Actions and spectrum:
thioridazine is an antipsychotic medication that belongs to the class of phenothiazines.
It works by blocking the dopamine receptors in the brain, which helps to reduce the symptoms of psychosis, including hallucinations, delusions, and disordered thinking. thioridazine also has a sedative effect, which can help to calm agitated or anxious individuals.
thioridazine is effective in treating a range of psychotic disorders, including schizophrenia and bipolar disorder. It may also be used to manage severe behavioral problems in children, such as aggression and hyperactivity.
Frequency not defined
NMS (infrequent but serious)
Anticholinergic effects
Oligomenorrhea/amenorrhea
Insomnia
Anxiety
Agitation
Weakness
Cerebral edema
Orthostatic hypotension
Dizziness
Anorexia
Constipation
Blood dyscrasia
Photosensitivity
Diarrhea
Ejaculatory disorder
Priapism (rare)
EPS (dystonia, muscle stiffness, parkinsonism, akathisia, tardive dyskinesia) (60%)
Sedation
Weight gain
Erectile dysfunction
Restlessness
Euphoria
Depression
Headache
Poikilothermia
Tachycardia
Lens opacities (prolonged use)
Dyspepsia
Ileus
ECG changes
Pruritis
Galactorrhea
Seizure (rare)
Cholestatic jaundice (rare)
Black Box Warning:
thioridazine has a black box warning for increased risk of mortality in elderly patients with dementia-related psychosis. This warning is also applicable to other antipsychotic drugs.
The use of thioridazine is also contraindicated in patients with a history of QT prolongation, including congenital long QT syndrome, a history of cardiac arrhythmias, recent acute myocardial infarction, uncompensated heart failure, or ongoing cardiac dysrhythmias.
Contraindication/Caution:
Contraindication:
- Known hypersensitivity to thioridazine
- QTc prolongation or other significant arrhythmias
- Recent acute myocardial infarction
- Uncompensated heart failure
- Concurrent use of the drugs that prolong the QT interval, such as certain antibiotics, antifungal agents, and antiarrhythmics
- Known or suspected CNS depression, including coma
- Children under 12 years of age
- Patients with liver disease, as thioridazine metabolism occurs primarily in the liver.
Caution:
- Cardiovascular effects: thioridazine can cause changes in the electrical activity of the heart, leading to fatal arrhythmia known as torsades de pointes.
- CNS depression: thioridazine is a sedative and can cause CNS depression, including drowsiness, dizziness, and impaired coordination. Patients should be advised not to operate heavy machinery or drive until they know how the medication affects them.
- Extrapyramidal symptoms (EPS): thioridazine can cause EPS, including acute dystonia, akathisia, and parkinsonism.
- Anticholinergic effects: thioridazine has anticholinergic properties, which can cause dry mouth, blurred vision, urinary retention, and constipation.
- Seizures: thioridazine can lower the seizure threshold, so caution is advised in patients with a history of seizures or other predisposing factors.
- Hyperprolactinemia: thioridazine can increase prolactin levels, leading to galactorrhea, gynecomastia, and menstrual irregularities in some patients.
- Hepatic impairment: thioridazine is primarily metabolized by the liver, and patients with hepatic impairment may have decreased clearance of the medication.
- Renal impairment: thioridazine is excreted by the kidneys, and patients with renal impairment may have decreased clearance of the medication.
- Elderly patients: Elderly patients may be more sensitive to the sedative and anticholinergic effects of thioridazine and may be more prone to developing EPS or other adverse effects.
Comorbidities:
thioridazine is an antipsychotic medication used to treat schizophrenia and other psychotic disorders. It is generally not recommended in patients with heart disease or arrhythmias, as it can cause QT prolongation and increase the risk of torsades de pointes, a potentially life-threatening cardiac arrhythmia. thioridazine should also be used with caution in patients with a history of seizures, liver disease, or kidney disease, as the medication may exacerbate these conditions. In addition, thioridazine should be used with caution in elderly patients, as they may be more susceptible to the medication’s side effects.
Pregnancy consideration: US FDA pregnancy category: Not assigned
Lactation: safety and efficacy not established
Pregnancy category:
- Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester.
- Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women.
- Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women.
- Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits.
- Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women.
- Category N: There is no data available for the drug under this category.
Pharmacology:
thioridazine is an antipsychotic medication that acts by blocking the dopamine receptors in the brain. It also exhibits anticholinergic, antiadrenergic, and weak serotonin receptor-blocking properties.
thioridazine undergoes extensive first-pass metabolism in the liver by the cytochrome P450 enzyme system, mainly CYP2D6, and is converted to its active metabolites, mesoridazine, and sulforidazine. These metabolites have a longer half-life than thioridazine and exhibit antipsychotic activity.
The exact mechanism of action of thioridazine is not known, but it is related to its antagonism of dopamine receptors in the mesolimbic and mesocortical pathways of the brain. This results in a decrease in the positive symptoms of schizophrenia like delusions and hallucinations.
thioridazine also exhibits some affinity for histamine H1 receptors, which can lead to sedation and weight gain. Its anticholinergic activity may contribute to dry mouth, blurred vision, constipation, and urinary retention.
Pharmacodynamics:
thioridazine is a typical antipsychotic agent that exerts its pharmacological effects by blocking postsynaptic dopamine D2 receptors in the mesolimbic and mesocortical areas of the brain.
It also blocks several other receptors, including serotonin (5-HT2A, 5-HT2C), histamine (H1), and alpha-adrenergic receptors, which contribute to its sedative and anticholinergic effects.
The blockade of dopamine D2 receptors in the nigrostriatal pathway is responsible for the extrapyramidal side effects associated with thioridazine use. The drug also has weak antimuscarinic activity, which contributes to its anticholinergic effects, such as dry mouth, blurred vision, constipation, and urinary retention.
thioridazine has a relatively slow onset of action and a long duration of action, with a half-life of approximately 10-20 hours. It is extensively metabolized in the liver, primarily by CYP2D6, and is eliminated primarily in the feces.
Pharmacokinetics:
Absorption
thioridazine is well absorbed orally but undergoes extensive first-pass metabolism in the liver, resulting in low bioavailability.
Distribution
thioridazine has a large volume of distribution and is highly protein-bound.
Metabolism
thioridazine is extensively metabolized in the liver, primarily by the CYP2D6 enzyme, to active metabolites such as mesoridazine. It also inhibits the activity of CYP2D6, which can lead to drug interactions with other medications metabolized by this enzyme.
Elimination and excretion
thioridazine and its metabolites are primarily eliminated via the feces, with a smaller fraction eliminated in the urine. The elimination half-life of thioridazine is approximately 10-20 hours, while the half-life of its metabolite mesoridazine is longer at approximately 30-40 hours.
Administration:
thioridazine is available in the form of tablets and oral solutions for oral administration. It can also be administered via intramuscular injection. The dosage of thioridazine depends on the patient’s age, weight, medical condition, and response to treatment.
It is usually taken 2 to 4 times daily with or without food. The tablets should be administered whole with a glass of water and should not be crushed, chewed or broken. The oral solution should be measured with a dose-measuring spoon or cup, which can be obtained from a pharmacist.
