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Antithyroid Drugs: Propylthiouracil, Carbimazole & Methimazole

Hey guys, welcome to endocrine pharmacology. In this video we will see

antithyroid drugs which includes propylthiouracil carbimazole and methimazole.

So let's start.

These drugs have pretty good gastrointestinal absorption. So they are given orally.

After absorption carbimazole is converted into methimazole.

So we will consider them together.

Now let's go to their main site of action that is thyroid gland.

As we have seen in video of thyroid hormone synthesis:

the thyroid peroxidase plays critical role in thyroid hormone synthesis.

These drugs inhibit this enzyme and thereby prevents synthesis of new hormones.

However thyroid gland has stored already synthesized hormones

which are secreted for about three weeks.

So this drug takes about three weeks for its effects to develop.

Now these drugs accumulates inside gland because of which

their effects last longer than what you would predict from their plasma half-life.

For example propylthiouracil has plasma half-life of 1-2 hours

however effect of its single dose lasts for about eight hours.

So it is given 2-3 times a day.

Carbimazole has plasma half-life of eight hours

but effect of its single dose lasts for an entire day so it is given once daily.

Now apart from this, propylthiouracil has an additional mechanism as well.

As we have seen in video of peripheral conversion of thyroid hormones;

most of the T3 is synthesized peripherally by deiodinase enzyme.

Propylthiouracil inhibits D1 among these enzymes

and thereby prevents peripheral synthesis of T3.

In contrast to the previous action, these action starts depleting T3 level immediately.

Now let's talk about uses of this drug.

Being antithyroid, these drugs are used for hyperthyroidism

like Graves disease, toxic nodular goiter, subacute thyroiditis etc.

There are three ways of using these drugs.

One is in young patients with moderate disease where these drugs are used alone as definitive therapy.

Such treatment usually lasts long and relapse rates are also high.

Patients with severe disease usually requires radioactive iodine or thyroidectomy.

Here these drugs are used along with radioactive iodine while awaiting its response

and before surgery to achieve euthyroid state.

For these indications carbimazlole or methimazole is usually preferred

because they require less frequent dosing and have less side effects.

Propylthiouracil on the other hand is reserved for some special situations.

One of them is thyroid storm where it's property of inhibition of

peripheral conversion of T4 into T3 comes handy.

And second is in pregnancy.

Propylthiouracil is more protein bound because of which

it's placental penetration is less as compared to other drugs.

Carbimazole and methimazole on the other hand enters into the placenta and produces fetal toxicities.

Did you notice how many times we have letter 'P' here. P in propylthiouracil,

P in peripheral conversion, P in pregnancy and P in protein bound.

This will help you remember these two special indications of propylthiouracil.

Now let's talk about adverse effects.

An obvious adverse effect that you can predict from its mechanism of action is hypothyroidism.

Reduced thyroid levels stimulates pituitary gland so it secretsthyroid stimulating hormone

which in turn causes growth of thyroid gland and may cause goiter.

Apart from this, rash and joint pain are among very common side effects of these drugs.

A rare but very serious side effect is a granulocytosis.

So be cautious if a patient under this drug develop any signs of infection.

Talking about drug specific side-effect;

propylthiouracil causes liver damage so it should be avoided in children and even young adults.

Carbimazole and methimazole causes fetal toxicities

like fetal goiter, coanal atresia, scalp defects and aplasia cutis.

Now let's a quick revision. These drugs are given orally.

They inhibits thyroid peroxidase.

They're used in hyperthyroidism

like Graves disease, toxic nodular goiter, subacute thyroiditis etc.

There are three ways of using these drugs.

Alone as definitely therapy, along with radioactive iodine while awaiting it's response

and before surgery to achieve euthyroid state.

For this usually Carbimazole or methimazole is preferred.

Propylthiouracil is used in thyroid storm as it inhibits peripheral conversion of T4 into T3,

and also in pregnancy as it is more protein bound and its penetration into placenta is minimal.

In side effects they causes hypothyroidism, goitre, rash and joint pain,

a serious side effect agranulocytosis. Liver damage by propylthiouracil and

foetal toxicities by carbimazole and methimazole.

That's it for this video.

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