Dr. Eduardo D.

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

 Hyperthyroidism (or symptoms of

hyperthyroidism).
 Cardiovascular toxicity (tachyarrhythmias,
angina, and infarction)
 CNS stimulation, insomnia.
 Levothyroxine
 Synthetic levo isomer of T4.
 PO and IV available.
 Preferred drug for hypothyroidism.
 Better standardization and stability and
long duration.
 Long half-life of T4.
 Facilitates maintenance of a steady
physiologic replacement.
 Liothyronine
 Synthetic L-T3.
 More difficult to monitor than T4.
 More expensive.
 Shorter duration of action.
 Treatment of choice for Mixedema coma.
 Liotrix
 Combination of levothyroxine and
liothyronine.
 Ratio of 4:1.
 No advantage over levothyroxine.
Antithyroid Drugs
 Antithyroid Drugs

 Inhibit the formation of thyroid

hormones.
 Used in the treatment of
hyperthyroidism.
 lodide
 Small amounts of iodine (75-100 ng/day)
are required for hormone synthesis.
 But high concentrations (+ 50 mg/day)
produce autoinhibition.
 lodide blocks the uptake of iodide,
inhibiting synthesis and release of thyroid
hormones.
 Diminishes vascularity of the gland.
 lodide
 Used only preoperatively to shrink the
gland. (prior to surgical removal of the
gland).
 Treatment of thyroid storm.
 It is given as Lugol's solution (iodine and
potassium iodide).
 Effects are visible within 24 hours. It is no
longer used in long-term therapy.
 lodide
 Adverse reactions

 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.

 Mild maculopapular rash, joint pain, headache,

nausea, and loss of hair.
 Rare: agranulocytosis.
 Crosses the placenta and enter breast milk,
which can lead to hypothyroidism in the fetus
and nursing infant.
 Pregnancy ?
 Radioactive iodine (131I)
 PO or IV.
 Rapidly taken, then is incorporated into
thyroglobulin.
 Leads to partial or total destruction of the
gland by emission of beta particles.
 Damage to surrounding tissue is minimal.
 Radioactive iodine (131I)
 Used in the treatment of hyperthyroidism.

 Side effects and toxicity.

 Mayor: hypothyroidism.
 Should be avoided during pregnancy.
 Propranolol
 Adjuncts in the treatment of
hyperthyroidism.
 Reduce the symptoms of the disease
(e.g., tachycardia. anxiety) until the
antithyroid drugs can take effect.
 Propranolol also inhibits the peripheral
conversion of T4 to T3 via 5' deiodinase.
We’ll be starting in 10min… sharply
Cli nical Ca se
 A 52 years-old male comes to your office
with a 1-month-old annoying pain on
arms and legs.
 HPI
 The pain is referred as tingling sensation,
located or hands and feet, that increases at
night and has disturbs his sleep. Nothing
reduces the pain.
 Also states that he has been feeling fatigued
for the past 2 months.
Cli nical Ca se
 PMI
 Hypothyroidism for the last 4 months (Euthyrox).
Loss of appetite for the last year.
 Essential Hypertension for the last 3 years (Losartan
+ Hydroclorothiazide).
 SH
 Alcohol (+) every day, up to 20-30oz.
 PE
 HR 100 RR 18 BP 139/89 BMI 40.
 Slight pale coloration of the skin and mucous
membranes.
 Neurological test unremarkable.
 Rest of the examination unremarkable.
High-Yield Slides.
Dr. Rosas Blum
Thyroid Hormones

• Crucial for normal development.

• Maintains metabolic homeostasis.
• Affects every organ system.
• Cretinism: diminish thyroid hormones.
Hypothyroidism

• Cold intolerance, hair changes, weight

gain.
• Treatment thyroid hormone replacement.
Hyperthyroidism

• Array of treatments
• PTU or methimazole.
• Iodine
• Radioactive Iodine.
• Surgery.
Myxedema

• Both hypo or hyperthyroidism.

• Refer different things.

• Myxedema w/hypothyroidism
• Apathy, listlessness, edema accumulates in
skin and other tissues.
• Broadening of facial features.
Myxedema

• Myxedema w/hyperthyroidism.

• Localized areas of hyperpigmentation.

• Usually in feet and lower legs.
B-Blockers

• Excess thyroid hormones, upregulation of

B-adrenergic receptors.
• Tachycardia, tremors, anxiety.
• Propranolol.
• Inhibits peripheral conversion of T4 to T3.
Thioamides

• 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.

• Low incidence of side effects.

• Agranulocytosis.
• Rash (common).
• Both crosses the placenta, but PTU is safer
because its high protein binding.
• Much safer that iodine or radioactive iodine.
Radioactive Iodine

• 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.
erosas@uag.mx