Diuretics are drugs that increase urine output by interfering with sodium reabsorption in the kidneys. They are commonly used to treat hypertension by lowering blood volume and pressure. The main classes of diuretics act on different parts of the kidney tubule: loop diuretics act on the ascending loop of Henle; thiazide diuretics act on the distal tubule; and potassium-sparing diuretics act on the late distal tubule or collecting duct. While all diuretics lower blood pressure, their specific sites of action determine their degree of natriuresis and potassium retention or loss.

1. DIURETICS AND HYPER TENSION
MIRZA FARHAN
PHARM.D
THE UNIVERSITY OF LAHORE

2. • Diuretics (dı¯-u¯-RET-iks) are substances that slow renal re-absorption of
water and thereby cause di-uresis, an elevated urine flow rate, which in
turn reduces blood volume.
• Diuretic drugs often are prescribed to treat hypertension (high blood
pressure) because lowering blood volume usually reduces blood pressure.
• Naturally occurring diuretics include caffeine in coffee, tea, and sodas,
which inhibits Na re-absorption, and alcohol in beer, wine, and mixed
drinks, which inhibits secretion of ADH.
• Most diuretic drugs act by interfering with a mechanism for reabsorption
of filtered Na.
• For example, loop diuretics , such as furosemide (Lasix®), selectively
inhibit the Na–K–2Cl symporters in the thick ascending limb of the loop
of Henle .
• The thiazide diuretics, such as chlorothiazide (Diuril®), act in the distal
convoluted tubule, where they promote loss of Na and Cl in the urine by
inhibiting Na–Cl symporter.

3. • Diuretics are drugs that cause an increase in
urine output.
• It is important to note that, except for the
osmotic diuretics, these drugs typically
enhance the excretion of solute and water.
• Therefore, the net effect of most diuretics is to
decrease plasma volume, but cause little
change in plasma osmolarity.

4. Five classes of diuretics
and their major sites of action are:
• Osmotic diuretics: proximal tubule and
descending limb of the Loop of Henle.
• Loop diuretics: ascending limb of the Loop of
Henle.
• Thiazide diuretics: distal tubule.
• Potassium-sparing diuretics: cortical
collecting duct.
• Carbonic anhydrase inhibitors: proximal
tubule.

5. Osmotic diuretics
• Osmotic diuretics such as mannitol act on the proximal tubule and, in
particular, the descending limb of the Loop of Henle — portions of the
tubule permeable to water.
• These drugs are freely filtered at the glomerulus, but not reabsorbed;
therefore, the drug remains in the tubular filtrate, increasing the
osmolarity of this fluid.
• This increase in osmolarity keeps the water within the tubule, causing
water diuresis.
• Because they primarily affect water and not sodium, the net effect is a
reduction in total body water content more than cation content.
• Osmotic diuretics are poorlyabsorbed and must be administered
intravenously.
• These drugs may be used to treat patients in acute renal failure and with
• dialysis disequilibrium syndrome.
• The latter disorder is caused by the excessively rapid removal of solutes
from the extracellular fluid by hemo-dialysis.

6. Loop diuretics
• Loop diuretics such as furosemide act on the ascending limb of the Loop of Henle,
a portion of the tubule permeable to sodium and chloride.
• The mechanism of action of these diuretics involves inhibition of the Na+, K+,
2Cl– symporter in the luminal membrane.
• By inhibiting this transport mechanism, loop diuretics reduce the reabsorption of
NaCl and K+ ions.
• Recall that reabsorption of NaCl from the ascending limb of the Loop of Henle
generates and maintains the vertical osmotic gradient in the medulla.
• Without the reabsorption of NaCl, this gradient is lost and the osmolarity of the
interstitial fluid in the medulla is decreased.
• When the osmolarity of the medulla is decreased, the reabsorption of water from
the descending limb of the Loop of Henle and the collecting duct is significantly
reduced.
• The net result of the loop diuretics includes reduced NaCl and water reabsorption
and, therefore, enhanced NaCl and water loss in the urine.
• The most potent diuretics available (up to 25% of the filtered Na+ ions may be
excreted) — the loop diuretics — may cause hypovolemia.

7. Thiazide diuretics
• Thiazide diuretics such as chlorothiazide act on the distal tubule, a
portion of the tubule that is permeable to sodium.
• The mechanism of action of these diuretics involves inhibition of
NaCl reabsorption by blocking the Na+, Cl– symporter in the
luminal membrane.
• The thiazide diuretics are only moderately effective due to the
location of their site of action.
• Approximately 90% of the filtered Na+ ions have already been
reabsorbed when the filtrate reaches the distal tubule.
• These drugs may be used for treatment of edema associated with
heart, liver, and renal disease.
• Thiazide diuretics are also widely used for the treatment of
hypertension.

