Usage
Propylthiouracil (PTU) is primarily prescribed for hyperthyroidism, including Graves’ disease and toxic multinodular goiter. It is particularly useful in patients who are intolerant to methimazole, or for whom radioactive iodine or surgery are not suitable options. It can also be used to manage thyrotoxic crisis and to prepare patients for thyroidectomy or radioactive iodine therapy. Its pharmacological classification is antithyroid agent. PTU works by inhibiting the synthesis of thyroid hormones, specifically by blocking the enzyme thyroid peroxidase, which is essential for the iodination and coupling of tyrosine residues in thyroglobulin, the precursor to thyroid hormones. It also partially blocks the peripheral conversion of thyroxine (T4) to triiodothyronine (T3).
Alternate Names
The drug is commonly known as PTU. No widely recognized international variations or popular brand names are currently available.
How It Works
Pharmacodynamics: PTU decreases thyroid hormone production, leading to a reduction in the symptoms of hyperthyroidism such as tachycardia, tremor, heat intolerance and weight loss.
Pharmacokinetics:
- Absorption: PTU is rapidly absorbed from the gastrointestinal tract, reaching peak plasma concentrations within 1-2 hours.
- Metabolism: It undergoes extensive hepatic metabolism.
- Elimination: Approximately 35% of the drug is excreted in the urine within 24 hours, both as the parent compound and its metabolites. The elimination half-life is relatively short, about 1-2 hours.
Mode of Action: PTU inhibits thyroid peroxidase, the enzyme responsible for iodination and coupling of tyrosine residues in thyroglobulin, thereby preventing the synthesis of thyroid hormones (T3 and T4). It also partially blocks the peripheral conversion of T4 to the more active T3. This occurs through direct enzyme inhibition. It doesn’t bind to thyroid hormone receptors or modulate neurotransmitters directly. Elimination occurs through hepatic metabolism and renal excretion.
Dosage
Standard Dosage
Adults:
- Initial: 100 mg every 8 hours (300 mg/day). Doses may be increased up to 900 mg/day, divided every 8 hours, based on patient response and severity of hyperthyroidism.
- Maintenance: 100-150 mg/day, often given in divided doses.
- Thyrotoxic crisis: Initially 600–1000 mg, followed by 200–300 mg every 4-6 hours. Maintain at 100–150 mg/day thereafter.
Children:
- 6-10 years: 50-150 mg/day, divided every 8 hours.
- Over 10 years: 150-300 mg/day, divided every 8 hours.
- Neonates (under 28 days): 5-10 mg/kg/day, divided every 8 hours.
Due to the risk of hepatotoxicity, PTU is generally not recommended for children unless methimazole is not tolerated and radioactive iodine or surgery are not options.
Special Cases:
- Elderly Patients: Initiate with lower doses and monitor closely.
- Patients with Renal Impairment: Dose adjustment not typically necessary.
- Patients with Hepatic Dysfunction: Use with caution and reduce the dose. Close monitoring of liver function is essential.
- Patients with Comorbid Conditions: Careful monitoring is advised, particularly in patients with diabetes or cardiovascular disease.
Clinical Use Cases
PTU does not have direct applications in scenarios such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like cardiac arrest. Its use is restricted to managing hyperthyroidism and related conditions.
Dosage Adjustments
Dose adjustments may be needed based on patient response and thyroid function tests (TSH, T3, T4). Consider reducing the dose by one-third every 4-6 weeks once euthyroidism is achieved, targeting a maintenance dose. Careful titration is required in patients with hepatic impairment.
Side Effects
Common Side Effects
- Nausea, vomiting, stomach upset
- Itching, rash, hives
- Headache, dizziness, drowsiness
- Joint or muscle pain
- Loss of taste or altered taste
- Hair loss
- Swollen glands (lymph nodes, salivary glands)
Rare but Serious Side Effects
- Hepatotoxicity: Liver injury, liver failure, even death. This is a serious concern, particularly in children and pregnant women.
- Agranulocytosis: A severe decrease in white blood cells, increasing susceptibility to infections. Symptoms may include fever, sore throat, mouth ulcers.
- Vasculitis: Inflammation of blood vessels.
- Hypersensitivity reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis.
Long-Term Effects
Chronic complications from prolonged use are rare, but careful monitoring for liver function and blood cell counts is necessary.
Adverse Drug Reactions (ADR)
Severe liver injury, agranulocytosis, and severe hypersensitivity reactions are clinically significant ADRs requiring immediate discontinuation of the drug and supportive care.
