Antipsychotic drugs for animals

Antipsychotic drugs for animals

Antipsychotic drugs for animals are agents which gives calmness in psychotic or maniac states of animals. Phenothiazines are used as antipsychotic drugs.

Phenothiazines are-

• Aliphatic compounds: Chlorpromazine, Triflupromazine
• Piperidine compounds: Thioridazine
• Piperazine compounds: Trifluoperazine, Fluphenazine, Thioproperazine
• Butyrophenones: Haloperidol, Trifluperidol, Doperidol, Penfluridol
• Thioxanthenes : Chlorprothixene, Thiothixene, Fluphenthixol
• Others : Pimozide, Molindone, Sulpiride, Loxapine, Reserpine
• Neuroleptics: Clozapine, Risperidone

Mechanism of action

• All antipsychotic drugs have potent dopamine (D₂) blocking action.
• Block the limbic system and mesocortical areas.
• Mainly block the adaptive changes to blockade of D₂ receptors.
• Firing of dopamine neurons and dopamine turnover increases initially.
• Over a period of time this subsides and gives way to diminished activity in the basal ganglia.

Pharmacological actions

On 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.

as Local anesthesia

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

On 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).

on Skeletal muscles

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

on Endocrine system

• 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.

Features of different antipsychotic drugs

• Triflupromazine: More potent than chlorpromazine produce muscle dystonia when injected .
• Thioridazine: Potency is low, marked central anticholinergic action, lowest incidence of extrapyramidal side effects, cardiac arrhythmia and interfere with male sexual function.
• Trifluoperazine, fluphenazine, thioproperazine: Highly potent. Have minimum autonomic action. Cause hypersensitivity reactions. Extrapyramidal side effects are marked. 
• Haloperidol: Potent antipsychotic with few autonomic effects. Less epileptogenic..
• Trifluperidol: Slightly potent than haloperidol
• Droperidol: A short acting neuroleptic, used in combinationn with anaesthesia.
• Penfluridol: A long acting neuroleptic
• Flupenthixol: A less sedative than chlorpromazine.
• Pimozide: A specific Dopamine antagonist. Has a long duration of action, considered for maintenance therapy.
• Loxapine: Action is quick and lasts for 12 hours. Sedation is less but cardiac and neurological toxicity is prominent.
• Clozapine: Is a atypical antipsychotic.. Weak D₂ blocking action. High incidence of agranulocytosis and other blood dyscriasis.
• Risperidone: Block D₂ and 5HT₂ receptors.

Adverse effects

• CNS : drowsiness, lethargy, mental confusion
• Alpha adrenergic blockade – hypotension, inhibition of ejaculation
• Anticholinergic: Dry mouth, constipation, urinary hesitancy
• Endocrinal: Glactorrhoea, gynaecomastia, infertility.
•  Extrapyramidal effects: Rigidity, tremor, shuffling gait
• Acute muscular dystonia – muscle spasms, torticollis, locked jaw.
• Akathesia – restlessness, feeling of discomfort, apparent agitation
• Tardive dyskinesia -purposeless involuntary facial and limb movements, constant chewing, pouting , puffing of cheeks, lip licking.
• Blue pigmentation of exposed skin, corneal opacity, retinal degeneration.
• Hypersensitivity reactions – rashes, urticaria, contact dermatitis, photosensitivity and agranulocytosis.

Uses of Antipsychotic drugs for animals

• Psychoses
• Mania
• Anxiety
• Antiemetic
• Pre-anaesthetic medication
• Potentiate hypnotics, analgesics, and anesthetics
• Tetanus