This is an interesting ppt illustrating the Pharmacology of Thyroid hormones and Anti-thyroid drugs for medical and paramedical students...

8. DR. V. SATHYANARAYANAN MBBS., M.D., ACME
PROFESSOR OF PHARMACOLOGY
SRM MCH & RC, KATTANKULATHUR
INDIA

10.  Thyroxine ( T4 )
 Triiodothyronine ( T3 )
 Calcitonin

11.  Iodide uptake
 Oxidation
 iodination
 Coupling
 Storage
 release
 Peripheral conversion of T4 to T3

14.  Highly bound to plasma proteins
 T4 – 90 - 95 % bound with TBG, TBPA,
albumin
 Only the free hormone available for action
 Deiodination, glucuronide / sulfate
conjugation occurs at liver
 Undergo enterohepatic circulation
 Finally excreted in urine

15.  By TSH from anterior pituitary
 Hypothalamus  TRH  anterior pituitary 
TSH  Thyroid  T3, T4 ------> inhibits TSH,
TRH
 Normal secretion of T4  70-90 mcg/day
 T3  15-30 mcg/ day

17.  Combines with specific nuclear thyroid
hormone receptors bound to “ thyroid
hormone response element”
 T3 binds with TR  heterodimerizes with RXR
( Retinoid X receptor )  undergo
conformational change  release the
corepressor  bind the coactivator
  induce gene transcription  production of
specific mRNA & specific pattern of protein
synthesis  various anatomic and metabolic
effects

21.  Growth and development – ( from tadpole to frog )
particularly nervous system
 Intermediary metabolism – enhance lipolysis,
lipogenesis
 promote glycogenolysis, gluconeogenesis 
hyperglycemia
 Synthesis of certain proteins but Overall
Negative nitrogen balance
 calorigenesis- increase BMR, increase O2
consumption

30.  CVS – increased sensitivity to catecholamines ,
increased beta receptors  increase heart rate,
BP, FOC  hyperdynamic circulation
 Nervous system – profound functional effect
 Skeletal muscle
 GIT – increased propulsive activity
 Haemopoiesis – facilitates erythropoiesis
 Reproduction – indirect effect, role in
maintenance of pregnancy and lactation

36. T3 T4
 Less circulating
 Less tightly bound to PP
 5 times more potent
 Faster acting
 Active hormone
 More avidly bound to
the nuclear receptor
 Major circulating
hormone
 More tightly bound to
PP
 Less potent
 Slowly acting
 Less active, transport
form , functions as
prohormone of T3
 Less avidly bound

39.  Replacement therapy in deficiency states
 Cretinism
 Adult hypothyroidism – oral levothyroxine 50-
200micrograms daily, for indefinitely, in empty
stomach
 Myxoedema coma
 Nontoxic goiter
 Thyroid nodule
 Papillary carcinoma of thyroid

48.  Longer acting
 Less risk of angina, arrhythmias, CHF
 Converted to T3
 Stable
 Less costly

49.  EMERGENCY
 Progressive mental deterioration
 Drug of choice ---L-thyroxine (T4) 200-500
micrograms or leothyronine 100 micrograms
i.v
 Followed by 100 mic.g i.v OD till oral therapy
 Corticosteroids
 Ventilatory , cardiovascular support
 Correction of hyponatremia
 Glucose

54.  Drugs used to lower the functional capacity of
the hyperactive thyroid gland

58.  INHIBIT HORMONE SYNTHESIS –
Propylthiouracil, methimazole, carbimazole
 INHIBIT IODIDE TRAPPING – thiocyanates,
Perchlorates, nitrates
 INHIBIT HORMONE RELEASE – iodine,
iodides of Na, K, organic iodide
 DESTROY THYROID TISSUE – Radioactive
iodine ( 131 I, 125 I, 123I )

61.  Bind to thyroid peroxidase and prevents
oxidation of iodide
 Thereby inhibit iodination of tyrosine residues
 Inhibit coupling of iodotyrosine residues to
form T3, T4
 Thereby inhibit T3, T4 synthesis
 Propylthiouracil, carbimazole, methimazole

63. PROPYLTHIOURACIL CARBIMAZOLE
 Less potent
 Faster acting
 Highly bound to PP
 Less pass across
placenta, milk
 Single dose acts for 4-8
hours
 No active metabolite
 2-3 daily doses required
 Inhibits peripheral
conversion of T4 to T3
 More potent
 Slower acting
 Less bound
 Large doses pass
 12-24 hours
 Produce active
metabolite
 Single daily dose
 Does not inhibit

66.  Hypothyroidism
 Goiter
 GI intolerance
 Skin rashes, urticaria, dermatitis
 Joint pain
 Agranulocytosis – rare but serious
 Loss of hair, graying, Loss of taste, fever, liver
damage
 Do routine WBC counts

