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
