This discussion was conducted over 2 classes. The slides are intended for BDS students. Please refer to books for further information.

1. Drugs Used InThyroid
Disorders
Dr. Pravin Prasad
MBBS, MD Clinical Pharmacology
Assistant Professor, Department of Clinical Pharmacology
Maharajganj Medical Campus, Kathmandu
8 June 2020 (26 Jestha 2077), Monday

2. Hypothyroidism and Dental presentations
 Salivary gland enlargement
 Compromised periodontal health-
delayed bone resorption
 Macroglossia, Glossitis
 Dysgeusia
 Delayed dental eruption, Enamel
hypoplasia
 Anterior open bite
 Micrognathia
 Thick lips
 Mouth breathing

3. By the end of this discussion, BDS 2nd year
students will be able to:
 Understand the physiology of thyroid hormone
 Explain the actions of thyroid hormone
Elaborate the mechanism of action of endogenous as well as
exogenous thyroid hormone preparations
 List the uses ofThyroid hormone supplements

4. Thyroid hormones: Introduction
Hormone Source Remarks
Triiodothyroxine,
T3
Thyroid follicles
Referred as thyroid
hormones
Tetraiodothyroxine,
T4

5. Thyroid Hormones: Introduction
Ref:
http://biology.clc.uc.edu/fankhauser/Labs/Anatomy_&_Physiology/A&P202/Endocrine_System/histology_jpgs/thyroid_400x_P
2252255lbd.JPG

6. Thyroid Hormone: Synthesis
Membrane BoundMembrane Bound
TSH

7. Thyroid Hormone: Synthesis
 Iodide Uptake
o Sodium-iodide symporter
o Stimulated byThyroid stimulating hormone
 Oxidation and Iodination
o Transported to apical membrane of thyroid cells by Pendrin
o Oxidized byThyroid Peroxidase enzyme (Stimulated byTSH)
o Binds to tyrosil residue bound toThyroglobulin chain (DIT, MIT
formed)

8. Thyroid Hormone: Synthesis
 Coupling
o Requires thyroid peroxidase, stimulated byTSH
o MIT+ DIT =T3
o DIT + DIT =T4 (more common)
 Storage and release
o Stored as thyroid colloid
o Released by endocytosis (TSH stimulated)
o T3 andT4 reaches circulation
Peripheral conversion ofT4 toT3

9. Thyroid Hormone:Transport
 Avidly bound to plasma proteins; 0.03%-0.08%T4 & 0.2-0.5%T3
in free form
Bound to 3 plasma proteins:
o Thyroxine Binding Globulin (TBG)
o Thyroxine Binding prealbumin (trans-thyretin)
o Albumin

10. Thyroid Hormone: Metabolism and Excretion
 Metabolic inactivation occurs by deiodination and
glucuronide/sulphate conjugation
o Primary site: Liver, others: salivary glands, kidney
o Plasma half lives:
 T4: 6-7 days
 T3: 1-2 days
 Excreted in bile  undergoes deconjugation  significant
enterohepatic circulation  finally excreted in urine.

11. Thyroid Hormones: Regulation of Secretion
Somatostatin (-)

12. Thyroid Hormones: Actions
 Intermediary Metabolism
o Lipid: indirectly enhances lipolysis; elevated plasma free fatty
acid; Lipogenesis also stimulated
o Carbohydrate: metabolism stimulated; tissue utilization of
sugar increased; glycogenolysis and gluconeogenesis
increased, faster absorption of glucose from intestine
o Protein: overall catabolic, prolong action: negative nitrogen
balance and tissue wasting.
 Calorigenesis
o Increase BMR

13. Thyroid Hormones: Actions
 Cardiovascular System
o Hyperdynamic state of circulation due: increased peripheral
demand, direct cardiac actions.
o Fast bounding pulse
 Nervous System
o Profound functional effects
 Gastrointestinal
o Increases propulsive activity

14. Thyroid Hormones: Actions
 Reproduction
o Indirect effect on Reproduction
o Maintenance of pregnancy and lactation
 Hematopoiesis
o Facilitates erythropoiesis
 Growth and Development
o Maturation of nervous system

15. Thyroid Hormones
 Mechanism of Action:
o Immediate action:
 Sensitization of adrenergic receptors to catecholamines 
tachycardia, arrhythmia, raised BP, tremor, hypoglycaemia
o Long term action:
 Penetrates cells by active transport
 Binds to nuclear thyroid hormone receptor bound to the thyroid
hormone response element (TRE)
 Conformation changes occur (heterodimerization of receptor with
retinoid X receptor (RXR))
 Releases co-repressor and binding of coactivator occurs
 Gene transcription induced  production of specific mRNA and
protein synthesis  metabolic and anatomic effects.

