Hypertension, antihypertensive effect

The efficacy of these diuretics led to their extensive use in the clinic, particularly in treatment of hypertension. In theory at least, reduction of the blood volume by diuresis should lead to a lowering of pressure (PV=RT). This expectation was in fact met in actual practice. Recent research does, however, seem to indicate that the thiazides have an antihypertensive effect beyond that explainable by a simple lowering of blood volume. 

The amphetamines and the anorexiants should not be given during or within 14 days after administration of monoamine oxidase inhibitors (see Chap. 31) because the patient may experience hypertensive crisis and intracranial hemorrhage. When guanethidine is administered with the amphetamines or the anorexiants, the antihypertensive effect of guanethidine may decrease. Coadministration of the amphetamines or the anorexiants with the tricyclic antidepressants may decrease the effects of the amphetamines or the anorexiants. 

Patients with asymptomatic left ventricular systolic dysfunction and hypertension should be treated with P-blockers and ACE inhibitors. Those with heart failure secondary to left ventricular dysfunction and hypertension should be treated with drugs proven to also reduce the morbidity and mortality of heart failure, including P-blockers, ACE inhibitors, ARBs, aldosterone antagonists, and diuretics for symptom control as well as antihypertensive effect. In African-Americans with heart failure and left ventricular systolic dysfunction, combination therapy with nitrates and hydralazine not only affords a morbidity and mortality benefit, but may also be useful as antihypertensive therapy if needed.66 The dihydropyridine calcium channel blockers amlodipine or felodipine may also be used in patients with heart failure and left ventricular systolic dysfunction for uncontrolled blood pressure, although they have no effect on heart failure morbidity and mortality in these patients.49 For patients with heart failure and preserved ejection fraction, antihypertensive therapies that should be considered include P-blockers, ACE inhibitors, ARBs, calcium channel blockers (including nondihydropyridine agents), diuretics, and others as needed to control blood pressure.2,49... 

Some optically active compounds have been studied [54], The benzazepinone diacid (CGS 12831, 27) was found to have the best in vitro inhibitor potency in a series of lactam compounds, but it showed only marginal biological activity following oral administration, presumably because of poor absorption. The corresponding monoethyl ester (CGS 14824A, 28) was much more potent in vivo [54, 56]. This compound (28) was found to produce dose-dependent antihypertensive effects in conscious normotensive and spontaneous hypertensive rats, generally similar to those produced by enalapril. Evaluation of (28) in healthy volunteers [57, 58] shows that it is an effective,... 

Maruyama, H., Sumitou, Y., Sakamoto, T., Araki, Y. and Hara, H. (2009) Biol. Pharm. Bull., Antihypertensive effects of flavonoids isolated from Brazilian green propolis in spontaneously hypertensive rats, 32(7), 1244-1250. 

Rauwolfia derivatives became available in the 1950s in western medicine for the treatment of hypertension. The antihypertensive effects of rauwolfia alkaloids occur from their depletion of monoamines in adrenal chromaffin cells and sympathetic ganglia, and perhaps central neurons as well (Oates 1996). 

Oxdralazine (67) is characterized by a bis(2-hydroxyethyl)amino group attached to position 6 of 3-hydrazinopyridazine. The antihypertensive effect of (67) has been studied in rats (spontaneous, desoxycorticosteron-induced, and renal hypertension) [223]. Its effect in the long-term treatment of hypertensive rats on plasma and kidney renin activities has been reported [224]. The effects of (67) on the general and cardiac haemodynamics of anaesthe-... 

Several peptides possessing antihypertensive effect proved to play a promising role in regnlating vascnlar fnnctions as described in the past researches. The present chapter is aimed to offer an overview of a new functionality of small peptides in preventing hypertension and vessel dysfunctions including atherosclerosis. 

Table 1 summarizes the antihypertensive effects of ACE inhibitory small peptides. Information of dosage is also listed. It is clear that small peptides can exert an antihypertensive action following oral administration to mild hypertensive subjects, similar to therapeutic ACE inhibitory drugs, despite their poor potency on ACE inhibitory activity. It seems likely that ca. 20-fold higher doses of small peptides than drugs are required to... 

Kawasaki T, Seki E, Osajima K, Yoshida M, Asada K, Matsui T, Osajima Y. (2000) Antihypertensive effect of valyl-tyrosine, a short chain peptide derived from sardine muscle hydrolyzate, on mild hypertensive subjects. 

Sekiya S, Kobayashi Y, Kita E, Imamura Y, Toyama S. (1992) Antihypertensive effects of tryptic hydrolysate of casein on normotensive and hypertensive volunteers. J Jpn Soc Nutr Food Sci 45 513-517. 

Kajimoto O, Maruyama H, Tokunaga K, Yoshida C, Suzuki K, Araki Y, Mishima S, Sakamoto A, Kajimoto Y, Hirata H. (2004) Antihypertensive effect of protease-treated royal jelly in subjects with high-normal or mild hypertension. J Nutr Food 7 53-71. 

Lee SH, Qian ZJ, Kim SK. (2010) A novel angiotensin 1 converting enzyme inhibitory peptide from tuna frame protein hydrolysate and its antihypertensive effect in spontaneously hypertensive rats. Food Chem 118 96-102. 

