Pharmacology what are hypothyroidism and hyperthyroidism and anti thyroid drugs

1. Anti Thyroid Drugs
BY
Muhammad Asad
Faisal shahzad
Alya anum
DOCTOR OF PHARMACY
4th smester

2. Introduction
 The neuroendocrine system, which is controlled by the
pituitary and hypothalamus, coordinates body functions by
transmitting messages between individual cells and tissues.
 This contrasts with the nervous system which
communicates locally by electrical impulses and
neurotransmitters directed through neurons to other
neurons or to specific target organs, such as muscle or
glands
 The endocrine system releases hormones into the
bloodstream, which carries these chemical messengers to
target cells throughout the body
 The thyroid gland is the source of two fundamentally
different types of hormones, iodothyronines and calcitonin.

3. Biosynthesis of Thyroid Hormones
 The major steps in the synthesis are
UPTAKE OF PLASMA IODIDE BY THE FOLLICLE CELLS
 Iodide is captured from the blood and moved to the lumen by two
transporters: the Na+/I− symporter (NIS) located at the basolateral
surface of the thyrocytes and pendrin1 (PDS), an I−/Cl−
OXIDATION OF IODIDE AND IODINATION OF TYROSINE
RESIDUES
 The oxidation of iodide and its incorporation into thyroglobulin
(termed the organification of iodide) is catalysed by
thyroperoxidase Iodination occurs after the tyrosine has been
incorporated into thyroglobulin
 The reaction forms mono- and diiodotyrosyl residues in
thyroglobulin just prior to its extracellular storage in the lumen of
the thyroid follicle

4. Biosynthesis of Thyroid Hormones
Formation of Thyroxine and Triiodothyronine from
Iodotyrosines
 of two diiodotyrosyl residues to form T4 or of one
monoiodotyrosyl and one diiodotyrosyl residues to form
T3. The same peroxidase catalyzes these oxidative
reactions
SECRETION OF THYROID HORMONE
 The thyroglobulin molecule is taken up into the follicle
cell by endocytosis (Fig. 33.1). The endocytotic vesicles
then fuse with lysosomes, and proteolytic enzymes act on
thyroglobulin, releasing T4 and T3 to be secreted into the
plasma

5. Synthesis and secretion of
thyroid hormone

6. REGULATION OF THYROID
FUNCTION
 Hypothalamic cells secrete thyrotropin releasing hormone
(TRH) into the capillaries of the pituitary portal system.
TRH stimulates the synthesis & release of thyroid
stimulating hormone (TSH). TSH stimulates an adenylyl
cyclase-mediated mechanism in the thyroid gland to
increase the synthesis& release of T4 & T3
 T4 & T3 act in a negative feedback fashion (mechanism)
to block the action of TRH on the pituitary gland & on the
hypothalamus to inhibit the synthesis & release of
TRH(detail from rang and dale pg 412)

7. REGULATION OF THYROID
FUNCTION

8. Mechanism of Action
 Both T4 and T3 must dissociate from thyroxine-binding
plasma proteins prior to entry into cells, either by
diffusion or by active transport. Within the cell, T 4 is
converted to T 3 by 5’-deiodinase, and the T 3 enters
the nucleus where T 3 binds to a specific T 3 receptor
protein,
 Large numbers of thyroid hormone receptors are found
in the most hormone-responsive tissues (pituitary, liver,
kidney, heart, skeletal muscle, lung, and intestine),
 while few receptor sites occur in hormone-unresponsive
tissues (spleen, testes).

9. Pharmacological actions of thyroid
hormones
EFFECTS ON METABOLISM
 The thyroid hormones produce a general increase in the
metabolism of carbohydrates, fats and proteins
 There is an increase in oxygen consumption and heat
production, which is manifested as an increase in the
measured basal metabolic rate
EFFECTS ON GROWTH AND DEVELOPMENT
The thyroid hormones have a critical effect on growth,
partly by a direct action on cells, and also indirectly by
influencing growth hormone production and

10. Pharmacological actions of
thyroid hormones
Cardiovascular Effects
 In hyperthyroidism, there is tachycardia,
increased stroke volume, increased cardiac
index, cardiac hypertrophy, decreased
peripheral vascular resistance, and increased
pulse pressure. In hypothyroidism, there is
bradycardia, decreased cardiac index,
pericardial effusion, increased peripheral
vascular resistance, decreased pulse pressure,
and elevation of mean arterial pressure.

11. THERAPEUTIC USES OF
THYROID HORMONE
 The major indications for the therapeutic
 use of thyroid hormone are for hormone
replacement therapy in patients with
hypothyroidism
 or cretinism and for TSH suppression
therapy in patients with thyroid cancer
and
 occasionally those with nontoxic goiter.

