This document provides information on drugs acting on the urinary system. It discusses different classes of diuretic drugs including high efficacy loop diuretics like furosemide, medium efficacy thiazide diuretics like hydrochlorothiazide, and weak adjunctive diuretics. Loop diuretics work by inhibiting sodium reabsorption in the ascending loop of Henle, thiazides inhibit sodium reabsorption in the distal convoluted tubule, and adjunctive diuretics utilize various mechanisms like inhibiting carbonic anhydrase or sodium channels. Common uses of diuretics include treating edema, hypertension, hypercalcemia, and increased intracranial pressure. Adverse effects can include electrolyte

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CHAPTER NO:02
DRUGS ACTING ON
URINARY SYSTEM
Prepared by,
RAMDAS BHAT
Assistant Professor
Srinivas college of Pharmacy
Mangalore
7795772463
Ramdas21@gmail.com

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INTRODUCTION
• DIURECTICS are class of drugs that increases the urinary output.
• These classes od drugs are usually used to treat edema and helpful in elimination of the
toxic metabolites from the kidneys.
Classification
On the basis of their intensity, diuretics are categorized as follows:
1) High Efficacy Diuretics (Inhibitors of Na+/K+/2Cl– Co-transport)
i) Sulphonyl Derivatives: Furosemide and Bumetanide.
ii) Phenoxy acetic Acid Derivatives: Ethacrynic acid.
iii) Organomercurials: Mersalyl.
2) Medium Efficacy Diuretics (Inhibitors of Na+/Cl– Symporter)
i) Benzothiadiazides (Thiazides): Chlorothiazide, Hydrochlorothiazide,
Benzthiazide, Hydroflumethiazide, and Clopamide.
ii) Thiazide-like Diuretics (Related Heterocyclics): Chlorthalidone,
Metolazone, Xipamide, and Indapamide.
3) Weak or Adjunctive Diuretics
i) Carbonic Anhydrase Inhibitors: Acetazolamide.
ii) Potassium Sparing Diuretics
a) Aldosterone Antagonists: Spironolactone.
b) Directly Acting Diuretics (Inhibitors of Renal Epithelial Na + Channel): Triamterene and
Amiloride.
iii) Osmotic Diuretics: Mannitol, Isosorbide, and Glycerol.
iv) Xanthine Derivatives: Theophylline.
High Efficacy Diuretics (High Ceiling or Loop Diuretics)
• They are also called as high ceiling or loop diuretics as they are acting on ascending loop
of Henle.
• They are most effective than other diuretics as the Ascending loop of Henle has higher
reabsorptive capacity than any other segment of the nephron. Hence, they are termed as
High ceiling or Na +/K+/2Cl– co-transporter inhibitors.
• Most commonly used Loop diuretic is Furosemide.
Mechanism of Action:
• Furosemide inhibits the reabsorption of NaCl and the Na+/K+/2Cl– symporter in the thick
ascending limb of Henle’s loop.
• It facilitates or increases urinary excretion of Na + and Cl – ions. High efficacy diuretics
prove to be highly efficient and show dose -dependent response (increase in dose results
in greater action).
• However, administration of exceedingly large amounts of the dose may cause dehydration
(high ceiling effect, i.e., maximal effect).

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• On oral administration, furosemide absorbs rapidly from the GIT.
• After intravenous administration, its action furosemide is even more rapid, i.e., within
10 minutes and duration of action is 2 hours.
• About 95% of furosemide is bound to the plasma proteins. Furosemide undergoes
metabolism in the liver and excretion by the kidneys. It has the ability to cross the
placental barrier and is also excreted in the breast milk.
THERAPEUTIC USES
Therapeutic uses of loop diuretics include:
1. Acute Pulmonary Oedema: These agents are found to be highly effective in acute
pulmonary oedema. In this condition, the vascular effect precedes the onset of diuretic
effect. A decrease in the left ventricular pressure is responsible for its therapeutic effect.
2. Refractory Oedema: Furosemide is used to treat refractory oedema related to congestive
cardiac failure and renal disease, in case other diuretics are not effective.
3. Acute Renal Failure: The rate of urine flow and excretion of K + ions increase during acute
renal failure. Loop diuretics can effectively convert oliguric renal failure into non-oliguric
renal failure. Yet, the duration of renal failure cannot be decreased by these agents.
4. hypercalcemia: In patients with hypercalcemia, intravenous administration of loop
diuretics along with normal saline infusion stimulates the excretion of Ca2+ ions. As a
result, the serum calcium level decreases.
5. Hyperkaliemia: Intravenous administration of furosemide along with saline infusion helps
treating hyperkaliemia.
6. Poisoning by Barbiturates and Halides: Furosemide with copious intravenous saline
(forced diuresis) is used in barbiturate and halide poisoning.
7. Raised Intracranial Pressure: Loop diuretics decrease the blood volume, and hence
reduce intracranial tension.

