DRUGS USED IN DRUGS USED IN HYPERTHYROIDISMHYPERTHYROIDISM

Objectives Objectives

At the end of 1At the end of 1stst lecture the studetns will lecture the studetns will be able to :be able to :

Classify common drugs used for Classify common drugs used for treatment of hyperthyroidism treatment of hyperthyroidism

Details the drugs regarding , mechanism Details the drugs regarding , mechanism of action , pharmacological effects , of action , pharmacological effects , clinical uses & side effects clinical uses & side effects

Recognize treatment of special cases of Recognize treatment of special cases of hyperthyroidism such as pregnancy, hyperthyroidism such as pregnancy, breast feeding , Gravebreast feeding , Grave,,s disease & s disease & thyroid stormthyroid storm 2

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HYPERTHYROIDISMHYPERTHYROIDISM

Elevated levels of TElevated levels of T33 and T and T44 in the blood. in the blood.

Causes :Causes : Adenomas / carcinomasAdenomas / carcinomas

ThyroiditisThyroiditis

AutoimmuneAutoimmune

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GRAVES' DISEASEGRAVES' DISEASE

Most common cause of hyperthyroidism Most common cause of hyperthyroidism 60-80%60-80%..

Autoimmune disorder associated with Autoimmune disorder associated with circulating immunoglobulins that bind circulating immunoglobulins that bind to and stimulate the thyrotropin ( TSH) to and stimulate the thyrotropin ( TSH) receptor , resulting in sustained thyroid receptor , resulting in sustained thyroid over activity & it can be familial.over activity & it can be familial.

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Manifestations of Manifestations of HyperthyroidismHyperthyroidism

NNervousness , irritability.ervousness , irritability. TremorsTremors palpitationpalpitation Weight lossWeight loss sweatingsweating Heat intoleranceHeat intolerance

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||Manifestations cont’dManifestations cont’d

DiarrheaDiarrhea short breathshort breath ItchingItching XophthalmosXophthalmos Thyroid Enlargement Thyroid Enlargement

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Treatment of HyperthyroidismTreatment of Hyperthyroidism

Thioamides ( antithyroid drugs)Thioamides ( antithyroid drugs)

IodidesIodides

.. Radioactive iodineRadioactive iodine

Beta blockersBeta blockers

SurgerySurgery

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THIOAMIDES:THIOAMIDES:

MethimazoleMethimazole

Propyl thiouracilPropyl thiouracil

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Mechanism of ActionMechanism of Action

Inhibit synthesis of thyroid hormonesInhibit synthesis of thyroid hormones By inhibiting By inhibiting peroxidaseperoxidase enzyme that enzyme that

catalyzes the iodination of tyrosine residues catalyzes the iodination of tyrosine residues in the thyroglobulin & couples iodotyrosines in the thyroglobulin & couples iodotyrosines to form T3 & T4.to form T3 & T4.

They block the conversion of T4 to T3 They block the conversion of T4 to T3 within the thyroid & in peripheral tissues within the thyroid & in peripheral tissues

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Pharmacokinetic comparision between Pharmacokinetic comparision between Propylthiouracil and MethimazolePropylthiouracil and Methimazole

PropylthiouracilPropylthiouracil MethimazoleMethimazole

Absorption Absorption Both are Both are rapidly and rapidly and

Absorbed from Absorbed from GITGIT

Protein Protein binding binding

80-90% 80-90% Most of drug is Most of drug is free free

accumulatiaccumulation on

Both are Both are accumulated in accumulated in

thyroidthyroid

Excretion Excretion Kidneys as inactive Kidneys as inactive metabolite within metabolite within 24 hrs 24 hrs

Excretion Excretion slow,60-70% of slow,60-70% of drug is drug is recovered in recovered in urine in 48 hrs urine in 48 hrs

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Pharmacokinetic comparision between Pharmacokinetic comparision between Propylthiouracil and MethimazolePropylthiouracil and Methimazole

PropylthiouracilPropylthiouracil MethimazoleMethimazole

Half life Half life 1.5 hrs ( short 1.5 hrs ( short half-life)half-life)

6 hrs ( long half-6 hrs ( long half-life)life)

Administration Administration Every 6-8 hrs Every 6-8 hrs As a single dose As a single dose

Pregnancy Pregnancy Both cross placenta Both cross placenta & fetal thyroid. & fetal thyroid.

It is highly protein It is highly protein bound ,crossing bound ,crossing placenta is less placenta is less readily so readily so recommended in recommended in pregnancy. pregnancy.

Concentrated inConcentrated in

Not recommended Not recommended in pregnancyin pregnancy

Breastfeeding Breastfeeding Less secreted in Less secreted in breast milkbreast milk

Recommended Recommended

secreted secreted

Not recommendedNot recommended

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Adverse Effects Adverse Effects

Cutaneous reactions Cutaneous reactions ( urticaria , maculopapular ( urticaria , maculopapular rash ) rash )

Arthralgia Arthralgia GI upset , GI upset , HepatotoxicityHepatotoxicity ( mainly with ( mainly with

methimazolemethimazole))

Most dangerous complication is Most dangerous complication is agranulocytosis agranulocytosis

occur within 90 days of treatmentoccur within 90 days of treatment

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IODIDES:IODIDES:

Mechanism of actionMechanism of action

Inhibit Inhibit synthesissynthesis and and release release of thyroid hormonesof thyroid hormones Block the Block the peripheral conversion of T4 to T3 .peripheral conversion of T4 to T3 .

