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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