This presentation provides knowledge about Diuretics,Role of sodium, types of urine output, General mechanism of action, Normal Physiolofy of urine formation, GFR Formation, Classes of Diuretics, diuretics abuse and recent discovery. An assignment for the subject, Advanced Pharmacology-I, 1st year M.Pharm, 1st semester.

1. Advanced
Pharmacology - I
“Diuretics”
By
Chetan A., M.pharm 1st Year(Pharmacology)
K.K. College of Pharmacy
Chennai, TamilNadu

2. Learning Objective
• Introduction
• Role of Sodium ion
• General Mechanism of Action
• Normal physiology of Urine
• GFR Formation
• Classes of Diuretics
• Abuse in sports
• Recent Discovery
• Facts
• Conclusion
• Reference

3. Diuretics
• A diuretic (“water pills”) is any substance that promotes diuresis, the increased
production of urine. This includes forced diuresis.
• There are several categories of diuretics. All diuretics increase the excretion of
water from bodies, although each class does so in a distinct way.
• Alternatively, an antidiuretic, such as vasopressin (antidiuretic hormone), is an
agent or drug which reduces the excretion of water in urine.
• Diuretics are used to treat heart failure, liver cirrhosis, hypertension, influenza,
water poisoning, Pregnancy associated oedema and certain kidney diseases.
• Some diuretics, such as acetazolamide, help to make the urine more alkaline
and are helpful in increasing excretion of substances such as aspirin in cases of
overdose or poisoning.

4. Diuretics
• Diuretics are sometimes abused by people with an eating disorder, especially
people with bulimia nervosa, with the goal of losing weight.
• The antihypertensive actions of some diuretics (thiazides and loop diuretics in
particular) are independent of their diuretic effect.That is, the reduction in
blood pressure occurs through other mechanisms and at lower doses than that
required to produce diuresis.
• A Natreuretic is any drug (agent) when introduced into the body increases the
out put of sodium ie., loss of sodium in urine.

5. Role of Sodium ions
• Where sodium goes, water follows.
• 20 to 25% of all sodium is reabsorbed into the bloodstream in the loop
of Henle, 5 to 10% in the distal tubules, and 3%
• in collecting ducts.
• If it is not absorbed, it is excreted with the urine.

6. Types of Urine output
• Normal output - 800 to 2,000 milliliters per day.
• Oliguria - Low urine output - 400 to 500 milliliters per day
• Polyuria - High urine output - 2500 to 3000 milliliteres per day

7. General Mechanism of Action
• Diuretics usually exert their actions by lowering significantly the
reabsorption of electrolytes from the tubules. Eg, Loop of henle, Distal &
Proximal convulated tubule.
• The enhanced electrolyte excretion is invariably associated with a
corresponding increase in water excretion to maintain the desired
osmotic balance.

8. Purpose of Diuretics
• To maintain urine volume. Eg, Renal Failure
• To mobilize edema fluid. Eg, Heart failure, Liver failure, Nephrotic syndrome.
• To control High blood pressure.
• Normal Values

9. Normal Physiology of Urine formation
 Urine formation occurs by
Glomerular filtration
Tubular Re-absorption
Tubular Secretion
 Two important functions of the kidney are:-
 To maintain a homeostatis balance of electrolytes and water.
 To excrete water soluble end products of metabolites.
 Each kidney contains approximately one million nephrons and is capable of
forming urine independently.
 The nephrons are composed of glomerulus, proximal tubule,loop of henle,
distal tubule.

10. Normal Physiology of Urine formation
 Approximately 1200 ml of blood per minute flows through both
kidneys.
 Ions such as sodium, chloride,calcium are reabsorbed.
 Total amount of glucose, amino acids, vitamins, proteins are reabsorbed.
 If the urine contains any of the above elements, it represents the
disorders.
 For example proteins such as albumin in higher amounts causes
albuminaria.

11. GFR Formation
 Normal cardiac output -5 lit/min. (exactly 4.7 litres)
 Out of that 20% goes to kidneys i.e.1 lit/min.
 1 lit of blood of has 40% of cells and 60%of plasma.
 600 ml of plasma is not entered into glomerulus only a part of plasma
can enter into it and the rest pass through the efferent arteriole.
 Only 20% can enter into glomerelus that is 120 ml.
 This 120 ml/min makes glomerular filtrate.

