thyroid hormones & drugs
TRANSCRIPT
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Dr. Eduardo D. RosasDr. Eduardo D. Rosas
BlumBlumDepartment ofDepartment of
PharmacologyPharmacology
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A 29 YO female complains of restlessness andA 29 YO female complains of restlessness and
increasing anxiety. HR 135bmp, PE: Tremors.increasing anxiety. HR 135bmp, PE: Tremors.Palpation on the neck reveals a 3cm nodule onPalpation on the neck reveals a 3cm nodule on
her thyroid gland. Laboratory test are sent toher thyroid gland. Laboratory test are sent to
confirm the diagnosis. In the meantime, withconfirm the diagnosis. In the meantime, with
drug could be given to acutely reduce herdrug could be given to acutely reduce herphysical symptoms?physical symptoms?
a)a) Propylthiouracil.Propylthiouracil.
b)b) Furosemide.Furosemide.
c)c) Prednisone.Prednisone.
d)d) Iodine.Iodine.
e)e) Propanolol.Propanolol.
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ThyroidThyroid
Secretes three hormones:Secretes three hormones:
Calcitonin, important in calciumCalcitonin, important in calcium
homeostasis.homeostasis.
Triiodothyronine (T3) and thyroxine (T4),Triiodothyronine (T3) and thyroxine (T4),
important in growth and metabolicimportant in growth and metabolic
function.function.
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Thyroid drugsThyroid drugs
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Thyroid HormonesThyroid Hormones
T4 and T3 are iodine-containing hormonesT4 and T3 are iodine-containing hormonesthat are analogs of tyrosine.that are analogs of tyrosine.
Regulated by TSH, which increases theRegulated by TSH, which increases the
Synthesis and secretion of theseSynthesis and secretion of thesehormones.hormones.
TSH secretion is regulated by negativeTSH secretion is regulated by negative
feed-back of the thyroid hormones; it isfeed-back of the thyroid hormones; it ispositively influenced by TRH from thepositively influenced by TRH from thehypothalamus.hypothalamus.
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Thyroid HormonesThyroid Hormones
lodide is necessary for thyroid hormonelodide is necessary for thyroid hormone
synthesis.synthesis.
Iodide is obtained from the diet and is absorbedIodide is obtained from the diet and is absorbed
from the gastrointestinal tract.from the gastrointestinal tract. Once in the gland iodide is oxidized to an activeOnce in the gland iodide is oxidized to an active
iodine intermediate, which iodinates tyrosineiodine intermediate, which iodinates tyrosine
residues of thyroglobulin.residues of thyroglobulin.
An aerobic condensation of iodinated tyrosineAn aerobic condensation of iodinated tyrosine
molecules results in production of T3 and T4.molecules results in production of T3 and T4.
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Thyroid HormonesThyroid Hormones
99% of T3 and T4 are bound to plasma99% of T3 and T4 are bound to plasma
proteins (thyroid-binding globulin).proteins (thyroid-binding globulin).
They are excreted in the bile and urine.They are excreted in the bile and urine.
T4 has a half-life of 6-7 days; T3 has aT4 has a half-life of 6-7 days; T3 has a
half-life of 1-2 days.half-life of 1-2 days.
Some of the circulating T4 is deiodinatedSome of the circulating T4 is deiodinatedto T3, the more potent and rapidly actingto T3, the more potent and rapidly acting
form.form.
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Thyroid HormonesThyroid Hormones
Activation of nuclear nonhistone proteinActivation of nuclear nonhistone proteinreceptors attached to DNA.receptors attached to DNA.
Binding leads to increased transcription ofBinding leads to increased transcription of
messenger RNA (mRNA).messenger RNA (mRNA). Increasing the synthesis of specific proteins. (T3Increasing the synthesis of specific proteins. (T3
x 10 potent).x 10 potent). Cell membranes receptors: increase amino acidCell membranes receptors: increase amino acid
and glucose uptake.and glucose uptake. Inner mitochondrial membrane receptors:Inner mitochondrial membrane receptors:
regulate energy metabolism.regulate energy metabolism.
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Thyroid HormonesThyroid Hormones
Effects in most major systems, including normalEffects in most major systems, including normal
growth and development.growth and development.
