Question
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- (a) Mention different groups of Anti-thyroid drugs available for clinical use. ( 4 mark(s)
- (b) Which anti-thyroid drug is used to treat hyperthyroidism in pregnancy. How it lowers thyroxine levels (i.e mechanism). What are its adverse effects. ( 3 mark(s)
- (c) Explain the rationale for use of propranolol in hyperthyroidism. ( 2 mark(s)
- (d) Briefly describe Insulin analogs. 6 mark(s)
Answer
a) Groups of anti-thyroid drugs
- Thioamides — Carbimazole, Methimazole, Propylthiouracil
- Iodides — Lugol’s iodine (Wolff-Chaikoff effect, pre-operative use)
- Radioactive iodine — I-131
- Beta-blockers — Propranolol (symptomatic adjunct)
b) Drug in pregnancy, mechanism, adverse effects Propylthiouracil (PTU) is preferred, particularly in the first trimester (Carbimazole carries a risk of aplasia cutis/choanal atresia).
Mechanism: PTU → inhibits thyroid peroxidase → blocks oxidation/organification of iodide and coupling of iodotyrosines → reduced T3/T4 synthesis; PTU additionally inhibits peripheral T4→T3 conversion.
Adverse effects: hepatotoxicity (rare fulminant hepatic failure), agranulocytosis, rash, ANCA-associated vasculitis.
c) Rationale for propranolol Controls the adrenergic symptoms of thyrotoxicosis (tachycardia, tremor, anxiety) rapidly, while thioamides take weeks to act; also inhibits peripheral T4→T3 conversion at high doses — useful in thyroid storm and pre-operative preparation.
d) Insulin analogs Insulin analogs are recombinant human-insulin molecules with amino-acid substitutions that alter self-aggregation, changing their onset/duration without changing their receptor action — designed to reproduce physiological insulin secretion more closely than regular/NPH insulin.
- Rapid-acting (Insulin Lispro — proline/lysine reversal at B28-B29; Insulin Aspart — proline→aspartate at B28; Insulin Glulisine — lysine/glutamic acid substitutions): reduced self-aggregation allows faster absorption from the subcutaneous depot — onset ~10-15 minutes, peak ~1 hour, duration 3-4 hours. Injected just before or even after meals, they mimic the physiological prandial insulin spike more closely than regular insulin (onset 30 min), improving post-prandial glucose control and reducing the interval-related hypoglycemia risk of regular insulin.
- Long-acting (Insulin Glargine — forms a microprecipitate at the physiological pH of subcutaneous tissue, releasing insulin slowly; Insulin Detemir — fatty-acid chain promotes albumin binding, prolonging action; Insulin Degludec — forms soluble multihexamers, giving an ultra-long, very flat profile): produce a smooth, peakless basal insulin level over 18-42 hours (depending on the specific analog), permitting once-daily dosing and reducing nocturnal hypoglycemia compared to NPH insulin’s pronounced mid-duration peak.
- Premixed analog formulations (e.g. biphasic Aspart, Lispro mix) combine a rapid-acting and an intermediate/protaminated component for convenient twice-daily dosing.
- Advantages over conventional (regular/NPH) insulin: closer mimicry of physiological basal-bolus secretion, greater dosing flexibility (rapid analogs can be given with or just after meals), significantly less nocturnal and inter-meal hypoglycemia, and more predictable day-to-day absorption (particularly with glargine/degludec compared to NPH’s variable peak).