Heart thyroid hormones effect

Thyroid hormone effects on the heart and peripheral vasculature... 

Within a programme aimed at the development of thyroid hormone analogues as potentially useful plasma cholesterol-lowering agents, the pyrida-zinone derivative SK F L-94901 (98) has been prepared and investigated in the U.K. [419-422]. Whereas naturally occurring thyroid hormones cannot be employed for this purpose because of their undesirable effect on heart rate, (98) has been found to represent a potent thyromimetic which retains hepatic activity but lacks cardiac activity. Structural modifications and QSAR studies have been carried out [422]. 

Z)-2,3-Methanothyronine 59 and its dibromo derivative 60 have comparable activity with the thyroxine 61, a thyroid hormone [66], which exhibited thyro-mimetic activities in basal metabolism and antigoiter tests (comparison of oxygen consumption and heart rate in normal and thyroidectomized rats) but did not have an inhibitory action on the metabolism developed by triiodothyronine [66]. (Z)-2,3-Methanohistidine 62, tested on rat liver, is an effective inhibitor of histidine decarboxylase, Eq. (23) [67]. 

In patients with longstanding hypothyroidism and those with ischemic heart disease, rapid correction of hypothyroidism may precipitate angina, cardiac arrhythmias, or other adverse effects. For these patients, replacement therapy should be started at low initial doses, followed by slow titration to full replacement as tolerated over several months. If hypothyroidism and some degree of adrenal insufficiency coexist, an appropriate adjustment of the corticosteroid replacement must be initiated prior to thyroid hormone replacement therapy. This prevents acute adrenocortical insufficiency that could otherwise arise from a thyroid hormone-induced increase in the metabolic clearance rate of adrenocortical hormones. 

Cardiovascular Effects. Thyroid hormones appear to increase heart rate and myocardial contractility, thus leading to an increase in cardiac output. It is unclear, however, if this occurrence is a direct effect of these hormones or if the thyroid hormones increase myocardial sensitivity to other hormones (norepinephrine and epinephrine). 

Q3 The thyroid hormones thyroxine and triiodothyronine have many metabolic effects. In adults they increase metabolic rate, oxygen and calorie consumption, stimulate carbohydrate metabolism and turnover of protein, deplete fat stores and increase catabolism of free fatty acids. Thyroid hormones stimulate heart rate and force and increase pulmonary ventilation, gastrointestinal motility and central nervous system (CNS) activity. Actions on the heart can result in an increased incidence of dysrhythmias. Thyroid hormones are critical for the normal growth and development of the infant, particularly in respect of skeletal growth and maturation of the CNS. 

Liothyronine Tabs. Liothyronine is the most rapidly effective thyroid hormone, a single dose giving maximum effect within 24 h and passing off over 24—48 h. It is not used in routine treatment of hypothyroidism because its rapid onset of effect can induce heart failure. Its main uses are in myxoedema coma and psychosis, both rare conditions. A specialised use is during the withdrawal of levothyroxine replacement (to permit diagnostic radioiodine scanning) in patients with thyroid carcinoma. 

Adverse effects of thyroid hormone parallel the increase in metabolic rate. The symptoms and signs are those of hyperthyroidism. Symptoms of myocardial ischaemia, atrial fibrillation or heart failure are liable to be provoked by too vigorous therapy or in patients having serious ischaemic heart disease who may even be unable to tolerate optimal therapy. Should they occur levothyroxine must be discontinued for at least a week and begim again at lower dosage. Only slight overdose is needed to precipitate atrial fibrillation in patients over 60 years. 

Quick relief can be obtained with a p-adrenoceptor blocking drug (judge dose by heart rate) though these do not block all the metabolic effects of the hormone, e.g. on the myocardium, and the basal metabolic rate is unchanged. For this reason they should not be used as sole therapy except in mild thyrotoxicosis in preparation for radioiodine treatment, and should be continued in these patients until the radioiodine has taken effect. They do not alter the course of the disease, nor biochemical tests of thyroid function. Any effect on thyroid hormonal action on peripheral tissues is clinically unimportant. It is desirable to choose a drug that is nonselective for pj and p2 receptors and lacks partial agonist effect (e.g. propranolol 20-80 mg 6-8-hourly, or timolol 5 mg once daily). Usual contraindications to P-blockade (see p. 478) should be observed, especially asthma. 

In patients with hypothyroidism, the stimulatory effect of thyroid hormone on the oxidation of fuels is diminished. As a consequence, the generation of ATP is reduced, causing a sense of weakness, fatigue, and hypokinesis. The reduced metabolic rate is associated with diminished heat production, causing cold intolerance and decreased sweating. With less demand for the delivery of fuels and oxygen to peripheral tissues, the circulation is slowed, causing a reduction in heart rate and, when far advanced, a reduction in blood pressure. 

Thyroid hormone has multiple effects on the cardiovascular system with various physiological consequences. Several genes that encode important regulatory and structural proteins in the heart have been shown to be thyroid hormone responsive. Thyroid hormone increases cardiac contractility, induces vasorelaxation and angiogenesis, prevents fibrosis and has favorable effects on lipid metabolism (reviewed by Pantos73). 

The role of thyroid hormone in the response of the heart to ischemia and reperfusion has not been extensively investigated due to the fact that thyroid hormone accelerates heart rhythm and increases oxygen consumption, effects which could be detrimental in the setting of ischemia and reperfusion. However, accumulating experimental evidence shows that either acute or chronic pretreatment with thyroid hormone can lead to cardioprotection. In an isolated working rat heart model, cardiac work and cardiac efficiency were increased after no-flow global ischemia and reperfusion in hearts acutely pretreated with Tr74 Furthermore, thyroxine pretreatment for two weeks resulted in increased recovery of function in isolated rat hearts subjected to zero-flow... 

On the basis of this experimental evidence, it seems likely that in the setting of the ischemic heart disease and hypothyroidism, thyroid hormone replacement may have adverse effects probably due to the loss of the cardioprotection conferred by hypothyroidism and not to the effects of thyroid hormone per se. In support to this notion are clinical observations showing that angina is not uncommon after thyroid hormone replacement in hypothyroid patients. 

Non cardiac effects with important consequences on the course of the ischemic heart disease are elicited in a thyroid hormone receptor iso form manner. In fact, TRal blockade by dronedarone prevented body weight gain by reducing food intake, an ef-... 

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