Contraindications
- Known hypersensitivity to PTU.
- History of severe adverse reactions to PTU (e.g., agranulocytosis, hepatitis).
- Breastfeeding.
Drug Interactions
- Coumarins (e.g., warfarin): PTU may potentiate the anticoagulant effects. Close monitoring of INR is required.
- Beta-blockers, digitalis, theophylline: Patients being treated for hyperthyroidism might require dose adjustments of these medications as their thyroid function normalizes.
- Other antithyroid drugs (e.g., methimazole): Avoid concurrent use.
- Sodium iodide I-131: Interaction with PTU might affect the efficacy of I-131 treatment.
Pregnancy and Breastfeeding
PTU is generally preferred over methimazole during the first trimester of pregnancy due to a lower risk of congenital malformations associated with methimazole. However, PTU carries a risk of hepatotoxicity for both mother and fetus. In the second and third trimesters, methimazole may be preferred. Breastfeeding is contraindicated while taking PTU as it is excreted in breast milk and can cause hypothyroidism in the infant. Close monitoring of both maternal and fetal thyroid function is essential during pregnancy.
Drug Profile Summary
- Mechanism of Action: Inhibits thyroid hormone synthesis and partially blocks peripheral conversion of T4 to T3.
- Side Effects: Nausea, vomiting, rash, itching, headache, hepatotoxicity (rare but serious), agranulocytosis (rare but serious).
- Contraindications: Hypersensitivity to PTU, breastfeeding.
- Drug Interactions: Coumarins, beta-blockers, digitalis, theophylline, other antithyroid drugs.
- Pregnancy & Breastfeeding: Use with caution during pregnancy; contraindicated while breastfeeding.
- Dosage: Adults: Initially 300 mg/day, maintenance 100-150 mg/day. Pediatric doses are available but use is restricted.
- Monitoring Parameters: Liver function tests, complete blood count, TSH, free T4, free T3.
Popular Combinations
PTU is usually used as monotherapy for hyperthyroidism. Beta-blockers may be co-administered to control the adrenergic symptoms of hyperthyroidism (e.g., tachycardia, tremors) until PTU takes effect.
Precautions
- General Precautions: Monitor liver function tests and complete blood counts regularly. Advise patients to report any signs of infection or liver dysfunction immediately.
- Specific Populations:
- Pregnant Women: Weigh the risks and benefits carefully. Monitor thyroid function in both mother and fetus.
- Breastfeeding Mothers: Contraindicated.
- Children & Elderly: Use with caution and adjust dosage as needed.
- Lifestyle Considerations: No known interactions with food or alcohol have been reported, but advise patients to inform their doctor about all medications, supplements, and lifestyle factors.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Propyl Thiouracil?
A: Adults: Initial dose is 300 mg/day (given in divided doses every 8 hours), which can be increased to up to 900 mg/day based on response. Maintenance dose is typically 100-150 mg/day. Pediatric and neonatal doses are available but use is restricted due to hepatotoxicity risk.
Q2: What is the most serious side effect of PTU?
A: Severe liver injury and agranulocytosis are the most serious potential side effects.
Q3: Can PTU be used during pregnancy?
A: It can be used, but with caution, especially during the first trimester. Methimazole may be preferred in the second and third trimesters. Close monitoring is necessary.
Q4: Can PTU be used while breastfeeding?
A: No, PTU is contraindicated during breastfeeding.
Q5: How does PTU work?
A: It inhibits thyroid hormone synthesis by blocking thyroid peroxidase. It also partially blocks peripheral conversion of T4 to T3.
Q6: What are the common side effects of PTU?
A: Nausea, vomiting, rash, itching, headache, altered taste sensation, and hair loss.
Q7: What should patients be monitored for while on PTU?
A: Liver function tests (LFTs), complete blood counts (CBCs), and thyroid function tests (TSH, T3, T4) are important monitoring parameters.
Q8: What are the alternatives to PTU for hyperthyroidism?
A: Methimazole, radioactive iodine therapy, and surgery are alternative treatments for hyperthyroidism.
Q9: How long does treatment with PTU typically last?
A: The course of therapy may last from 6 months to 3 years, with the goal of achieving remission.
Q10: Can PTU be used to treat a thyroid storm?
A: Yes, PTU can be used in the management of thyroid storm at a high initial dose, alongside supportive care and other agents like iodine and beta-blockers.
