The therapy (Whelton et al., 2017). MechanismThe therapy (Whelton et al., 2017). Mechanism

effectiveness and precautions of the use of diuretics in treating hypertension


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to the 2017 guideline realised by The American College of Cardiology (ACC) and
the American Heart Association (AHA), hypertension is regarded when systolic
pressure greater than 130 mm Hg or diastolic blood pressure is greater 80 mm Hg
(Whelton et al., 2017). Hypertension is a critical
preventable cause of cardiovascular disease including stoke and cardiac
failure. Hypertension
can also result in renal failure, cognitive impairment and blindness. According
to WHO, there are annually 9.4 million of deaths caused by complication from
hypertension worldwide (WHO, 2015). Hypertension is divided into types
including primary hypertension and secondary hypertension. Primary hypertension
is resulted from unknown cause but probably related to lifestyle factors such
as high salt and fat content of diet, cigarette smoking and alcohol intake.
Secondary hypertension is caused by an underlying condition, such as renovascular
disease, endocrine disorder and certain medications (Whelton et al., 2017). Diuretics
are drugs that can increase urine excretion, is commonly used in treating
hypertension. Diuretics is divided into several classes including thiazide,
thiazide-related, loop and potassium sparing diuretics (Shah et al., 2004). In
the current clinical practice guideline, thiazide class of diuretics is one of
the antihypertensive agents preferred in initial uncomplicated hypertension
therapy (Whelton et al., 2017).  

Mechanism of different diuretics

All the
diuretics possess natriuretic action, which increase the excretion of sodium as
well as the accompanying water. Therefore, the reduction in extracellular fluid
volume leads to decrease in cardiac output and ultimately, reducing blood
pressure. Loop diuretics including frusemide, bumetanide and ethacrynic acid
are the most potent diuretics. They reduce reabsorption of sodium at the thick
ascending loop of Henle through inhibiting the Na-K-Cl co-transport system on
the apical membrane of renal tubule. Normally, a large amount of sodium is
being reabsorbed in the site of action of loop diuretics. Therefore, massive
amount of sodium and water is excreted in the urine. Loop diuretics are effective
despite patient with severe renal impairment. Thiazide and thiazide-like
diuretics, act on the early portion of distal convoluted tubule by inhibiting
the apical Na-Cl co-transport system. The natriuretic action is limited in this
class of diuretics because the amount of sodium reabsorption is normally little
at their site of action. Potassium sparing diuretics, including spironolactone,
triamterene and amiloride usually used in combination with loop diuretics and
thiazide in order to prevent hypokalaemia. Spironolactone is a competitive aldosterone
antagonist, which is able to reduce aldosterone-dependent sodium-potassium
exchange in the distal convoluted tubule. Triamterene and amiloride block the
apical sodium channel directly at the distal tubule resulting in decreased
sodium-potassium exchange (Shah et al., 2004).

Effectiveness of diuretics in treating

are numerous randomised controlled trials indicated the diuretics treatment
could reduce coronary heart disease, stroke and mortality in patients with
hypertension (James et al., 2014). In the Medical Research Council trial, which
studied 4396 elderly patients randomised to receive diuretic, beta blocker or
placebo, showed that the diuretic group with low-dose
thiazide combined with a potassium-sparing diuretic had significantly reduced the
risks of coronary heart disease by 44% and stroke by 31% when compared with the
placebo group (MRC, 1992). In a more recent trail, which compared three
different classes of antihypertensive drugs including thiazide related
diuretics chlorthalidone, angiotensin converting enzyme inhibitors lisinopril
and calcium channel blockers
by studying 33357 individuals with hypertension and other risk factor for
coronary heart disease. The trial showed that subjects who receiving amlodipine
and lisinopril have a significantly higher systolic blood pressures and higher rate
of heart failure when compared with chlorthalidone. Moreover, the lisinopril
group had an increased rate of cardiovascular disease and stroke when compared
with chlorthalidone (ALLHAT, 2002).


lower dose of diuretics is effective in treating patients with mild primary hypertension
but the pressure lowering effect is slow which might occur after several weeks
(Blowey, 2016). The effectiveness depends no several factors, including the
age, racial group and renal function of the patient. Also, the effectiveness of
thiazide diuretics could be increased when combined with moderate sodium
restriction. Side effects including electrolyte and metabolic abnormalities
will be resulted when using higher dose of diuretics (Shah et al., 2004). For
patient with impaired renal function whose glomerulus filtration rate lower
than 30 mL/min , thiazides are usually not effective, and loop diuretics will
be the drug of choice. For treating moderate to severe hypertension patient,
thiazide diuretics combined with other antihypertensive drugs is commonly
prescribed (Whelton et al., 2017).

