Antihypertensive drugs essential

If 50% of Europeans with essential hypertension are affected by this disease because of an elevated secretion of endogenous ouabain, then there might be a chance to block its interaction at the cardiac glycoside binding site of Na+/K+-ATPase and thus lower blood pressure. This therapeutic approach seems to be successfiil. Recent studies provide evidence that the cardenolide analogue Rostafuroxin (PST 2238 Fig. 4) at very low concentrations can overcome the ouabain-induced tise of hypertension in experimental animals [6]. This compound has recently entered the phase I of clinical trials and is certainly a prototype of a new class of antihypertensive drugs. 

Hypertension infrequently results from another disease, such as a catecholamine-secreting tumor (pheochro-mocytoma) in most cases the cause carmot be determined essential (primary) hypertension. Antihypertensive drugs are indicated when blood pressure cannot be sufficiently controlled by means of weight reduction or a low-salt diet. In principle, lowering of either cardiac output or peripheral resistance may decrease blood pressure (cf p. 306,... 

Teprotide was used as an active antihypertensive drug in patients with essential hypertension, but due to a lack of oral activity it was administered parenterally. Teprotide has been the first lead for novel orally active AC E-inhibitors, with three important lead-molecules having been discovered as follows succinyl-L-proline, (2S)-methylsuccinyl-L-proline and 3-mercaptopropanoyl-L-proline affording at the end the first successful drug in this class captopril, as discovered by Ondetti, Rubin and Cushman [1] (Fig. 6.3). 

Tranquilizers are drugs essentially used in the management and, treatment of psychoses and neuroses. They specifically exert their action on the lower brain areas to produce emotional calmness and relaxation without appreciable hypnosis sedation euphoria or motor impairment. In addition many of these drugs also display clinically beneficial actions, for instance skeletal muscle relaxants, antihypertensive, antiemetic and antiepileptic properties. 

Monotherapy with these mixed-acting antihypertensive drugs reduces blood pressure as effectively as other major antihypertensives and their combinations (15,16,17). In the stepped-care approach to antihypertensive drug therapy, mixed a/p-blockers are recommended for initial management of mild to moderate hypertension (step 1). Both drugs effectively lower blood pressure in essential and renal hypertension. Carvediioi also is effective in ischemic heart disease. 

Second and subsequent weeks Increase dosage to 50 mg 4 times daily. Maintenance Adjust dosage to lowest effective level. Twice daily dosage may be adequate. In a few resistant patients, up to 300 mg/day may be required for a significant antihypertensive effect. In such cases, consider a lower dosage of hydralazine combined with a thiazide or reserpine or a beta-blocker. However, when combining therapy, individual titration is essential to ensure the lowest possible therapeutic dose of each drug. 

Endothelin converting enzyme (ECE) has yet to be fully characterized. It is a membrane-located enzyme found in the vascular endothelium. It is essential in the production of endothelin in the body since it converts the inactive precursor big ET-1 to endothelin-1. It is an unusual enzyme because it cleaves at a Tyr-Val link. Like endopeptidase-24.11, it is inhibited by phosphoramidon (so is a metalloproteinase), and these two enzymes are often colocated. Furthermore, monoclonal antibody co-precipitation studies indicate they share a common epitope, and a homology to the extent of about 39%, ECE is also similar to the bacterial metalloprotease thermolysin, but is more specific. If a specific inhibitor is discovered that can act in vivo, then clearly such a drug could modulate endothelin production throughout the body, which would have important consequences (e.g. in antihypertensive therapy). 

As expected, this drug is very effective in renovascular, malignant, and essential hypertensives characterized by high renin levels. Surprisingly, however, it is also effective in patients with normal renin levels and even in some low renin patients. The doses of captopril used in these studies were 50-100 times those previously shown to be required to block the conversion of angiotensin I to angiotensin II, so inhibition of the CE may not completely account for its antihypertensive action. ... 

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