Increased basal metabolic rate and activation ofIncreased basal metabolic rate and activation of
oxygen consumption.oxygen consumption.
Thermogenic effect (increased heat production).Thermogenic effect (increased heat production).
Increased plasma glucose and free fatty acids,Increased plasma glucose and free fatty acids,
reduction in plasma cholesterol and triglycerides.reduction in plasma cholesterol and triglycerides. Increased HR, maturation of the CNS.Increased HR, maturation of the CNS.
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Thyroid DrugsThyroid Drugs
Replacement therapy.Replacement therapy.
Treatment for hypothyroidism.Treatment for hypothyroidism.
Suppress TSH secretion.Suppress TSH secretion. Levo isomers are more potent inLevo isomers are more potent in
increasing basal metabolic rate.increasing basal metabolic rate.
Once absorbed, their pharmacokinetic andOnce absorbed, their pharmacokinetic anddynamic properties are identical todynamic properties are identical to
endogenous thyroid hormones.endogenous thyroid hormones.
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Thyroid DrugsThyroid Drugs
Advers e reac tionsdvers e reac tions
Hyperthyroidism (or symptoms ofHyperthyroidism (or symptoms ofhyperthyroidism).hyperthyroidism).
Cardiovascular toxicity (tachyarrhythmias,Cardiovascular toxicity (tachyarrhythmias,
angina, and infarction)angina, and infarction) CNS stimulation, insomnia.CNS stimulation, insomnia.
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LevothyroxineLevothyroxine
Synthetic levo isomer of T4.Synthetic levo isomer of T4.
PO and IV available.PO and IV available.
Preferred drug for hypothyroidism.Preferred drug for hypothyroidism. Better standardization and stability andBetter standardization and stability and
long duration.long duration.
Long half-life of T4.Long half-life of T4. Facilitates maintenance of a steadyFacilitates maintenance of a steady
physiologic replacement.physiologic replacement.
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LiothyronineLiothyronine
Synthetic L-T3.Synthetic L-T3.
More difficult to monitor than T4.More difficult to monitor than T4.
More expensive.More expensive. Shorter duration of action.Shorter duration of action.
Treatment of choice for Mixedema coma.Treatment of choice for Mixedema coma.
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LiotrixLiotrix
Combination of levothyroxine andCombination of levothyroxine and
liothyronine.liothyronine.
Ratio of 4:1.Ratio of 4:1.
No advantage over levothyroxine.No advantage over levothyroxine.
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Antithyroid DrugsAntithyroid Drugs
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Antithyroid DrugsAntithyroid Drugs
Inhibit the formation of thyroidInhibit the formation of thyroid
hormones.hormones.
Used in the treatment ofUsed in the treatment of
hyperthyroidism.hyperthyroidism.
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lodidelodide
Small amounts of iodine (75-100 ng/day)Small amounts of iodine (75-100 ng/day)
are required for hormone synthesis.are required for hormone synthesis.
But high concentrations (+ 50 mg/day)But high concentrations (+ 50 mg/day)
produce autoinhibition.produce autoinhibition.
lodide blocks the uptake of iodide,lodide blocks the uptake of iodide,
inhibiting synthesis and release of thyroidinhibiting synthesis and release of thyroid
hormones.hormones.
Diminishes vascularity of the gland.Diminishes vascularity of the gland.
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lodidelodide
Used only preoperatively to shrink theUsed only preoperatively to shrink the
gland. (prior to surgical removal of thegland. (prior to surgical removal of the
gland).gland).
Treatment of thyroid storm.Treatment of thyroid storm.
It is given as Lugol's solution (iodine andIt is given as Lugol's solution (iodine and
potassium iodide).potassium iodide).
Effects are visible within 24 hours. It is noEffects are visible within 24 hours. It is no
longer used in long-term therapy.longer used in long-term therapy.
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lodidelodide
Adverse reactionsAdverse reactions
Hypersensitivity reaction .Hypersensitivity reaction .
Drug fevers, metallic taste, bleeding disordes.Drug fevers, metallic taste, bleeding disordes.
Gastric irritation.Gastric irritation.
Long-term use can lead to sudden disinhibitionLong-term use can lead to sudden disinhibition
of hormone synthesis, producing acuteof hormone synthesis, producing acutehyperthyroidism.hyperthyroidism.
