DR.Dr.

Endang Isbandiati Soediono, MS, SpFK

Dept.Pharmacology & Therapy, Medical Faculty, Airlangga University,
Dept.Clinical Pharmacology, Dr.Soetomo Teaching Hospital,
SURABAYA
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PANCREATIC
ADRENOCORTICAL
THYROID
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(1) uptake of iodide ion
(2) Iodide oxidation and iodination of tyrosil groups
(3) coupling of iodotyrosine

iodothyronines
(4) proteolysis of thyroglobulin

release of thyroxine & triiodothyronine

(5) conversion of thyroxine to triiodothyronine

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 Biosynthesis of
Thyroid Hormone

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A. Thyroid- Pituitary Feedback Mechanism

B. Autoregulation
iodide uptake & thyroid ho. synthesis

. intrathyroidal
. TSH independent

C. Abnormal Thyroid Stimulators

TSH-R Ab (stim) or TSI ~ TSH-R

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Pharmacokinetics
. Absorption
T4 > duodenum & ileum

intraluminal factors (food, drugs, flora)

T3 > completely
minimally intraluminal

T3 & T4 : severe myxedema with ileus

parenteral therapy (iv)

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. hyperthyroidism
. hepatic microsomal inducers
(rifampin, phenobarbital, carbamazepine, phenytoin)

Clearance T3 & T4

HL

. Pregnancy, estrogen, oral-contraceptives

TBG

Total & bound state

free hormone : N
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TBG ~ T3/T4

T3 and T4

cell

T4 T3
T3 nucleus

R ~ T3 ( α & β )

RNA formation

protein synthesis

Na+/K+ ATPase

ATP & oxygen consumption

Calorigenic Effects
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Protein synthesis GH secretion & action

nervous, skeletal, reproductive tissues

mental retardation and dwarfism

(congenital cretinism)

Thyroid hyperactivity
Sympathetic nervous system overactivity
( catecholamine level are not increase)

number β – R or
β - R signal
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. Levothyroxine :

thyroid replacement and suppression

(stability, low cost, long HL, lack of allergenic
foreign protein, content uniformity)

. Liothyronine :
more active (greater risk of cardiotoxicity,
shorter HL, higher cost)
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Reduction of activity and hormone effects :
. Interfere production
. Modify tissue response
. Glandular destruction

1. Thioamides
. Methimazole (Carbimazole)
. Propylthiouracil (PTU)

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Pharmacokinetics

PTU : rapid absorption; peak level 1 h

Bioavailability 50 – 80% (first-pass effect)
HL : 1,5 h
Excretion : kidney, glucoronide, 24 h

Methimazole : completely absorption

HL :6h
Excretion : 48h, urine

Thioamides cross the placental barrier

(PTU is strongly PB)
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. PTU
peripheral deiodination T4

T3
T3
faster OOA
DOC pregnancy, nursing mother

. Methimazole
single daily dose; more potent; less expensive

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MOA : multiple mechanisms
hormon synthesis
iodotyrosine coupling
peripheral deiodination (PTU >)
OOA : 3 – 4 weeks

Toxicity :
maculopapular rash, fever, urticaria,
vasculitis, arthralgia, lupus-like,
cholestatic jaundice, hepatitis,
lymphadenopathy, hypoprothrombonemia

Cross sentivity :
(PTU, Methimazole) 50%
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2. ANION INHIBITORS
Monovalent anions :
.perchlorate (ClO4-)
.pertechnetate (TcO4-)
.thiocyanate (SCN-)
(block) iodide uptake
Potassium Perchlorate
competitive inhibitor of iodide
short-term: Amiodarone-induced hyperthyroid
antithyroid : overcome by iodine administration
A.e. : irreversible aplastic anemia, nephrotic sy.
Clinical use : iodide-induced hyperthyroidism

