• Learn the phenothiazines as a group (promethazine, thioridazine, prochlorperazine and chlorpromazine)
  • Know the PD well.
  1. Typical anti-psychotics of the phenothiazine class
  1. The main efficacy of the phenothiazines is due to D2 receptor blockade. However, these drugs are dirty drugs, and therefore have the following:
    • Α-blockade
    • Muscarinic blockade
    • H1 receptor blockade
    • 5-HT2 blockade

Its other effects are due to blockade of other channels:

Receptor Effect
Alpha blockade
  1. Orthostatic hypotension (most important)
  2. Impotence
  3. Failure to ejaculate
    • Note that Chlorpromazine (largactil) has the highest affinity for alpha receptors and therefore most likely to cause hypotension.
Muscarinic blockade
  1. Failure of accommodation
  2. Confusional state
  3. Dry mouth/no sweating
  4. Urinary retention/constipation
  5. Tachycardia


Blind as a bat, mad as a hatter, red as a beet, hot as a hare, dry as a bone, the bladder and bowel has lost their tone, and the heart runs alone.

Dopaminergic blockade
  1. CNS – Parkinson like effects, e.g. akasthisia, dystonia and tardive dyskinesia
  2. Endocrine effects – amenorrhoea, galactorrhea, infertility and impotence
H1 blockade
  1. Sedation
Combined H1/5HT-2 block
  1. Weight gain

The anti-psychotics also cause QT-prolongation (increased risk of TdP). Overall CVS effects are reduced MAP, reduced TMR and overall reduced SV (hypotension and tachycardia)

  1. PO, IV, IM
  1. Very lipid soluble drugs
  2. Strongly protein bound (~99%) and very large Vd à 7L/kg. They overall have longer clinical duration than expected for T ½.
  1. Usually metabolized by liver CYP 450 enzymes and excreted by the urine.
  2. Bioavailability tends to be low (chlorpromazine and thioridazine have bioavailability of only 25%)
  3. Enzyme inhibitors (cimetidine/amiodarone/ketoconazole) may interfere with their metabolism.
  4. At therapeutic doses, anti-psychotics neither induce nor inhibit liver enzymes.
  1. Urine
  1. Initially designed to treat psychotic episodes, mania and psychotic depression
  2. Other indications as follows:
    • Prochlorperazine (stemetil): anti-emetic and anti-vertigo
    • Promethazine (Phenergan): allergic reaction
    • Chlorpromazine (largactil): headaches
Special precautions
  1. Use with other anti-psychotics or other CNS depressants may potentiate effects.
  2. Enzyme inducers, e.g. phenobarbitone or phenytoin may reduce its effects.
Adverse events As above
  1. Main toxicological concerns in OD are CNS depression, hypotension, tachyarrhythmias and TdP.
  2. Benztropine is the antidote for dystonic reactions.
Withdrawal syndrome
Special notes