12. ABNORMALITIES OF THYROID
FUNCTION
 HYPERTHYROIDISM (THYROTOXICOSIS
 In thyrotoxicosis, there is excessive activity of the
thyroid hormones, resulting in a high metabolic rate,
an increase in skin temperature and sweating, and a
marked sensitivity to heat
 Types
a. Diffuse toxic goitr(Grave desease)
b. is indicated by the name, patients with exophthalmic goitre
have protrusion of the eyeballse
 it is an autoimmune disorder caused by IgG antibodies that
bind to and activate the TSH receptor. Because of the persistent
activation of the TSH receptor,there is increasedsecretion of
thyroid bormone

13. Diffuse toxic goitr(Grave
desease

15. HYPOTHYROIDISM
 A decreased activity of the thyroid results
in hypothyroidism, failure of the thyroid
gland to produce sufficient thyroid
hormone
 example
 myxoedema.

17. The Antithyroid Drugs:
 Reduction of thyroid activity and hormone
effects can be accomplished by agents that
interfere with the production of thyroid
hormones,
 A large number of compounds interfere
either directly or indirectly with the
synthesis, release, or action of thyroid
hormones

18. Classification of Antithyroid Drugs
Inhibitor of hormone
synthesis
 Carbimazole
 Methimazole
 Propylthiouracil
Inhibitor of hormone
release
 Iodine
 Iodides of Na, k
 Organic iodides
Radioactive iodine
 131I (Radioactive
iodine)
Ionic inhibitors
 Thiocynate(-SCN)
 Perchlorates(-ClO4)
 Nitrates(NO3)

19. 1. Inhibitor of hormone synthesis
 Methimazole (carbimazole)
 Propyl thiouracil (PTU)
 These 2 are the major drugs used in the treatment of
thyrotoxicosis (Carbimazoles converted to methimazole in
vivo).
MOA: These drug inhibit thyroid hormone production by
a) inhibiting thyroid peroxidase which is required in
intrathyroidal oxidation of Iodide.
b) by inhibiting the iodination of tyrosine
c) by inhibiting coupling of MIT and DIT to form thyroid
hormones
d) propylthiouracil also inhibits peripheral conversion of T4
TO T3 by inhibiting DID -1 enzyme

20. a. Carbimazole
- More potent given in a single daily dose
-Completely absorbed & readily accumulated
in thyroid gland
-Excreted in urine but slower than PTU.
-Has some immunosuppressive action leading
to decrease in serum TSH receptor
antibodies.
-Has little effect on conversion of T4 to T3
-Crosses placenta.
-It is excreted in breast milk.

21. Adverse effect
 The most common adverse effect is a
maculopapular
 pruritic rash (4–6%), at times
accompanied by systemic signs such as
fever. Rare adverse effects include an
urticarial rash vasculitis, a lupus-like
reaction, lymphadenopathy, acute
arthralgia

22. b. Propyl thiouracil ( PTU)
 Dose is 10 times that of Carbimazole given every
6-8 hrs.
 Rapidly absorbed with a bioavailability of 50-80
%
 Excreted in urine within 24 hrs
 Has no immunosuppressive effect
 It inhibits the peripheral conversion of T4 to T3
 Crosses placenta less readily, Preferable in
pregnancy
 Not excreted in breast milk

23. THERAPEUTIC USES
The antithyroid drugs are used as definitive
treatment of hyperthyroidism, to control the
disorder in anticipation of a spontaneous
remission in Graves’ diseas

24. 2. Inhibitor of hormone release
 Iodine
 Iodides of Na, k
 Organic iodides
Mechanism of action
 Iodide salts inhibit organification (iodination of
tyrosine) and thyroid hormone release.
 These salts also decrease the size & vascularity of the
hyperplastic thyroid gland
 inhibition of thyroglobulin proteolysis
 The usual forms of this drug are lugol's
solution(iodine & potassium iodide) and saturated
solution of potassium iodide

25. therapeuticUse of Iodide
 Iodide salts are used in thyroid storm(severe
thyrotoxicosis) & to prepare the patient for
surgical resections of the hyperactive thyroid
 Adverse effect
 They include
 acneiform rash (similar to that of bromism),
swollen salivary glands, mucous membrane
ulcerations, conjunctivitis, rhinorrhea, drug
fever, metallic taste, bleeding disorders, and
rarely, anaphylactoid reactions

26. 3. Radioactive iodines
 Radioactive iodine is administered as sodium salt
of 131I dissolved in water and taken orally. 131I
emits x ray as well as β particles
 USES
 Most common indication is hyperthyroidism due to
Graves’ disease or Toxic nodular goitre.
 Response is slow , it starts after 2 weeks and
gradually increases reaching peak at 3 month.

27. 4. ANION INHIBITORS
 Includes monovalent anioins such as
 perchlorate (ClO 4 – ),
 pertechnetate
 (TcO 4 – ), thiocyanate (SCN – )
 MOA
 block uptake of iodide by the gland
through competitive inhibition of the
iodide transport mechanism