12. Classes of Diuretics
• High Ceiling/ Loop Diuretics
• Furosemide, Torasemide, Ethacrynic acid
• Thiazides
• Hydrochlorothiazide, Chlorothiazide
• Carbonic Anhydrase Inhibitors
• Acetazolamide, Methazolamide
• Potassium-Sparing Diuretics
• Spirinolactone, Amiloride, Triamterene
• Osmotic Diuretics
• Glucose, Mannitol, Urea
• Low Ceiling Diuretics
• Thiazides
• Calcium-Sparing Diuretics
• Thiazides, K+ Sparing Diuretics

14. 1. Loop diuretics
Mechanism of Action
• Loop diuretics, such as furosemide, inhibit the body's ability to reabsorb sodium at
the ascending loop in the nephron, which leads to an excretion of water in the urine.
• They act by inhibiting the luminal Na/K/2Cl symporter.
• Increase renal prostaglandins, resulting in the dilation of blood vessels and reduced
peripheral vascular resistance.
Brands
• Bumetanide (Bumex) - (0.5 to 20 mg)
• Ethacrynic acid (Edecrin)
• Furosemide (Lasix) - (2.5 to 20 mg)

15. 1. Loop diuretics
• Potent diuresis and subsequent loss of fluid.
• It causes Potassium depletion.

16. 1. Loop diuretics
• Pharmacological action:
Increase reabsorption of Uric acid in proximal tubule
Furosemide (weak carbonic anhydrous inhibitor) increases excretion of HCO3
-
and phosphate ions.
• Pharmacokinetics
– These are completely absorbed orally.
– Onset of action is 2-5 hrs.
– Half life is 1.5 hrs
– Duration of action is 2-4 hrs.

17. 1. Loop diuretics
• Therapeutic use
Edema associated with CHF or
hepatic or renal disease.
Control of hypertension.
In Acute renal failure
In Hyperkalemia
In Hypercalcemia
• Side Effects
– Ototoxicity
– Hypovolemia, Hyperglycemia
– Hypokalemia, Hyperuricemia
– Metabolic Alkalosis
– Dizziness, headache, tinnitus,
blurred vision
– Nausea, vomiting, diarrhea
– Agranulocytosis, neutropenia,
thrombocytopenia

18. 2. Thiazide Diuretics
Mechanism of action
• Thiazide diuretics such as hydrochlorothiazide act on the distal convoluted tubule
and inhibit the sodium-chloride symporter leading to a retention of water in the urine,
as water normally follows penetrating solutes
• . The short-term anti-hypertensive action is based on the fact that thiazides decrease
preload, decreasing blood pressure.
• The long-term effect is due to an unknown vasodilator effect that decreases blood
pressure by decreasing resistance.
Brands
• Hydrochlorothiazide (Esidrix, HydroDIURIL)
• Chlorothiazide (Diuril)
• Trichlormethiazide (Metahydrin)

19. 2. Thiazide Diuretics
Drug Effects
• Lowered peripheral vascular resistance
• Depletion of sodium and water
Therapeutic use
• Hypertension
• Edematous states
• Idiopathic hypercalciuria
• Diabetes insipidus
• Adjunct agents in treatment of CHF, hepatic cirrhosis
• Treatment of glaucoma.
• These are given in combination with amiloride,allopurinol to prevent the formation of
calcium stones in hyper calciuric patients.

20. 2. Thiazide Diuretics
Side effects
– Dizziness, headache, blurred vision, paresthesias, decreased libido
– Anorexia, nausea, vomiting, diarrhea, Vertigo
– Impotence
– Urticaria, photosensitivity
– Hypokalemia, glycosuria, hyperglycemia
– Ortho static Hypotension

21. 3. Carbonic Anhydrous Inhibitor
• Carbonic anhydrase inhibitors inhibit the enzyme carbonic anhydrase
which is found in the proximal convoluted tubule. This results in several
effects including bicarbonate accumulation in the urine and decreased
sodium absorption.
• Acetazolamide (Diamox)
• Methazolamide (Neptazane)

22. 3. Carbonic Anhydrous Inhibitor
Therapeutic use:
• Used as weak diuretic
• Used in glaucoma
– Urinary alkalinization, High-altitude sickness
• In Epilepsy
• Used with miotics to lower intraocular pressure before ocular surgery
Side effects:
• Hypo kalaemia. Renal calculi.
• Nausea, loss of hearing, loss of apetite.

23. 4. Potassium Sparing Diuretics
• These are diuretics which do not promote the secretion of potassium into
the urine; thus, potassium is retained and not lost as much as with other
diuretics.
• Brands
• Spirinolactone (Aldactone)
• Amiloride (Midamor)
• Triamterene (Dyrenium)

24. 4. Potassium Sparing Diuretics
Mechanism of action:
• Prevent potassium from being pumped into the tubule, thus
preventing its secretion
• They act by inhibiting sodium reabsorption in the late distal
tubule and thus indirectly spare potassium excretion.
• Work in collecting ducts and distal convoluted tubules
• Interfere with sodium-potassium exchange
• Competitively bind to aldosterone receptors
• Block the resorption of sodium and water usually induced by
aldosterone.