They produce a They produce a temporary remission temporary remission of of symptoms ( less than 10 days).symptoms ( less than 10 days).

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Anti –thyroid agents ( Mechanissm)

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Clinical uses Clinical uses

PriorPrior to thyroid to thyroid surgerysurgery to to decrease vascularity decrease vascularity & size of the gland .& size of the gland .

Following radio active iodine therapy.Following radio active iodine therapy.Examples Examples

Organic iodides Organic iodides as :iopanoicas :iopanoic acidacid or or ipodateipodate Potassium iodide Potassium iodide

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Precautions /toxicity:Precautions /toxicity:

Should not be used as a single therapyShould not be used as a single therapy

Should not be used in pregnancyShould not be used in pregnancy

May produce May produce iodism iodism ( acniform rash, ( acniform rash, swelling of salivary glands, mucous swelling of salivary glands, mucous membrane ulceration, metallic taste membrane ulceration, metallic taste bleeding disorders and rarely anaphylaxis ).bleeding disorders and rarely anaphylaxis ).

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RADIOACTIVE IODINERADIOACTIVE IODINE 131131 I isotope I isotope ( therapeutic effect due to ( therapeutic effect due to

emission of emission of ββ rays ) rays )

Accumulates in the thyroid gland and Accumulates in the thyroid gland and destroys parenchymal cells, destroys parenchymal cells, producing a producing a long-term decrease long-term decrease in in thyroid hormone thyroid hormone levels. Clinical improvement may take 2-levels. Clinical improvement may take 2-3 months3 months

Half -life 5 daysHalf -life 5 days Cross placenta & excreted in breast milkCross placenta & excreted in breast milk Easy to administer ,effective , painless Easy to administer ,effective , painless

and less expensiveand less expensive

Radioactive Iodine ( con.)Radioactive Iodine ( con.)

Available as a solution or in Available as a solution or in capsulescapsules

Clinical uses Clinical uses Hyperthyroidism mainlyHyperthyroidism mainly in old in old

patients (above 40)patients (above 40) GravesGraves,, disease disease Patients with toxic nodular goiterPatients with toxic nodular goiter As a diagnostic As a diagnostic

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DisadvantagesDisadvantages

High incidence of High incidence of delayed delayed hypothyroidismhypothyroidism

Large doses have Large doses have cytotoxic cytotoxic actions actions ( necrosis of the follicular ( necrosis of the follicular cells followed by fibrosis )cells followed by fibrosis )

May cause May cause genetic damagegenetic damage May cause leukemia & neoplasia May cause leukemia & neoplasia

((carcinogenic carcinogenic ))

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ADRENOCEPTOR BLOCKING AGENTS:ADRENOCEPTOR BLOCKING AGENTS:

Adjunctive therapy Adjunctive therapy to relief the adrenergic to relief the adrenergic symptoms of hyperthyroidism such as symptoms of hyperthyroidism such as tremor, palpitation, heat intolerance and tremor, palpitation, heat intolerance and nervousness. nervousness.

E.g. E.g. Propranolol, Atenolol , Metoprolol.Propranolol, Atenolol , Metoprolol.

Propranolol Propranolol is contraindicated in is contraindicated in asthmatic asthmatic patientspatients

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THYROIDECTOMYTHYROIDECTOMY

Sub-total thyriodectomy is the treatment of Sub-total thyriodectomy is the treatment of choice in very large gland or multinodular choice in very large gland or multinodular goitergoiter

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THYROID STORMTHYROID STORM

A sudden acute exacerbation A sudden acute exacerbation of all of of all of the symptoms of thyrotoxicosis, the symptoms of thyrotoxicosis, presenting as a presenting as a lifelife threatening threatening syndrome.syndrome.

There is hyper metabolism, and There is hyper metabolism, and excessive adrenergic activity, excessive adrenergic activity, deathdeath may may occur due to heart failure and shock.occur due to heart failure and shock.

Is a medical emergency . Is a medical emergency . Propranolol Propranolol 1-2mg slows IV or 40-80 mg 1-2mg slows IV or 40-80 mg

orally every 6 hoursorally every 6 hours

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Potassium iodide Potassium iodide 10 drops orally 10 drops orally daily ordaily or

PropylthiouracilPropylthiouracil 250 mg orally 250 mg orally every six hours or 400 mg every every six hours or 400 mg every six hours rectally.six hours rectally.

HydrocortisoneHydrocortisone 50 mg IV every 6 50 mg IV every 6 hours to prevent shock.hours to prevent shock.

If above methods fail If above methods fail peritoneal peritoneal dialysisdialysis..

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Thyrotoxicosis during pregnancyThyrotoxicosis during pregnancy

Therapy with Therapy with 131131I or subtotal thyroidectomy I or subtotal thyroidectomy prior prior to to pregnancy to avoid acute exacerbation during pregnancy to avoid acute exacerbation during pregnancy or after deliverypregnancy or after delivery

During pregnancy radioiodine is contraindicated.During pregnancy radioiodine is contraindicated.

PropylthiouracilPropylthiouracil is the better choice during is the better choice during pregnancy. pregnancy.