This lecture includes classification of antithyroid drugs, mechanism of action, adverse effect, therapeutic uses and advantage and disadvantages of them

1. Hello there!
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2. It is……Hyperthyrodim
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3. Dr. Kiran G. Piparva
Assistant Professor, Pharmacology
All India Institute of Medical Science, Rajkot
Date: 25/11/2022

4. • Hyperthyroidism:
● Common causes
● Graves' disease
● Toxic nodule
● Toxic multinodular goiter
● Medications:
especially amiodarone (can occur any time during therapy) and lithium
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5. Evaluation
● Screen with: TSH: highest sensitivity & specificity
● Confirm with: Free T4, when indicated free T3 (early presentation)
● Evaluate further for antibodies
Thyroid auto antibodies:
1. Grave’s disease: Anti-TSHR Ab
2. Autoimmiune thyroiditis,
Anti-Tg Ab: Anthyrogloin antibodies
Anti-TPO Ab Antithyroid peroxidase antibodies
● Radioactive iodine uptake.

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• SubclinicalHyperthyroidism
• Low TSH (< 0.4 mIU/L)
• Normal T4 & T3
● Thyrotoxicosis/Hyperthyroidism:
○ Low TSH (< 0.1 mIU/L)
○ Elevated T4, elevated T3 or both
Low TSH
Normal T3 & T4
Low TSH
High T3 & T4

7. Toxic adenoma

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Classification of antithyroid drugs…

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Mechanism of antithyroid drugs…

10. Antithyroid drugs: Thioamides:
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Propylthiouracil, Methimazole, Carbimazole
Mechanism of action: Inhibit synthesis of thyroid hormones-
• Bind to thyroid peroxidase (TPD) enzyme & inhibit it
• Inhibit Iodination of tyrosine residue in thyroglobulin
• Inhibit formation of MIT & DIT
• Inhibit coupling of MIT and DIT to from T3 and T4
• Blood levels of T3 and T4 are reduced progressively - Action
manifest after a lag period of few days.
• Thyroid colloid depleted over time
• No effect on iodine trapping & hormone release

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Antithyroid drugs- Thioamide- Propylthiouracil/ carbimazole
Goitrogen – if given in excess, they
cause enlargement of thyroid by
feedback release of TSH
Propylthiouracil

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Antithyroid drugs: Pharmacokinetics
Propylthiouracil

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• Low incidence
• S/E: over treatment: Hypothyroidism & goiter :Reversible on
stoppage of drug–
• ADR: GI intolerance, pruritus, urticaria, drug fever, arthralgia,
lymphadenopathy, skin rashes, loss or graying of hair, disguesia
• Rare: Leucopenia, thrombocytopenia, agranulocytosis (0.1.to 0.2%,
reversible)
• Pregnancy: Propylthiouracil is preferred in pregnancy & lactation:
Foetal goiter & hypothyroidism
• Partial cross reactivity between Propylthiouracil and carbimazole
Adverse Drug Reaction: Thioamides:

15. • Propylthiouracil – Tablet 50 mg
For control- 50 – 150 mg TDS
For maintenance- 25-50 mg BD or TDS
Methimazole – not available in India
• Carbimazole – Tablet 5, 10, 20 mg
For control- 5-15 mg TDS
For maintenance- 2.5 – 5 mg OD/BD
Drug dosage

16. Pregnant woman- Propylthiouracil is preferred
1. Treatment of hyperthyroidism: Grave’s disease & toxic nodular goiter
as-
• Definitive treatment:
• Indication- Children, young adults, recent small goiter, frail elderly
• Remission: Grave’s disease- 50% of patients in 1-2 yrs
Toxic goiter-remission: rare- RA131I, surgery preferred
• In frail elderly patients with multinodular goiter who are less responsive to
RA131I, permanent therapy with antithyroid drugs can be given
Therapeutic uses of antithyroid drugs:

