Carvedilol Analysis

Baroreceptors activate the sympathetic nervous system, with an increase in heart rate and blood pressure and vasoconstriction, causing beta receptor downregulation, and further increased adrenergic tone with pathological activation of the renin-angiotensin-aldosterone-system (Johnson, 2014). Angiotensin II releases catecholamine and stimulates renin release, which raises tone and pressure on the heart, and leads to aldosterone secretion, also increasing the pressure load on the heart; water and sodium retention through the presence of vasopressin and aldosterone add to preload (Johnson, 2014). This model is used to explain the compensatory mechanisms employed to maintain cardiac reserve, the ability of the heart to respond to increased needs; additional neurohormonal changes involve natriuretic peptides, atrial natriuretic peptide, brain natriuretic peptide and endothelin 1 (Johnson, 2014; Porth,

Intro- Heart Failure is a multifactorial disease due to significant diminishing of heart pumping action. This is occurs in response to many underlying disease such as diabetes, hypertension, myocardial infarction and cardiac myopathies. These conditons lead to hemodynamic instability, neuroendocrine imbalances and structural remodeling of cardiac myocytes. Early less sever hf allows for compensatory mechanisms such as neuroendocrine stimulation- (beta adrenbergic r endothelin norepinephrine r), and hypertrophy which allow for sufficient left ventricular pumping action. However as hf develops these mechanisms become unable to compensate for the progressive underlying disease which results in further loss of contraction and relaxation efficiency and loss of regulation.

Nitroglycerin dilates blood vessels by affecting vascular smooth muscle. In stable angina, it decreases cardiac oxygen demand, and in variant angina, it increases oxygen supply ( Moini, 2012).

Prolonged tachycardia - may impair subendocardial blood flow and increase myocardial oxygen consumption; both may ultimately contribute

The class I anti- arrhythmogenic drugs, which include subclasses Ia (disopyramide), Ib (lignocaine/lidocaine), and Ic (flecainide/encainide) were tested in ischemic pig models to determine efficacy (Aupetit, Loufoua-Moundanga, Facuon, and Timour, 1997). This was quantified by measuring changes in the electrical fibrillation threshold (EFT) after the addition of the individual drugs during increasing periods of ischemia. The results showed an increase in incidence of spontaneous ventricular fibrillation after each drug treatment when in the ischemic environment. Another result was a decrease in the duration of monophasic action potentials (MAP) after the drug treatment. Because this time became shorter, the critical level for triggering fibrillation was reached sooner (Aupetit, et al., 1997). Lastly, the impaired intraventricular conduction, a direct result of the ischemia, was worsened by the depressant effects of the anti-arrhythmic drugs. Though these drugs do have anti-arrhythmic properties, adding them to the environment of heart failure results in decreased efficacy (Aupetit, et al.,

Amlodipine has been established to block contraction and restore blood flow in coronary arteries and arterioles in response to calcium, potassium epinephrine, serotonin, and thromboxane A2 analog in experimental animal models and in human coronary vessels in vitro. This inhibition of coronary spasm is responsible for the effectiveness of Amlodipine in vasospastic (Prinzmetal's or variant) angina.

Propranolol is a beta-blocker. Beta-blockers affect the heart and circulation (blood flow through arteries and veins).

Since this enzyme is being blocked, the blood vessels are able to widen and relax, causing the blood to flow through the vessels much easier. This relaxation and widening of the vessel will cause the blood pressure to decrease because the heart does not have to work as hard. The medication should be taken once each morning, with or without food. Take the pill with a full glass of water. Make sure you are checking your blood pressure each morning before taking your pill. If your blood pressure is lower than what the doctor has set your guidelines than withhold the drug and contact your physician. Make sure to take exact amount of medication prescribed by your

