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THYROID AND ANTI THYROID
DRUGS
Role of the Thyroid gland
 participates in normalizing growth and
development and energy levels and the proper
functioning and maintenance of tissues / organs
 critical for the nervous, skeletal and reproductive
tissues
 it affects secretion and degradation rates of all
hormones
Function of the Thyroid Gland
 secretion of the following
hormones:
 triiodothyronine (T3) ; 59% iodine
 tetraiodothyronine (T4; also known
as thyroxine); 65% iodine
 calcitonin
Biosynthesis of thyroid hormones
Steps in Biosynthesis
 Iodide trapping
 Oxidation of iodide to iodine
 Iodide Organification
 Formation of T4 and T3
 Release of T4 and T3
Peripheral metabolism of thyroid hormones
 The primary pathway for the peripheral metabolism of thyroxine (T4) is
deiodination  deiodination of T4 may occur by monodeiodination of the outer
ring, producing 3,5,3'-triiodothyronine (T3), which is three to four times more
potent than T4
Basic pharmacology of thyroid & antithyroid drugs
Thyroid hormones
 A model of thyroid hormone action is depicted in Figure 38-4
•
T3 and T4 are
triiodothyronine and
thyroxine, respectively.
•
PB, plasma binding
protein;
•
F, transcription factor;
R, receptor; PP,
proteins that bind at
the proximal promoter.
Figure 38-4. Regulation of transcription by thyroid hormones
Hypothyroidism
 A syndrome resulting from a deficiency of thyroid
hormones and is manifested largely by a reversible
slowing down of all body functions.
 There is a striking retardation of growth and
development.
 In children, manifested as dwarfism and severe MR.
Synthetic Thyroid Hormone
 synthetic levothyroxine (synthetic T4)
 Brand names: Eltroxin (Glaxo), Euthyrox (Merck)
 for hormone replacement therapy in hypothyroidism
 DOSE
 Infants and Children require more T4/Kg body weight than adults
 Average dose for an infant -10-15 micrograms/kg/d
 Average dose for an adult – 1.7micrograms/kg/d
 Once daily
 Pharmacokinetics
 should be taken 30min before or 1 hour after meals (delayed absorption for
soy, other foods and drugs)
 takes 6-8 weeks to reach steady state levels
 Labs should be repeated after 2 months
Synthetic Thyroid Hormone
 reasons for its use:




stability
content uniformity
low cost
lack of allergenic foreign
protein
 easy laboratory
measurements of serum
levels
 long half-life (7days)
 once a day dosing
Synthetic Thyroid Hormone
 Uses
 Hormone replacement therapy
In young patients or those with mild disease- full replacement therapy started
In older patients and in patients with cardiac disease -start treatment with reduced
dosage
 Myxedema Coma – medical emergency
Loading dose – of T4 – 300-400micrograms I/V initially f/by `50micrograms daily
I/V T3 – more cardiotoxic and difficult to moniter
 Hypothyroidism and Pregnancy – daily dose –adequate
Synthetic Thyroid Hormone
 synthetic liothyronine
(synthetic T3) is 3-4x
more potent
 not used alone for long
term treatment
secondary to short half
life and large peaks in
serum T3 levels
 increase risk for cardiac
side effects secondary to
hyperthyroid states
during treatment
Hyperthyroidism
 A thyroid disorder caused by an antibodymediated auto-immune reaction, but the trigger
for this reaction is still unknown
 most common cause of hyperthyroidism
Anti-thyroid Drugs
 Thioamides
 Iodides
 radioactive iodine
 Beta adrenoceptor
blocking agents
Mechanism of action of anti thyroid drugs
Thioamides
 Methimazole
 Propylthiouracil (PTU) Carbimazole
 MOA:
 inhibit synthesis by acting against
iodide organification (both)
 coupling of iodotyrosines (both)
