Thyroid hormones cardiac effects

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]. 

Calcium Acetate (PhosLo) [Calcium Supplement/ Anti arrhythmic/Mmeral/ Electrolyte] Uses ESRD-associated hyper-phos-phatemia Action Ca " supl w/o aluminum to X P04 absorption Dose 2-4 tabs PO w/ meals Caution [C, ] Contra t Ca Disp Gelcap SE Can t Ca, hypophosphatemia, constipation Interactions t Effects OF quinidine X effects W/ large intake of dietary fiber, spinach, rhubarb X effects OF atenolol, CCB, etidronate, tetracyclines, fluoroquinolones, phenytoin, Fe salts, thyroid hormones EMS Pts have reduced renal Fxn, monitor ECG for signs of electrolyte disturbances OD S/Sxs of hypercalcemia (confusion, weakness, GI upset, constipation, N, V, and cardiac arrhythmias) give IV fluid for diuresis symptomatic and supportive Calcium Carbonate (TumS/ Alka Mints) [Antacid/ Calcium Supplement/Mineral/ Electrolyte] [OTC] Uses Hyperacidity associated w/ peptic ulcer Dz, hiatal hernia, etc Action Neutralizes gastric acid Dose 500 mg—2 g PO PRN -1- in renal impair Caution [C, ] Disp Chew tabs, susp SE t -1- PO constipation Interactions X Effect OF tetracyclines, fluo-... 

Management of hypothyroidism consists of identifying the underlying cause and then providing thyroid hormone replacement to normalize thyroid sta-ms. The goal of treatment is to reduce semm TSH levels to normal, which for most assays is roughly between 0.5 and 3 mU/1. Oversuppression of TSH levels is probably not advisable, as overtreatment may predispose to cardiac arrhythmias (particularly atrial fibrillation), and may have subtle effects on bone mineral density. 

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. 

Metaproterenol (Alupent, Metaprel) [Bronchodilator/ Beta-Adrenergic Agonist] Uses Asthma reversible bronchospasm Action Sympathomimetic bronchodilator Dose Adults. Neb 0.2-0.3 mL in 2.5-3.0 mL of NS Peds. Neb 0.1-0.2 mL/kg of a 5% soln in 2.5 mL NS Caution [C, /-] Contra Tach, other arrhythmias Disp Aerosol 0.65 mg/inhal soln for inhal 0.4, 0.6% tabs 10, 20 mg syrup 10 mg/5 mL SE Nervousness, tremors (common), tach, HTN Interactions T Effects W/ sympathomimetic drugs, xanthines T risk of arrhythmias W/ cardiac glycosides, halothane, levodopa, theophylline, thyroid hormones T HTN W/ MAOIs effects W/ BBs EMS Separate additional aerosol use by 5 min fewer 3i effects than isoproterenol longer-acting monitor lung sounds before/after administration... 

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). 

In contrast to other protein-bound drugs for which a loading dose is given to achieve rapid steady-state concentrations, a slow and stepwise increase in thyroid hormone replacement therapy is advisable. This is preferred mainly to avoid sudden cardiac adverse effects, especially in older patients with long-standing myxedema. Moreover, since thyroid hormone substitution can change the metabolic clearance of this drug, steady-state concentrations are obtained only after several months (SEDA-6, 363). 

Case Conclusion GM began thyroid hormone therapy with T4. Her dose was initiated at the lower-than-recom-mended dose because GM has a history of AF, which may increase her sensitivity to the cardiac effects of T4. GM will return to the clinic in 4 to 6 weeks to assess her thyroid function and symptoms. Symptoms should begin to resolve in 2 to 3 weeks and should disappear by 6 weeks. 

D Levothyroxine is the drug of choice for hypothyroidism since it provides the necessary hormone without causing the inaease peak effect of Tj administration, levothyroxine is converted to Tj in the periphery. Liotrix contains T4 and T3 in a 4 1 ratio. This combination is not necessary since the T4 is converted to T3 and the short rz> of liotrix requires multiple daily doses. Desiccated thyroid is unreliable in potency since it is standardized to iodine content and not to T4 or T3 content. Triiodothyronine is also not preferred since rapid gastric absorption can lead to hyperthyroid symptoms and can lead to cardiac effects. 

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... 

A beneficial effect of thyroid hormone on left ventricular remodeling is also reported. In an experimental model of acute myocardial infarction in rats, a decline in serum T3 was observed associated with left ventricular dysfunction and changes in T3 responsive genes. Treatment with high doses of T3 for three weeks resulted in improved cardiac function with normalization of most of the changes in gene expression.89 Similarly, administration of DITPA (a thyroid analogue) after myocardial infarction in rabbits was associated with improved cardiac function.90... 

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-... 

Thyroid hormone enhances cardiac contractility and exerts a positive chronotropic effect on the heart, increasing heart rate by a mechanism that may involve more than a potentiation of the )S-adrenergic effect. In the... 

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