17. 2. Preparation before thyroidectomy-
• To render the patient euthyroid before surgery to avoid thyrotoxic
crisis (surgical storm) in post operative period;
• Antithyroid drugs ---followed by iodides for 10 days prior to
surgery
3. With radioactive iodine-
Initial control with anti-thyroid drugs till the action of RAI starts
i.e. 2-3 months
Antithyroid drugs 1-2 wks gap RAI ATDs after 1 wk
started  gradually withdrawn over 3 months
Therapeutic uses of antithyroid drugs:

18. Advantages-
 Hypothyroidism if occurs is reversible
 Useful in children & young adults
 Can be used in pregnancy and lactation
- Thyroidectomy and RA 131I are contraindicated in
pregnancy
- With antithyroid drugs risk of hypothyroidism and
fetal goiter
- Propylthiouracil – preferred; high plasma protein
binding so less transfer across placenta and milk secretion
 Avoids risk & complications of surgery
Therapeutic uses of antithyroid drugs:
Disadvantages-
• Prolong / life long
treatment not feasible in
uncooperative patients
• Relapse in 50% patient
• Drug toxicity-
agranulocytosis

19. 2. Iodine & Iodides

20. M/A
How it works???? Itself important constituent of hormone??????
All facets of thyroid function affected
fastest acting antithyroid drug
2. Iodine & Iodides
1. Transport: Excess iodides inhibits its own transport into thyroid
cells by interfering with NIS expression on cell membrane
2. Decrease TSH action and also cAMP induced stimulation
3. Endocytosis of colloid and proteolysis of thyroglobulin inhibited
4. Inhibit hormone release -- ‘thyroid constipation’

21. • Quickest acting but control is partial
• In grave’s disease: if gland is enlarged - Shrinkage of thyroid
gland- gland become firm and less vascular
• Peak effect 10-15 days
• Response with iodine and iodides – identical because elemental
iodine - converted (reduction) to iodides in intestine
Thyroid escape- rebound hyperthyroidism

22.  Excess iodide rapidly and briefly interferes with iodination of tyrosil
and thyronil residue of thyroglobulin (probably by altering redox
potential of thyroid cells) -->
 Reduced synthesis of T3/T4
 Wolff-Chaikoff effect:
 ‘Thyroid escape’ after few days
Iodides and thyroid escape

23. ● Lugol’s Iodine
(5% iodine in 10% KI): 5-10 drops/day;
●Iodide (sod./pot.): 100-300mg/day(therapeutic),
5-10mg/day (prophylactic) for endemic goiter
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Iodine & Iodides preparations
Acute Hypersensitivity- (triggered by even minute quantity): Stop drug
Chronic overdose (iodism)-
• Salivation, rhinorrhoea, lacrimation, eye lid swelling, rashes, headache, mucus membrane
inflammation, burning in mouth, GI symptoms – reversible after stoppage
• May cause flaring of acne in adolescent
• In pregnancy – foetal/infantile goiter and hypothyroidism)
• Long term use can cause hypothyroidism and goiter
• Thyrotoxicosis may be aggravated in multinodular goiter
ADR: Iodine & Iodides

24. 3.
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25. • 131I : radiation half life 8
days
• Concentrated in thyroid
only
Radioactive Iodine Beta particles- destroy
follicular cells of thyroid
Gamma rays (X-
rays), - traverse
through tissue-
detected externally -
useful for scanning,
tracer studies

26. Na131I dissolved in water given ORALLY
1. Diagnostic- 25 -100 micro curie; counting or scanning of thyroid
simultaneously
No damage to thyroid gland at this dose
2. Therapeutic- 3 – 6 mili curie (as per size)
Grave’s disease or Toxic goiter
Response is slow- onset 2 wks, peak 3 mths
Repeat dose if needed after 3 months- 30-40% patient require repeat
dose
3. Metastatic papillary carcinoma of thyroid
As Palliative therapy after thyroidectomy
Much higher dose and prior TSH stimulation requir

27. • Advantages-
• Cure is permanent
• Convenient & effective
• Easy to use
• OPD
• No surgery related complications
• Suitable for patients after 35 years
of age and if CHF, angina or any
other contraindication to surgery is
present
Radioactive Iodine
• Disadvantages-
Hypothyroidism (5-10%)
irreversible
Delayed onset of action
C/I- Pregnancy
Less suitable for children and adult
<35 yrs age; more likely to develop
hypothyroidism and require T4
therapy life long