25. 4. Potassium Sparing Diuretics
Therapeutic use:
• Hyperaldosteronism
• Hypertension
• Reversing the potassium loss caused by Potassium-losing drugs
• Treatment of CHF (Amiloride)
• Liddle’s syndrome(pseudo-hyper aldosteronism).
• Amiloride is used to treat lithium induced nephrogenic diabetes insipidus.
Side effects
• Dizziness, headache
• Cramps, nausea, vomiting, diarrhea
• Urinary frequency, weakness
• Gynecomastia, Amenorrhea, irregular menses (Spirinolactone)

26. 5. Osmotic Diuretics
Mechanism of action:
• Osmotic diuretics (e.g. mannitol) are substances that increase osmolarity but have limited
tubular epithelial cell permeability. They work primarily by expanding extracellular fluid and
plasma volume, therefore increasing blood flow to the kidney, particularly the peritubular
capillaries. This reduces medullary osmolality and thus impairs the concentration of urine in
the loop of Henle.
• Mannitol are low molecular weight compounds that are freely filtered through bowmans
capsule.
• They have limited reabsorption because of high water solubility & produce osmotic effect.
• Pull water into the blood vessels and nephrons from the surrounding tissues
Brand
• Mannitol (Resectisol, Osmitrol)

27. 5. Osmotic Diuretics
Therapeutic use:
• Used in the treatment of patients in the early, oliguric phase ofARF
• Topromote the excretion of toxic substances
• Reduction of intracranial pressure
• Treatment of cerebral edema
Side effects:
• Convulsions
• Thrombophlebitis
• Pulmonary congestion
• Headaches, chest pains, tachycardia, blurred vision, chills, and fever

28. Abuse in Sports
• A common application of diuretics is for the purposes of
invalidating drug tests.
• Diuretics increase the urine volume and dilute doping agents
and their metabolites.
• Another use is to rapidly lose weight to meet a weight category
in sports like boxing and wrestling.

29. Recent Discovery
1. Who May Benefit from Diuretics in OSA? A Propensity Score-Match Observational Study
(B.Revol et,al. 2020)
Background:
• Diuretics have been reported as effective for reducing obstructive sleep apnea (OSA) severity by
preventing fluid retention and reducing rostral fluid shift. This study was included a propensity score-
matched cohort analysis of data.
Result:
• In this study it was found that Diuretics reduced OSA severity in overweight or moderately obese
patients (p=0.03) and in patients with hypertension (p<0.01), particularly in hypertensives with a body
mass index between 25 and 35 kg/m2 (p<0.01). Diuretics had no significant effect on OSA severity in
patients with self-reported low physical activity or heart failure.
Conclusion:
• Diuretics appear to have a positive impact on OSA severity in overweight or moderately obese patients
with hypertension. A prospective study is needed to confirm that diuretics are of interest in combined
therapies for hypertensive patients with OSA.

30. Recent Discovery
2. Effect of Loop Diuretics on the Fractional Excretion of Urea in Decompensated Heart
Failure (Zachary L.Cox et,al. 2020)
Background:
• Fractional excretion of urea (FEUrea) is often used to understand the etiology of acute kidney injury
(AKI) in patients receiving diuretics. Although FEUrea demonstrates diagnostic superiority over
fractional excretion of sodium (FENa), clinicians often assume FEUrea is not affected by diuretics.
Prospective cohort study.
Result:
• Mean baseline FEUrea was 35.2% ± 10.5% and increased by a mean 5.6% ± 10.5% following 80
mg (40–160 mg) of furosemide equivalents (P < .001). The magnitude of change in FEUrea was
clinically important as the distribution of change in FEUrea was similar to the overall distribution of
baseline FEUrea.
Conclusion:
• FEUrea is meaningfully affected by loop diuretics. The degree of change in FEUrea is highly variable
between patients and commonly of a magnitude that could reclassify across categories of FEUrea.

31. Facts
• Rapid parenteral administration of loop diuretics can cause hearing loss
and tinnitus.
• High doses can trigger profound diuresis, leading to hypovolemia and
cardiovascular collapse.
• With Furosemide patient may develop photosensitivity. Be caution from
sunburns.
• Some loop diuretics may pass into breast milk.
• Can relieve shortness of breath.
• Help patient to live longer with heart failure

32. Conclusion
• Diuretics are the first line agents to treat hypertension.
• When effects are not sufficient, it can be given in the form of
combinations with other anti hypertensive's.
• Some of these agents has the capacity to reabsorb more calcium so they
can be prescribed for the patients suffering from osteoporosis.

33. Reference
• Google Search
• Wikipedia
• Slideshare
• Elsevier Inc.
• Padhmaja
• Tripathi

34. Quote
~“Series of failures teaches us to be patient & to work even harder. If
you’re having a bad day, don’t worry, some of them didn’t woke up this
morning, atleast you had a day.”
“Positivity is everywhere. There is good in every bad. We just need a
mindset to visualize it”.

35. Thank you