Thyroid &

Antithyroid Drugs
 Thyroid Gland-
Hormones
 Hormones of Thyroid Gland
– Thyroxine(T4)
– Triiodothyronine(T3)
– Calcitonin
 Thyroid Gland-Steps of
Thyroid Hormone Synthesis
 Iodide uptake or trapping
 Oxidation of iodide
 Iodination of tyrosine
 Coupling
 Proteolysis & Release
 Deiodination
 Thyroid Hormone-
Mechanism of Action
 Thyroid hormone diffuse easily into their target
cells
 Once inside, they bind and activate a specific
intracellular receptor
 The hormone-receptor complex travels to the
nucleus and binds a DNA-associated receptor
protein
 This interaction prompts DNA transcription to
produce mRNA
 The mRNA is translated into proteins, which bring
about a cellular effect
Thyroid Hormones-Relation
between T4 & T3
 Thyroid secretes T4>T3
 T4 is 15 times more tightly PPB
 T3 is 5 times more potent and acts faster
1-2 days vs 6-8 days
 T3 has more affinity for nuclear receptor
 1/3 T4 is converted to T3 in peripheral
tissues
 T3 is more cardiotoxic than T4
 Thyroid Hormones-
Therapeutic Uses of T4 &
 T3 µg/day
Cretinism - T4 12.5-50
 Adult Hypothyroidism – T4 50 µg/day for 2-
3 weeks then 100-200 µg/day
 Myxoedema coma – T3 50 µg IV followed by
25 µg 8 hourly till patient can take T4 orally
Hydrocortisone – 100-300 mg/day,
treatment of hypothermia, dehydration,
infection
 Nontoxic Goitre – Lugol’s iodine if iodine
deficiency,T4 50 µg/day followed by 100-
200µg/day or partial thyroidectomy if there
are symptoms of enlarged thyroid gland
 Antithyroid Drugs-
Classification
 Inhibits hormone synthesis–
Propylthiouracil/Carbimazole/Methimazole
 Inhibits iodide trapping–
Thiocyanates/ Perchlorates/Nitrates
 Inhibits hormone release– Iodine/Iodides/
Organic iodides
 Destroy thyroid tissue– Radioactive iodine
(I 131, I 125, I 123 etc.)
 Antithyroid Drugs-Sites of
Action
 Inhibits iodide uptake or trapping–
Thiocyanates/Perchlorates/Nitrates
 Inhibits oxidation of iodide , Iodination of
tyrosine, Coupling– (Thioamides)
Propylthiouracil/Carbimazole/Methimazole
 Inhibits proteolysis & release- Iodine/Iodides/
Organic Iodides
 Inhibits deiodination– Propylthiouracil/Beta
blockers/Corticosteroids
 Thioamides-
Pharmacokinetics
 Propylthiouracil – rapid oral absorption,
bioavailability is 50-80%, plasma T(1/2) is
1.5 h, excreted by kidney as inactive
glucuronide
 Methimazole – complete oral absorption,
slow renal excretion, plasma T(1/2) is
6h
 Propylthiouracil vs.

