Antipsychotics Free Pharmacology Notes – 2021

Antipsychotics are the drugs that are used in Psychosis. Psychosis is a mental disorder that may be a result of Schizophrenia. Schizophrenia is a mental disorder that affects a person’s ability to think, feel and behave clearly. The exact reason behind Schizophrenia is still unknown but there are three hypotheses, based on neurotransmitters used to explain the pathogenesis of schizophrenia. In this note, we will learn about different antipsychotic drugs, their mechanism of action, they have any side effects or not. Read the full note for complete details about Antipsychotic drugs.

Antipsychotics Free Pharmacology Notes - 2021
Antipsychotics Free Pharmacology Notes – 2021

What are Antipsychotics ?

Antipsychotics are the drugs that work against Psychosis which may be a result of mental disorders like Schizophrenia. The exact reason behind the Schizophrenia but researchers give three hypotheses which may the reason behind Schizophrenia.

Dopamine Hypothesis

The dopamine hypothesis was put forward by Arvid Carlsson. It is believed that Dopamine abnormality is the basis for most of the manifestations of schizophrenic patients. An excess amount of dopamine in some areas of the brain is considered responsible for schizophrenia. Typical antipsychotic drugs like Haloperidol bind to D2 receptors of DA. However, dopamine antagonists are not a cure for all schizophrenics. Probably, other neurotransmitters are involved.

5-HT/Serotonin Hypothesis

The role of 5-HT in schizophrenia is based on the finding that LSD, a central 5-HT2
receptor agonists produce hallucinations and sensory disturbances, which are symptoms. observed in psychosis. Atypical neuroleptics like Clozapine and Olanzapine are potent
5-HT2A receptor antagonists. These receptors modulate the release of DA in some areas of
the brain. Hence, both 5-HT and DA hypotheses for schizophrenia are compatible.

Glutamate Hypothesis

The involvement of glutamate is based on the finding that glutamate-NMDA receptor
antagonists like Phencyclidine and Ketamine when administered to a normal subject,
produce psychotic symptoms like hallucinations and thought disorders. In addition,
reduced glutamate densities have been reported in the brains of schizophrenics. Drugs
which may enhance NMDA receptor activity may be useful in treating schizophrenia.

Classification of Antipsychotics

Antipsychotic drugs are classified between Typical or First Generation Antipsychotics and Atypical or Second-Generation Antipsychotics.

Typical or First Generation Antipsychotic Drugs

Typical antipsychotic drugs are further classified into:

  • Phenothiazines: Phenothiazines have many effects, including Central Nervous System depression, autonomic nervous system depression (antiadrenergic and anticholinergic effects), antiemetic effects, lowering of body temperature, hypersensitivity reactions, and others. They are further sub-classified based on side chains attached to phenothiazines.
    • Aliphatic side chain: Chlorpromazine
    • Piperidine side chain: Thioridazine
    • Piperazine as side chain: Trifluoperazine, Perfenazine, Fluphenazine
  • Thioxanthenes: Flupenthixol, Thiothixene, Zuclopenthixol.
  • Butyrophenones: Haloperidol, Benperidol, Droperidol.
  • Miscellaneous: Pimozide, Penfluridol, Molindone, Loxapine, Sulpiride, Amisulpride, Remoxipride

Atypical or Second Generation Antipsychotic Drugs

Clozapine, Olanzapine, Quetiapine, Zotepine, Risperidone, Ziprasidone, Paliperidone, Aripiprazole, Sertindole, Asenapine

Mechanism of Action

Typical Antipsychotic Drugs

  • Typical or First generation antipsychotics act as antagonist at brain dopamine D2 receptors.
  • Typical antipsychotic drugs also blocks the muscarinic acetylcholine receptors, anti histamine receptors, and alpha adrenoceptors.

Atypical Antipsychotic Agents

  • Atypical or Second-generation antipsychotic agent is predominant antagonism of 5-HT2A receptors with a lesser degree antagonism of dopamine D2 receptors.
  • Atypical antipsychotic agents have efficacy against negative symptoms especially clonazepam.

All antipsychotic drugs exhibit a latent period of 2-3 weeks for attaining therapeutic
effects. The majority of them are given orally; however, their bioavailability increases tenfold
when given by the intramuscular route.

Therapeutic Uses

Antipsychotic agents are usually use in three type of indications.

