Pharmacology for Anaesthesia and Intensive Care

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25 Corticosteroids and other hormone preparations

Kinetics

When administered enterally both T 3 and T 4 are well absorbed from the gut. Once

in the plasma they are more than 99% bound to albumin and thyroxine-binding

globulin. Some T 4 is converted within the liver and kidneys to T 3 or to the inactive

reverse T 3 .Metabolism occurs in the liver and the conjugated products are excreted

in bile. Up to 40% may be excreted unchanged in the urine.

Drugs used in the treatment of hyperthyroidism

Carbimazole

Carbimazole is a prodrug, being rapidly converted to methimazole in vivo.

Mechanism of action

Carbimazole prevents the synthesis of new T 3 and T 4 byinhibiting the oxidation

of iodide to iodine and by inhibiting thyroid peroxidase, which is responsible for

iodotryrosine synthesis and the coupling of iodotyrosines. Stored T 3 and T 4 is unaf-

fected and so treatment with carbimazole requires weeks before the patient becomes

euthyroid.

Side effects

These include rashes, arthralgia and pruritus. Agranulocytosis occurs rarely and

may be heralded by a sore throat. It crosses the placenta and may cause foetal

hypothyroidism; however, it is not contraindicated during breast feeding as only

tiny amounts enter the breast milk.

Kinetics

Carbimazole is well absorbed from the gut and completely converted to methimazole

during its passage through the liver. It increases the vascularity of and is metabolized

within the thyroid gland. It is minimally plasma protein-bound.

Propylthiouracil

This oral preparation blocks the iodination of tyrosine and partially blocks the

peripheral conversion of T 4 to T 3 .There is no parenteral formulation and it is reserved

for those patients intolerant of carbimazole. It has a slightly higher incidence of

agranulocytosis.

Propranolol

Propranolol is aβ-blocker with negative inotropic and chronotropic activity. It will

help control the sympathetic effects of a thyrotoxic crisis. However, it also blocks the

peripheral conversion of T 4 to T 3 and blocks hypersensitivity to the actions of cate-

cholamines. It is relatively contraindicated for patients with heart failure or reversible

airflow limitation. Guanethidine may be considered as an alternative in these cases.