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ThioamidesThioamides
Propyithiouracil (PTU), methimazole.Propyithiouracil (PTU), methimazole.
Inhibit the peroxidase enzymes catalyzingInhibit the peroxidase enzymes catalyzing
the oxidation of iodide, thus reducing thethe oxidation of iodide, thus reducing the
synthesis of thyroid hormones.synthesis of thyroid hormones.
PTU also inhibits the peripheralPTU also inhibits the peripheral
deiodination of T4 to T3.deiodination of T4 to T3.
Delay in onset (until preformed hormonesDelay in onset (until preformed hormones
have been metabolized).have been metabolized).
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ThioamidesThioamides
Used for control of hyperthyroidism untilUsed for control of hyperthyroidism until
surgery.surgery.
Suppression of thyroid hormone synthesisSuppression of thyroid hormone synthesis
until the effect of radioactive iodide begins.until the effect of radioactive iodide begins.
Long-term therapy of mild-to-moderateLong-term therapy of mild-to-moderate
hyperthyroidism.hyperthyroidism.
The drugs are given PO.The drugs are given PO.
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ThioamidesThioamides
Adverse reactions.Adverse reactions.
Mild maculopapular rash, joint pain, headache,Mild maculopapular rash, joint pain, headache,
nausea, and loss of hair.nausea, and loss of hair.
Rare: agranulocytosis.Rare: agranulocytosis.
Crosses the placenta and enter breast milk,Crosses the placenta and enter breast milk,
which can lead to hypothyroidism in the fetuswhich can lead to hypothyroidism in the fetusand nursing infant.and nursing infant.
Pregnancy ?Pregnancy ?
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Radioactive iodine (131I)Radioactive iodine (131I)
PO or IV.PO or IV.
Rapidly taken, then is incorporated intoRapidly taken, then is incorporated into
thyroglobulin.thyroglobulin.
Leads to partial or total destruction of theLeads to partial or total destruction of the
gland by emission of beta particles.gland by emission of beta particles.
Damage to surrounding tissue is minimal.Damage to surrounding tissue is minimal.
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Radioactive iodine (131I)Radioactive iodine (131I)
Used in the treatment of hyperthyroidism.Used in the treatment of hyperthyroidism.
Side effects and toxicity.Side effects and toxicity.
Mayor: hypothyroidismMayor: hypothyroidism..
Should be avoided during pregnancy.Should be avoided during pregnancy.
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Well be starting in 10min sharply
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Cli nical Ca seli nical Ca se A 52 years-old male comes to your officeA 52 years-old male comes to your office
with a 1-month-old annoying pain onwith a 1-month-old annoying pain on
arms and legs.arms and legs.
HPIHPI
The pain is referred as tingling sensation,The pain is referred as tingling sensation,
located or hands and feet, that increases atlocated or hands and feet, that increases at
night and has disturbs his sleep. Nothingnight and has disturbs his sleep. Nothing
reduces the pain.reduces the pain.
Also states that he has been feeling fatiguedAlso states that he has been feeling fatigued
for the past 2 months.for the past 2 months.
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Cli nical Ca seli nical Ca se PMIPMI
Hypothyroidism for the last 4 months (Euthyrox).Hypothyroidism for the last 4 months (Euthyrox).Loss of appetite for the last year.Loss of appetite for the last year.
Essential Hypertension for the last 3 years (LosartanEssential Hypertension for the last 3 years (Losartan
+ Hydroclorothiazide).+ Hydroclorothiazide). SHSH
Alcohol (+) every day, up to 20-30oz.Alcohol (+) every day, up to 20-30oz.
PEPE
HR 100 RR 18 BP 139/89 BMI 40.HR 100 RR 18 BP 139/89 BMI 40. Slight pale coloration of the skin and mucousSlight pale coloration of the skin and mucous
membranes.membranes. Neurological test unremarkable.Neurological test unremarkable. Rest of the examination unremarkable.Rest of the examination unremarkable.
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High-Yield Slides.High-Yield Slides.
Dr. Rosas BlumDr. Rosas Blum
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Thyroid HormonesThyroid Hormones
Crucial for normal development.Crucial for normal development.
Maintains metabolic homeostasis.Maintains metabolic homeostasis.