Carbimazol
Propylthiouracil Carbimazole

 less potent  3 times more potent
 Highly PPB  Less PPB
 Cross less- placental  Cross- large amount
barrier/milk
 Duration of action- 4-8  12-24 hrs, single daily
hrs, multiple dose/day dose
required  Produce active
 No active metabolites metabolites
 Inhibits peripharal methimazole
convertion of T4 to T3  Does not inhibit
 Thioamides – Therapeutic
Uses
 Graves’ disease-Methimazole–single morning
dose of 30-40mg/day then 5-15mg/d
Propylthiouracil-100-
150mgTDS/QDS for 4-8 weeks then 50-
100mg/d
 Preoperative preparation for thyroidectomy
 Thyroid storm
 Along with radioactive iodine for initial control
 Thioamides –Adverse
Effects
 Rash with fever
 G I intolerance
 Joint pain, vasculitis
 Loss or greying of hair
 Liver damage
 Hypoprothombinemia
 Agranulocytosis
 Iodine/Iodide-Salient
Features
 Is concentrated 25 times more in
thyroid gland
 Excess iodine –↓ release, ↑storage of
hormone, involution of gland, gland
become more firmer and less
vascular
 Surgery will be easier
 Iodine/Iodide-Therapeutic
Uses
 Thyroid crisis/storm
 Preparation for thyroidectomy
 Antiseptic/Expectorant
 Radio contrast media
 Prophylaxis of Endemic Goiter
 Iodine/Iodide–Adverse
Effects
 Allergic reaction
 Iodism
– Acneiform rash/swollen salivary glands/
mucous membrane ulcerations/
conjunctivitis/rhinorrhea/drug
fever/metallic taste/bleeding
disorders/anaphylactoid reactions
 Radioactive Iodine-Salient
Features
 Administered orally, concentrated in
thyroid gland
 Emits- β rays causes radiation &
destruction of thyroid tissue- γ rays used
for detection with Geiger counter
 Overdose - treated with NaI or KI,
increased fluid intake, diuretics
 Radioactive Iodine-Uses
 Hyperthyroidism for all ages
– Except females of child bearing age
group
– Beneficial effects felt in 1 month
– So in early part of therapy add beta
blocker and thioamides
 With thyroidectomy in thyroid cancer
 For thyroid function test
 Radioactive Iodine–
Uses(cont.)
 Advantages  Disadvantages
 Simple & pleasant  Slow action
therapy  Dose escalation
 No immediate difficult
mortality  Hypothyroidism-
need replacement
therapy & follow up
 ↑risk of leukaemia
 Role of Beta Blockers
 As many of the symptoms of
thyrotoxicosis mimic those associated
with sympathetic stimulation, beta
blocker is effective
 Βeta blockers without intrinsic
sympathomimetic activity are preferred
 Propranolol most widely used in therapy
of thyrotoxicosis
 Preparation for
Thyroidectomy
Hyperthyroid state
Carbimazole + β-blocker
30-60 mg/d 20-40mg/d
Euthyroid state (about 6 weeks)
Iodide for 7-10 days
0.1-0.3 mL TDS
(130mg I2/mL Lugol’s I2)
Surgery
 Thyroid Storm/Crisis
 Thioamide- CM (60-120 mg/d) or PTU (600-1200
mg/d) oral/rectal enema
 IV Propranolol (1-2 mg slow iv or 40-80 mg oral)
preceded by Atropine (1-2 mg iv)
 Iodide (Lugol’s Iodine-0.3ml TDS or KI- 60mg TDS)
 IV Hydrocortisone (100 mg QDS)/
Dexamethasone(2mg QDS)
 Chlorpromazine if mental disturbances
 Aspirin & cooling if hyperthermia
 Plasmapheresis or peritoneal dialysis
 Exophthalmos
 Orbital Decompression
 Prednisolone(60 mg OD )
 Guanethidine(5 % eye drop BD)
 Artificial Tears(1% methyl cellulose)
Hyperthyroidism-Choice
of Treatment
 Three possible lines of treatment, viz.
– Antithyroid drugs
– Radioiodine
– Surgery
Hyperthyroidism-Choice
of Treatment(contd.)
 Antithyroid drugs are generally preferred:
– If goitre is small and diffuse

– May be used in pregnancy

 Radioiodine–commonly used for patients of all
ages, both diffuse and nodular goitre except in
pregnancy
 Surgery–if obstruction of neck vein/trachea or
nodular goitre or thyroid malignancy
 For Further Reading!..
 Basic & Clinical Pharmacology by Bertram
G. Katzung (9th Edition)(Chapter 38)
 Clinical Pharmacology by D. R. Laurence, P.
N. Bennett & M. J. Brown (8th Edition)
(Chapter 37)
 Goodman & Gilman’s The Pharmacological
Basis of Therapeutics(10th Edition)(Chapter
57)
THANK YOU !