Pharmacology by dffhrtcv3

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									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.
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
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
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
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     5 – 60 days       Compulsive, repetitive motions;
(Akathesia)                        agitation

Tarditive        Months to years   Lip-smacking, worm-like tongue
dyskinesia                         movement, ‘fly-catching’
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,
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
Psychotherapeutic
Medications
• Dysfunction related to neurotransmitter
  imbalance.
  – Norepinephrine.
  – Dopamine.             Monoamines
  – Seratonin.
• Goal is to regulate excitory/inhibitory
  neurotransmitters.
Anti-Psychotic Drugs
(Neuroleptics)
• Schizophrenia
  – Loss of contact with reality & disorganized
    thoughts
  – Probable cause: increased dopamine release
  – Tx. Aimed at decreasing dopamine activity

                  • Phenothiazines
Two Chemical        •   Chlorpromazine
  Classes:        • Butyrophenones
                    •   haloperidol (Haldol®)
Other Uses for Antipsychotics
•   Bipolar depression
•   Mania
•   Prevention of emesis (H1 block)
•   Psychotic symptoms of Alzheimer
•   Temporary psychoses from other illness
Antipsychotic mechanism of
action (MOA)
• Mechanism is similar
• Strength vs. Potency
  – Phenothiazines – low potency
  – Butyrophenones – high potency
• Receptor Antagonism
  –   Dopamine2 in brain            Therapeutic effects
  –   Muscarinic cholinergic
  –   Histamine                     Uninteded effects
  –   Norepi at alpha1
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
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.
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     5 – 60 days       Compulsive, repetitive motions;
(Akathesia)                        agitation

Tarditive        Months to years   Lip-smacking, worm-like tongue
dyskinesia                         movement, ‘fly-catching’
Treatment of EPS
• Likely caused by blocking central
  dopamine2 receptors responsible for
  movement
• Anticholinergic therapy rapidly effective
  – diphenhydramine (Benadryl®)
Antipsychotic Agents
Classic drugs (D2-Affinity)
• chlorpromazine (Largactile®)
• thioridazine (Mellaril®)
• trifluoperazine (Stelazine®)
• haloperidol (Haldol®)
Antipsychotic Agents
Newer drugs (5HT2-Affinity)
• Clozapine.
• Olanzapine.
• Quetiapine.
• Risperidone.
• Ziprasidone.

								
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