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ANTI-THYROID DRUGS

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ANTI-THYROID DRUGS

ANTI-THYROID DRUGS
  • Drugs causing thyroid inhibitors.
  • Inhibit thyroxine synthesis
  • Lowers functional capacity of hyperactive thyroid gland 

Drugs: Propylthiouracil, Methimazole & Carbimazole

Mechanism of action:

  • Blocks thyroxine synthesis by, 
    • Inhibit thyroid peroxidases
    • Prevent iodide oxidation.
    • Inhibit iodination of tyrosine residues in thyroglobulin.
    • Inhibit coupling iodotyrosine residues forming T3 & T4
Actions unaffected include:
  • Trapping of iodide
  • T3 & T4 action in peripheral tissues & pituitary.

Pharmacokinetics:

  • Orally absorbed
  • Transfer across placenta & milk (less with propylthiouracil)
  • Liver metabolism 
  • Urinary excretion – metabolites 
  • Longer plasma 1/2 life
  • No interaction bt. Propylthiouracil & Carbimazole

Adverse effects:

    • Congenital malformations (Specific to carbimazole)
    • Aplasia cutis congenita (Scalp or patchy hair defect)
  • Other side effects: 
    • GI intolerance 
    • Skin rashes 
    • Joint pain
  • Reversible effects: 
    • Agranulocytosis
    • Treatment-induced reversible Hypo-thyroidism.

Indications: (mainly Propylthiouracil)

1. Thyroid Storm: 

  • Propylthiouracil – 600-900mg/day.
  • Inhibitory action on peripheral conversion of T4 to T3 

2. Thyrotoxicosis in Grave’s disease & Toxic Nodular Goitre in pregnancy

  • Hormone store determines clinical improvement.
  • Responses seen after 1-2 wks.
  • Less response in Iodide loaded patients.

3. As a pre-operative medication 

4. In conjunction with Radioactive iodine (I131)

  • Anti-thyroid drugs (Initial control) –>1-2 wks gap —> I131 —> Anti-thyroid drugs (after 5-7 days) —> Gradual withdrawal after 3 mons

Contraindications:

  • In pregnancy 
  • Radioactive I131 & thyroidectomy
    • Destruction of fetal thyroid
  • Carbimazole:
    • Hyperthyroid pregnant women
    • Cause Aplasia Cutis Congenital.
Advantages of anti-thyroid drugs:

1. Hyperthyroidism in Pregnancy: 

  • DOC:
  • Propylthiouracil (low doses)
    • Less transfer across milk & placenta
    • High plasma binding property
    • No risk of congenital malformations 
    • Fetal protection
    • Comparatively safe usage in children & young adults

2. Preferences over surgery I131:

  • Surgical risk reduced.
  • Avoids injury to Parathyroid and Laryngeal N.

Disadvantage:

  • Drug toxicity.
  • Prolonged & life-long treatment.
  • High relapse rate.
  • Restricted usage – Uncooperative patients.
Comparison Bt. Propylthiouracil & Carbimazole:
Propylthiouracil:
  • MOA: 
  • Plasma t1/2: 1-2 HrsDose-related potency
    • Multiple dosages required
    • Duration of action: 4 -8 Hrs
  • Peripheral conversion of T4 to T3 inhibited

Major advantage:

  • Highly plasma protein bound
  • So less trans-placental & milk diffusion
  • No active metabolite
  • Hence,No congenital malformations associated

Side effects:

  • Reversible Fetal hypothyroidism
  • Transient leukopenia
Carbimazole:
  • MOA: No inhibitory effects; Antagonize propylthiouracil
  • Plasma t1/2: 6-10 Hrs
  • 3 times more potent
  • Duration of action: 12-24 Hrs
  • Given OD
  • Major disadvantage:
    • Active metabolite – Methimazole
    • Increased trans-placental & milk diffusion
  • Maculopapular pruritic rash
  • Agranulocytosis

Effects in Pregnancy:

Congenital malformation:

  • Scalp or patchy hair defect (aplasia cutis congenita)
  • Choanal atresia
  • Sacral pilonidal sinus
  • Tracheoesophageal fistula
  • Fetal goiter
  • Hypoplastic or absent phalanges (low set fifth finger)
  • Psychomotor delay
  • Minor facial anomaly (Flat face, low set ears & upper lip traction)

Exam Important

ANTI-THYROID DRUGS:
  • Inhibit thyroxine synthesis
  • Drugs included: Propylthiouracil, Methimazole & Carbimazole.
  • Blocks thyroxine synthesis by, 
    • Inhibits thyroid peroxidases.
    • Inhibit iodination of tyrosine residues in thyroglobulin.
    • Inhibit coupling iodotyrosine residues forming T3 & T4.
  • Actions unaffected include, T3 & T4 action in peripheral tissues & pituitary.
  • Transfer across placenta & milk (less with propylthiouracil).
  • Adverse effects include congenital malformations (Specific to carbimazole) & Aplasia cutis congenita.
Propylthiouracil:
  • MOA: Peripheral conversion of T4 to T3 inhibited.

Major advantage:

  • Highly plasma protein bound.
  • So less trans-placental & milk diffusion.
  • No active metabolite.
  • Hence, No congenital malformations associated.
Carbimazole:
  • Antagonize propylthiouracil.
  • Plasma t1/2 : 6-10 hrs.
  • 3 times more potent.
  • Duration of action: 12-24 hrs.

Major disadvantage:

  • Active metabolite – Methimazole.
  • Increased trans-placental & milk diffusion.

Effects in Pregnancy:

Congenital malformation:

  • Scalp or patchy hair defect (aplasia cutis congenita).
  • Choanal atresia.
  • Hypoplastic or absent phalanges (low set fifth finger).
  • Minor facial anomaly (Flat face, low set ears & upper lip traction).

Indications: 

  • Thyroid Storm: 
  • Thyrotoxicosis in Grave’s disease & Toxic Nodular Goitre in pregnancy
Contraindications:
  • In pregnancy

Carbimazole:

  • Hyperthyroid pregnant women.
  • Causes Aplasia Cutis Congenita.

Advantages of anti-thyroid drugs:

1. Hyperthyroidism in Pregnancy: 

  • DOC: Propylthiouracil (low doses).
  • Less transfer across placenta & milk.
  • High plasma protein binding ability.
  • No risk of congenital malformations. 

2. Preferences over surgery / I131

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