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Though utilized for the treatment of several diseases, the high efficacy diuretics are not
employed as antihypertensive agents since they have a high diuretic potential, short duration
of action, and high dose requirement.
ADVERSE EFFECTS
The adverse reactions of high efficacy diuretics include:
1) Effects Related to Renal Actions: Loop diuretics severely disrupt water and electrolyte
balance and may manifest as:
i) Hypokalemia and metabolic hypochloremia alkalosis resulting from the exchange of K+ and
H+ ions with Na+ ions in the distal tubule.
ii) Depletion of calcium on chronic administration.
iii) Hypovolemia and hypotension.
iv) Hyperuricemia (may precipitate attack of gout), except with the uricosuric drugs
(indacrinone and ticrynafen).
v) Hypomagnesaemia which is reversed by oral magnesium supplementation. There may be
wasting on chronic administration.
2) Effects Related to Extra-Renal Actions: These effects include:
i) Dose-related, reversible ototoxicity with loss of hearing. It is more with ethacrynic acid.
ii) Pancreatitis.
iii) Hypersensitivity (e.g., skin rash, blood dyscrasias, and allergic interstitial nephritis) in
patients allergic to sulphonamides.
iv) Myalgia may occur with bumetanide and piretanide.
v) GIT upset may occur due to ethacrynic acid.
vi) Hepatic encephalopathy in hepatic cirrhosis.
Drug Interactions
Loop diuretics interact with the following drugs and cause toxicity:
1. They interact with aminoglycoside, antibiotics, and increase ototoxicity.
2. They interact with cephalosporins and cause kidney damage.
3. Indomethacin decreases the efficiency of loop diuretics because they inhibit the synthesis
of vasodilator prostaglandins in the kidney.
4. They increase the toxicity caused by digitalis and result in cardiac abnormalities due to
hypokalemia
Contraindications
Contraindications to the use of furosemide include:
1) Presence of anuria.
2) Hypersensitivity to compounds.
3) Allergy to sulpha drugs.
Medium Efficacy Diuretics (Thiazides and Thiazide- Like Drugs)
Thiazide diuretics are referred to as moderately efficacious diuretics as a majority (nearly
90%) of the filtered sodium is already re-absorbed even before it reaches the distal tubule.

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They comprise of two distinct groups of diuretics:
1. Thiazide: These diuretics, e.g., chlorothiazide, hydrochlorothiazide, polythiazide, etc.,
contain a benzothiadiazine ring.
2. Thiazide-Like: These diuretics, e.g., chlorthalidone, indapamide, metolazone, etc., do not
contain benzothiadiazine ring, but an un -substituted sulphonamide group. The most
commonly used thiazide is chlorothiazide.
Mechanism of Action
• Thiazide diuretics act by blocking the Na+/Cl– co-transport system and exert their actions
on the distal convoluted tubules.
• Carbonic anhydrase activity is also inhibited by these drugs and they increase the
excretion of bicarbonate ions, Mg+ and K+.
• These agents also inhibit the excretion of Ca ++ ions and uric acid in the urine which leads
to hypercalcemia and hyperuricemia, respectively.
Pharmacokinetics
• Absorption of thiazides is fast, when they are administered orally.
• The organic acid secretory system excretes these agents in the proximal tubule of kidneys.
• They inhibit the excretion of uric acid resulting in hyperuricemia.
• Onset of action generally occurs in 1-2 hours, with the maximal effect occurring in 4 -6
hours.
• The action lasts for 8-12 hours.
Therapeutic Uses
Medium efficacy diuretics have the following therapeutic uses:
1. Oedema: Cardiac, hepatic and renal oedema associated with chronic heart failure,
cirrhosis, nephrotic syndrome, chronic renal failure, and glomerulonephritis can be
successfully treated using thiazides. However, when the GFR falls below 30ml/min,
thiazides are not effective. These agents cannot be employed in the treatment of acute
pulmonary oedema.