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3. Iodides
MOA
. Wolff-Chaikoff effect
. hormone release
. gland vascularity
A.e. : hypersensitive reactions
Pregnancy :
vaginal Povidone or topical iodine

iodine serum concentration

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3. IODIDE(continued)

Susceptible individu :
hyperthyroidism (jodbasedow)
hypothyroidism

Clinical Use of Iodide

Disadvantages : intraglandular stores of iodine >>>
Should not be used alone : “escape” block
Cross placental barrier : fetal goiter
Toxicity : acneiform rash, swolen salivary glands,
mucous membrane ulceration, conjunctivitis,
rhinorrhea, drug fever, metallic taste, bleeding,
anaphylactoid reaction
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4. IODINATED CONTRAST MEDIA

Ipodate and Iopanoic acid ( po)

Diatrizoate (iv)
Rapidly inhibit conversion T4 to T3
Adjunctive therapy : thyroid storm
Relatively nontoxic
( alternative : Iodide or Thioamides CI)

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5. RADIO ACTIVE IODINE
I 131 : tx. thyrotoxicosis
Absorption : rapid
Parenchyma destruction : few weeks
Crosses the placenta
Excreted in breast milk

6. ADRENOCEPTOR - BLOCKING AGENTS

Sympathophlegic agents :

. Guanethidine
. Reserpine
. Beta-blockers (without ISA)

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Hypothyroidism

Deficiency of thyroid hormones

Slowing down of all body functions

Children: growth & development retardation

Dwarfism and irreversible mental retardation

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Levothyroxine
Children & infants : more T4 /kg BW than adults
Steady states : 6 – 8 weeks
Old pts. : very sensitive heart
Young pts. : immediate full replacement tx.

Special Problems
A Myxedema and Coronary Artery Disease
Correction of myxedema cautiously

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 Special Problems (continued)
B Myxedema Coma : end state of untreated
hypothyroidism
Weakness, stupor, hypothermia, hypoventilation,
hypoglycemia, hyponatremia, water intoxication,
shock, and death
Loading dose of Levothyroxine

C Hypothyroidism and pregnancy

A modest increase of Thyroxine dose (20 – 30%)

D Subclinical Hypothyroidism
E Drug-induced Hypothyroidism
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1 Grave’s disease (diffuse toxic goiter)
A. Antithyroid drug therapy
Most useful in young , small glands, and mild disease
Methimazole or PTU : 1 – 15 years
B. Thyroidectomy
Treatment of choice: very large glands or multinodular
Potassium iodide (+) : 2 weeks prior surgery
C. Radio Active Iodine
( Heart dis. or severe thyrotoxicosis and elderly: Methimazole)
D. Adjuncts to Antithyroid Therapy
Acute phase : . β - blockers to control tachycardia
. Diltiazem
. Barbiturate
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2 Toxic Uninodular Goiter &
Toxic Multinodular Goiter
Single toxic tx. : surgical or radio iodine
Toxic multinodular : Methimazole or PTU and
subtotal thyroidectomy

3 Subacute Thyroiditis
Transient thyrotoxicosis :
“spontaneously resolving hyperthyroidism”
Tx. : supportive

4 Thyrotoxicosis Factitia
Tx. Supportive & discontinuing excessive medication
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Special Problems

. Thyroid storm / thyrotoxic crisis :

life-threatening

Hypermetabolism: excessive adrenergic activity

. Opthalmopathy
. Dermopathy
. Thyrotoxicosis during pregnancy
. Neonatal Grave’s disease
. Subclinical Hyperthyroidism
. Amiodarone-Induced Thyrotoxicosis
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TSH

A syndrome of thyroid enlargement without

excessive hormone production

iodide deficiency
tx. Iodide
Hashimoto’s thyroiditis
goitrogens
dyshormonogenesis
tx. Thyroxine

neoplasms

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a) benign

thyroxine tx

b) malignant

. near total thyroidectomy

. (post op. radioiodine tx)
. Levothyroxine
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