HT2-Affinity) Clozapine.
Olanzapine.
Quetiapine.
Risperidone.
Ziprasidone.

12. Other Uses for Antipsychotics
Bipolar depression
Mania
Prevention of emesis (H1 block)
Psychotic symptoms of Alzheimer
Temporary psychoses from other illness

13. Antipsychotic mechanism of action (MOA)
Mechanism is similar
Strength vs. Potency
Phenothiazines – low potency
Butyrophenones – high potency
Receptor Antagonism
Dopamine2 in brain
Muscarinic cholinergic
Histamine
Norepi at alpha1
Therapeutic effects
Uninteded effects

14. Antipsychotic Side Effects
Dose dependent Extrapyramidal symptoms (EPS)
Tarditive dyskinesia may be irreversible.
Anticholinergic effects (atropine-like)
Dry mouth, blurred vision, photophobia, tachycardia, constipation)
Orthostatic hypotension α1 adrenergic block
Sedation
Decreased seizure threshold
Sexual dysfunction

15. Antipsychotic Side Effects
Hyperprolactinemia
Gynecomastia
Amenorrhea-glactorrhia and infertility.
Dopamine is inhibitory of prolactin secretion.
Weight gain
Neuroliptic malignant syndrome (malignant hyperthermia, muscle rigidity, sweating, autonomic instability ttt by dantrolene, diazepam, and dopamine agonist.

16. Extrapyramidal Symptoms
Reaction
Onset
Features
Acute dystonia
Hours to 5 days
Spasm of muscle of tongue, neck, face & back
Parkinsonism
5 – 30 days
Tremor, rigidity, shuffling gait, drooling, stooped posture, instability
Restlessness (Akathesia)
5 – 60 days
Compulsive, repetitive motions; agitation
Tarditive dyskinesia
Months to years
Lip-smacking, worm-like tongue movement, ‘fly-catching’

17. Treatment of EPS
Likely caused by blocking central dopamine2 receptors responsible for movement
Anticholinergic therapy rapidly effective
diphenhydramine (Benadryl®)

18. Thank You Team