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2. Hypertension: It can be effectively treated using thiazides. In the elderly and obese
patients, thiazides alone (as monotherapy) are useful in the treatment of mild
hypertension. For the treatment of moderate and severe hypertension, they are
employed as a combinational therapy along with other anti-hypertensives.
Advantages of thiazides as anti-hypertensives include:
a) Low-cost, good efficiency and tolerability, decreased cardiovascular morbidity and
mortality,
b) Effective even when administered once a day,
c) Shows better patient compliance, and
d) Additive or synergistic effect with other anti-hypertensive agents.
3. Calcium Nephrolithiasis: Calcium re-absorption is increased by the use of thiazides by the
following two mechanisms:
a) Increased re-absorption in the proximal tubule due to volume depletion.
b) Direct increase in Ca2+ ion re-absorption in the distal convoluted tubule. Thus, the
excretion of Ca 2+ ions i n urine is increased by the action of thiazides, and hence these
agents effectively treat calcium nephrolithiasis.
4. Diabetes Insipidus: Nephrogenic diabetes insipidus is primarily treated using thiazides.
Upto 50% of urine volume is decreased by the action of thiazides. They act possibly by the
following mechanisms:
a) They promote complete re-absorption of water in the proximal tubule by volume
depletion.
b) They increase the sensitivity of the collecting tubules to ADH.
5. Bromide Intoxication: Bromine (a halogen) is excreted by renal processes in a manner
similar to those for excretion of Cl – ions. Thus, bromine intoxication may be treated using
thiazides.
Adverse Effects
• Though the safety margin of thiazides is wide and the toxic effects are very rare, yet, in
some conditions the following adverse effects may be seen:
1. Electrolyte disturbances may be seen in the form of hyponatremic, hypochloremia
metabolic alkalosis together with hypokalemia and may manifest as weakness,
fatigability, and paraesthesia (Pricking of a needle).
2. In patients susceptible to diabetes mellitus, the suppression of insulin release from the
pancreas may exacerbate glycosuria and Hyperglycaemia.
3. Inhibition of uric acid secretion in proximal renal tubules causes decreased urinary
excretion of uric acid, which may cause hyperuricemia. This condition may act as a
precipitating factor for an acute attack of gout in patients susceptible to it.
4. Administration of high doses of thiazides may result in reversible hyperlipidemia
(increase in serum cholesterol and LDL).
5. In some patients, hypersensitivity reactions may occur.
6. Thiazides decrease the renal excretion of ammonia, and thus can precipitate hepatic
encephalopathy in patients with hepatic insufficiency.

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Drug Interactions
Drug interactions of thiazide diuretics include:
1. They increase the potency of other anti -hypertensive agents, and this property of
thiazides is used therapeutically.
2. They induce hypokalemia, which in turn brings about the following effects:
a) Increases digitalis toxicity,
b) Increases the chances of polymorphic ventricular tachycardia resulting from quinidine and
other anti-arrhythmic agents used, and
c) Increases the potency of neuromuscular blockers and decreases the action of
sulphonylureas.
3. The use of cotrimoxazole along with diuretics increases the prevalence of
thrombocytopenia.
4. NSAIDs reduce anti-hypertensive activity of thiazides and furosemide.
5. The tubular secretion of thiazides is competitively inhibited by probenecid (a drug used in
gout), which decreases the action of thiazide by reducing the concentration in the tubular
fluid. On the other hand, the uricosuric action of probenecid is diminished by probenecid.
6. Patients undergoing diuretic therapy show an increase in the serum level of lithium due
to increased reabsorption of Li + ions (and Na + ions) in the proximal tubule.
Contraindications
• In patients sensitive to sulpha drugs, thiazide diuretics should be used cautiously.
• If possible, these drugs should be avoided in such patients.
Weak or Adjunctive Diuretics
• The third category of diuretics based on their intensity is the weak diuretics.
• They are named so because they exert a very weak action of their own, and hence are
usually employed as an adjunctive agent to potentiate the effects of other agents.
• Thus, they are also termed as adjunctive diuretics.
Mechanism of Action
The mechanism of action of each class of weak diuretics is given below:
Carbonic Anhydrase Inhibitors:
• Acetazolamide inhibits carbonic anhydrase enzyme, thus prevent the formation of H +
ions.
• As a result, the exchange of Na+/H+ ions do not take place.
• The Na+ ions are excreted in the urine along with 3 HCO- ions. In the distal convoluted
tubule, increased Na+/K+ exchange leads to loss of K+ ions.
• Thus, the overall effect is the loss of Na+, K+ and HCO3- ions in the urine or alkaline urine.

