THYROID & ANTITHYROID AGENTS BY MR. BHAVESH AMRUTE( M.PHARM PHARMACEUTICAL CHEMISTRY)

1. THYROID & ANTITHYROID
AGENTS
BY
Mr.Bhavesh Bharat Amrute
(M.Pharm,Pharmaceutical Chemistry)

4.  participates in normalizing growth and development
and energy levels and the proper functioning and
maintenance of tissues / organs
 critical for the nervous, skeletal and reproductive
tissues
 it affects secretion and degradation rates of all
hormones

5.  Secretion of the following hormones:
◦ Triiodothyronine (T3) ; 59% iodine
◦ Tetraiodothyronine (T4; also known as
thyroxine); 65% iodine
◦ Calcitonin

6.  Iodide Metabolism
◦ The recommended daily adult iodide (I-) intake is 150 mcg
 Biosynthesis of Thyroid Hormones
 Transport of Thyroid Hormones
◦ thyroxine-binding globulin (TBG)
◦ about 0.04% of total T4 and 0.4% of T3 exist in the free
form.

9.  Iodide trapping
 Oxidation of iodide to iodine
 Iodide Organification
 Formation of T4 and T3
 Release of T4 and T3

10. PERIPHERAL METABOLISM OF THYROID
HORMONES
The primary pathway for the peripheral metabolism of thyroxine (T4) is
deiodination deiodination of T4 may occur by monodeiodination of the outer
ring, producing 3,5,3'-triiodothyronine (T3), which is three to four times more
potent than T4

12. A model of thyroid hormone action is depicted in Figure 38-4
Figure 38-4. Regulation of transcription by thyroid hormones
•T3 and T4 are
triiodothyronine
and thyroxine,
respectively.
•PB, plasma
binding protein;
•F, transcription
factor; R, receptor;
PP, proteins that
bind at the
proximal promoter.
BASIC PHARMACOLOGY OF THYROID &
ANTITHYROID DRUGS
THYROID HORMONES

13.  A syndrome resulting from a deficiency of thyroid hormones
and is manifested largely by a reversible slowing down of all
body functions.
 There is a striking retardation of growth and development.
 In children, manifested as dwarfism and severe MR.

14.  synthetic levothyroxine (synthetic T4)
 Brand names: Eltroxin , Euthyrox,Levoxyl, Levothroid, Synthroid
 for hormone replacement therapy in hypothyroidism
 DOSE
 Infants and Children require more T4/Kg body weight than adults
 Average dose for an infant -10-15 micrograms/kg/d
 Average dose for an adult – 1.7micrograms/kg/d
 Once daily
 Pharmacokinetics
 should be taken 30min before or 1 hour after meals (delayed absorption for
soy, other foods and drugs)
 takes 6-8 weeks to reach steady state levels
 Labs should be repeated after 2 months

15.  Reasons for its use:
◦ stability
◦ content uniformity
◦ low cost
◦ lack of allergenic foreign
protein
◦ easy laboratory
measurements of serum
levels
◦ long half-life (7days)
◦ once a day dosing

16.  Uses
 Hormone replacement therapy
In young patients or those with mild disease- full replacement therapy started
In older patients and in patients with cardiac disease -start treatment with
reduced dosage
 Myxedema Coma – medical emergency
Loading dose – of T4 – 300-400micrograms I/V initially f/by `50micrograms
daily
I/V T3 – more cardiotoxic and difficult to moniter
 Hypothyroidism and Pregnancy – daily dose –adequate

17.  synthetic liothyronine
(synthetic T3) is 3-4x
more potent
 (Cytomel,Triostat)
 not used alone for long
term treatment secondary
to short half life and large
peaks in serum T3 levels
 increase risk for cardiac
side effects secondary to
hyperthyroid states during
treatment

18.  A thyroid disorder caused by an antibody-mediated
auto-immune reaction, but the trigger for this reaction is
still unknown.

