Thyroid Hormones & Drugs
Thyroid Hormones & Drugs
Rosas
Blum
Department of
Pharmacology
A 29 YO female complains of restlessness and
increasing anxiety. HR 135bmp, PE: Tremors.
Palpation on the neck reveals a 3cm nodule on
her thyroid gland. Laboratory test are sent to
confirm the diagnosis. In the meantime, with
drug could be given to acutely reduce her
physical symptoms?
a) Propylthiouracil.
b) Furosemide.
c) Prednisone.
d) Iodine.
e) Propanolol.
Thyroid
Secretes three hormones:
Calcitonin, important in calcium
homeostasis.
Triiodothyronine (T3) and thyroxine (T4),
important in growth and metabolic
function.
Thyroid drugs
Thyroid Hormones
T4 and T3 are iodine-containing hormones
that are analogs of tyrosine.
Regulated by TSH, which increases the
Synthesis and secretion of these
hormones.
TSH secretion is regulated by negative
feed-back of the thyroid hormones; it is
positively influenced by TRH from the
hypothalamus.
Thyroid Hormones
lodide is necessary for thyroid hormone
synthesis.
Iodide is obtained from the diet and is absorbed
from the gastrointestinal tract.
Once in the gland iodide is oxidized to an active
iodine intermediate, which iodinates tyrosine
residues of thyroglobulin.
An aerobic condensation of iodinated tyrosine
molecules results in production of T3 and T4.
Thyroid Hormones
99% of T3 and T4 are bound to plasma
proteins (thyroid-binding globulin).
They are excreted in the bile and urine.
T4 has a half-life of 6-7 days; T3 has a
half-life of 1-2 days.
Some of the circulating T4 is deiodinated
to T3, the more potent and rapidly acting
form.
Thyroid Hormones
Activation of nuclear nonhistone protein
receptors attached to DNA.
Binding leads to increased transcription of
messenger RNA (mRNA).
Increasing the synthesis of specific proteins. (T3
x 10 potent).
Cell membranes receptors: increase amino acid
and glucose uptake.
Inner mitochondrial membrane receptors:
regulate energy metabolism.
Thyroid Hormones
Effects in most major systems, including normal
growth and development.
Increased basal metabolic rate and activation of
oxygen consumption.
Thermogenic effect (increased heat production).
Increased plasma glucose and free fatty acids,
reduction in plasma cholesterol and triglycerides.
Increased HR, maturation of the CNS.
Thyroid Drugs
Replacement therapy.
Treatment for hypothyroidism.
Suppress TSH secretion.
Levo isomers are more potent in
increasing basal metabolic rate.
Once absorbed, their pharmacokinetic and
dynamic properties are identical to
endogenous thyroid hormones.
Thyroid Drugs
Advers e reac tions
Hypersensitivity reaction .
Drug fevers, metallic taste, bleeding disordes.
Gastric irritation.
Long-term use can lead to sudden disinhibition
of hormone synthesis, producing acute
hyperthyroidism.
Thioamides
Propyithiouracil (PTU), methimazole.
Inhibit the peroxidase enzymes catalyzing
the oxidation of iodide, thus reducing the
synthesis of thyroid hormones.
PTU also inhibits the peripheral
deiodination of T4 to T3.
Delay in onset (until preformed hormones
have been metabolized).
Thioamides
Used for control of hyperthyroidism until
surgery.
Suppression of thyroid hormone synthesis
until the effect of radioactive iodide begins.
Long-term therapy of mild-to-moderate
hyperthyroidism.
The drugs are given PO.
Thioamides
Adverse reactions.
• Array of treatments
• PTU or methimazole.
• Iodine
• Radioactive Iodine.
• Surgery.
Myxedema
• Myxedema w/hypothyroidism
• Apathy, listlessness, edema accumulates in
skin and other tissues.
• Broadening of facial features.
Myxedema
• Myxedema w/hyperthyroidism.
• PTU, methimazol.
• Interfere in the incorporation of iodine to
thyroglobulin.
• Slow onset.
• Main therapy or used prior surgery.
• PTU inhibits conversion of T4 to T3.
Thioamides
• Adverse effects.
• Highly Effective.
• Contraindicated in pregnancy (destroys
fetal gland).
• Low incidence of side effects.
Iodine
• Oldest drug.
• Reduce gland size, vascularity and fragility.
• Temporal treatment (prior to surgery).
• Contraindicated in pregnancy (neonatal
goiter).
• Adverse: hypersensibility reaction, brassy
taste, burning of mouth and gums.
Interactions w/receptors
• Amiodarone.
• Structurally resembles thyroid hormones.
• May cause hypo or hyperthyroidism.
• Lithium
• L-Dopa
• Estrogens
A 29 YO female complains of restlessness
and increasing anxiety. HR 135bmp, PE:
Tremors. Palpation on the neck reveals a
3cm nodule on her thyroid gland.
Laboratory test are sent to confirm the
diagnosis. In the meantime, with drug
could be given to acutely reduce her
physical symptoms?
Propylthiouracil.
Furosemide.
Prednisone.
Iodine.
Propanolol.
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