Pharmacology of Propylthiouracil (PTU)

Thionamide (Antithyroid Drug): Propylthiouracil (PTU)

• PTU is a second-line drug for hyperthyroidism, used primarily for managing hyperthyroidism.
• It is preferred in specific cases, including the first trimester of pregnancy, thyroid storm, and for clients intolerant to methimazole.
• Mechanism of Action:
  • Inhibits thyroid peroxidase, decreasing thyroid hormone synthesis.
  • Impedes peripheral conversion of thyroxine (T4) to triiodothyronine (T3), lowering thyroid hormone levels.
  • This peripheral action makes it ideal for thyroid storm.
  • Decreased T3 and T4 levels affect the negative feedback mechanism, leading to increased thyroid-stimulating hormone (TSH) secretion. TSH levels are monitored to achieve a euthyroid state.
• Indications:
  • Primarily used to manage hyperthyroidism.
  • Preferred in the first trimester of pregnancy, thyroid storm, or for methimazole intolerance.
• Adverse Effects:
  • Liver Injury: A rare but serious adverse effect, potentially leading to transplantation or death. Routine laboratory testing is usually ineffective due to rapid onset.
  • Agranulocytosis: Decreased white blood cell count, increasing infection susceptibility. Usually develops in the first two months of therapy, often presenting with sore throat and fever. Requires PTU discontinuation.
  • Hypothyroidism: Possible with supratherapeutic doses, causing transition from hyperthyroidism to hypothyroidism. Dosage reduction or temporary thyroid hormone replacement may be needed.
• Precautions:
  • Use with caution in clients with liver dysfunction.
  • Use with caution in immunocompromised clients due to potential infection risk.
• Contraindications:
  • Contraindicated in the first trimester of pregnancy due to fetal harm. Use is safe in the second and third trimesters.
  • Contraindicated in clients with liver dysfunction.
• Drug Interactions:
  • Warfarin: May enhance the effect of anticoagulants like warfarin.
  • Drugs affecting white blood cell counts: Requires careful monitoring due to the risk of agranulocytosis.
• Dosing and Administration:
  • Dosing is individualized based on condition severity and client response.
  • PO administration, usually once per day.
  • High initial doses, gradually reduced to a maintenance dose based on TSH.
  • Treatment typically lasts 1-2 years.
  • If hyperthyroidism recurs after discontinuation, alternative treatments like methimazole, radiation therapy, or surgery may be considered.
• Client Teaching:
  • Promptly report any signs of infection or adverse effects to their healthcare provider.
  • Discuss pregnancy or attempts to become pregnant with their provider as PTU is unsafe during the first trimester.
  • Monitor for signs of hyper- and hypothyroidism and report them to their provider.
• Lab Monitoring:
  • Thyroid Function Labs: Monitor TSH levels to confirm euthyroid state (goal range 0.5-2 microunits/mL).
  • Complete Blood Count (CBC): Monitor for agranulocytosis.
• Black Box Warning:
  • PTU carries a risk of serious liver damage, potentially fatal and requiring transplantation.
  • PTU may interact with medications affecting liver function.
  • Requires careful monitoring when administered with drugs impacting white blood cell counts due to the risk of agranulocytosis.

PTU Dosing and Administration

• Dosing is individualized based on the condition, severity, and client response.
• PO administration, usually multiple times a day due to its short half-life.
• For severe cases, start with high doses, gradually lowering them to a maintenance dose based on TSH levels.
• Treatment typically lasts 1–2 years.

PTU Client Teaching

• Advise clients to report any signs of liver toxicity immediately.
• Advise immediate reporting of any signs of infection or adverse effects.
• Inform clients that PTU is considered unsafe in the second and third trimesters of pregnancy, and alternative treatment may be necessary.
• Encourage monitoring for signs of hyper- and hypothyroidism, requiring immediate reporting to their provider.

PTU Lab Monitoring

• Thyroid Function Labs: Monitor TSH levels to confirm euthyroid state.
• Complete Blood Count (CBC): Monitor for agranulocytosis.
• Liver Function Tests (LFTs): May be necessary in clients with suspected liver toxicity.

Thionamide (Antithyroid Drug)

• Propylthiouracil (PTU) is a thionamide drug used to manage hyperthyroidism by reducing thyroid hormone synthesis.
• PTU is considered a second-line treatment for hyperthyroidism, except in the first trimester of pregnancy, thyroid storm, or when methimazole is not tolerated.
• PTU inhibits the enzyme thyroid peroxidase, reducing thyroid hormone synthesis, and inhibits the peripheral conversion of thyroxine (T4) to triiodothyronine (T3), lowering thyroid hormone levels in the blood.
• The peripheral action of PTU makes it preferable in thyroid storm.
• Lowered T3 and T4 levels alter the negative feedback mechanism to the pituitary gland, leading to increased thyroid-stimulating hormone (TSH) secretion.
• TSH monitoring helps determine if a euthyroid state is achieved.