74.  Grave’s disease – young patients as definitive
therapy for 12 months
 Toxic nodular goiter- in elderly weak patients
 Preoperatively in goiter with hyperthyroidism
 Hyperthyroidism in pregnancy and lactation
 Along with radioactive iodine
 Thyroid storm – propylthiouracil is used

79.  No surgical risk, scar,
 No chances of injury to parathyroids or
recurrent laryngeal nerve
 Hypothyroidism, if induced, is reversible
 Can be used in children and younger adults

86.  Relapse rate is high
 Prolonged treatment , even life long is needed
 Drug toxicity
 Not suitable for uncooperative patients

90.  Thiocyanates, perchlorates, nitrates
 Inhibit iodide trapping
 Toxic - bone marrow, liver, kidney,
brain
 Not used now

92.  Fastest acting thyroid inhibitor
 Inhibit release of thyroid hormones – thyroid
constipation
 Reduce T3, T4 synthesis  wolff- Chaikoff
effect )
 Shrinks thyroid gland, makes it less vascular
and firm  May produce thyroid escape later
 Available as Lugol’s iodine or as potassium
iodide solution  3 drops 3 times a day

95.  Preoperative preparation for
thyroidectomy- given for 10 days before
surgery
 Thyroid storm – Lugol’s iodine 6-10
drops
 As iodized salt to prevent endemic goiter
 Protection against radioactivity following
a nuclear accident
 Antiseptic – tincture iodine

103.  Acute reaction- in sensitive people-
hypersensitivity – swelling of lips, angioedema,
fever, joint pain, lymphadenopathy
 Chronic overdose – iodism – inflammation of
mucous membranes, increased secretions,
burning sensation in mouth
 Hypothyroidism, goiter
 Fetal goiter if given in pregnancy

110.  Thyroidectomy, I131 are contraindicated
 With drugs ---- risk of foetal
hypothyroidism, goiter
 Low doses of propylthiouracil is
preferred
 Methimazole also safer

112.  131 I , 123 I, 125 I
 Release beta particles which penetrate 0.5
– 2 mm of tissue
 Destroy thyroid tissue
 Taken orally as sodium salt of 131 I
dissolved in water in a single dose

114.  Used for diagnosis ( 25 – 100 micro curie
) and
 treatment of hyperthyroidism due to
grave’s disease or toxic nodular goiter (
3-6 milli curie )
 Palliative therapy for metastatic
carcinoma of thyroid after surgery

118.  Simple
 Convenient
 Given as outpatient basis
 Inexpensive
 No surgical risk, of scar, injury to parathyroid,
nerves
 Once hypothyroidism is controlled Cure is
permanent
 Treatment of choice after 25 yrs, in patients for
whom surgery is contraindicated

127.  Hypothyroidism – 40-60%
 Long latent period of response ( 3
months )
 Contraindicated during pregnancy
 Risk of thyroid carcinoma  Not
suitable for children

132.  PROPRANOLOL
 Blocks manifestations of thyrotoxicosis due to
sympathetic overactivity
 Inhibit peripheral conversion of T4 to T3
 Give only symptomatic relief
 Little effect on thyroid function & hypermetabolic
state
 Used in hyperthyroidism while awaiting response
 Alongwith iodide for preoperative preparation
 Particularly useful in Thyroid storm

145.  Emergency in hyperthyroidism
 Propranolol 1-2 mg I.V – gives dramatic
symptomatic relief, most valuable measure
 Propylthiouracil 200- 300 mg orally 6th hourly –
reduce T3,T4 synthesis & peripheral conversion
 Iopanoic acid 0.5- 1g OD oral – inhibit T3,T4
release and their peripheral conversion
 Oral/rectal potassium iodide or Lugol’s iodine
6-10 drops inhibit T4 release

146.  Hydrocortisone 100mg 8th hourly followed by
oral prednisolone – helps to tide over crisis,
adrenal insufficiency, inhibits peripheral T4
T3 conversion
 If tachycardia is not controlled add diltiazem
60-120 mg BD orally
 Anxiolytics
 antibiotics
 Rehydration
 external cooling

149.  Lithium
 Amiodarone
 Sulfonamides
 Phenytoin
 Carbamazepine
 Rifampicin

150.  Thyroid hormones are T3 and T4
 They are useful in treating hypothyroidism
 Antithyroid drugs decrease thyroid function
 They are useful in hyperthyroidism
 Propylthiouracil is preferred for emrgencies and
in pregnancy, carbimazole for others
 Radioactive iodine also can be used for
hyperthyroidism
 Betablockers are also useful especially in thyroid
storm