Angina pectoris

The goal of treatment is to prevent myocardial hypoxia either by raising blood flow (oxygen [02] supply) or by lowering myocardial oxygen demand (02 demand) (A). 

Owing to their large caliber, the proximal coronary segments do not normally contribute significantly to flow resistance. However, in coronary sclerosis or spasm, pathological obstruction of flow occurs here. Whereas the more common coronary sclerosis cannot be overcome pharmacologically, the less common coronary spasm can be relieved by appropriate vasodilators (nitrates, nifedipine). 

The caliber of arteriolar resistance vessels controls blood flow through the coronary bed. Arteriolar caliber is determined by myocardial 02 tension and local concentrations of metabolic products, and is automatically adjusted to the required blood flow (B, healthy subject). This metabolic autoregulation explains why anginal attacks in coronary sclerosis occur only during exercise (B, patient). At rest, the pathologically elevated flow resistance is 

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The intramyocardial pressure, i.e., systolic squeeze, compresses the capillary bed. Myocardial blood flow is halted during systole and occurs almost entirely during diastole. Diastolic wall tension ( preload ) depends on ventricular volume and filling pressure. The organic nitrates reduce preload by decreasing venous return to the heart. 

As for MI, but may be more difficult to distinguish from other conditions causing 

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Other agents are also used for the treatment of manic-depressive disorders based on preliminary clinical results (177). The antiepileptic carbamazepine [298-46-4] has been reported in some clinical studies to be therapeutically beneficial in mild-to-moderate manic depression. Carbamazepine treatment is used especially in bipolar patients intolerant to lithium or nonresponders. A majority of Hthium-resistant, rapidly cycling manic-depressive patients were reported in one study to improve on carbamazepine (178). Carbamazepine blocks noradrenaline reuptake and inhibits noradrenaline exocytosis. The main adverse events are those found commonly with antiepileptics, ie, vigilance problems, nystagmus, ataxia, and anemia, in addition to nausea, diarrhea, or constipation. Carbamazepine can be used in combination with lithium. Several clinical studies report that the calcium channel blocker verapamil [52-53-9] registered for angina pectoris and supraventricular arrhythmias, may also be effective in the treatment of acute mania. Its use as a mood stabilizer may be unrelated to its calcium-blocking properties. Verapamil also decreases the activity of several neurotransmitters. Severe manic depression is often treated with antipsychotics or benzodiazepine anxiolytics. 

Nitroglycerin remains the dmg of choice for treatment of angina pectoris. It has also been found useful for the treatment of congestive heart failure, myocardial infarction, peripheral vascular disease, such as Raynaud s disease, and mitral insufficiency, although the benefits of nitroglycerin in mitral insufficiency have been questioned. 

Other P"Adrenoceptor Blocking Agents. Carteolol hydrochloride (Table 1) is also a Class II antiarrhythmic agent. In three separate studies in patients having angina pectoris, carteolol was considered effective as evidenced by a reduction in the frequency and severity of anginal episodes, reduction in the amount of nitroglycerin consumed, improvement of ECG parameters, or an increase in the duration of trea dmill exercise (42). 

Nifedipine (Table 3) is a potent vasodilator that selectively dilates resistance vessels and has fewer effects on venous vessels. It does not cause reflex tachycardia during chronic therapy. Nifedipine is one of the first-line choices for black or elderly patients and patients having concomitant angina pectoris, diabetes, or peripheral vascular diseases. Nifedipine, sublingually, is also suitable for the treatment of hypertensive emergencies. Nifedipine does not impair sexual function or worsen blood Hpid profile. The side effects are flushing, headache, and dizziness. 

Each of the transdermal nitroglycerin systems is effective in treating angina pectoris when worn for 12—16 h followed by an off period. The FDA recommends the period without dmg (8—12 h) to mitigate the possibiUty of the patient acquiring a tolerance to the antianginal effects of nitrate therapy. Thus, a noncontinuous dosing schedule of nitrates is recommended even with the transdermal deflvery system (81). 

Aggravation of cardiovascular disease (i.e., decreased exercise capacity in patients with angina pectoris, intermittent claudication, or peripheral arteriosclerosis)... 

Dihydropyridines not only are intermediates for the synthesis of pyridines, but also are themselves an important class of N-heterocycles an example is the coenzyme NADH. Studies on the function of NADH led to increased interest in the synthesis of dihydropyridines as model compounds. Aryl-substituted dihy-dropyridines have been shown to be physiologically active as calcium antagonists. Some derivatives have found application in the therapy of high blood pressure and angina pectoris. For that reason the synthesis of 1,4-dihydropyridines has been the subject of intensive research and industrial use. The Hantzsch synthesis has thus become an important reaction. 