 Blocks peripheral conversion of T4 to T3
(PTU)
Thioamides
 Pharmacokinetics:
 almost completely absorbed in the GIT
 serum half life: 90mins(PTU) ; 6 hours (methimazole)
 excretion: kidney – 24 hours (PTU) ; 48 hours
(Methimazole)
 can cross placental barrier (lesser with PTU)
 Methimazole 10x more potent than PTU
 PTU more protein-bound
Thioamide uses
 Definitive therapy
 Graves disease
 Toxic nodular goitre
 Preoperatively
 In thyrotoxic patients
 Along with RAI
Thioamides
 AE:
 maculopapular rash
 benign transient leukopenia
 agranulocytosis
 hepatitis (PTU) ; cholestatic jaundice (Methimazole)
 vasculitis
 lupus-like syndrome
Iodine131
 preparations: sodium iodide 131
 MOA: trapped within the gland and
enter intracellularly and delivers
strong beta radiations destroying
follicular cells
 Penetration range-400-2000µm
 Clinical uses: Grave’s, primary
inoperable thyroid CA
 Contraindication: pregnancy
Iodine131
 Advantages
 Easy administration
 Effectiveness
 Low expense
 Absence of pain
Iodine131
 Thioamides should be given initially and stop 3 days
before radioactive iodine administration

131I dosage
generally ranges between 185 MBq to
555 MBq repeated after 6 months
 Adverse effects
 permanent hypothyroidism
 potential for genetic damage
 may precipitate thyroid crisis
Anion Inhibitors
 Monovalent anions such as perchlorates,
pertechnetate and thiocyanate can block uptake of
iodide by the gland by competitive inhibition
 can be overcome by large doses of iodides
 useful for iodide-induced hyperthyroidism
(amiodarone-induced hyperthyroidism)
 rarely used due to its association with aplastic
anemia
Inorganic Iodines
 major anti-thyroids before
the introduction of
thioamides (1950s)
 preparations:
 strong iodine solution
(Lugol’s)
 potassium iodide
 iodone
Inorganic Iodines
 MOA:
 acutely blocks release of thyroid hormone from the gland
by inhibiting thyroglobulin proteolysis
 inhibit iodide organification
 Uses:
 useful in thyroid storms: 2-7 days
 Preoperatively - iodides decrease vascularity, size and fragility
of hyperplastic gland
 Caution:
 it may delay onset of thioamide effects; should be given after
initiation of thioamides
 The gland will escape from inhibition after 2-8 weeks.
Iodinated Contrast Media
 Iodinated contrast media
Ipodate (oral)
Iopanoic acid (oral)
Diatrizoate (intravenous)
valuable in hyperthyroidism (but is not labeled for this
indication)
 MOA: inhibits conversion of T4 to T3 in the liver, kidney,
brain and pituitary
Another MOA is due to inhibition of hormone release
secondary to iodide levels in blood
 Useful in thyroid storms (adjunctive therapy)
Beta Blockers
 Drugs: Propranolol, Metoprolol, Atenolol
 MOA:
 Membrane-stabilizing action: inhibits T4 to T3
 Ameliorate many disturbing s/sxs of hyperthyroidism
secondary to increased circulating catecholamines by
blocking beta receptors
 Indications: Grave’s, Thyroid storm
Corticosteroids
 Prednisone is given for patients with Grave’s
ophthalmopathy
 1mg/kg/day (60mg/day 3 divided doses); if it
should be given for more than 4 weeks, taper to
decrease risk of adrenal crisis
Thyroid storm
 Sudden exacerbation of throtoxic symptoms
 Life threatening condition
 Vigorous management
 Propanalol 1-2mg i/v or 40-80mg PO Q6h
 Diltiazim 90-120mg Po Q8-6 hrs or 5-10mgs
intravenous infusion/hour
Thyroid storm
 Potassium iodide
 Propylthiouracil
 Hydrocortisone
 Supportive therapy
 Plasmapheresis/peritoneal dialysis
Hyperthyroidism and
Pregnancy
 Ideal situation- treat before pregnancy
 Pregnancy-Radioactive iodine CI
 Propylthiouracil
 Dose limitation≤ 300mgs/day
 Methimazole alternative- fetal scalp defects