Resistant hypertension is defined as uncontrolled blood
pressure i.e. more than 140/90 (130/80 in diabetics) with maximum dose of three
different class of antihypertensive drugs of this one diuretics is mandatory. Hypertensive
patient whose blood pressure is controlled with four or more antihypertensive
drugs are called controlled resistant hypertensive.
Around 14% of patients with hypertension are having resistant
hypertension. Patient with uncontrolled BP are prone for CVA, IHD, heart
failure and CKD. So optimal control of blood pressure is important. Patient with resistant hypertension are volume
overloaded so adding an optimum diuretics reduces chance of uncontrolled blood
|Diuretics and site of action|
Recently published study by Bobrie et al
shows benefits adding diuretics which act at multiple levels in nephron. The
rationale for low-dose sequential nephron blockade is to neutralize the effects
of intrarenal compensatory increases in sodium reabsorption at unblocked sites
along the nephron triggered by the use of high-dose diuretics acting at a
single site. Apart from this low dose of diuretics reduces chance of side
Bobrie et al
study was prospective, randomized, open blinded endpoint study of 167
patients. At base line after treatment of 4 weeks with irbesartan 300
mg/day, hydrochlorothiazide 12.5 mg/day and amlodipine 5 mg/day, ambulatory
blood pressure was more than 135/85. These were randomized to sequential nephron
blocked n=82 Vs sequential rennin-angiotensin system blockade n=85. Spironolactone
25 mg/day in or ramipril 5 mg/day in were added for 4 weeks respectively to sequential
diuretic and RAAS blocked group respectively.
At 12 weeks, the mean difference
of ambulatory blood pressure in daytime was 10/4 mmHg between sequential diuretic
and RAAS group (95% confidence interval: 7-14/2-7; P < 0.001/P = 0.0014)
Ambulatory blood pressure of less than 135/85 was achieved
in 58% in sequential diuretics group as compared 20% in sequential RAAS blocked.
If this is confirmed by larger trials than it may reduce prevalence of resistant
hypertension by 5-6%
Diuretics and site of action.
- Spironolactone:-connecting tubule and cortical
- Furosemide: - Ascending limb of Henle.
- Hydrochlorothiazide :-Distal tubule
- Amiloride Aldosterone-independent blocker , cortical
Labels: For Doctors, Hypertension, Intermediate Level