Antihypertensives tolerance development

Psychoeducation of the patient and family is required to avoid the development of hopelessness in both the patient and family, and the clinician. Comparing these strategies with other treatments of medical disorders can be useful to help patients and their families understand the medication plan and to improve compliance with and tolerance of treatment. In this instance the example of hypertension is appropriate diuretics may be used alone, or combined with other antihypertensives in different trials, according to response. 

Pindolol. The antihypertensive beta-blocker pindolol was studied in 32 subjects in a crossover study comparing pindolol (20 mg, twice daily), methylphenidate, and placebo (Buitelaar et al., 1996). Pindolol significantly reduced ADHD symptoms, but two subjects developed nightmares and hallucinations on the medication. Because lower doses were not examined in this study, it is possible that lower doses may be effective and better tolerated. 

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

As early as in the 1970s, the potential use of cannabinoid ligands as antihypertensive agents had been considered (Archer 1974 Crawford and Merritt 1979 Varma et al. 1975 Zaugg and Kyncl 1983), in the hope that their neurobehavioral and cardiovascular effects could be separated. Although an early study in normotensive rats indicated rapidly developing tolerance to the hypotensive and bradycardic effects of THC (Adams et al. 1976), a subsequent study in spontaneously hypertensive rats (SHR) found no evidence for tolerance for the same effects during a similar, 10-day treatment period (Kosersky 1978). 

An adverse effect of prazosin and its congeners is the first-dose effect marked postural hypotension and syncope may occur 30-90 minutes after the initial dose. The mechanisms responsible for exaggerated hypotensive response and the subsequent development of tolerance to the effect are not clear an action in the CNS to reduce sympathetic outflow may contribute. Risk of the first-dose phenomenon is minimized by limiting the initial dose (e.g., 1 mg at bedtime), by increasing the dosage slowly, and by introducing additional antihypertensive drugs cautiously. Since orthostatic... 

P receptor antagonists do not usually cause salt and water retention, and diuretic administration is not necessary to avoid edema or the development of tolerance. However, diuretics do have additive antihypertensive effects when combined with /5 blockers. The combination of a /5 receptor antagonist, a diuretic, and a vasodilator is effective for patients who require a third drug. /5 Adrenergic receptor antagonists are preferred drugs for hypertensive patients with conditions such as myocardial infarction, ischemic heart disease, or congestive heart failure. 

With the availability of newer drugs that are both effective and well tolerated, the use of reserpine has diminished because of its CNS side effects. Nonetheless, there has been some interest in using reserpine at low doses, in combination with diuretics, in hypertension therapy, especially in the elderly. Reserpine is used once daily with a diuretic, and several weeks are necessary to achieve a maximum effect. The daily dose should be limited to 0.25 mg or less, and as little as 0.05 mg/day may be effective when a diuretic is also used. Reserpine is considerably less expensive than many other antihypertensive drugs thus, it is still used in developing nations. 

The risk of ACE inhibitor-induced renal impairment in patients with or without renovascular disease can be potentiated by diuretics. " In an analysis of 74 patients who had been treated with captopril or lisinopril, reversible acute renal failure was more coimnon in those who were also treated with a diuretic (furosemide and/or hydrochlorothiazide) than those who were not (11 of 33 patients compared with 1 of 41 patients). Similarly, in a prescription-event monitoring study, enalapril was associated with raised creatinine or urea in 75 patients and it was thought to have contributed to the deterioration in renal function and subsequent deaths in 10 of these patients. However, 9 of these 10 were also receiving loop or thiazide diuretics, sometimes in high doses. Retrospective analysis of a controlled study in patients with hypertensive nephrosclerosis identified 8 of 34 patients who developed reversible renal impairment when treated with enalapril and various other antihypertensives including a diuretic (furosemide or hydrochlorothiazide). In contrast, 23 patients treated with placebo and various other antihypertensives did not develop renal impairment. Subsequently, enalapril was tolerated by 7 of the 8 patients without deterioration in renal function and 6 of these patients later received diuretics. One patient was again treated with enalapril with recurrence of renal impairment, but discontinuation of the diuretics (furosemide, hydrochlorothiazide, and triamterene) led to an improvement in renal function despite the continuation of enalapril. ... 

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