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• Decompensated hyperthyroidism
• Hospitalization ICU
• Propranolol: 1-2 mg slow IV, followed by 40-80mg oral 6 hrly,
• Symptomatic relief and reduce peripheral conversion of T4 to T
• if tachycardia is not controlled add Diltiazem 60-120 mg BD
• Propylthiouracil 200 -300 mg oral 6 hrly
• Reduce hormone synthesis
• Also reduce peripheral conversion of T4 to T3
Thyrotoxic crisis / Thyroid storm

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• Iopanoic acid 0.5- 1g oral OD or Ipodate (iodine containing contrast media)
• Inhibits thyroid hormone release
• Inhibits peripheral conversion of T4 to T3
• Hydrocortisone 100 mg iv 8 hrly, followed by prednisolone orally
• Help to recover from crisis by covering adrenal insufficiency
• Inhibit peripheral conversion of T4 to T3
• Oxygen, IV fluids, Cold sponging
• Treat precipitating cause- infections, injury
Thyrotoxic crisis / Thyroid storm

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Treatment Advantage Disadvantage Comment
Anti-
thyroid drugs
•Noninvasive,
•Lower initial cost,
•Low risk of permanent
hypothyroidism
•Low cure rate
•ADRs
•Drug compliance
•First line in children,
adolescents, and in pregnancy
•Initail treatment in severe cases
and preoperatively
Radioactive
iodine
(131 I)
•Cure is permanent
•Most cost effective
•Permanent hypothyroidism
•C/I – pregnancy, lactation
•Risk of carcinoma and genetic
damage
•Best treatment for toxic nodules
and toxic multinodular goiter
Surgery •Rapid, effective
treatment in patients
with large goiter
•Most invasive
•Complications (parathyroid
injury, recurrent laryngeal nerve
injury, pain, scar)
•Most costly
•Permanent hypothyroidism
•Option for patients who refuse
RAI
•Useful when suspicious
coexisting nodule in gland
•Can be tried in pregnancy if
major ADRs from drugs
Comparison of different treatment modalities

31. Case study…
● A 28 years old female patient complains of palpitation, increased motor activity, intolerance
to heat, frequent motions and weight loss in spite of increased appetite for past 2 months.
● Patients on examination revealed….,
● CVS: BP 140/84, Tachycardic but no M/R/G
● CNS: +fine tremor on exam
● General examination: Eye: +lid lag, mild R proptosis, no chemosis, +mild conjunctival
injection
● Neck: thyroid mildly enlarged, nontender, no bruit, no nodules
● Skin: warm, moist, no rash You suspect thyrotoxicosis
and send TSH and FT4
○ TSH <0.01
○ Ft4 3.9
Uptake and scan: Normal uptake (10-30%): Scan is a picture of thyroid –hot/cold nodules

32. What is the most likely cause of her symptoms?
● Graves’ disease
● Thyroiditis
● Overactive nodule(s)
● Thyroid hormone ingestion

33. Hyperthyroid states – High uptake
● Graves’ disease
○ Most common cause in young to middle-aged people
○ Circulating immunoglobulin attaches to TSH receptor and stimulates
formation of goiter and excessive production of thyroid hormone
● Toxic nodular goiter
○ Multinodular – middle-aged to elderly people.
■ Probably results from development of autonomy in longstanding goiters
○ Solitary
● Rare: Pituitary resistance to thyroid hormone regulation – rare TSH
secreting pituitary tumor – rare
● Uptake and scan: Normal uptake (10-30%)
● Scan is a picture of thyroid – ie. hot/cold nodules

34. Treatment
● Beta blockers: Propranolol 40mg once a daily
○ Control the hyperthyroid symptoms which are secondary to increased
beta adrenergic receptors
○ Block T4 to T3 conversion
● Carbimazole 5mg once a day : first line agent EXCEPT in first trimester
of pregnancy and storm (use PTU)

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Thank you!
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