Affects every organ system.Affects every organ system. Cretinism: diminish thyroid hormones.Cretinism: diminish thyroid hormones.
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HypothyroidismHypothyroidism
Cold intolerance, hair changes, weightCold intolerance, hair changes, weightgain.gain.
Treatment thyroid hormone replacement.Treatment thyroid hormone replacement.
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HyperthyroidismHyperthyroidism
Array of treatmentsArray of treatments
PTU or methimazole.PTU or methimazole.
IodineIodine Radioactive Iodine.Radioactive Iodine.
Surgery.Surgery.
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MyxedemaMyxedema
Both hypo or hyperthyroidism.Both hypo or hyperthyroidism.
Refer different things.Refer different things.
Myxedema w/hypothyroidismMyxedema w/hypothyroidism
Apathy, listlessness, edema accumulates inApathy, listlessness, edema accumulates inskin and other tissues.skin and other tissues.
Broadening of facial features.Broadening of facial features.
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MyxedemaMyxedema
Myxedema w/hyperthyroidism.Myxedema w/hyperthyroidism.
Localized areas of hyperpigmentation.Localized areas of hyperpigmentation. Usually in feet and lower legs.Usually in feet and lower legs.
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B-BlockersB-Blockers
Excess thyroid hormones, upregulation ofExcess thyroid hormones, upregulation ofB-adrenergic receptors.B-adrenergic receptors.
Tachycardia, tremors, anxiety.Tachycardia, tremors, anxiety. Propranolol.Propranolol.
Inhibits peripheral conversion of T4 to T3.Inhibits peripheral conversion of T4 to T3.
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ThioamidesThioamides
PTU, methimazol.PTU, methimazol.
Interfere in the incorporation of iodine toInterfere in the incorporation of iodine to
thyroglobulin.thyroglobulin. Slow onset.Slow onset.
Main therapy or used prior surgery.Main therapy or used prior surgery.
PTU inhibits conversion of T4 to T3.PTU inhibits conversion of T4 to T3.
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ThioamidesThioamides
Adverse effects.Adverse effects.
Low incidence of side effects.Low incidence of side effects. Agranulocytosis.Agranulocytosis.
Rash (common).Rash (common).
Both crosses the placenta, but PTU is saferBoth crosses the placenta, but PTU is saferbecause its high protein binding.because its high protein binding.
Much safer that iodine or radioactive iodine.Much safer that iodine or radioactive iodine.
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Radioactive IodineRadioactive Iodine
Highly Effective.Highly Effective.
Contraindicated in pregnancy (destroysContraindicated in pregnancy (destroys
fetal gland).fetal gland). Low incidence of side effects.Low incidence of side effects.
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IodineIodine
Oldest drug.Oldest drug. Reduce gland size, vascularity and fragility.Reduce gland size, vascularity and fragility.
Temporal treatment (prior to surgery).Temporal treatment (prior to surgery). Contraindicated in pregnancy (neonatalContraindicated in pregnancy (neonatal
goiter).goiter).
Adverse: hypersensibility reaction, brassyAdverse: hypersensibility reaction, brassytaste, burning of mouth and gums.taste, burning of mouth and gums.
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InteractionsInteractionsw/receptorsw/receptors
Amiodarone.Amiodarone.
Structurally resembles thyroid hormones.Structurally resembles thyroid hormones.
May cause hypo or hyperthyroidism.May cause hypo or hyperthyroidism.
LithiumLithium
L-DopaL-Dopa
EstrogensEstrogens
A 29 YO f l l i f tlA 29 YO f l l i f tl
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A 29 YO female complains of restlessnessA 29 YO female complains of restlessness
and increasing anxiety. HR 135bmp, PE:and increasing anxiety. HR 135bmp, PE:
Tremors. Palpation on the neck reveals aTremors. Palpation on the neck reveals a3cm nodule on her thyroid gland.3cm nodule on her thyroid gland.
Laboratory test are sent to confirm theLaboratory test are sent to confirm the
diagnosis. In the meantime, with drugdiagnosis. In the meantime, with drug
could be given to acutely reduce hercould be given to acutely reduce herphysical symptoms?physical symptoms?
Propylthiouracil.Propylthiouracil.
Furosemide.Furosemide. Prednisone.Prednisone. Iodine.Iodine.
Propanolol.Propanolol.
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