VPT 321: Veterinary Neuropharmacology (2+1) copy 1

PHARMACOLOGICAL ACTIONS 

CNS

• In normal animals it produces indifference to surroundings, psychomotor slowing, emotional quietening, reduction in initiative and tendency to sleep.
• The effects are neutral and unpleasant.
• In psychotic it reduces erratic behaviour, agitation and aggressiveness and produces control over the symptoms.
• Anxiety is relieved. Hyperactivity,hallucinations and delusions are suppressed.
• All Phenothiazines, thioxantheses, butyrophenones have same antipsychotic efficacy.
• The aliphatic and piperidine compounds have low potency, produce more sedation.
• Antipsychotic drugs take weeks to develop to produce sedation leading to tolerance to sedative effect.
• Vigiliance is impaired, intelligence and performance are not disturbed.
• The disturbed sleep pattern in a psychotic is normalized.
• Chlorpromazine lowers seizure threshold and precipitate fits in untreated epileptics. Renders the patient poiklothermic.
• Neuroleptic, at times has a potent antiemetic action exerted through the CTZ.
• In animals selectively inhibits “conditioned avoidance response”
• Catalepsy is produced.
• Clozapine has a weak D₂ blocking action.
• The extrapyramidal effects are due to dopaminergic blockade in the basal ganglia 
• Neuroleptics have a varying degree of alpha adrenergic blocking activity.
• Anticholinergic property is weak
• Have a weak H₂ antihistaminic and anti-5HT action.

Local anaesthesia 

• Chlorpromazine is potent local anaesthetic, irritant
• Others have weak membrane stabilizing property.

CVS

• Neuroleptics produce hypotension due to action on central and as well as peripheral sympathetic tone.
• High doses of chlorpromazine directly depress heart and produces ECG changes (QT prolongation and suppression of T waves).

Skeletal muscle 

• Have no effect on muscle.
• Spinal reflexes are not affected.

Endocrine

• Neuroleptic consistently increase prolactin resulting galactorrhoea and gynaecomastia.
• Tolerance to sedative and hypotensive develops within days or weeks.
• Oral absorption is unpredictable and bioavailability is low
• So preferred i.m or i.v administration. Cross blood brain barrier hence concentration in the brain is higher than plasma.