THYROID AND ANTITHYROID DRUG

IODIDE METABOLISM
- 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
ANTITHYROID AGENTS
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 :
PHARMACOKINETICS THIOAMIDES
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
METHIMAZOLE
- 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
PHARMACODYNAMICS OF THIRAMIDES
- 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 Thioamodes
Adverse 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 Thiomides
Agranulocytosis
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 (ClO
4
-
)
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