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Potassium Sparing Diuretics:
• The late distal tubule and the collecting duct have two types of cells, i.e., the principal cell
and intercalated cells.
• The Na+ ion channel present in the luminal membrane of the principal cells provides
pathway for the entry of Na + ions into the cells, down the electrochemical gradient.
• This electrochemical gradient is created by the basolateral Na + pump.
• The luminal membrane is highly permeable to Na + ions, thereby creating a lumen
negative trans -epithelial potential difference.
• This potential difference provides an important driving force enabling the secretion of K+
ions into the lumen
• The H + is secreted into the tubular lumen by the intercalated cells.
• This secretion occurs by the H+-ATPase pump or proton pump and the lumen negative
trans-epithelial voltage difference that acts as the driving force.
• The potassium sparing diuretics (amiloride and triamterene) block the Na+ ion channels
in the luminal membrane of the principal cells in the late distal tubule and collecting duct.
• This inhibits the transport of Na+ ions through the cells, thereby reducing the luminal
secretion of H + ions from the intercalated cells and K+ ions from the principal cells.
• The net effect is increased in the excretion of Na+ ions in the urine and retention of K+
and H+ ions.
Osmotic Diuretics:
• These diuretics are named so as they utilize their osmotic action to draw water from the
tissues.
• As a result, excretion of water and electrolytes increases.
• Osmotic diuretics mainly act on the loop of Henle.

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Xanthine Diuretics:
These diuretics act by the following two mechanisms:
1. Inhibition of Na+ ions and water reabsorption in the proximal convoluted tubule,
2. Increasing the renal blood flow by both cardiac and vascular actions.
3. However, these agents do not alter the balance of acid and base in the body nor do they
facilitate the loss of K+ ions.
PHARMACOKINETICS:
Carbonic Anhydrase Inhibitors

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Potassium Sparing Diuretics
Osmotic Diuretics:
• These diuretics are poorly absorbed when administered orally.
• Hence, they are effective only on parenteral administration.
• Their oral administration results in osmotic diarrhoea.
• Mannitol does not undergo metabolism.
• Excretion of these agents is by glomerular filtration.
• These drugs do not undergo significant tubular reabsorption or secretion, and are
excreted within 30-60 minutes.
Xanthine Diuretics:
• The half-life of theophylline depends on the patient age, liver function, smoking status,
and any drug therapy.
• Smoking decreases the half-life by 50%. In children aged 1 -9 years, the half-life can be as
much as 50% shorter than that in adults. Pulmonary oedema and liver disease prolong the
half-life up to 24 hours.
Therapeutic Uses
Following are the therapeutic uses of each class of weak diuretics:
1. Carbonic Anhydrase Inhibitors: Acetazolamide is self-limiting in nature. It produces
adverse effects like acidosis and hypokalemia. Thus, it is not used as a diuretic anymore.
Currently it is being employed for the treatment of:
a) Glaucoma: As an adjuvant to other ocular hypotensive.
b) Alkalinizing Urine: For urinary tract infection or to promote excretion of certain acidic
drugs.
c) Epilepsy: As an adjuvant in absence of seizures when primary drugs are not fully effective.
d) Acute Mountain Sickness: Symptomatic relief as well as prophylaxis.
2. Potassium Sparing Diuretics: Triamterene and amiloride are used together with thiazide
and loop diuretics. They do not allow hyperkaliemia to occur and increase the natriuretic
and antihypertensive response slightly.
3. Osmotic Diuretics: These diuretics are used in:
a) Reduction of intracranial pressure in cerebral oedema and intraocular pressure in
glaucoma,
b) Prevention of oliguria or anuria, and
c) Differentiation of pre -renal failure from renal failure (acute tubular necrosis), once
oliguria has set in. For this purpose, 100ml (20%) mannitol is administered to the patient
in the form of a test dose. In case urinary output in more th an 30ml in the next hour, 300

