Thyroid Drugs and Antithyroid Agents

Thyroid Drugs and Antithyroid Agents

Thyroid Drugs and Antithyroid Agents

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Thyroid Physiology & Regulation - Gland Central Control

  • HPT Axis: Hypothalamus secretes TRH (Thyrotropin-Releasing Hormone), stimulating Anterior Pituitary to release TSH (Thyroid-Stimulating Hormone). TSH acts on thyroid gland to produce $T_3$ & $T_4$.
  • Regulation:
    • Negative feedback: ↑$T_3$/$T_4$ levels inhibit TRH & TSH secretion.
    • Iodide levels: Essential for hormone synthesis; excess acutely inhibits (Wolff-Chaikoff effect).
  • Hormones:
    • $T_4$ (Thyroxine): Major circulating prohormone; converted to $T_3$ peripherally.
    • $T_3$ (Triiodothyronine): More potent, active form; primarily from $T_4$ deiodination.

HPT Axis Regulation

⭐ Wolff-Chaikoff effect: High iodide acutely inhibits thyroid hormone synthesis (organification) & release. Autoregulatory; escape phenomenon follows.

Hypothyroidism & Thyroid Drugs - Low & Slow Fixes

  • Goal: Euthyroid state. Monitor TSH (target 0.5-2.5 mIU/L).
  • Levothyroxine (T4): Preferred drug.
    • Oral, daily. Start: 1.6 mcg/kg/day; elderly/cardiac: 12.5-25 mcg/day.
    • Take on empty stomach.
  • Liothyronine (T3): Potent, rapid onset, short t½.
    • Uses: Myxedema coma, diagnostic.
  • 📌 "Low & Slow": starting dose & titration.
FeatureLevothyroxine (T4)Liothyronine (T3)
Half-life (t½)~7 days~1 day
PotencyLowerHigher (3-4x)
OnsetSlowRapid
UseChronic replacementAcute (Myxedema coma)
Main ADR RiskHyperthyroidism (if dose ↑)↑Cardiotoxicity

Hyperthyroidism & Antithyroid Agents - Fast & Furious Takedown

  • Thioamides: Inhibit thyroid peroxidase (TPO).
    FeaturePTU (Propylthiouracil)Methimazole (MMI)
    MOAInhibits TPO; ↓ peripheral T4→T3 conversionInhibits TPO (more potent)
    UsesThyroid storm, 1st trimester pregnancy (📌 PTU for Pregnancy & Peripheral)Preferred (except above)
    Specific ADRsHepatotoxicity, ANCA+ vasculitisTeratogenic (aplasia cutis), cholestasis
  • Iodides (Lugol’s, SSKI): Wolff-Chaikoff effect (↓TH synthesis/release), ↓ gland vascularity. Use: Pre-op, thyroid storm. ⚠️ Escape phenomenon.
  • Radioactive Iodine ($^{131}I$): Destroys follicles. Dose: 5-15 mCi. CI: Pregnancy. ADR: Hypothyroidism.
  • Beta-blockers (e.g., Propranolol): Symptomatic relief (Propranolol 40-80mg q6h in storm); high doses ↓ T4→T3. Sites of action of drugs on thyroid hormone pathway

⭐ Agranulocytosis (WBC < 500/mm³) is a critical ADR of thioamides (PTU/MMI). Presents with fever, sore throat. Management: Stop drug immediately + G-CSF.

Special Situations & ADRs - Tricky Thyroid Tales

  • Thyroid Storm: Life-threatening! ABCs, Propranolol, PTU (preferred, blocks T4→T3), then Iodine (1hr later), Hydrocortisone.
  • Myxedema Coma: IV Levothyroxine (300-500 mcg bolus, then 50-100 mcg/day) + IV Hydrocortisone (rule out adrenal insufficiency).
  • Antithyroids in Pregnancy/Lactation:
    DrugPregnancyLactation
    PTU1st trimester (MMI teratogenic)✅ Preferred (low milk transfer)
    Methimazole2nd/3rd trimester; ❌ 1st (aplasia cutis)Monitor infant TFTs
  • Key ADRs:
    • Thionamides: Agranulocytosis (⚠️ Sore throat, fever - STOP drug!), rash.
    • PTU: Severe hepatotoxicity (Black Box Warning).

⭐ Amiodarone-Induced Thyrotoxicosis (AIT): Type 1 (↑synthesis, vascular) → Thionamides. Type 2 (destructive, non-vascular) → Steroids.

High‑Yield Points - ⚡ Biggest Takeaways

  • Levothyroxine (T4): Drug of choice for hypothyroidism; long half-life.
  • Thioamides (Methimazole, PTU): Treat hyperthyroidism by inhibiting thyroid peroxidase.
  • PTU: Blocks peripheral T4→T3 conversion; preferred in 1st trimester pregnancy, thyroid storm.
  • Methimazole: Generally preferred over PTU (less hepatotoxic), except specific cases.
  • Radioactive Iodine (I-131): For thyroid ablation in hyperthyroidism/cancer.
  • Beta-blockers: Control hyperthyroidism symptoms (tachycardia, tremors).
  • Agranulocytosis: Serious thioamide side effect; monitor fever/sore throat_

Practice Questions: Thyroid Drugs and Antithyroid Agents

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Regarding thyroid hormone all are true except:

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Flashcards: Thyroid Drugs and Antithyroid Agents

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First Aid Pharmacology: Endocrine_____ and Aplastic Anemia are rare hematological complications of propylthiouracil and methimazole use

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First Aid Pharmacology: Endocrine_____ and Aplastic Anemia are rare hematological complications of propylthiouracil and methimazole use

Agranulocytosis

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