- The recommended daily adult iodide (I-) intake 150 g (200 g during pregnancy)

- Iodide ingested from : food, water, medication

- Iodide ingested is rapidly absorbed and enters extracellular fluid pool

- Iodide intake increase fractional iodine up take by the thyroid is diminished

Biosynthesis of thyroid humane

Pharmacokinetics of Thyroid Hormone- Thyroxin is well absorbed in duodenum

and ileum - Oral bioavailability of thyroid hormone :

The metabolism of both T3 and T4 are increased by dregs that induce hepatic microsomal enzymes

1. Thioamides - Consist of Methimazole and PropyHhiouracil (PTU)- Methimazole is ± ten times more potent than PTU- cd The chemical structure of thioamides are shown below :

PTU- Rapidly absorbed, reaching peak serum levels after 1

hour - The volume of distribution approximates total body water

with accumulation in the thyroid gland- Half-life is 1,5 hours- Excreted by the kidney as the inactive glucuronide within

24 hours - PTU is given every 6 -10 hours with a single 100 mg dose- PTU crosses the placental barrier less readily and

concentrated by fetal thyroid- It is more strongly protein – bound - It is not secreted in sufficient quantity in breast mille to

preclude breast - feeding

- Completely absorbed but at variable rates- Volume of distribution is similar to PTU - Half-life is 6 hours - Excretion is slower than PTU ; 65,70 % of

dose is recovered in the urine in 48 hours - Methimazole is given in 24 hours with a

single 30 mg dose- Methimazole crosses the placental barrier

and consentrated by fetal thyroid

- Prevent hormone synthesis by inhibiting the thyroid peroxidase – catalysed reactions

- Blocking iodine organification- Thioamides blocle coupling of the

iodotyrosines - Thioamides do not in hibit up take of iodive

by the gland - PTU & methimazole in hibit the peripheral

deiodination of T4 and T3

Toxicity of ThioamodesAdverse effect of thioamides are :- Maculopapular pruritic rash »- Fever -Urticarial rash- Vasculitis- Arthralgia- A lupus-like reaction- Cholestatic jaundice- Hepatitis- Lymphadenopathy- Hypoprothrombinemia- Exfoliative dermatitis- Polyserositis

Complication of ThiomidesAgranulocytosis Infrequent but potentially fatal adverse reaction Heccurs in 0,3 – 0,6 % of patient The risk of agranuloagtosis may be increased in older patient and in those receiving high – dose methimazole therapy (over 40 mg / d)

2. Anion Inhibitors Consist of monovalent anions such as : Perclorate (ClO4

-) Pertechnetate (Tc04-) Thiocyanate ( SCN-) This agents block up take of oidide by the gland through compotitive in hibition of the iodide transport mechanism The major clinical use of potassium perchlorate is to block thyroidal reuptake of 1- in patient with iodide induced hyperthyroidism

Side effect of potassuim perchlorate is aplastic anemia

3. Iodides Rarely used as sole therapy Pharmacidynamics Inhibit organifacation and hormon release Decrease the size and vascularity of the hyperplastic gland valuable as preoperative preparation for surgeng Dosage > 6 mg daily inhibit hormon release ; inhibit thyroglobulin proteolysis Clinical use of Iodide

Iodides are used after onset ofThioamide therapy

Iodides should not be used alone its with drawal may produce severe exacerbation of tyrotoxicosis

Iodides cross the placental barrier and can cause fetal goiter

Side effect : acineiform rash, swollen salivary gland mucous membrane ulcerations conjunctivitis rhinorrhea drug fever bledding disorders reraly anaphylactoid reactions