8. Potassium-sparing
• Potassium-sparing diuretics act on the late
portion of the distal tubule and on the cortical
collecting duct.
• As a result of their site of action, these diuretics
also have a limited effect on diuresis compared
to the loop diuretics (3% of the filtered Na+ ions
may be excreted).
• However, the clinical advantage of these drugs is
that the reabsorption of K+ ions is enhanced
reducing the risk of hypokalemia.

9. Types of potassium-sparing diuretics
• Two types of potassium-sparing diuretics have different
mechanisms of action.
• Agents of the first type, which include spironolactone,are also
known as aldosterone antagonists.
• These drugs bind directly to the aldosterone receptor and prevent
this hormone from exerting its effects. Agents of the second type,
which include amiloride, are inhibitors of the tubular epithelial
Na+ channels.
• Acting on the Na+ channels in the luminal membrane, these drugs
prevent movement of Na+ ions from the filtrate into the epithelial
cell.
• Because this transport of Na+ ions into the cell is coupled to the
transport of K+ ions out of the cell, less potassium is lost to the
filtrate and therefore the urine.

10. • Potassium-sparing diuretics are often co-
administered with thiazide or loop diuretics
in the treatment of edema and hypertension.
• In this way, edema fluid is lost to the urine
while K+ ion balance is better maintained.
• The aldosterone antagonists are particularly
useful in the treatment of primary
hyperaldosteronism.

11. Carbonic anhydrase inhibitors
• Carbonic anhydrase inhibitors such as
acetazolamide act in the proximal tubule.
• These drugs prevent the formation of H+
ions, which are transported out of the tubular
epithelial cell in exchange for Na+ ions.
• These agents have limited clinical usefulness
because they result in development of
metabolic acidosis.

12. HYPER TENSION
• About 50 million Americans have hypertension (hı¯-
per-TEN-shun), or persistently high blood pressure.
• It is the most common disorder affecting the heart and
blood vessels and is the major cause of heart failure,
kidney disease, and stroke.
• In May 2003, the Joint National Committee on
Prevention, Detection, Evaluation, and Treatment of
High Blood Pressure published new guidelines for
hypertension because clinical studies have linked what
were once considered fairly low blood pressure
readings to an increased risk of cardiovascular disease.

13. Category Systolic (mmHg) Diastolic (mmHg)
Normal Less than 120 Less than 80
Prehypertension 120–139 or 80–89
Stage 1 hypertension 140–159 or 90–99
Stage 2 hypertension Greater than 160 or Greater than 100

14. Types and Causes of Hypertension
• Between 90 and 95% of all cases of
hypertension are primary hypertension, a
persistently elevated blood pressure that
cannot be attributed to any identifiable cause.
• The remaining 5–10% of cases are secondary
hypertension, which has an identifiable
underlying cause.

15. Several disorders cause secondary
hypertension:
• Obstruction of renal blood flow or disorders
that damage renal tissue may cause the
kidneys to release excessive amounts of renin
into the blood.
• The resulting high level of angiotensin II
causes vasoconstriction, thus increasing
systemic vascular resistance.

16. • Hypersecretion of aldosterone—resulting, for
instance, from a tumor of the adrenal cortex—
stimulates excess reabsorption of salt and
water by the kidneys, which increases the
volume of body fluids.

17. • Hypersecretion of epinephrine and
norepinephrine may occur by a
pheochromocytoma (fe¯-o¯ -kro¯-mo¯-sı¯-TO¯
-ma), a tumor of the adrenal medulla.
• Epinephrine and norepinephrine increase
heart rate and contractility and increase
systemic vascular resistance.

18. Drug Treatment of Hypertension
• Drugs having several different mechanisms of action are effective in lowering
blood pressure.
• Many people are successfully treated with diuretics (dı¯-u¯-RET-iks), agents that
decrease blood pressure by decreasing blood volume, because they increase
elimination of water and salt in the urine.
• ACE (angiotensin-converting enzyme) inhibitorsblock formation of angiotensin II
and thereby promote vasodilation and decrease the secretion of aldosterone.
• Beta blockers (BA¯ -ta) reduce blood pressure by inhibiting the secretion of renin
and by decreasing heart rate and contractility.
• Vasodilators relax the smooth muscle in arterial walls, causing vasodilation and
lowering blood pressure by lowering systemic vascular resistance. An important
category of vasodilators are the calcium channel blockers, which slow the inflow of
Ca2 into vascular smooth muscle cells.
• They reduce the heart’s workload by slowing Ca2 entry into pacemaker cells and
regular myocardial fibers, thereby decreasing heart rate and the force of
myocardial contraction.

19. REFERENCES
• Essentials Of Human Physiology For Pharmacy
by LAURIE KELLY.
• Principles of ANATOMY & PHYSIOLOGY Gerard
J. Tortora Bergen Community College Bryan
Derrickson Valencia Community College 13th
Edition