T T T

Tivity of exogenous administered ANP(99-126). Because of the poor bioavailability of CGS 24592, a series of prodrugs were investigated. CGS 25462 (271) provided significant and sustained antihypertensive effect in the DOCA salt-hypertensive rat after oral administration. 2.1.1 4 Uricosuric Agents. In humans, one of the principal products of purine metabolism (i.e., uric acid) is implicated in several human diseases such as gout. Guanine and adenine are both converted to xanthine (272)...

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In vivo involvement of renal carbonic anhy-drase inhibition. As is the case with the thia-zide diuretics, elevated serum uric acid levels are seen, but there may well be less propensity for hyperglycemia (149-151). In contrast to the thiazide diuretics, insignificant amounts of the drug are excreted unchanged in humans and in dogs. The metabolites are compounds monohydroxylated on the cyclohexane ring. Neither the compound nor its metabolites are stored in the body tissues (152a). 2.1.7.4...

Antianginal Agents and Vasodilators Future Directions

There is increasing evidence of a relationship between apoptosis and pathophysiology in both ischemic and nonischemic cardiomyopathies, and a large number of papers published since 1997 suggest a link between some of the major genetic and biochemical regulators of apoptosis in the heart. There has been a quest for a therapeutic agent that would delay the onset of apoptosis in the ischemic heart. In the future, several therapeutic interventions can be developed to prolong the survival of smooth...

Ono2 Ono2

Chemical structures of various currently used vasodilators for the treatment of angina. 4.6.2 Vasodilating Agents. Various compounds that are currently used as vasodilators are described below. Structures of these compounds are depicted in Fig. 1.6, and some of their properties such as bioavailability, halflife, and some possible side effects are illustrated in Table 1.1. Amyl Nitrite (1) (Fig. 1.6, Table 1.1) This drug is an aliphatic compound with an unpleasant odor. It is a...

Calcium Channel Blockers

Verapamil was the first calcium-channel blocker (CCB). It was first used in Europe (1962) and then in Japan for its antiarrhythmic and coronary vasodilator effects. The have become prominent cardiovascular drugs during the last 40 years. Many experimental and clinical studies have defined their mechanism of action, the effects of new drugs in this therapeutic class, and their indications and interactions with other drugs. Calcium plays a significant role in the excitation-contraction coupling...

Vasodilators

A number of the simple organic nitrates and nitrites find application in both the short- and long-term prophylactic treatment of angina pectoris, myocardial infarction, and hypertension. Most of these nitrates and nitrites are formulated by mixing with suitable inert excipients such as lactose, dextrose, mannitol, alcohol, and propylene glycol for safe handling, because some of these compounds are heat sensitive, very flammable, and powerful explosives. The onset, duration of action, and...

Types of Angina

Stable angina is also called chronic angina, exertional angina, typical or classic angina, angina of effort, or atherosclerotic angina. The main underlying pathophysiology of this, the most common type of angina, is usually atherosclerosis, i.e., plaques that occlude the vessels or coronary thrombi that block the arteries. This type of angina usually develops by exertion, exercise, emotional stress, discomfort, or cold exposure and can be diagnosed using EKG. Therapeutic...

H2no2s

Autonomic Instability

Urine Volume in Rats (mL kg at 1 mg kg) Urine Volume in Rats (mL kg at 100 mg kg) Urine Volume in Rats (mL kg at 1 mg kg) Urine Volume in Rats (mL kg at 100 mg kg) 6Dose (in mg kg) that increases 5-h urine volume by 50 6Dose (in mg kg) that increases 5-h urine volume by 50 tion of 0.2 mg kg i,v. in the dog, accompanied by a continuous infusion of 5 mannitol solution, led to a diuretic effect starting 40 min postinjection. After 2 h, a diuretic effect could still be detected. An antihypertensive...

Pharmacological Evaluation of Diuretics

The following three statements or generalizations are direct quotes from a study by K. H. Beyer and refer to the pharmacological evaluation of drugs in general and to diuretics in particular 20 . The more closely one can approximate under controlled laboratory conditions the physiological correlates of clinically defined disease, the more likely one will be able to modulate it effectively. In vitro experiments are apt to be inadequate and hence misleading when employed solely to anticipate the...

Arylalkylamines and Benzothiazepines

These drugs vary in their relative cardiovascular effects and clinical doses but have the most pronounced direct cardiac effects e.g., verapamil, Fig. 1.7 . Bepridil Hydrochloride 8 Fig. 1.7, Table 1.2 Bepridil is a nondihydropyridine calcium channel blocking agent with antianginal and antiarrhythmic properties. This compound inhibits calcium ion influx across L-type slow, low voltage calcium channels 76 . However, unlike other agents, it also inhibits calcium ion influx across receptor...

N

During PTCAe Angina, mild hypertension Stable angina Hypertension Hypertension Hypertension hypertension Hypertension, angina pectoris Subarachnoid hemorrhage Hypertension, angina pectoris Hypertension Reflex tachycardia, angina Antiatherogenic effects CNSd aND No data obtained because of limited literature information. Compounds 18, 19, 20, 21, 22, and 23 are not available in USA. 6LVFS Left Ventricular Fractional Shortening. CLVEF Left Ventricular Ejection Fraction. dCNS adverse effects...

Cns

CNS, gingival hyperpsia, blood dyscrasias aCNS adverse effects include headache, dizziness, nausea, vomiting, diarrhea, flushing, weakness, rash, and syncope. depolarization shifting the intracellular threshold potential toward zero , decreases transmembrane permeability to the passive influx cf sodium slowing the process of phase 0 depolarization, which decreases impulse velocity , and increases action potential duration 201 .Physiologically, this results in a reduction in SA node impulse...