Antipsychotic Agents

1
Antipsychotic Agents Schizophrenia

• Antipsychotic Agents
• 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

• Antipsychotic Agents
• 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

• 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
Other Uses for Antipsychotics

• Bipolar depression
• Mania
• Prevention of emesis (H1 block)
• Psychotic symptoms of Alzheimer
• Temporary psychoses from other illness

11
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
12
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 a1 adrenergic block
• Sedation
• Decreased seizure threshold
• Sexual dysfunction

13
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.

14
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
15
Treatment of EPS

• Likely caused by blocking central dopamine2
  receptors responsible for movement
• Anticholinergic therapy rapidly effective
• diphenhydramine (Benadryl)

16
Antipsychotic Agents

• Classic drugs (D2-Affinity)
• chlorpromazine (Largactile)
• thioridazine (Mellaril)
• trifluoperazine (Stelazine)
• haloperidol (Haldol)

17
Antipsychotic Agents

• Newer drugs (5HT2-Affinity)
• Clozapine.
• Olanzapine.
• Quetiapine.
• Risperidone.
• Ziprasidone.

18
(No Transcript)