Tiapride

Usage

Tiapride is prescribed for the treatment of:

• Tardive dyskinesia: Characterized by involuntary, repetitive movements, often affecting the face and tongue.
• Agitation and aggression: Particularly in elderly patients with dementia or other neuropsychiatric disorders.
• Alcohol withdrawal syndrome: To manage associated symptoms.
• Schizophrenia: Though less common, it can be used to manage symptoms of this disorder.
• Huntington’s chorea
• Gilles de la Tourette’s syndrome

Pharmacological Classification: Tiapride is classified as an atypical antipsychotic.

Mechanism of Action: Tiapride primarily acts as a dopamine D2 and D3 receptor antagonist, meaning it blocks the action of dopamine at these receptors in the brain. This action helps reduce excessive dopamine activity, which is believed to contribute to symptoms like agitation, aggression, and dyskinesias. It has a preferential action on limbic system dopamine receptors, which gives rise to rapid onset of therapeutic benefit.

Alternate Names

While “Tiapride” is the generic name, it may be marketed under various brand names such as Tiapridal. There are no widely recognized international or regional variations of the name.

How It Works

Pharmacodynamics: Tiapride’s primary effect is the blockade of dopamine D2 and D3 receptors, particularly in the limbic system. It has lower affinity for receptors in other areas of the brain, which accounts for its reduced propensity for extrapyramidal side effects (movement disorders) compared to typical antipsychotics. It also has a weak effect on presynaptic dopamine receptors, leading to increased dopamine turnover. It has also been shown to increase the cerebral blood flow.

Pharmacokinetics:

• Absorption: Tiapride is rapidly absorbed after oral administration.
• Metabolism: It undergoes minimal metabolism.
• Elimination: Primarily excreted unchanged through the kidneys, with a half-life of 3-4 hours.

Receptor Binding/Neurotransmitter Modulation: Tiapride specifically targets dopamine D2 and D3 receptors, acting as an antagonist. This modulation of dopamine neurotransmission is central to its therapeutic effects.

Elimination Pathways: Renal excretion is the primary route of elimination for tiapride.

Dosage

Standard Dosage

Adults:

The standard adult dose for tardive dyskinesia is 300-600 mg/day, divided into two or three doses. For agitation and aggression in the elderly, the recommended dose is 200-300 mg/day, often starting at a lower dose and titrating up as needed. The maximum daily dose is typically 300mg.

Children:

Tiapride is not generally recommended for children under 18 years of age, as its safety and efficacy in this population have not been fully established. However, when use becomes necessary in children (e.g. Tourettes syndrome), it is given with an initial dosage of 50-100 mg/day, increased up to 150-500 mg/day as needed.

Special Cases:

• Elderly Patients: Start with a lower dose and titrate carefully due to increased sensitivity and risk of side effects.
• Patients with Renal Impairment: Dosage reduction is necessary based on the degree of impairment.
• Patients with Hepatic Dysfunction: While specific dose adjustments are not typically required, caution is advised.
• Patients with Comorbid Conditions: Consider potential interactions with other medications and underlying conditions.

Clinical Use Cases

The dosages mentioned under “Standard Dosage” are applicable to the clinical scenarios you listed (intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations). There are no specific dosage guidelines for these specific cases with Tiapride.

Dosage Adjustments

Dose adjustments are necessary for patients with renal impairment, starting with a lower dose and titrating based on response and tolerance.

Side Effects

Common Side Effects

• Drowsiness
• Dizziness
• Headache
• Dry mouth
• Constipation
• Insomnia
• Tremor
• Increased saliva production

Rare but Serious Side Effects

• Tardive dyskinesia (paradoxical worsening or new onset)
• Neuroleptic malignant syndrome
• QT prolongation
• Extrapyramidal symptoms (movement disorders)
• Hyperprolactinemia
• Rhabdomyolysis
• Blood dyscrasias (abnormalities in blood cell counts)

Long-Term Effects

• Tardive dyskinesia
• Metabolic changes (weight gain, dyslipidemia, hyperglycemia)

Adverse Drug Reactions (ADR)