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-500ml can be safely administered to continue diuresis. However, if the urinary output
does not go beyond 30ml in the next one hour, it should be discontinued. This is a unique
usage of mannitol.
4. Xanthine Diuretics: Currently, these diuretics are rarely in use. These agents are
employed only as bronchodilators.
Drug Interactions
• Weak diuretics undergo the following interactions with other drugs:
• Carbonic Anhydrase Inhibitors: The drug interactions of acetazolamide are enlisted
Potassium Sparing Diuretics:
When these diuretics are administered with ACE inhibitors or angiotensin II receptor blockers,
they increase the risk of hyperkaliemia.
Osmotic Diuretics: When these diuretics are administered with lithium, the renal excretion of
lithium increases, thus decreasing its effectiveness.
Xanthine Diuretics:
Drug interactions seen with these diuretics include:
• When these diuretics are administered with allopurinol, cimetidine, macrolide antibiotics
(e.g., erythromycin), quinolones (e.g., ciprofloxacin), influenza vaccine, or oral
contraceptives, an increase in serum concentration of the drug is observed.
• When these diuretics are administered with sympathomimetics or caffeine, they may
show additive effects, stimulating the heart and CNS.
• Administration of theophylline (1, 3-dimethylxanthine) along with rifampicin causes an
increase in theophylline metabolism.
• As a result, concentration of theophylline in the body decreases.
• Foods like charcoal -broiled, high -protein food, and low -carbohydrate food may interact
with xanthine and decrease its serum level by several metabolic mechanisms.2.
Contraindications
The contraindications of each class of weak diuretics are given below:
1. Carbonic Anhydrase Inhibitors: Absolute contraindications to carbonic anhydrase
inhibitors include patients with:
a) Hypersensitivity,
b) Low serum levels of sodium or potassium,
c) Noticeable kidney and liver disease or dysfunction,

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d) Suprarenal gland failure,
e) Hyperchloremic acidosis,
f) Adrenocortical insufficiency,
g) Severe pulmonary obstruction,
h) Cirrhosis, and
i) Long-term use in patients with chronic non -congestive closed -angle glaucoma.
2. Potassium Sparing Diuretics:
• Aldosterone antagonists or potassium sparing diuretics (e.g., spironolactone) causes
severe hyperkaliemia (which may even prove to be fatal) in susceptible patients.
• In case potassium sparing diuretics are used, oral administration of potassium should be
discontinued.
• It should be used cautiously in patients with chronic renal insufficiency.
• Metabolism of triamterene and spironolactone may be impaired in patients with liver
diseases, and hence the dose should be carefully adjusted.
• Concentration of eplerenone may be increased by the administration of strong CYP3A4
inhibitors (e.g., ketoconazole and itraconazole).
3. Osmotic Diuretics: These diuretics are contraindicated in patients with:
a) Severe renal disease,
b) Severe pulmonary congestion or frank pulmonary oedema,
c) Active intracranial bleeding (except during craniotomy),
d) Severe dehydration,
e) Progressive renal damage or dysfunction after mannitol therapy, and
f) Progressive heart failure or pulmonary congestion after mannitol therapy.
4. Xanthine Diuretics:
Absolute contraindications to these diuretics include patients with:
a) Known drug allergy,
b) Uncontrolled cardiac dysrhythmias,
c) Seizure disorders,
d) Hyperthyroidism, and
e) Peptic ulcers.

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• Anti-diuretic drugs decrease the volume of urine by suppressing urine formation.
• These drugs are primarily indicated for patients with diabetes insipidus.
Classification
Anti-diuretics are classified as follows:
a) Antidiuretic Hormone (ADH, Vasopressin): Desmopressin, Lypressin, and Terlipressin.
b) Thiazide Diuretics: Amiloride.
c) Miscellaneous: Indomethacin, Chlorpropamide, and Carbamazepine.
ANTIDIURETIC HORMONE (ADH):
• It is a hormone or a protein secreted from the Hypothalamus binding to the precursor
protein called as Neurophysin into the Posterior pituitary gland (Neurohypophysis).
• They are now released from Neurohypophysis along with the Oxytocin.
• They are also called as the Vasopressin.
• The rate of release of ADH is mainly dependent on the Osmoreceptors present in
Hypothalamus and also by the volume receptor present in left atrium right atrium and
Pulmonary veins.
• The release of ADH is inhibited by the GABA and Atrial natriuretic peptide (ANP) (is a
hormone secreted from the right atrium in response to atrial stretch from hypervolemia
as well as in response to hypertension).
ADH receptors
1. V1 Receptors
• At all sites except for sites of V2 (i.e., Collecting Duct cells.
• Further classified as V1a and V1b.
a) V1a: vascular smooth muscles (including that of vasa recta in renal medulla), uterine,
visceral smooth muscles, interstitial cells in renal medulla, cortical CD cells, adipose tissue,
brain, platelets, liver, etc
b) V1b: anterior pituitary, certain areas in brain and in pancreas
2. V2 Receptors:
• More sensitive
• Present in Collecting duct and principal cells of kidney. It Regulates their water
permeability.
• Also present in AscLH (Ascending loop of Henle) cells: Activates Na+K+2Cl- cotransporter.
• Endothelium: vasodilator.

