Thyroid and Antithyroid Drugs [Compatibility Mode]

7/31/2019 Thyroid and Antithyroid Drugs [Compatibility Mode]

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Thyroid and Antithyroid DrugsThyroid Gland

Secretes:Tetraiodothyronine (T4) [Thyroxine]Triiodothyronine (T3)oT3 and T4 normalise growth development, body temperature and energy levels

CalcitoninoRegulation of calcium metabolismBiosynthesis of Thyroid Hormone1. Transportation of iodide into thyroid gland by the sodium/iodide symporter (NIS)2. Iodide is oxidised to iodine by thyroidal peroxidase. Iodine rapidly iodinates tyrosine residues

to form monoiodotyrosine (MIT) and diiodotyrosine (DIT)3. Two DIT combine to form T4 (L-Thyroxine); 1 MIT plus one DIT combine to form T34. Secretion of thyroid hormoneMetabolismThe primary pathway for peripheral metabolism of T4 is deiodination

Monodeiodination of the outer ring produces 3,5,3-triiodothyronine (T3), which is 3 to 4 timesmore potent than T4

Deiodination in the inner ring produces 3,3,5-triiodothyronine (rT3), which is metabolicallyinactive Ipodate, -blockers, corticosteroids, severe illness or starvation inhibit 5-deiodinase (necessary

for the conversion of T4 to T3) resulting in low T3 and high rT3Pharmacokinetics

Given orally T4 best absorbed in the duodenum and ileumOral bioavailability: T4 (80%), T3 (95%)

Can also be administered intravenously

Metabolism of both T4 and T3 is increased by drugs that induce hepatic microsomal enzymes(eg, rifampicin, phenobarbital, carbamazepine, phenytoin)

Mechanism of Action Free forms of T4 and T3 enter the cell by diffusion or active transportT4 is converted to T3 by 5-deiodinaseT3 enters the nucleus and binds to specific T3 receptor protein

Lead to increased formation of RNA and subsequent protein synthesisEffects of Thyroid Hormones Responsible for optimal growth, development, function and maintenance of all body tissues Critical for nervous, skeletal and reproductive tissues Thyroid deprivation in early life results in irreversible mental retardation and dwarfism Have a great influence on the metabolism of drugs, carbohydrates, fats, proteins and vitamins Influence the secretion and degradation of almost all other hormonesHypothyroidismDecreased basal metabolic rateSlow speech

Deep hoarse voice

LethargyBradycardia

Mental impairmentCauses of Hypothyroidism

Iodine deficiencyAutoimmune disease

Drugs (lithium)Post irradiationManagement of hypothyroidismDrug-induced hypothyroidism is treated by removing the depressant agentAll other forms are managed by replacement therapy

Most satisfactory preparation is thyroxine (T4)Adult, initially 50-100mcg (od) before breakfast for 4 weeks, then increase by 25-50mcg every4 weeks until euthyroid

Hyperthyroidism

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Increased basal metabolic rate

Heat intoleranceExophthalmos

Increased inotropic and chronotropic effects

ArrythmiasCauses of Hyperthyroidism

Autoimmune diseaseTumours/Nodular growth

TSH secreting tumoursDrugs (amiodarone)Thyroditis (viral)Management of HyperthyroidismRadioactive iodine: Iodine isotope 131I

Given orally rapidly absorbed taken up by the gland

Emits and rays ( rays cytotoxic; T1/2 = 5 days; penetration range = 400-2000 m)Beneficial effects take 1-2 months

Advantages: easy administration, effectiveness, low cost, absence of pain

Side effects: Hypothyroidism; not recommended in children and pregnant women

Thioureylenes - ThioamidesCarbimazole, methimazole, propylthiouracilMethimazole is 10 times more potent than propylthiouracil

Carbimazole is converted to methimazole in vivo Inhibit thyroid peroxidase catalysed reaction and block iodine organification Inhibit peripheral deiodination of T4 to T3

Delayed response due to large hormone storesGiven orallyThioureylenes - ThioamidesT1/2: propylthiouracil = 1,5 hrs; methimazole = 6 hrsT

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has little effect on duration of antithyroid action since they accumulate in the glandCross placenta/ appear in breast milkPropylthiouracil is preferable in pregnancy

Excreted in urineSide effects: rashes, headaches, nausea, jaundice, agranulocytosisIodine/iodide

Lugols iodine (Potassium iodide)Given orally

Inhibit organification and hormone releaseRapid improvement: 2-7 daysDecrease the vascularity of the hyperplastic gland in 10-15 days (useful in preparation for

surgery)

Iodine/iodideUseful in thyroid storm

Good for adjunct therapySide effects:AllergiesCross placenta thus chronic use in pregnancy should be avoidedOther DrugsBeta Blockers - PropranololDecrease signs and symptomsUseful in preparation for surgery

Treatment of thyroid storm20-40 mg orally 6-8 hourly

Diltiazem 90-120 mg tds or qid where propranolol is contraindicatedOther Drugs

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Guanethidine N.A. blocker eye drops to decrease exophthalmosBarbituratesAccelerate T4 breakdown

Adequate nutrition and vitamin supplements

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Thyroid and Antithyroid Drugs [Compatibility Mode]