16. Thyroid Hormone: Mechanism of Action

17. Thyroid Formulations
 Available as:
o l-thyroxine (levothyroxine): oral, injectable
 More sustained and uniform action
o Triiodothyroxine: injectable form
 Higher risk of cardiac arrhythmia

18. Levothyroxine: Pharmacokinetics
 Oral bioavailability: ~ 75%
 Should be administered in empty stomach
CYP3A4 inducers: increase the metabolism of levothyroxine

19. Thyroid Hormones: Uses
 Cretinism
 Adult Hypothyroidism
Myxoedema coma
 Nontoxic Goitre
Thyroid Nodule
 Papillary carcinoma of thyroid
 Empirical use

20.  Chandna S, Bathla M. Oral manifestations of thyroid disorders
and its management. Indian J Endocrinol Metab. 2011
Jul;15(Suppl 2):S113-6. doi: 10.4103/2230-8210.83343. PMID:
21966646; PMCID: PMC3169868.
 López-Santacruz DDSH. D., Herrera-Badillo DDSD. A.,
Márquez-Preciado DDSR.,Torre-Delgadillo DDSG., & Rosales-
Berber DDSM. Ángel. (2019). Improvement in Oral Health and
Compliance in a Child with Congenital Hypothyroidism. Case
Report. Odovtos - International Journal of Dental Sciences, 21(3),
45-51. https://doi.org/10.15517/ijds.2019.37850

21. THANK YOU

22. ANTI-THYROID
DRUGS
Dr. Pravin Prasad
MBBS, MD Clinical Pharmacology
Assistant Professor, Department of Clinical Pharmacology
Maharajganj Medical Campus, Kathmandu
15 June 2020 (1 Asar 2077), Monday

23. Hyperthyroidism and Dental presentations
 Increased susceptibilities to
caries, periodontal disease
 Enlargement of extra
glandular thyroid tissue
 Burning mouth syndrome
 Accelerated dental eruption
 Maxillary and Mandibular
osteoporosis
 Development of connective
tissue diseases like Sjogren’s
syndrome, SLE

24. Classification
 Inhibits Hormone synthesis (Thioamides)
o Propylthiouracil, Methimazole, Carbimazole
Inhibits iodine trapping (ionic inhibitors)
o Thicynates, Perchlorates, Nitrates
 Inhibits hormone release
o Iodine, Iodides of Na and K, Organic Iodide
 DestroyThyroidTissue
o Radioactive iodine (131I, 125I, 123I)

25. Antithyroid Drugs
 Mechanism of Action:
o Binds to the Thyroid Peroxidase and prevent oxidation of
iodide/iodotyrosil residues thereby:
 Inhibit iodination of tyrosine residues in thyroglobulin
 Inhibit coupling of iodotyrosine residues to forT3 andT4
o Thyroid colloid is depleted over time and blood levels of thyroid
hormones are progressively lowered.
o Propylthiouracil also inhibits peripheral conversion of T4 to T3 by
Deiodinase (D1)

26. Comparing thioamides

27. Thioamides: Pharmacokinetics
 Well absorbed orally
Widely distributed (enters milk and placenta)
 Higher concentration in thyroid, longer intrathyroid half life
 Metabolised in liver
Excreted in urine

28. Thioamides:Adverse Effects
 Due to Overtreatment:
o Hypothyroidism, goiter
Important side effects:
o Gastrointestinal intolerance, skin rashes, joint pain
 Infrequent side effects:
o Loss or graying of hair, loss of taste, fever, liver damage
 Rare but serious:
o Agranulocytosis

29. Thioamides: Uses
 ControlThyrotoxicosis in:
o Grave’s Disease
o Toxic Nodular Goiter
o Can be used as:
 Definitive therapy for Grave’s Disease
 Preoperatively in thyrotoxic patients
 Along with 131I
 Propylthiouracil: early pregnancy, thyroid storm

30. Ionic Inhibitors
 Mechanism of Action
o Inhibits iodide trapping by NIS into the thyroid T3 andT4 not
synthesised
 Toxic and not clinically used these days

31. Iodine and Iodides
 Fastest acting thyroid inhibitor
 Peak effects seen after 10-15 days
 Mechanism of Action (not clear):
o Inhibition of hormone release- ‘thyroid constipation’
 Endocytosis of colloid and proteolysis of thyroglobulin
stopped
 Excess of iodine inhibits its own transport by interfering with
expression of NIS
 AttenuatesTSH induced thyroid stimulation
 Rapid and brief interference with iodination of tyrosil and
thyronil residues ofThyroglobulin

32. Iodine and Iodides: Uses
 Preoperative preparation
 Thyroid storm
Prophylaxis of endemic goiter
 As antiseptic

33. Iodine and Iodide: Adverse Effects
 Acute Reaction
 Chronic overdose (iodism)
Long term use of high doses:
o Hypothyroidism and goitre
 Flaring of acne in adolescents
 Pregnancy/Lactating mothers:
o Foetal/infantile goitre and hypothyroidism
Aggravation of thyrotoxicosis in multinodular goitre

34. Radioactive Iodine
 131I emits X-rays and β-particles
o X-rays: tracer studies
o β-particles: destructive effect on thyroid tissues
 Mechanism of Action:
o Concentrated by thyroid, incorporated into colloid  emits radiation
from within the follicle  undergo pyknosis and necrosis followed by
fibrosis
o Partial ablation can be achieved

35. Radioactive Iodine
 Administered as sodium salt of 131I dissolved in water and taken
orally.
Use:
o Diagnostic: 25-100 mcCurie is given: no damage to thyroid cells
occur at this dose
o Therapeutic:
 Hyperthyroidism due to Grave’s disease orToxic nodular
goitre
 Average Dose: 3-6 mCurie; higher dose for toxic
multinodular goitre

36. Beta blockers in Hyperthyroidism
 Non selective beta blockers (Propanolol)
 Control the symptoms of hyperthyroidism (thyrotoxicosis)
o Symptoms due to sympathetic overactivity
 Indications:
o While awaiting response to thioamides or 131I.
o Along with iodide for preoperative preparation
o Thyroid storm (thyrotoxic crisis)

37. THANK YOU