Side effect and precaution of diuretics in
treating hypertension

common side effects of diuretics treatment are electrolyte imbalance and
metabolic disorder. Hypokalaemia which
is defined as serum potassium level lower or equal to 3.5 mmol/L, is the
commonly occurred side effect when patient is treated with high dose thiazide
or loop diuretics. K supplement or K sparing diuretic is often used when
dealing with diuretics associated hypokalaemia. K sparing diuretic is used in
combination with thiazide or loop diuretics in order to conserve urinary potassium
(Sica, 2004).


from hypokalaemia, hyponatraemia is another side effect that could occurred in
thiazide diuretics treated patients particularly in elderly and female. The
reduction of renal function of elderly resulting in decreased free water
excretion accounts for the thiazide-induce hyponatraemia. Also, if medication
that reduce free eater excretion is used concurrent with thiazide diuretics,
hyponatraemia could be developed. Excessive water intake to compensate the
thirsty feeling induced by diuretics would result in dilution of sodium, and
subsequently leads to hyponatraemia. The clinical manifestations of
hyponatraemia include fatigue, nausea, seizures and even coma. Restriction of
fluid intake or withdrawal of thiazide diuretics treatment is suggested for
patients who developed mild and asymptomatic hyponatraemia. If severe and
symptomatic hyponatraemia is encountered, urgent treatment with saline or
hypertonic saline should be given carefully to avoid restoration of serum
sodium level rapidly (Egom et al., 2011).


electrolyte imbalance is extremely dangerous, serum Na and K level of patients
should be closely monitoring before and during the administration of diuretics.
Actions should be taken promptly if the serum level is outside the normal range
of Na or K (Sica, 2004).

It was
long suspected that patients who are treated with thiazide diuretics chronically
would have a higher risk of developing new-onset type 2 diabetes mellitus. It
is suggested the genesis of glucose intolerance is associated with the
thiazide-induce hypokalaemia which could leads to reduction of insulin released
from pancreatic ? cell. Since the ATP-dependent K+ channel plays an important
role in the control of insulin secretion. Also, the impaired insulin secretion
is reversible when patients received K+ supplement. Therefore, hypokalaemia might
be the cause of thiazide-induced hyperglycaemia (Palmer, 2011). However, a recent
meta-analysis concluded that low-dose of thiazide diuretics would not cause clinically
significant increase in fasting plasma glucose (Mukete and Rosendorff, 2013). As
a result, low dose thiazide diuretics is generally safe even in patients with existing
diabetes (Shah et al., 2004). Other than hyperglycaemia, thiazide diuretics could
reduce renal clearance of urate, and causing the increase in serum uric acid level.
Since urate and thiazide diuretics share the same organic anion transporter for
tubular secretion, and therefore, less urate will be secreted when there is competition
with thiazide diuretics (Sica, 2004). As a result, patient with history of gout
should avoid thiazide diuretics therapy (Whelton et al., 2017).


Discussion and conclusion

clinical trials have proven the effectiveness of diuretics in treating
hypertension. According to the current guidelines, diuretics remain one of the
several antihypertensive drugs for treatment of primary hypertension (Whelton et
al., 2017). Low dose of diuretics instead of high dose should always be prescribed
in diuretics therapy for hypertensive patients in order to reduce side effects.
However, despite low dose of diuretics is used, side effects including hypokalaemia,
hyponatraemia and hyperuricemia are inevitable. Therefore, the serum level of potassium,
sodium and urate should be carefully monitored before and during the diuretics
therapy. K supplement or K sparing diuretics in combination with thiazide
diuretics should be considered for patient with hypokalaemia. Patients with
history of gout should avoid thiazide diuretics therapy. For patients with moderate
to severe chronic kidney disease with glomerulus filtration rate lower than 30
mL/min, loop diuretics is preferred over thiazide. Besides antihypertensive
drugs, lifestyle modifications is also important in prevention and treatment of
hypertension. It is recommended to have diet rich in fibre and low in fat, reduce
dietary sodium, lose weight, increase physical activity and reduce alcohol
consumption in order to reduce blood pressure (Whelton et al., 2017).