Review of Pharmacology - 9E (2015)

Review of Pharmacology
1. Inhibitors of Na + –I – Symporter
Iodine is trapped in the follicular cells with Na + :I - symporter. Thiocyanate, fluoborate,
perchlorate, pertechtenate and nitrates inhibit this transporter and thus thyroid hormone
synthesis. These drugs are very toxic and are obsolete now. Thiocyanate is produced by
cabbage, cigarette smoking and sodium nitroprusside.
Propylthiouracil is drug of choice
for hyperthyroidism in first trimester
of pregnancy and in
lactation. For all other patients,
methi mazole is preferred.
2. Thyroid Peroxidase Inhibitors
Thyroid peroxidase enzyme catalyzes three reactions (oxidation, organification and coupling)
in the process of thyroid hormone synthesis. Carbimazole, methimazole and propylthiouracil
act by inhibiting this enzyme. These drugs inhibit the formation of new thyroid hormones
but their action manifests only when already stored pool of T 3
and T 4
is utilized. Thus, a
lag period of 1-3 weeks is present. These drugs can rarely cause reversible agranulocytosis
(most serious adverse effect) whereas most common adverse effect associated with these
drugs is maculopapular pruritic rash. Carbimazole is a prodrug and acts after conversion to
methimazole. Major differences between carbimazole and propylthiouracil are that the latter:
• Has high Plasma protein binding.
• Can be used in pregnancy (because less transfer across placenta due to high PPB).
• Is less potent.
• Has shorter plasma half-life, so requires multiple daily dosing.
• Also inhibits peripheral conversion of T 4
to T 3
.
Endocrinology
Uses
• Thyroid peroxidase inhibitors are used for the control of thyrotoxicosis in patients
with Graves’ disease and toxic nodular goiter.
• Propylthiouracil is drug of choice for hyperthyroidism in first trimester pregancancy
and lactation. For all other patients, methimazole is preferred.
• These are also used in young patients before performing thyroidectomy.
• Another use of antithyroid drugs is to make the patient euthyroid before application
of radioactive iodine.
Note: Propylthiouracil has been found to be hepatotoxic and FDA has declared methimazole as
preferred drug over propylthiouracil for all patients except in first trimester of pregnancy and lactation.
3. Inhibitors of Thyroid Hormone Release
Iodides are the fastest acting
anti-thyroid drugs.
Sodium iodide, potassium iodide and Lugol’s solution act as ‘thyroid constipating agents’ by
inhibiting the release of T 3
and T 4
. These drugs are the fastest acting anti-thyroid drugs.
These agents make thyroid gland shrink in size and decrease its vascularity. These properties
are utilized in preoperative preparation of thyroid gland. Thyroid storm is another indication
of these drugs. Iodine is also used as an antiseptic and expectorant. Lithium can cause
hypothyroidism by inhibiting the release of thyroid hormones.
In sensitive individuals, acute reaction consisting of swelling of lips, angioedema, fever,
joint pain and petechial hemorrhages can occur. Chronic overdose of iodides is called
iodism. Major symptoms are inflamed mucus membranes, increase in secretions (salivation,
lacrimation and rhinorrhoea), headache, rashes and gastrointestinal distress. These drugs
may also cause flaring up of acne in adolescents.
4. Drugs Causing the Destruction of Thyroid Gland
I 131 is the most commonly used
radioactive iodine with a half-life
of 8 DAYS
I 131 is the most commonly used radioactive iodine with a half-life of 8 DAYS (stable isotope
of iodine is I 127 ). When administered (as sodium salts, orally), these are actively taken up
by the thyroid gland and stored in the colloid. Here, it emits x-rays and β-particles. Latter
can penetrate only 0.5-2mm of tissue and destroy the gland from within. Concentration of
radioactive iodine by the thyroid gland is responsible for its selective thyroid destroying effect.
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