Prenyl amine (66) was long used in the treatment of angina pectoris, in which condition it was believed to act by inhibiting the uptake and storage of catecholamines in heart tissue. Droprenilamine (69), an analogue in which the phenyl ring is reduced, acts as a coronary vasodilator. One of several syntheses involves simple reductive alkylation of 1,1-diphenyl-propylamine (67) with cyclohexyl acetone (68)... 

Thromboxane A-2 has been implicated in a number of disorders of the circulatory system including coronary artery spasms, unstable angina pectoris, traumatic and endotoxic shock, and heart attacks. It is formed normally very near its receptors and is rapidly deactivated by metabolizing enzymes so circulating levels are quite low. Furthermore, it is opposed in its actions by the prostacyclins. When these controls are defective, pathology results and drugs can be the resort in attempts to restore the normal healthy balance. For one example, furegrelate (6) is a throm-... 

DHPs are potent arterial vasodilators. They act on resistance vessels and therefore reduce peripheral vascular resistance, lower arterial blood pressure, and antagonize vasospasms in coronary or peripheral arteries. By reducing afterload, DHPs also reduce cardiac oxygen demand. Together with their vascular spasmolytic effect, this explains most of the beneficial actions of DHPs in angina pectoris. Most DHPs are only licensed for the therapy of hypertension, some of them also for the treatment of angina pectoris and vasospastic (Prinzmetal) angina. 

Typical KCO members are diazoxide, pinacidil, cromakalim, and nicorandil. KCOs activate KATP channels by binding to SUR subunits. Diazoxide and nicorandil are clinically used in treatment of PHHI and angina pectoris, respectively. 

Nitroglycerin has long been used for the treatment of acute attack of angina pectoris, and its stable analogs are available to prevent the anginal attack. Nitrovaso-dilators such as sodium nitropmsside liberate NO from their molecules in the tissue (thus, called NO donors) and elicit actions via cyclic GMP like those seen with endogenously synthesized NO. 

Afferent input from cutaneous and visceral nociceptors is known to converge on spinal neurons, which accounts for the referral of pain between visceral and cutaneous structures (e.g. cardiac pain gets referred to the chest and left upper arm in patients suffering from angina pectoris). Projection neurons in the spinal dorsal horn project to cell nuclei in supraspinal areas such as the thalamus, brainstem and midbrain. Of these, the synaptic junctions in the thalamus play a very important role in the integration and modulation of spinal nociceptive and non-nociceptive inputs. Nociceptive inputs are finally conducted to the cortex where the sensation of pain is perceived (Fig. 1). The mechanisms via which the cortex processes nociceptive inputs are only poorly understood. 

Vasodilators are a group of dtugs, which relax the smooth muscle cells of the blood vessels and lead to an increased local tissue blood flow, a reduced arterial pressure and a reduced central venous pressure. Vasodilators reduce the cardiac pre-load as well as after-load and thereby reduce cardiac work. They are used in a variety of conditions including hypertension, cardiac failure and treatment/prevention of angina pectoris. Major groups are Ca2+-channel blockers (e.g. dihydropyridines), NO-donators (e.g. organic nitrates), K+-channel openers (minoxidil), phosphodiesterase inhibitors (e.g. sildenafil), Rho-kinase inhibitors (e.g. Y27632) or substances with unknown mechanism of action (e.g. hydralazine). Inhibitors of the... 

These dm are primarily used in the treatment of hypertension (see the Summary Drug Table Adrenergic Blocking Drugs also see Chap. 39) and certain cardiac arrhythmias (abnormal rhythm of the heart), such as ventricular arrhythmias or supraventricular tachycardia They are used to prevent reinfarction in patients with a recent myocardial infarction (1—4 weeks after MI). Some of these dm have additional uses, such as the use of propranolol for migraine headaches and nadolol for angina pectoris. 

Control of blood pressure in perioperative hypertension and in immediate postoperative period, CHF associated with acute Ml, angina pectoris unresponsive to recommended doses of nitrates or beta blockers... 

Acute relief of an attack of angina pectoris or prophylaxis of angina pectoris... 

Deponit, Minitran, Prevention of Nitro-Dur, angina pectoris... 

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