Question 16

Classify the anti-psychotic drugs (25% marks).

Outline the pharmacology of haloperidol (75% marks). 

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College Answer

Excellent answers were able to provide a classification of antipsychotics based on either typical/atypical
or first/second generation categories, provide examples of each and identify key differences in
mechanism and effects. They also distinguished between butyrophenones and phenothiazines within the
typical antipsychotic group. Haloperidol was identified as a butyrophenone, with description of
pharmaceutics, dose and route, as well as pharmacodynamics and pharmacokinetics. Key adverse
effects were detailed, focusing on those specific to haloperidol, including a description of different types
of extrapyramidal symptoms and QT prolongation/ torsades de pointes.

Discussion

For 20% of the marks, you would really only need to do something like this:

  • Typical antipsychotics
    • Phenothiazines (chlorpromazine)
    • Butyrophenones (haloperidol, droperidol)
  • Atypical antipsychotics
    • Phenylpiperaxines  (aripiprazole)
    • Dibenzodiazepine (clozapine, quetiapine)
    • Thienobenzodiazepines (olanzapine) 
    • Benzisothiazoles and benzisoxazoles (risperidone, lurasidone)

As for haloperidol:

Class Antipsychotic
Chemistry Butyrophenone
Routes of administration Oral, IV, IM, s/c
Absorption Rapidly and completely absorbed; oral bioavailability is about 60%
Solubility pKa 8.66; minimally water-soluble
Distribution VOD=18L/kg; 92% protein-bound
Target receptor D2 receptors, as well as muscarinic cholinergic receptors, histamine receptors and alpha-adrenergic receptors
Metabolism Hepatic metabolism into inactive metabolites
Elimination Inactive metabolites are renally cleared
Time course of action Elimination half-life of 14-36 hours
Mechanism of action Antipsychotic effects are mediated mainly by the D2 antagonist effect on the dopaminergic neurons in the mesolimbic system
Clinical effects Sedation (antihistamine effect).
Extrapyramidal side effects (dystonia, oculogyric crisis, laryngospasm, akathisia, rigidity, parkinsonism and tardive dyskinesia)
Hyperprolactinaemia (dopamine blockade)
Postural hypotension and sexual dysfunction (α-adrenergic receptor blockade)
Anticholinergic side effects (xerostomia, urinary retention, tachycardia, constipation, blurred vision, tachycardia and delirium)
Lowered seizure threshold
QT interval prolongation
Single best reference for further information Tyler et al (2017)

References

Fischer-Barnicol, David, et al. "Typical and atypical antipsychotics–The misleading dichotomy." Neuropsychobiology 57.1-2 (2008): 80-87.

Sadek, Joseph. "Antipsychotics." Clinician’s Guide to Psychopharmacology. Springer, Cham, 2021. 113-145.

Zareba, Wojciech, and David A. Lin. "Antipsychotic drugs and QT interval prolongation." Psychiatric quarterly 74.3 (2003): 291-306.