  • Psychiatric indications: They are primarily used to treat schizophrenia. In addition, they are also used to treat drug-induced psychoses like delusions associated with LSD, Amphetamine-induced psychoses, and delirium following infectious psychoses. They are also used to treat schizoaffective disorders in which schizo refers to schizophrenia and affective refers to mania.
  • Neuro-psychiatric indications: It involves use in Tourette’s syndrome which is marked by tics, grunts, and vocalizations that are frequently obscene. Haloperidol and Pimozide are preferred for this condition. In addition, they are also useful for Huntington’s disease which involves progressive choreoathetosis and dementia. Haloperidol and Chlorpromazine are preferred for this condition.
  • Non-psychiatric indications: All antipsychotics have antiemetic effects of varying degrees. It is due to the blockade of the D2receptor in CTZ as well as in GIT. Prochlorpromazine is preferred for this purpose. Antipsychotic like Promethazine is used as a pre-operative sedative since it has antihistaminic, anticholinergic and antiemetic effects also. Droperidol is a short-acting antipsychotic with antiemetic, sedative, and anticonvulsant effects. Parenteral chlorpromazine or Haloperidol is useful in controlling intractable hiccups.

Adverse Effects

Adverse Effects of Typical or First Generation Antipsychotics

  • Extrapyramidal Motor Effects: Due to Dopamine D2 receptors blockade in the nigrostriatal pathway.
    • Acute dystonia
    • Akathisia
    • Parkinsonism
    • Tardive Dyskinesia
  • Endocrine Effects: Due to blockade of dopamine D2 receptor in tuberohypophyseal pathway that increase the release of prolactin.
    • Gynaecomastia
    • Galactorrhoea
    • amenorrhea in women
    • sexual disinfection or infertility in men
  • Adverse Cardiac Effects
  • Increased risk for cerebrovascular events and all- cause mortality in dementia patients.
  • Lowers seizure threshold.
  • Increased triglycerides
  • Hyperglycaemia

Adverse effects of Atypical or Second Generation Antipsychotics

  • Extrapyramidal Motor Effects
    • Considerably less compared to typical antipsychotics
    • Blockage of 5-HT2A receptors increases dopamine in the striatum preventing extrapyramidal effects.
  • Cardiotoxicity: Less associated with QT prolongation at therapeutic doses
  • High risk of new onset diabetes and diabetes ketoacidosis esp. with clozapine and olanzapine
  • Agranulocytosis common with clozapine esp. in first 6 months

Drug Interactions

Drug interactions of Antipsychotic drugs are given in the below table

DrugEffects
AntacidsDecreased absorption of antipsychotic drugs
AnticholinergicsIncreased anticholinergic effects
AlcoholMore sedation
Antithyroid drugsIncreased risk of agranulocytosis (with Clozapine)
BarbituratesDecreased antipsychotic effects, more sedation
Carbamazepine/PhenytoinDecreased antipsychotic effects and lowering of
seizure threshold
ChloroquineMay precipitate extrapyramidal symptoms with
Phenothiazines
LithiumEnhancement of neurotoxicity and precipitation of
NMS (Haloperidol)
LevodopaDecreased efficacy of neuroleptics
Oral contraceptivesMay potentiate hyperprolactinemia
Cigarette smokingIncreased metabolism of antipsychotics; higher
dose needed
Drug interactions with antipsychotic drugs

Preparations of various antipsychotic drugs are given in below table

DrugFormulations and strength
Chlorpromazine25 mg, 50 mg, 100 mg, 200 mg
tablet; 25 mg/ml injection
Fluphenazine25 mg/ml injection
Trifluoperazine5 mg, 10 mg tablet
Thioridazine10 mg, 25 mg, 50 mg, 100 mg
tablet
Flupenthixol0.5 mg, 1 mg, 3 mg tablet;
20 mg/ml depot injection
Zuclopenthixol200 mg/ml injection
Haloperidol1.5 mg, 5 mg, 10 mg, 20 mg tablet;
2 mg/ml, 5 mg/ml injection,
50 mg/ml depot injection
Penfluridol20 mg tablet
Pimozide2 mg, 4 mg tablet
Loxapine10 mg, 25 mg capsule; 25 mg/ml
liquid
Sulpiride100 mg, 200 mg, 400 mg tablet
Amisulpiride50 mg, 100 mg, 200 mg tablet
Levosulpiride25 mg tablet
Clozapine25 mg, 50 mg, 100 mg tablet
Olanzapine2.5 mg, 5 mg, 7.5 mg, 10 mg,
15 mg, 20 mg tablet
Risperidone1 mg, 2 mg, 3 mg, 4 mg tablet;
1 mg/ml syrup
Ziprasidone20 mg, 40 mg, 80 mg tablet
Paliperidone3 mg, 6 mg, 9 mg ER tablet
Aripiprazole10 mg, 15 mg, 20 mg, 30 mg
tablet
Quetiapine25 mg, 50 mg, 100 mg, 200 mg,
300 mg tablet
Available preparations of antipsychotic drugs

Conclusion

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