Common Side Effects and Adverse Reactions

• Liver injury can occur, but it is rare. It can be severe, requiring transplants or causing death.
• Agranulocytosis, a decrease in white blood cell count, can occur, increasing infection risk.
• Hypothyroidism can occur with supratherapeutic doses, requiring dose reduction or temporary thyroid hormone replacement.

Precautions and Contraindications

• Use with caution in clients with liver dysfunction.
• Use with caution in clients with immunosuppression due to increased infection risk.
• Contraindicated in the first trimester of pregnancy due to fetal harm risks. Use in the second and third trimesters is safe.
• Contraindicated in clients with liver dysfunction.

Drug Interactions

• Monitor for interactions with anticoagulants like warfarin; PTU may enhance their effect.
• Monitor for interactions with drugs that impact white blood cell counts due to the risk of agranulocytosis.

Dosing and Administration

• Dosing varies based on the condition, severity, and client response.
• Consult drug dosing guidelines for individualized dosing.
• Administered orally (PO) once per day.
• High initial doses are often used for severe disease, followed by reduction to a maintenance dose based on TSH levels.
• Treatment typically lasts 1-2 years.

Client Teaching

• Advise clients to promptly report any signs of infection or adverse effects to their healthcare provider.
• Advise pregnant clients, or those attempting pregnancy, to discuss with their provider as PTU is not safe in the first trimester.
• Advise clients to be aware of the signs and symptoms of hyperthyroidism and hypothyroidism and report them to their healthcare provider.

Labs to Monitor

• Monitor TSH levels 3-12 weeks after treatment initiation to determine if a euthyroid state is achieved. TSH should reach normal levels (0.5-2 microunits/mL).
• Monitor complete blood count (CBC) due to the potential for agranulocytosis.
• Liver function tests (LFTs) may be required if liver toxicity is suspected.

Thionamide (Antithyroid Drug)

• Propylthiouracil (PTU) is a medication primarily used to manage hyperthyroidism.
• PTU is a second-line treatment for hyperthyroidism, except in specific situations.

Mechanism of Action

• PTU inhibits the enzyme thyroid peroxidase, reducing thyroid hormone synthesis.
• PTU impedes the peripheral conversion of thyroxine (T4) to triiodothyronine (T3), lowering thyroid hormone levels in the bloodstream.
• This peripheral action makes PTU preferable in thyroid storm.

Indications and Therapeutic Uses

• PTU is preferred for hyperthyroidism in the first trimester of pregnancy, thyroid storm, or in clients intolerant to methimazole.

Side Effects and Adverse Reactions

• Liver Injury: PTU can cause serious liver damage, requiring a transplant or potentially causing death.
• Agranulocytosis: PTU can decrease white blood cell counts, increasing infection risk.
• Hypothyroidism: Supratherapeutic PTU doses can cause hypothyroidism.

Precautions and Contraindications

• Precautions: Use caution in clients with liver dysfunction or immunosuppression.
• Contraindications: Contraindicated in the first trimester of pregnancy due to fetal harm risk.

Black Box Warning

• PTU can cause serious liver damage, requiring a transplant or potentially causing death.

Drug Interactions

• PTU can interact with anticoagulants like warfarin, enhancing their effect.
• PTU requires careful monitoring when administered with drugs that impact white blood cell counts due to the risk of agranulocytosis.

Dosing, Administration, & Client Teaching

• Dosing varies based on condition, severity, and client response.
• PO administration is preferred, multiple times per day due to a short half-life.
• PTU is used in the first trimester of pregnancy while methimazole is indicated for the second and third trimesters.
• Treatment usually lasts 1-2 years.

Labs to Monitor

• Thyroid Function Labs: Monitor TSH levels to determine if euthyroid state has been achieved.
• Complete Blood Count (CBC): Monitor CBC to detect agranulocytosis.
• Liver Function Tests (LFTs): Monitor LFTs if liver toxicity is suspected.

This quiz covers the key aspects of Propylthiouracil (PTU), a second-line antithyroid drug primarily used for managing hyperthyroidism. Explore its mechanism of action, indications for use, and potential adverse effects. Ideal for those studying pharmacology and endocrinology.