Hypertension - Starting dose usually is 180 to 240 mg once daily. Maximum antihypertensive effect usually is observed by 14 days of chronic therapy. May be titrated to a maximum dose of 540 mg daily. 

Hypertension 180 to 240 mg once daily. Maximum antihypertensive effect is usually achieved by 14 days chronic therapy. Usual range is 240 to 360 mg once daily experience with doses more than 360 mg is limited. 

When treating acute hypertensive episodes in patients with chronic hypertension, discontinuation of infusion is followed by a 50% offset of action in 30 minutes but plasma levels of drug and gradually decreasing antihypertensive effects exist for about 50 hours. 

For initial therapy, start with the 0.1 mg system. If, after 1 or 2 weeks, desired blood pressure reduction is not achieved, add another 0.1 mg system or use a larger system. Dosage greater than two 0.3 mg systems usually does not improve efficacy. Note that the antihypertensive effect of the system may not commence until 2 to 3 days after application. Therefore, when substituting the transdermal system in patients on prior antihypertensive therapy, a gradual reduction of prior drug dosage is advised. Previous antihypertensive treatment may have to be continued, particularly in patients with severe hypertension. 

Hypertension - Administer with or without food. The usual recommended starting dose is 16 mg once daily when used as monotherapy in patients who are not volume-depleted. Candesartan can be administered once or twice daily with total daily doses ranging from 8 to 32 mg. Most of the antihypertensive effect is present within 2 weeks maximal blood pressure reduction generally is obtained within 4 to 6 weeks of treatment. 

The chief use of reserpine is in the treatment of mild to moderate hypertension. As with other sympathetic depressant drugs, tolerance to the antihypertensive effects of reserpine can occur, owing to a compensatory increase in blood volume that frequently accompanies decreased peripheral vascular resistance. Reserpine, therefore, should be used in conjunction with a diuretic. 

Kita, S., Y. Matsumura, S. Morimoto, et al. Antihypertensive effect of sesamin. 11. Protection against two-kidney, one-clip renal hypertension and cardiovascular hypertrophy. Biol PharmBull 1995 18(9) 1283-1285. Kamal-Eldin, A., D. Pettersson, and L. A. Appelqvist. Sesamin (compound from sesame oil) increases tocopherol levels in rats fed ad libitum. Lipids 1995 30(6) 499-505. 

Tricyclic antidepressants potentiate the pressor effects of directly acting sympathomimetic amines, such as adrenaline (epinephrine) or noradrenaline (norepinephrine), to cause hypertension. Small amounts of these, such as may be present in local anaesthetic solutions, can be dangerous. Tricyclic antidepressants will inhibit the antihypertensive effects of the older anti hypertensive drugs, such as adrenergic neurone-blocking agents, e.g. guanethidine, a-methyl-DOPA, and clonidine. 

Finally, one should note that all of the agents that lower blood pressure by altering sympathetic function can elicit compensatory effects through mechanisms that are not dependent on adrenergic nerves. Thus, the antihypertensive effect of any of these agents used alone may be limited by retention of sodium by the kidney and expansion of blood volume. For this reason, sympathoplegic anti hypertensive drugs are most effective when used concomitantly with a diuretic. 

Hydralazine, a hydrazine derivative, dilates arterioles but not veins. It has been available for many years, although it was initially thought not to be particularly effective because tachyphylaxis to its antihypertensive effects developed rapidly. The benefits of combination therapy are now recognized, and hydralazine may be used more effectively, particularly in severe hypertension. The combination of hydralazine with nitrates is effective in heart failure and should be considered in patients with both hypertension and heart failure, especially in African-American patients. 

Minoxidil is a very efficacious orally active vasodilator. The effect results from the opening of potassium channels in smooth muscle membranes by minoxidil sulfate, the active metabolite. Increased potassium permeability stabilizes the membrane at its resting potential and makes contraction less likely. Like hydralazine, minoxidil dilates arterioles but not veins. Because of its greater potential antihypertensive effect, minoxidil should replace hydralazine when maximal doses of the latter are not effective or in patients with renal failure and severe hypertension, who do not respond well to hydralazine. 

Inhibition of the renin-angiotensin system with ACE inhibitors or ARBs may be incomplete because the drugs disrupt the negative feedback action of Ang II on renin secretion and thereby increase plasma renin activity. Other antihypertensive drugs, notably hydrochlorothiazide and other diuretics, also increase plasma renin activity. Aliskiren not only decreases baseline plasma renin activity in hypertensive subjects but also eliminates the rise produced by ACE inhibitors, ARBs, and diuretics and thereby results in a greater antihypertensive effect (Figure... 

Wang, J., Hu, J., Cui, Z., Bai, X., and Du, Y. (2008b). Purification and identification of a ACE inhibitory peptide from oyster proteins hydrolysate and the antihypertensive effect of hydrolysate in spontaneously hypertensive rats. Food Chem. Ill, 302-308. 

Jung, W. K., Mendis, E., Je, J. Y., Park, P. J., Son, B. W., Kim, H. C, Choi, Y. K., and Kim, S. K. (2006b). Angiotensin-I-converting enzyme inhibitory peptide from yellowfin sole (Limanda aspera) frame protein and its antihypertensive effect in spontaneously hypertensive rats. Food Chem. 94, 26-32. 

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