Antihypertensive agents combination

Diuretics, ACE inhibitors, ARBs, and CCBs are primary agents acceptable as first-line options based on outcome data demonstrating CV risk reduction benefits (Table 10-2). /TBIockers may be used either to treat a specific compelling indication or as combination therapy with a primary antihypertensive agent for patients without a compelling indication. 

When diuretics are combined with other antihypertensive agents, an additive hypotensive effect is usually observed because of independent mechanisms of action. Furthermore, many nondiuretic antihypertensive agents induce salt and water retention, which is counteracted by concurrent diuretic use. 

Because data suggest that doxazosin (and probably other oq-receptor blockers) are not as protective against CV events as other therapies, they should be reserved as alternative agents for unique situations, such as men with benign prostatic hyperplasia. If used to lower BP in this situation, they should only be used in combination with primary antihypertensive agents. 

Thus, diuretics, alone or in combination with other antihypertensive agents, represent the cornerstone of our antihypertensive armamentarium. 

Another important diuretic contains both triamterene and hydrochlorothiazide. Triamterene is a diuretic and is known to increase sodium and chloride ion excretion but not potassium ion. It is used in conjunction with a hydrothiazide, which is an excellent diuretic but also gives significant loss of potassium and bicarbonate ions. If the triamterene were not included potassium chloride would have to be added to the diet. Hydrochlorothiazide is an antihypertensive agent as well but, unlike other antihypertensives, it lowers blood pressure only when it is too high, and not in normotensive individuals. These two drugs are made by a number of different manufacturers and do not appear in our top 35 list, but they would rank high if all brands were combined. 

Initial dosage 50 mg once daily, used alone or in combination with other antihypertensive agents. If an optimal response is not achieved, increase to 100 mg/day. Dosage greater than 100 mg/day is unlikely to produce any further benefit. 

Adults - Initially, 50 to 100 mg/day in single or divided doses. May also be combined with diuretics, which act more proximally, and with other antihypertensive agents. Continue treatment for 2 weeks or more because the maximal response may not occur sooner. Individualize dosage. 

When diuretic therapy is indicated for the treatment of primary hypertension, the thiazide-type compounds (e.g., chlorothiazide, hydrochlorothiazide) are generally the drugs of choice. They can be used alone or in combination with other antihypertensive agents Approximately 30% of patients with mild hypertension may be treated effectively with thiazide therapy alone. 

Diuretics are frequently used in combination with other antihypertensive agents. The appropriateness of this combination becomes even more apparent when it is realized that nondiuretic antihypertensives (e.g., hydralazine or diazoxide) produce some increase in plasma volume that if not corrected, would lead to an eventual decrease in their activity (see Chapter 20). 

Quetiapine is metabolized by hepatic CYP 3A3/4. Concurrent administration of cytochrome P450-inducing drugs, such as carbamazepine, decreases blood levels of quetiapine. In such circumstances, increased doses of quetiapine are appropriate. Quetiapine does not appreciably affect the pharmacokinetics of other medications. Pharmacodynamic effects are expected if quetiapine is combined with medications that also have antihistaminic or a-adrenergic side effects. Because of its potential for inducing hypotension, quetiapine also may enhance the effects of certain antihypertensive agents. 

The antihypertensive agent 278 has been 14C-labelled by carbonation of the 2-lithiated indole, 279 (R = Li), with 14CC>2 and subsequent combination with a preformed peptide side chain. In 279 (R = H) the indole nitrogen has been converted into its benzenesulphonyl derivative to direct properly the lithiation while the 2-hydroxy-3-isopropylaminopropoxy side chain has been protected as oxazolidin-2-one290. 

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. 

Using cionidine in combination with another antihypertensive agent may attenuate the development of tolerance to clonidine s antihypeitensive effects... 

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