Thyroid Hormones and anti thyroid drugs.ppt

thyroid hormones and antithyroid drugs

1. Anti – Thyroid
drugs

2. Thyroid hormones
T4 - Thyroxine
T3 - Triiodothyronine
Calcitonin
Thyroid gland secretes …

3. Actions

Growth & Development
Metabolism
Calorigenesis
CVS
Nervous system
Skeletal muscle
GIT
Kidney
Haemopoiesis
reproduction

4. Hypothalamus
Anterior pituitary
Thyroid gland
TRH
TSH
T3 & T4

5. Biosynthesis and release of thyroid
hormones
1.Uptake of iodide
2.Oxidation and iodination
3.Coupling
4.Colloid resorption
5.Proteolysis
6.Deiodination

6. Cell
ECF
Lumen I
-
I
-
I
-
I
+
HOI
EOI
DIT
MIT
DIT
MIT
T
4
T
3
DIT
MIT
T
4
T
3
T
3
TPO
H
2
0
2
TPO
H
2
0
2
Tg

7. Peripheral conversion of T
4 to T
3
T
4
T
3
rT
3
D2
D3 D1
Liver
Kidney
thyroid
Placenta
Skin
Brain
Uterus
Brain
Heart
Skeletal muscle
D1,D2,D3 – deiodinase isozymes

8. Mechanism of action
T
3
T
3, T
4
Thyroid hormone response element
Gene transcription
Protein synthesis
T
4

9. Hyperthyroidism

10. Thyroid HyperfunctionThyroid Hyperfunction
Diffuse Toxic Goitre
(Grave’s disease (or) Basedow’s disease)
•Young adults
•Thyrotoxicosis
•Opthalmopathy
Toxic Nodular Goitre
(Plummer’s disease)
• Older patients

11. Thyroid inhibitors
Anti thyroid drugsIonic inhibitorsIodides Radioactive
iodine
Propylthiouracil
Methimazole
carbimazole
Thiocyanates
Perchlorates
Nitrates
Iodides of
Na
2+
/ K
+
Iodine
131
I
125
I
123
I
These drugs are used to lower the functional
capacity of hyperactive thyroid gland

12. Antithyroid drugs
Belong to the family – Thioamides
Propylthiouracil – prototype
Mechanism of action
Inhibits iodination of tyrosine in thyroglobulin
Inhibits peroxidase & H2O2
Inhibits coupling of iodotyrosine to form T
3
& T
4
Propylthiouracil-inhibits peripheral conversion of T
4 to T
3
(Carbimazole & Methimazole do not have this action )

13. Pharmacokinetics
Antithyroid drugs
Well absorbed orally, widely distributed, concentrated
in thyroid, cross placenta, enter milk, metabolized in
liver, excreted in urine
Carbimazole : 5-15 mg t.d.s. (5mg tab)
Propylthiouracil : 50 – 100 mg t.d.s (50 mg tab.)
Methimazole : 5 – 10 mg once daily (5, 10 mg tab.)

14. USES
Thyrotoxicosis
Grave’s disease & Toxic nodular Goitre
 Preoperatively
 Along with I
131
Adverse effects
Urticarial papular rash
Agranulocytosis
Antineutrophilic Cytoplasmic Antibodies (ANCAs)

15. Ionic inhibitors
Monovalent anions – inhibit iodide trapping
Eg Perchlorate - CLO
4
-
Thiocyanate - SCN
-
Nitrate - NO
3
Toxic, Not used now

16. Iodine & Iodides
Fastest acting thyroid inhibitor
Gland becomes less vascular, firm and shrinks
Peak effect : 10 – 15 days
Thyroid constipation – Inhibits hormone release
Thyroid escape – thyrotoxicosis returns with
vengence
Wolf – Chaikoff effect – excess iodide inhibits
hormone synthesis by reducing its own transport in
thyroid cells

17. Lugol’s solution
KI (10%) + I
2 (5 %): 5-10 drops/ day (1 drop–6.3 mg)
USES
Preoperative: 10 days prior surgery, make the
gland firm, less vascular and easier to operate
Thyroid storm – sodium and potassium iodide i.v /
orally
Prophylaxis of endemic goitre – iodized salt / oil
Antiseptics – Povidone I
2
, Tincture I
2
Expectorant

18. Adverse effects
Acute reaction: angioedema, swelling of lips,
eyelids, fever, joint pain, thrombocytopenia
Chronic reaction (Iodism): salivation,
lacrymation, sneezing, rhinorrhea
Hypothyroidism and Goitre (Long term use)
Given to pregnant or lactating mother - Fetal /
infantile goitre
Flaring of acne in adolescents

19. Radio active iodine
131
I – most commonly used, t
½
- 8 days
123
I – rarely used for diagnostic purpose, t
½
- 13

hrs
131
I (concentrated in thyroid)
Gamma rays β particles
Monitored by counterPenetrate 0.5-2 mm thyroid tissue
Affects thyroid follicles from within

20. Radio active iodine
131
I - used as sodium salt dissolved in water
- taken orally
Diagnostic : 25 – 100 μ curie
Therapeutic : 3 – 6 m curie
Hyperthyroidism due to Grave’s disease &
Toxic multinodular goitre
Response – after 2 wks ; Peak action – 3 mon
(If needed dose is repeated)

21. Radio active iodine
Advantages
Simple, inexpensive, given on OPD basis
Cure is permanent
No scar, surgical risk, damage to parathyroid
Used in older patients, H/o angina, CHF
Disadvantages
Hypothyroidism, worsens opthalmopathy
Latent period of response
Contraindicated in Pregnancy, young patients

22. Apical membrane
Basement membrane
Cell
ECF
Lumen
I
-
I
-
I
-
I
+
DIT
MIT
DIT
MIT
T
4
T
3
T
3
TPO +
H
20
2 Tg
Tg
TPO +
H
2
0
2
DIT , MIT
T4, T3
Tg
SCN-,
CLO4-
Iodide,
Lithium
Thionamides,
Iodides
ThionamidesThionamides

23. Precipitating factors
Acute illness (e.g. stroke, infection, trauma)
Withdrawal of antithyroid drugs
Thyroid surgery
Radioiodine, Iodinated contrast agents
Thyroid storm
Uncommon life-threatening exacerbation of
thyrotoxicosis

24. Clinical features
Severe thyrotoxicosis
Fever, Delirium, Seizure, coma
Treatment
Propylthiouracil 600mg loading dose
Lugol's iodine at least one hour later
Beta-blocker (In asthmatics – Diltiazem preferred)
Supportive measures
Treatment of precipitating cause

25. Adjuvant drugs
β blockers reduce sympathetic effects of
thyrotoxicosis
Propranolol: 20 – 40 mg 4 times/day
If patient is asthmatic
Diltiazem: 60 – 120 mg 4 times/day
Dexamethasone: 0.5 – 1 mg 2 times/day
Cholestyramine: to bind thyroid hormones in gut