Carvedilol (CAR, Figure 1) is a racemic mixture in which nonselective β-adrenoreceptor blocking action resides in the (-) enantiomer whereas blocking α1-adrenergic receptors is due to both (+) and (-) enantiomers at the same potency. The (-) isomer of CAR is administered in congestive heart failure in combination with diuretic therapy and ACE inhibitors. (-) CAR reduces lipid peroxidation level, as is

The sympathetic pathway is considered the flight or fight system, causing vasoconstriction and increased heart rate. The parasympathetic pathway decreases heart rate and vasodilation. Any autonomic-anticholinergic medication blocks the parasympathetic pathway by binding of the neurotransmitter acetylcholine, the sympathetic pathway has control, allowing the heart rate to increase causing tachycardia and cause ischemia. According to Parlow, Van Vlymen, & Odell (1997), there is a noted increase in patients’ heart rate over a prolong period of time due to the blocking (after anticholinergic administration) of the parasympathetic system which could ultimately cause ischemia.

Pharmacologic interventions are used to prevent blood clots from occurring in the body. Coronary vasodilators and antithrombotic drugs are used to increase oxygen delivery to the myocardium. Vasodilators and cardiac depressants, which decrease heart rate and contractility), are drugs used to decrease the oxygen demand. A decrease in demand compensates for the lack of oxygen going to the myocardium . Vasodilators include calcium channel blockers and nitrodilators; cardioinhibitory drugs include beta-blockers and calcium channel blockers; and antithrombotic drugs include anticoagulants and antiplatelet

The mechanism for fall in arterial pressure after intravenous induction is multifactorial. The fall in arterial pressure after the propofol is associated with both, vasodilatation with reduced preload and afterload and myocardial depression because of the negative inotropic effect.2,14-16 This hypotension is caused by inhibition of sympathetic nervous system and impairement of baroreceptor regulatory mechanism.17 Similar to our results, Saricoaglu et al14 found that propofol was associated with significant fall in arterial blood pressure as compared to etomidate and attributed this hypotension to the negative ionotropic effect of propofol. Conversely, etomidate distinctively have the capacity to bind and stimulate peripheral alpha-2 beta adrenergic receptors with subsequent vasoconstriction18 and its lack of effect on sympathetic nervous system and baroreceptor function.2,19 These unique effects may be responsible for the haemodynamic stability after the

Since the evolution of H2S as an essential gasotransmitter at cellular level, and based on the fact that H2S characteristically similar to NO; researchers aimed to investigate the physiological effects of H2S on cardiovascular system, proposing that H2S donors may become a potential treatment for various cardiovascular abnormalities including atherosclerosis, hypertension, vasoconstriction and cellular apoptosis induced by reactive oxygen species [24-26]. The cellular mechanism by which H2S induce cardiovascular effects is not well illustrated yet. A recent study suggested that H2S can reduce heart rate and blood pressure through KATP channel activation when intracerebroventricular NaHS (H2S donor) significantly reduced the blood pressure and heart rate of experimental rats, while Glibenclamide, a potent KATP channel blocker, effectively attenuated and reversed the effect of NaHS on heart rate and blood pressure [38].

Calcium channel blockers cause coronary vasodilation and afterload reduction, in addition to reducing contractility of the myocardium. They are now considered a secondary treatment when beta-blockers and/or nitrates are not fully effective. None of the calcium channel blockers have been shown to lower the mortality in coronary artery disease, and may increase mortality because they raise heart

The focus of this essay is on targets and receptors in the treatment of conditions of the cardiovascular system. In the heart we have Adrenergic receptors. These are a type of g protein couple receptors that are targets of the catecholamines .Catecholamines are hormones produced by the adrenal glands the main ones being Dopamine, Epinephrine(adrenaline) and norepinephrine .The types of adrenergic receptors are alpha,beta 1 and beta 2.Alpha receptors are located on the arteries. When they are stimulated by epinephrine or norepinephrine , the arteries constrict. This has the effect of increasing blood pressure and the blood flow returning to the heart.