Pharmacology of thyroid hormones.pdf

7/30/2019 Pharmacology of thyroid hormones.pdf

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Dr.U.P.Rathnakar

MD.DIH.PGDHM 1

Thyroid hormones

BDSMay 2013


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T4&T3 Actions

Growth&development

Metabolism

Calorigenesis CVS

Nervous system

Sk.Muscles GIT

Blood

Reproduction 11


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Thyroid hormones

Uses

Cretinism [Congenital

Hypothyroidism]

Adult hypothyroidism Myxoedema coma

Non-toxic goiter

Thyroid nodule

Papillary carcinoma of thyroid

Non-specific uses

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PreparationsL-Thyroxine [T4]

Liothyronine[T3]

Oral & i.v


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13

oxidation

1

23

45

Conversion

61to5TSH ACTIVATES1

Ionic inhibitors

block

2

Carbimazole

Methimazole

Propylthiouracil

1-2-3-5

Iodides

6Propranolol,

Prednisolone,

Propylthiouracil

131I

2

2

NIS

Pendrin

Antithyroids drugs


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CLASSIFICATION

1. Inhibitors of iodide trapping (anion inhibitors): Thiocyanates, perchlorates.

2. Thyroid hormone synthesis inhibitors

Propylthiouracil, methimazole, carbimazole. (Thioamides or thioureaderivatives)

3. Hormone release inhibitors: Iodine, iodides of Na + and K+, organic iodide.

4. Thyroid tissue-destroying agent: Radioactive iodine (131I).

5. Others: Propranolol, atenolol, diltiazem, dexamethasone.

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IONIC INHIBITORS

Not used because of ADEs

Monovalant anions like iodides

Thiocynates: can cause liver, kidney, bonemarrow and brain toxicity[cabbage,

cigarette smoking]

Perchlorates: produce rashes, fever,aplastic anaemia, agranulocytosis

Nitrates: are weak drugs, can induce

methemoglobinaemia and vascular effects15


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Antithyroid drugs[Popylthiouracil-Methimazole-Carbimazole]

MOA

Inhibit peroxidase

Oxidation of Iodides-Inhibited Iodination of tyrosine-inhibited

Coupling-Inhibited

Synthesis of T3&T4 inhibited

Effective only after stores of iodinated

thyroglobulin depleted.

Propylthiouracil inhibits [5 DI] peripheral

conversion of T4 to T3 16


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Pharmacokinetic Features of

Anti-thyroid Drugs[Carbimazole is the prodrug of Methimazole

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Peripheral conversion Inhibits No

[More than PTU]


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Antithyroid drugs

Adverse effects Hypothyroidism and goiter -reversible

G.i. intolerance

Rare but serious adverse effect- aganulocytosis (1 in

500 to 1000 cases)-periodic counts-reversible.

Rashes and joint pain.

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Antithyroid drugs

Therapeutic uses1. Definitive treatment, in Graves' disease

2. With radioactive iodine, to hasten recovery

while awaiting the effects of radiation

3. To control the disorder in preparation forsurgical treatment

4. Thyroid storm

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Antithyroids and

Preoperative use Pts rendered euthyroid-to reduce

operative[Subtotal thyroidectormy]

morbidity & mortality

Others

Iodides-less vascularity, less friable

Dexamethasone, propranolol-7 daysbefore

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Adjuant therapy

with Antithyroid drugs No intrinsic antithyroid activity

blockers-palpitations, tremor,anxiety

Propranolol or atenolol Diltiazem

Dexamethasone

Radiological contrast media Cholestyramine

Rituximab-TSI21


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Thyroid storm (thyrotoxic crisis)

[Life threatening]

Propranolol, iodides, PTU, Prednisolone

Propranolol 1-2 mg slow i.v. may be followed by 40-80

mg oral every 6 hours .

Propylthiouracil 200-300 mg oral 6 hourly

Hydrocortisone 100 mg i.v. 8 hourly followed by oral

prednisolone)

To tide over crisis, cover any adrenal insufficiency Diltiazem 60-720 mg BD

Rehydration, anxiolylics, external cooling and

antibiotics22


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Iodides

Inhibit all aspects of iodine metabolism by

the thyroid gland.

Acute inhibition of the synthesis of T4& T3

Wolff-Chaikoff effect

Vascularity is reduced, gland firm.

Thyroid constipation Symptoms reappear- Thyroid escape

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Iodides- Preparations

Lugol's solution- 5% iodine and 10% KI- 8

mg of iodine / drop

Saturated solution of potassium iodide

(SSKI) al-50 mg / drop

Dose -16-36 mg TID

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Iodides-ADEs

Acute Angioedema and laryngeal.

Multiple cutaneous hemorrhages may be present.

Fever, arthralgia, lymph node enlargement, and eosinophilia.

Chronic- Iodism

Unpleasant brassy taste and burning in the mouth and throat

Coryza, sneezing, and irritation of the eyes with swelling of the eyelids

Parotid and submaxillary glands -enlarged and tender, -mistaken for mumps

Skin lesions are common Diaarhoea

Disappear spontaneously within a few days after stopping

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Radioactive Iodine

Radioactive isotopes of Iodine-123I and 131I 123I, -emitter -in diagnostic studies

131I emits both rays and particles- used

therapeutically for thyroid destruction Trapped and incorporated and deposited in the colloid

of the follicles

Destructive particles originate within the follicle and

act almost exclusively on the parenchymal cells of thethyroid, damage to surrounding tissue.

radiation passes through the tissue and can be

quantified by external detection 26


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Radioactive Iodine

Therapeutic Uses

Advantages

Safe-no mortality

Not expensive

No risks of surgery

No hospitalization

Disadvantages

Long time for control

Not in young

CI pregnancy

Radiation thyroiditis

[Worsening of

ophthalmopathy and

hyperthyroidism] Increase shown in -cancer,

including stomach, kidney,

and breast

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Pharmacology of thyroid hormones.pdf

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