• Neuroleptic malignant syndrome
• Severe allergic reactions

Contraindications

• Hypersensitivity to tiapride
• Pheochromocytoma
• Prolactin-dependent tumors (e.g., prolactinoma, breast cancer)
• Concomitant use of levodopa or dopamine agonists
• Concomitant use of drugs that prolong QT interval

Drug Interactions

• CNS depressants: Increased sedation
• Antihypertensives: Increased risk of orthostatic hypotension
• Levodopa and dopamine agonists: Mutual antagonism
• QT prolonging drugs: Additive effect on QT prolongation
• Alcohol: Increased sedation and other side effects
• Anticholinergics: Reduced efficacy of Tiapride

Pregnancy and Breastfeeding

• Pregnancy Safety Category: While not assigned a formal FDA category, tiapride should generally be avoided during pregnancy unless the benefits clearly outweigh the risks.
• Breastfeeding: Tiapride is excreted in breast milk. Breastfeeding is generally not recommended during treatment.

Drug Profile Summary

• Mechanism of Action: Dopamine D2 and D3 receptor antagonist.
• Side Effects: Drowsiness, dizziness, dry mouth, constipation, extrapyramidal symptoms, tardive dyskinesia (rare), neuroleptic malignant syndrome (rare).
• Contraindications: Hypersensitivity, pheochromocytoma, prolactin-dependent tumors, concomitant use of levodopa or dopamine agonists.
• Drug Interactions: CNS depressants, antihypertensives.
• Pregnancy & Breastfeeding: Generally avoided.
• Dosage: Adults: 300-600 mg/day for tardive dyskinesia, 200-300 mg/day for agitation/aggression in the elderly. Not generally recommended for children.
• Monitoring Parameters: Monitor for extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, prolactin levels, and ECG changes.

Popular Combinations

Tiapride is sometimes used in combination with other medications for specific conditions like Tourette Syndrome, but no combinations are consistently deemed “popular.” Any such combination should be made with careful consideration of potential drug interactions.

Precautions

• General Precautions: Pre-existing cardiovascular disease, renal/hepatic impairment, epilepsy, Parkinson’s disease.
• Specific Populations: Avoid or use cautiously in pregnant/breastfeeding women, children, and the elderly.
• Lifestyle Considerations: Avoid alcohol and activities requiring alertness (driving, operating machinery) due to potential drowsiness and dizziness.

FAQs

Q1: What is the recommended dosage for Tiapride?

A: The standard dosage for adults is 300-600 mg/day for tardive dyskinesia and 200-300 mg/day for agitation/aggression in the elderly. Pediatric use is not typically recommended.

Q2: What are the common side effects of Tiapride?

A: Common side effects include drowsiness, dizziness, dry mouth, constipation, insomnia, and tremor.

Q3: Is Tiapride safe during pregnancy and breastfeeding?

A: It’s generally not recommended during these periods due to potential fetal or neonatal risks.

Q4: What are the serious side effects to watch out for?

A: Neuroleptic malignant syndrome, tardive dyskinesia, QT prolongation, extrapyramidal symptoms, and rhabdomyolysis are rare but potentially serious.

Q5: Does Tiapride interact with other medications?

A: Yes, it interacts with CNS depressants, antihypertensives, levodopa, dopamine agonists, and QT prolonging drugs. Alcohol should also be avoided.

Q6: Can Tiapride be used in elderly patients?

A: Yes, but with caution and at lower starting doses due to increased sensitivity.

Q7: What conditions is Tiapride contraindicated in?

A: Hypersensitivity to tiapride, pheochromocytoma, prolactin-dependent tumors, concomitant use of levodopa, concomitant use of QT-prolonging drugs, and acute intoxication with alcohol or other CNS depressants.

Q8: How does Tiapride work at the cellular level?

A: It blocks dopamine D2 and D3 receptors, inhibiting dopamine neurotransmission.

Q9: What is the elimination half-life of Tiapride?

A: The half-life is approximately 3-4 hours.

Q10: How long does it take for Tiapride to start working?

A: The onset of therapeutic effect can vary, but it may take several weeks for optimal results to be seen, particularly in tardive dyskinesia.