Lecture 13- Pharmacology Of The Thyroid Hormones Flashcards
The thyroid gland
Has 2 physiological functions;
-secretion of the thyroid hormones= important for growth and development and for energy metabolism
-secretion of calcitonin = regulates circulating levels of calcium
Thyroid hormones;
-tetraiodothyronine; thyroxine T4= primary hormone
-triiodothyronine; T3= greater biological activity than T4- specifically generated at its site of action in peripheral tissues by deiodination of T4
^both are iodine-containing amino acids
-iodine= essential for thyroid hormone synthesis
Main steps in the synthesis, storage + secretion of thyroid hormones are=
1. Uptake of plasma iodide by follicle cells
2. Oxidation of iodide + iodination of tyrosine residues of thyroglobulin
3. Secretion of thyroid hormone
Diagram of TH- Slide 3
Regulation of thyroid secretion
Is regulated by variations in the circulating levels of anterior pituitary thyroid stimulation hormone (TSH)
TSH- governed by the hypothalamic thyrotropin-releasing hormone (TRH)
Production of TSH= regulated by a negative feedback effect of thyroid hormones on the anterior pituitary gland
Plasma iodide conc= influences thyroid function
Regulation of thyroid secretion
Reduced iodine intake with reduced plasma iodide conc= DECREASE of hormone production and INCREASE in TSH production
INCREASED plasma iodide= opposite effect
Overall feedback mechanism responds to changes of iodide slowly over long periods of of time
Diets deficient in iodine= continuous excessive compensatory secretion of TSH -> INCREASE in vascularity hypertrophy of the gland
‘Derbyshire neck’ condition- dietary iodine were once scarce
Regulation of thyroid secretion
Iodide= essential for TH synthesis but excess of endogenous / exogenous iodide (30x the daily req) inhibits the increased thyroid hormone production = occurs in thyrotoxicosis
Actions of thyroid hormones
Effects on metabolism;
TH= produce a general INC in the metabolism of carbs, fats + proteins
T3= 3-5x more active than Tv
-INC in oxygen consumption + heat production = manifested as an INC in the measured basal metabolic rate
-Calorigenic action = important part of the response to a cold environment
Exogenous administration of TH= augmented cardiac rate + output + INC tendency to dysrhythmias= atrial fib
Actions of thyroid hormones
Effects on growth and development;
TH= critical effect on growth, partly by a direct action on cells + indirectly influencing growth hormone production and potentiating its effects on its target issues
Hormones= essential for normal growth and maturation of the CNS
Hyperthyroidism; thyrotoxicosis
= excessive activity of the TH = high metabolic rate, INC in skin temp + sweating and a marked sensitivity to heat
Nervousness, tremor, tachycardia, heat sensitivity + INC appetite= loss of weight
2 common types;
*Diffuse toxic goitre; Graves’ disease/ exophtalmic goitre= organ-specific autoimmune disease caused by thyroid-stimulating immunoglobulins directed at the TSH receptor. Enhanced sensitivity to catecholamines
*Toxic nodular goitre= caused by a benign neoplasm / adenoma and may develop in pts with long-standing simple goitre
-simple, non-toxic goitre = caused by a dietary deficiency of iodine - if prolonged causes a rise in plasma TSH -> INC in the size of the gland
Treatment of hyperthyroidism
May be treated; pharmacologically, surgically or by destruction of the thyroid gland by Bparticles emitted by radioactive iodine (131I)
Radioiodine (131I)
First line treatment for hyperthyroidism
Bparticles= short range, absorbed by the tissue + exert a powerful cytotoxic action that is restricted to the cels of the thyroid follicles
-administered orally in solution as sodium 131I
-rapidly absorbed, conc by the thyroid + incorporated into storage follicles
-destruction of the thyroid parenchyma = evident within few weeks of administration
Advantages;
Ease of administration, effectiveness, low exposure + absence of pain
Disadvantages;
Should not be administered to pregnant woman/nursing mothers= destroys the foetal thyroid gland and is excreted in milk
-theoretical risk of thyroid cancer
Thioureylenes
Carbimazole, methimazole + propylthiouracil
Decrease the output of TH from the gland and cause a gradual reduction in the signs + symptoms of thyrotoxicosis
Known to inhibit the oxidative processes req for iodination of tyrosyl groups + coupling of iodotyrosines to form T3 + T4
-^ do not have an effect on the thyroglobulin already stored in the gland
*propylthiouracil = reduces deiodination of T4 to T3 in peripheral tissues
Thioureylenes
Pharmacokinetics;
-given orally
*Carbimazole= rapidly converted to methimazole- distributed throughout the body water and has a plasma half-life of 6-15hrs
Clinical response to Carbimazole = take several weeks bc T4 has a long half-life. Also thyroid may have large stores of hormone which need to be depleted before the drugs action can be fully manifest
Both *methimazole + *propylthiouracil = cross placenta and appear in milk
Unwanted effects;
Granulocytopenia, rashes; maculopapular pruritic rash, headaches, nausea, jaundice + pain in joints
Iodine/iodide
Iodine -> converted in vivo to iodide (I-) = temporarily inhibits the release of thyroid hormones
High doses of iodine are given to thyrotoxic patients= symptoms subside within 1-2days
Inhibition of the secretion of TH + over a 10-14 day period a marked reduction in vascularity of the gland = becomes smaller and firmer
Iodine= given orally in a solution with potassium iodide
Adrenoceptor blocking agents
B blockers; metoprolol, propranolol + atenolol
Used as adjuncts in the management of thyrotoxicosis (thyroid storm) since the symptoms mimic those associated with sympathetic stimulation
B blockers = cause clinical improvement of hyperthyroid symptoms but do not typically alter TH Levels.
IV administration= effective in treating thyroid storm
Hypothyroidism
Decreased activity of the thyroid results in hyperthyroidism + myxoedema
Is an immune-mediated destruction of the thyroid gland
Manifestations; low metabolic rate, slow speech, deep hoarse voice, lethargy, bradycardia, sensitivity to cold + mental impairment
Therapy of thyroid tumours with radioidine = hyperthyroidism
Thyroid deficiency during development caused by congenital absence/incomplete development of the thyroid in newborns -> cretinism= characterised by gross retardation of growth + mental deficiency
Hypothyroidism
Treatment;
Unless it is caused by iodine deficiency = treated with iodide
-administer the TH themselves as replacement therapy
*Thyroxine (levothyroxine)= preferred due to being better tolerated + longer half life
*thiiodothyronine
Unwanted effects;
Overdose, signs+symps of hyperthyroidism; nervousness, intolerance to heat + unexp weight loss
-risk of precipitating angina pectoris, cardiac dysrhythmias or even cardiac failure
