Hypertension combination therapy

Hypertension (monotherapy) PO Initially, 5-lOmg/day. Range 20-40 mg/day. Hypertension (combination therapy) PO Discontinue diuretic 2-3 days prior to initiating benazepril, then dose as noted above. If unable to discontinue diuretic, begin benazepril at 5 mg/day. 

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... 

Phentermine use should be avoided in patients concomitantly receiving or having received an MAOI within the preceding 14 days. Combination therapy with any stimulant or MAOI has the potential for causing hypertensive crisis. Alcohol is not recommended for patients prescribed phentermine.38... 

Nifedipine is used for preventing and relieving angina pectoris attacks, for hypertension, and as an ingredient in combination therapy for chronic cardiac insufficiency. Synonyms of this drug are adalat, corinfar, procardia, and nifecor. 

These agents inhibit the Na-i- ion channei in the iuminai epitheiium. This causes hyperpolarisation of the iuminai membrane and iimits the transfer of cations across the iuminai surface. Flyperpolarisation not only prevents the reabsorption of Na-i- but aiso reduces the excretion of intracellular cations such as K+, Ca2+, Fi+ and Mg2+. The abiiity of sodium ion channel inhibitors to reduce the excretion of K+ is used to conserve body K+ in patients who are taking thiazide or loop diuretics and for this reason they are more commoniy known as the K-i-sparing diuretics. They are rarely used alone because their diuretic action is weak, instead they are administered in combination with thiazide or ioop diuretics for their antikaiuretic effect. Combination therapy is also synergistic when used in the treatment of hypertension. 

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. 

Valsartan (22) is an orally active, angiotensin II antagonist that is marketed under the name Diovan by Novartis for hypertension. Novartis has also developed a combination therapy, valsartan plus hydrochlorothiazide, for the second-line therapy of hypertension. The synthesis is straightforward from a stereochemical viewpoint because a chiral pool synthesis is used. The stereogenic center is derived from L-valine (Scheme 31.17).220 223... 

Therapeutic uses Thiazide diuretics decrease blood pressure in both the supine and standing positions postural hypotension is rarely observed, except in elderly, volume-depleted patients. These agents counteract the sodium and water retention observed with other agents used in the treatment of hypertension (for example, hydralazine). Thiazides are therefore useful in combination therapy with a variety of other antihypertensive agents including (3-blockers and ACE inhibitors. Thiazide diuretics are particularly useful in the treatment of black or elderly patients, and in those with chronic renal disease. Thiazide diuretics are not effective in patients with inadequate kidney function (creatinine clearance less than 50 mls/min). Loop diuretics may be required in these patients. 

Flutamide (EULEXIN, EUFLEX) Nonsteroidal LH increased T increased Monotherapy Combination therapy Potency spared Breast tenderness, nausea and vomiting, diarrhea, rectal bleeding, hot flashes, cystitis, increased appetite, sleep disturbances, hepatotoxicity, anemias, hemolysis, headache, dizziness, malaise, blurred vision, anxiety, depression, decreased libido, hypertension, complications in patients with cardiovascular disease... 

Bicalutamide (CASODEX) Nonsteroidal LH increased T increased Combination therapy Potency spared Less diarrhea than with flutamide Libido unaffected In combination therapy with a LH-RH analog hot flushes, diarrhea, general pain, constipation, asthenia, hypertension In monotherapy dizziness, confusion, nausea, vomiting, rash and hepatitis... 

On retrospective assessment of a large number of cirrhotic patients, some of whom we treated for more than 10 years, it is our impression that long-term administration of spironolactone -I- molsidomine + P-blocker is of therapeutic value for portal hypertension and, at least as far as this problem is concerned, also for primary and progressive pulmonary hypertension. Such combination therapy is also pharmacologically plausible, (s. p 743)... 

Manolis AJ, Grossman E, Jelakovic B, Jacovides A, Bernhardi DC, Cabrera WJ, Watanabe LA, Barragan J, Matadamas N, Mendiola A, Woo KS, Zhu JR, Mejia AD, Bunt T, Dumortier T, Smith RD. Effects of losartan and candesartan monotherapy and losartan/hydrochlorothiazide combination therapy in patients with mild to moderate hypertension. Losartan Trial Investigators. Chn Ther 2000 22(10) 1186-203. 

Based on the weight of all evidence, ACE inhibitors/ARBs are preferred first-line agents for controlling hypertension in diabetes. The need for combination therapy should be anticipated, and thiazide diuretics should be the second agent added in most patients to lower BP. Based on scientific evidence, /3-blockers and CCBs are useful evidenced-based agents in this population but are considered add-on therapies to the aforementioned agents. 

In September 1997, the FDA requested the manufacturers of fenfluramine and dexfenfluramine to voluntarily withdraw their products from the market. This was done following case reports of valvular heart disease in patients taking either medication as monotherapy or in combination with another anorexic agent, phentermine. Because no association has been found between phentermine alone and valvular heart disease, it is still available. Isolated case reports of pulmonary hypertension and phentermine monotherapy have been reported, but present data do not support an association. Although fenfluramine and phentermine were both approved by the FDA to be used as anorectic agents, the combination therapy, fen-phen, was never approved. 

Discuss combination therapy with trandolapril in the treatment of hypertension. 

Discuss combination therapy in the treatment of essential hypertension. 

Combinations of drugs often are employed to therapeutic advantage when their beneficial effects are additive or synergistic or because therapeutic effects can be achieved with fewer drug-specific adverse effects by using submaximal doses of drugs in concert. Combination therapy often constitutes optimal treatment for many conditions, including heart failure see Chapter 33), hypertension see Chapter 32), and cancer see Chapter 51). This section addresses pharmacodynamic interactions that produce adverse effects. 

THIAZIDE DIURETICS The thiazide diuretics (diuril, hydrodiuril, others) are most frequently used in the treatment of hypertension they play a more restricted role in the treatment of CHF. Thiazides exhibit true synergism with loop diuretics the natriuresis that follows coadministration exceeds the summed effects of the drugs administered individually. This synergism is the rationale for combination therapy in patients who appear refractory to loop diuretics. Thiazides are associated with a greater degree of wasting for comparable volume reduction than are loop diuretics. 

For a few years, hexamethonium and hydralazine were mainstays in the treatment of severe hypertension. They were reasonably effective in lowering blood pressure, but often caused severe side-effects. The final dmg developed in those early days, reserpine, was the product of more than two decades of research into compounds derived from Rauwolfia serpentina, a plant used for centuries by physicians and herbalists on the Indian subcontinent. The quality of the result obtained with the various dmgs used in mono- or combined therapy to treat hypertension proved clearly that fatal outcomes associated with this disease are caused by high blood pressure. ... 

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