Antithyroid Drugs

dr. Novita Carolia, M.Sc.

Pharmacology and Therapy
Faculty of Medicine Lampung University
 Thyroid Hormone
synthesis & secretion
Secretes
Triiodothyronin (T3)
Thyroxin (T4)
Calcitonin

Uptake of iodide ion

Stimulated by TSH
Inhibited by Potassium Perchlorate

Iodination

I I2
I2 + Thyroglobulin MIT and DIT
Inhibited by methimazole & PTU
 Release
Condensation

To act in the tissues T4

T3 + I
DIT and MIT Enter the Inhibited by
T3 and T4 general PTU and
Inhibited by circulation adrenergic
Methimazole Inhibited by antagonist
and PTU Iodide
Stimulated
by TSH
 Functions of Thyroid hormone

Facilitates normal growth and maturation

Maintains the level of metabolism

Hepatic glycogenolysis
glucose storage
Inhibit gluconeogenesis
Inhibit lypolysis
Plasma amino acid
 Thyroid dysfunction

Thyroid hormone resistance & TSH secretion

Hashimotos Thyroiditis
Hypothyroidism Myxoedema
Pituitary disease

Overproduction of endogenous H
Hyperthyroidism Exposure to excess exogenous H
 Drug for Hypothyroidism

Levothyroxine
Isomer T4 , some are converted to T3
Long half life
Steady state : 6 - 8 weeks
Toxicity hyperthyroidism: Arrhythmia, tachycardia, anginal pain, etc.
Precautions: Heart disease

Liothyronine (L- Triiodothyronine sodium)

Isomer T3
OOA > rapid; DOA > shorter
RODA: p.o, iv
Indication:
- severe hypothyroidism
- 5-deiodinase deficiency: cannot convert T4 to T3
CI & AR =Levothyroxine

Liotrix (T3 &T4)

Thyroid USP & Thyroglobulin

 Treatment of Hyperthyroidism

Thioureylenes / Carbimazole, methimazole,

Thionamides (>< propylthiouracil
synthesis)

Iodide, potassium perchlorate

Anion inhibitors (><
release)

Propranolol, atenolol, etc.

Beta- adrenoceptor
antagonist (>< action)

Surgical
Radioiodine (removal Destruction by radioactive iodine (131I)
thyroid gld.) which emitted beta particles
 Inhibiting hormone synthesis

Methimazole

Carbimazole (active metabolite of

Methimazole)

Propylthiouracil

Effectiveness is delayed until stored hormone

is depleted
Not effective for thyroid storm/crisis
Adverse effects: agranulocytosis, rash, edema
Practical consideration

Methimazole: starting dose 15-

30mg/day (single daily dose)
PTU: starting dose 300mg/days ( 3
devided doses)
Overly aggressive methimazole
dosing iatrogenic hypothyroidism
Follow up testing thyroid function: 4-6
weeks
 Practical consideration

Maintain dose: methimazole 5-10mg/days

PTU : 100-200 mg/days

Follow up after 1st 4-6 weeks: every 2-3

months 4-6 months
Cooper,D.S.,2010. antithyroid drugs. The N Engl.J.Med; 352:9 (905-14).
 Side effect

Methimazole: dose related

PTU: dose related

Minor SE: cutaneus reaction (skin rash,

urticaria), arthralgia, GI upset
Arthralgia the antithyroid arthritis synd.
Major SE: hepatotoxicity, agranulocytosis,
vasculitis,etc.
Major SE

Agranulocytosis( gran count

<500/mm3)
0,37% patients (PTU) & 0,35%
patients (methimazole)
First 90 days of treatment.
Older patients
Hepatotoxicity: 0,1-0,2% (PTU)
Vasculitis: caused by PTU
Cooper,D.S.,2010. antithyroid drugs. The N Engl.J.Med; 352:9 (905-14).
 Blockade Hormone release
Drugs: Iodide

Combined with PTU or Methimazole

Effective for thyroid storm

Administered prior to surgery

Decreases the vascularity of the gland

Not useful for long-term therapy

Adverse reactions:
Ulceration of mucous membranes
Metallic taste in the mouth
rashes
 Blocking the action

T3 : active form in the tissue

To act in the tissues T4 T3

inhibited by PTU and adrenergic antagonist

adrenergic antagonist also normalizes

heart beat
 blocker: propanolol

Efective in 24-36 hours after admision

HR/min

CO

hyperhydrosis

tremor

Medication before surgery, or

radiotherapy (I131)
Yodium

Thyroid crisis or before surgery

15 mg/days (devided dose) 2 weeks
before surgery
0,5 ml (10 drps) 3 times/day for 10
days before and after surgery.
surgery

Thyroid gland ablation therapy

Indication: young patients, failed
therapy of AT, AT drugs allergy,
Before surgery: drug combination
therapy (thionamid (6-8 weeks before
surg), yodium (10-14 days before
surg), and propanolol (10 days before
surg)) due to euthyroid condition.
Radiotherpy (I131)

Low cost
Thyroid gland hyperfunction cells
destruction
Dose: 140-160 micro Ci/gr or 80
micro Ci/gr
Discontinuation of drug
treatment
After 12-18 months of therapy
Relapse usually occurs within the 1st 3-6
months after medication is stoped.
75% of women in remission who became
pregnant will have a postpartum relapse
of graves disease.
Life long follow up after remission
Relapse therapy: radioiodine
(methimazole before it)
Pregnancy

CI : radioiodine,
propanololteratogenic effect
Surgery, antithyroid (low dose PTU)

Delayed surgery until 1st trimester

spontanious abortion
Thyroid storm

Fever,delirium,tachycardi,dehydration.
PTU: 300 mg/6 hours

Lugol: 100drps/6 hours

Propanolol 80 mg/6 hours

 THANKS
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