19.  Thioamides
 Iodides
 radioactive iodine
 Beta adrenoceptor blocking agents

21.  Methimazole
 Propylthiouracil (PTU) Carbimazole
 MOA:
◦ inhibit synthesis by acting against iodide
organification (both)
◦ coupling of iodotyrosines (both)
◦ Blocks peripheral conversion of T4 to T3
(PTU)

22.  Pharmacokinetics:
◦ almost completely absorbed in the GIT
◦ serum half life: 90mins(PTU) ; 6 hours (methimazole)
◦ excretion: kidney – 24 hours (PTU) ; 48 hours
(Methimazole)
◦ can cross placental barrier (lesser with PTU)
◦ Methimazole 10x more potent than PTU
◦ PTU more protein-bound

23.  Definitive therapy
◦ Graves disease
◦ Toxic nodular goitre
 Preoperatively
◦ In thyrotoxic patients
 Along with RAI

24.  Adverse Effects:
◦ maculopapular rash
◦ benign transient leukopenia
◦ agranulocytosis
◦ hepatitis (PTU) ; cholestatic jaundice (Methimazole)
◦ vasculitis
◦ lupus-like syndrome

25.  preparations: sodium iodide 131
 MOA: trapped within the gland and
enter intracellularly and delivers
strong beta radiations destroying
follicular cells
 Penetration range-400-2000µm
 Clinical uses: Grave’s, primary
inoperable thyroid CA
 Contraindication: pregnancy

26.  Advantages
◦ Easy administration
◦ Effectiveness
◦ Low expense
◦ Absence of pain

27.  Thioamides should be given initially and stop 5-7 days before
radioactive iodine administration
 131I dosage generally ranges between 80-120uCi/g of
estimated thyroid wt. corrected for uptake. May be repeated
after 6 months
 Adverse effects
◦ permanent hypothyroidism
◦ potential for genetic damage
◦ may precipitate thyroid crisis

28.  Monovalent anions such as perchlorates, pertechnetate and
thiocyanate can block uptake of iodide by the gland by
competitive inhibition
 can be overcome by large doses of iodides
 useful for iodide-induced hyperthyroidism (amiodarone-
induced hyperthyroidism)
 rarely used due to its association with aplastic anemia

29.  major anti-thyroids before the
introduction of thioamides
(1950s)
 preparations:
◦ strong iodine solution (Lugol’s)
◦ potassium iodide
◦ iodone

30.  MOA:
◦ acutely blocks release of thyroid hormone from the gland by
inhibiting thyroglobulin proteolysis
 inhibit iodide organification
 Uses:
◦ useful in thyroid storms: 2-7 days
◦ Preoperatively - iodides decrease vascularity, size and fragility of
hyperplastic gland
 Caution:
◦ it may delay onset of thioamide effects; should be given after
initiation of thioamides
◦ The gland will escape from inhibition after 2-8 weeks.

31.  Iodinated contrast media
Ipodate (oral)
Iopanoic acid (oral)
Diatrizoate (intravenous)
valuable in hyperthyroidism (but is not labeled for this
indication)
 MOA: inhibits conversion of T4 to T3 in the liver, kidney,
brain and pituitary
Another MOA is due to inhibition of hormone release
secondary to iodide levels in blood
 Useful in thyroid storms (adjunctive therapy)

32.  Drugs: Propranolol, Metoprolol, Atenolol
 MOA:
◦ Membrane-stabilizing action: inhibits T4 to T3
◦ Ameliorate many disturbing s/sxs of hyperthyroidism
secondary to increased circulating catecholamines by blocking
beta receptors
 Indications: Grave’s, Thyroid storm

33.  Prednisone is given for patients with Grave’s
ophthalmopathy
 1mg/kg/day (60mg/day 3 divided doses); if it should be
given for more than 4 weeks, taper to decrease risk of
adrenal crisis

34.  Sudden exacerbation of throtoxic symptoms
 Life threatening condition
 Vigorous management
◦ Propanalol 1-2mg i/v or 40-80mg PO Q6h
◦ Diltiazem 90-120mg Po Q8-6 hrs or 5-10mgs intravenous
infusion/hour

35.  Supportive therapy
 Plasmapheresis/peritoneal dialysis

36.  Ideal situation- treat before pregnancy
 Pregnancy-Radioactive iodine CI
 Propylthiouracil
◦ Dose limitation≤ 300mgs/day
 Methimazole alternative- fetal scalp defects

37. THANK YOU…..!