the above presentation contain the history of the thyroid disorder, including the definition of thyrotoxicosis, and its two main cause that are graves' disease and another toxic nodular goiter and the classification of drugs that are used in hyperthyroidism i.e. hormone sythesis inhibitor, hormone release inhibitors, destroy thyroid tissue, and inhibit ionic trapping with it's example including the adverse effect and side effect and marketted preparation of the same and the agents which cause hypothyroidism and the agents which are used to prescribe in the pregnancy
2. Thyroid gland – Wharton in 1656
Physiological significance was recognized by Graves
and Basedow.
Isolation and Crystallisation of Thyroxine(T4) –
Kendall in 1915.
Antithyroid drugs were developed as derivatives of
Thiourea which was disovered to cause goiter in rats.
3. Thiourea was the 1st drug used in man,followed by
Thiouracil – Introduced by Astwood in 1951.
T3 --- detected ,isolated,and synthesized by Gross and
PittRivers in 1952.
4. It is due to excessive secretion of thyroid hormones.
The two main cause are
1. Graves’ disease
2. Toxic nodular goiter
5. An autoimmune disorder;
Here, the IgG get bind to TSH receptor and mimic TSH
and secrete the hormones,
This lead to increase the thyroid level in the patients
Due to feed back effect the TSH level get low which
cause swelling of periorbital tissue.
6. It produce thyroid hormone dependent of TSH, mostly
occure to nontoxic goiter
Occular changes are generally absent.
10. Three general categories into which most of the agents
can be assigned:
Thioureylenes include all the compounds currently
used clinically
Aniline derivatives, of which the sulfonamides make
up the largest number, embrace a few substances that
have been found to inhibit thyroid hormone synthesis
Polyhydric phenols, such as resorcinol, which have
caused goiter in humans when applied to abraded skin.
11. Inhibit hormone synthesis by inhibiting peroxidase.
Propylthiouracil also inhibits peripheral de-iodination
of T4 and T3.
Methimazole is more potent and longer acting than
propylthiouracil.
Slow in onset ~ 4 weeks.
Thiocarbamide group – essential for anti thyroid
activity
12. Well absorbed orally, widely distributed
highly plasma protein bound
t1/2 = 1 – 10hrs
Partly metabolized in the liver and the thyroid gland ;
Carbimazole is converted to its active metabolite,
Methimazole.
Cross placental barrier and are secreted in breast milk
excreted in the urine unchanged
13. Common adverse effects includes maculopapular rash,
GI side effects, arthralgia.
Hypothyroidism
Rare – exfoliative dermatitis, vasculitis ,lupus-like
reaction…
Severe hepatitis – seen with propylthiouracil
Agranulocytosis ( reversible) – dangerous complication
14. USES:
1) Non-operative therapy of hyperthyroidism.
2) Preoperative therapy of hyperthyroidism: combined
with iodide.
3) Thyrotoxic crisis: combined with propanalol,larger
dose of iodide…
15.
16. Iodine – oldest and fastest acing agent. - paradoxical
effect on thyroid gland.
Iodides blocks the organification and release, through
inhibition of proteolysis.
It decrease the size and vascularity – used before
surgery.
Jod-Basedow phenomenon in susceptible individuals
It is an ideal agent for the treatment of severe
thyrotoxicosis and preoperatively.
17. 1) Preoperative therapy of hyperthyroidism: combined
with thiourea derivatives
2) Thyrotoxic crisis: combined with thiourea
derivatives(PTU)
3) Prophylaxis of endemic goiter.
18. 1) Acute effects:
hypersensitivity to iodine. Manifestations are
swelling of lips, eyelids, angioedema of larynx, fever,
joint pain, petechial hemorrhages.
19. 2) Chronic intoxication (iodism)
Others – salivary gland inflammation and acne.
Long term use of high doses – Hypothyroidsm and
goiter
Chronic use in pregnancy avoided – fetal/infantile
goiter
20.
21. I-131 is the only isotope used in treatment of
thyrotoxicosis while others are used in diagnosis.
Administered as sodium salts of I–131 orally.
t1/2 – 8 days
Therapeutic effect depends on emission of beta rays –
destroys the thyroid gland.
22. Most common indication – hyperthyroidism due to
Grave’s disease and Toxic Nodular Goiter.
Indicated in elderly patients, allergy to thioamides,
recurrent hyperthyroidism and in patients with systemic
diseases contraindicating surgery.
Average therapeutic dose- 3-6m curie
23. Simple,inexpensive
No surgical risk ,scar or injury to parathyroids and
nerves
Contol of hyperthyroidism is permanent
24. Focal soreness in the neck
Hypothyroidism
Damage to fetal thyroid
Thyroid carcinoma,Leukemia..
Radiation induced genetic damage
25.
26. Monovalent ions like perchlorate, pertechnetate,
thiocyanate ,nitrates inhibit the iodide trapping by the
thyroid gland.
Anion inhibitors are uncommon in use because of
serious toxicity.
These are effective in iodine induced hyperthyroidism
27.
28. Lithium is known to inhibit synthesis and release of
thyroid hormones.
Amiodarone – inhibits peripheral conversion of T4
toT3.
Antiepileptic drugs /Rifampicin – enhance hormone
metabolism.
Sulphonamides, PAS – inhibits iodination and coupling
reaction.
29.
30. Occurs in about 0.2 – 0.4% of all pregnancies
Due to Grave’s Disease (common), Toxic nodules,
Thyroiditis…
RISK –
Fetal and Neonatal Hyperthyroidism
The drug mainly used is Methimazole due to its lower
hepatotoxic potential.