Thyroid & Antithyroid drugs Flashcards
How is iodine synthesized into thyroid hormones?
iodine is covalently bound to tyrosine residues in the thyroglobulin molecules via thyroperoxidase.
MIT + DIT = triiodothyronine (T3)
DIT + DIT = thyroxine (T4)
what is reversible triiodothyronine (rT3)?
- isomer of T3.
- derived from T4 through deiodinase.
- blocks action of T3.
what are the synthesis and secretion steps of thyroid hormones?
- uptake of iodine
- synthesis of thyroglobulin from A.A
- iodination
- condensation
What are the physiological effects of thyroxine?
- increase BMR via Na/K ATPase
- increase RR
- increase temperature
- increase O2 - potentiates the effects of catecholamines
- increase CO
- enhances HR - promotes CNS development.
PK of thyroid T3 and T4?
- T3 formed from deiodination (5’-deiodinase) of T4 in the peripheral tissues, liver, kidney.
- Thyroxin-binding protein transport T3 and T4
- T3 has greater affinity than T4
Physiological controls of thyroid gland?
- the pituitary gland is regulated by hypothalamus (TRH)
- – activated by cold, acute psychosis, circadian and pulsatile rhythm.
- – inhibited by severe stress.
- thyroid gland is under control of the pituitary gland (TSH)
- negative feedback is from T3 and T4.
MOA of thyroid hormones?
- signaling mechanism is via TRH-IP3 mediated, TSH-cAMP mediated, T3 & T4 binds with receptor in the nucleus.
- mechanism: binds c intracellular receptors that control gene expression c RNA formation and protein synthesis.
- proteins synthesized depends on tissues involved
What are some thyroid preps?
Levothyroxine (T4) - longer t1/2
Liothyronine (T3) - short t1/2
Levothyroxine
Liothyronine
uses?
cretinism (thyroid hormone syn defect) adult hypothyroidism (myxedema)
Levothyroxine
Liothyronine
A.E?
tremors
tachycardia
arrythmias
heat intolerance
what are some P450 inductions that can increase the metabolism of T3 and T4?
rifampin
phenobarbital
phenytoin
primary hypothyroidism?
Hashimoto's thyroiditis - anti-TPO radiation exposure "I" deficiency excision drugs - lithium, amiodarone
secondary hypothyroidism?
pituitary pathology.
- radiation, surgery or tumor
- decrease TSH
Tertiary hypothyroidism?
hypothalamus pathology.
decreased TRH
hypothyroidism lab diagnosis?
elevated TSH
decreased total T4
decreased free T4
decreased T3
clinical fts of hypothyroidism?
cold tolerance constipation poor memory hair loss - queen anne's sign (thinning of hair lateral third of eye brow) carpal tunnel syndrome hoarse voice puffy face bradycardia delayed DTRs
describe cretinism…
fts: mentally retarded, short stature child c protruding umbilicus, pot belly, pale& puffy face and tongue is protruding
causes: lack of dietary iodine; defect in T4 syn or devel failure of thyroid
screen and tx pts, including congenital defect, c T4 (c/in -2 wks of life)
hyperthyroidism lab diagnosis?
decreased TSH
elevated T4
elevated free T4
elevated T3
hyperthyroidism causes?
Graves' disease toxic multinodular goiter toxic adenoma molar pregnancy postpartum thyrotoxicosis postviral thyroiditis
PE/History of Hyperthyroidism?
weight loss heat tolerance nervousness palpitation bowel frequency insomnia abnl menses
what are fts of Graves?
ophthalmopathy
pertibial myxedema
what are two thioamides to treat hyperthyroidism?
propythiouracil
methimazole
what are two iodine & iodide salts to treat hyperthyroidism?
lugol sln
potassium iodide
what is a beta blocker used in hyperthyroidism?
propanolol
propythiouracil
methimazole
MOA?
block iodination of thyroglobulin
inhibit coupling rxn of DIT c MIT & DIT
inhibit thyroperoxidase
Which thioamides is preferred in thyroid storm and why?
propythiouracil d/t its inhibitory effect on 5-deiodinase that result in decrease peripheral conversion from T4 and T3.
what are the two uses for propythiouracil?
- reserved for pts who are intolerant to methimazole
2. preferred in thyroid storm.
propythiouracil
methimazole
A.E?
propythiouracil:
rash, arthralgia
rare - agranulocytosis, aplastic anemia, hepatotoxicity, vasculitis
methimazole:
less A.E
possible teratogenic.
What is the Wolff-Chaikoff effect?
give large doses of iodide inhibit thyroid synthesis.
What is the Jod-Basedow phenomenon?
multinodular goiter devel after Wolff-Chaikoff effect is lost after 10-14 days.
lugol sln
potassium iodide
actions?
decrease vascularity and size of the thyroid gland.
lugol sln
potassium iodide
uses?
before surgery for easy thyroid excision.
conjunction c PTU, and beta blockers in thyrotoxic crisis
lugol sln
potassium iodide
preparations?
Lugol: a mixture of iodine and postassium iodide.
KI: saturated sln.
lugol sln
potassium iodide
A.E?
chronic iodide intoxication (iodism)
anaphylactoid rxn
- angioedema, swelling of larynx, eyelids
brassy taste
burning of teeth and gums
enlargement of parotid and maxillary glands
Radioactive iodine 131(I)
MOA?
taken up and sequestered by thyroid gland -> damage the tissue through emission of toxic beta rays, no effect on other tissues.
Radioactive iodine 131(I)
uses?
hyperthyroidism
Graves’ disease
refractory to other antithyroid drugs and persistent sx’s even after a subtotal thyroidectomy
Radioactive iodine 131(I)
A.E?
hypothyroidism
Radioactive iodine 131(I)
contraindications?
pregnant women and nursing mothers.
propanolol
MOA?
prevents conversion of T4 and T3
nadolol or atenolol
uses?
control tachycardias, htn, a fib during thyroid storm
esmolol use?
control intra-operative thyroid storm
diltiazem use?
Ca channel blocker - use in thyroid storm for pts c asthma
what is thyroid storm?
assoc c extreme effects of hyperthyroidism
- caused by illness, surgery, and other stresses
what are the two iodinated radiocontrast media?
diatrizoate
iohexol
diatrizoate
iohexol
MOA?
suppress conversion of T4 and T3 in peripheral tissues, kidney, and liver.
diatrizoate
iohexol
uses?
rapidly reduce T3 conc in thyrotoxicosis
Perchlorate
thiocyanate
pertechnetate
MOA?
inhibit iodide conc in the gland by blocking transportation
Perchlorate
thiocyanate
pertechnetate
A.E?
aplastic anemia
what are drugs that can induce hypothyroidism?
amiodarone
interferon alpha & IL-2
lithium
amiodarone
fts?
structurally similar to thyroxine
amiodarone
A.E and tx?
iodine assoc hyperthyroidism - tx c thiamides
autoimmune mediated infl - tx c steroids
hypothyroidism - tx c levothyroxine
Lithium
MOA?
inhibits release of hormones (hypothyroidism) and thyroid enlargement.
what are the two goitrogens?
cabbage
cassava
what is the function of the thyroid gland?
- take up iodine and convert it into thyroid hormones.