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VASOPRESSIN ANALOGUES:
ACTION ON VARIOUS ORGANS
1. Kidneys:
• Acts on CD principal cells
• renders them water permeable and increases the water absorption and makes the urine
concentrated.
2. Blood Vessels:
• Constricts through V1 receptors: raises blood pressure
• Dilates through V2 receptors: endothelium dependent NO (Nitric oxide) production.
3. GIT:
• Increased peristalsis: evacuation and expulsion of gases
4. Uterus:
• Contracted by acting on oxytocin receptors
5. Central Nervous System:
• Endogenous AVP may be involved in regulation of temperature, systemic circulation,
ACTH release, learning of tasks
Lypressin Terlipressin Desmopressin (dDAVP)
8-lysine vasopressin Synthetic prodrug of
vasopressin
Synthetic peptide
Less potent than
AVP
Bleedingesophageal
varices
Selective V2 agonist
V1 and V2 activity Less severe adverse effects
that lypressin
12 times more potent than AVP
Long duration of
action i.e., 4-6 hrs
Negligible vasoconstrictoractivity
Substitute for
AVP for V1
actions
Longer duration of action 8-12
hrs
PreparationofchoiceforallV2
mediatedactions
Intranasal route preferred
(bioavailability 10-20%) oral (1-
2%; avoids nasal side effects)

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6. Others:
• Induces platelet aggregation, hepatic glycogenolysis
• Release of factor VIII and von Willebrand’s factor from vascular endothelium: V2
receptor mediated.
MECHANISM OF ACTION OF ADH
V2 receptors:
• V2- sub receptors are present on the basolateral membrane (membrane facing towards
the blood) of the cells of collecting duct.
• Once ADH comes and binds to the V2- sub receptors they undergo activation and the
activated receptors now increases the formation of cAMP- dependent protein kinase
intracellularly.
• Intracellular accumulation of cAMP-PK increases with increase in the V2 receptor
activation.
• Upon accumulation of cAMP-PK it in turn phosphorylates related proteins.
• This inturn stimulates the exocytosis of an AQUAPORIN-2 (WCV- Water channel
containing vesicle).
• AP-2 now undergo exocytosis and are inserted onto the apical membrane (membrane
facing towards the urine) of the cells of collecting duct. AP-2 is a temporary channel that
are now formed that disappears once the process of absorption of water gets over.
• The endocytosis and degradation of AP-2 gradually decreases with time that causes
increase in AP-2 in the Apical membrane.
• More the V2 receptor activation more and more AP-2 is inserted in the apical
membrane.
• AP-2 causes the increase in the absorption of water from the apical membrane into the
cells of the collecting duct.

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• 2 channels namely Aquaporin-3 and Aquaporin-4 are present towards the basolateral
membrane of the Collecting duct cells. These channels are permanent.
• These channels allow the movement of water into the Basolateral membrane thereby
causing maintains the water balance inside the blood.
V1 receptors:
• The V1a receptors on activation cause constriction of vasa recta. As a result, the inner
medulla receives a decreased blood flow and this helps to maintain a high osmolarity in
this area, thereby contributing to anti-diuresis.
• Other actions of V1 receptors that increase prostaglandin production from the interstitial
cells and directly decrease the response of collecting duct cells to V2 receptor stimulation
restrict the water permeability mediated by V 2 receptors.
• Under physiological conditions, actions of V 1 receptors may aid in limiting the effect of
V2 receptors when the blood concentration of ADH is very high. This is because the actions
of V2 are produced at much lower levels of ADH.
Pharmacokinetics
• Trypsin destructs AVP, therefore is orally inactive.
• It should be administered either by a parenteral route or by intranasal route.
• Rapid enzymatic cleavage of the peptide chain of AVP occurs in many organs, particularly
in the liver and kidneys.
• The plasma half -life of AVP administered as a drug is short (approximately 25 minutes).
• The activity of aqueous vasopressin lasts only for 3-4 hours.
Uses:
Based on V2 Actions:
• Diabetes Insipidus (Neurogenic)
• Bedwetting in children and nocturia in adults
• Renal Concentration Test
• Hemophilia, von Willebrand’s Disease
Based on V1 Actions:
• Bleeding Esophageal Varices
• Before abdominal radiography
Adverse Effects
• Selective drugs produce lesser side effects
• Transient headache and flushing: frequent
• Local Application: Nasal irritation, congestion, rhinitis, ulceration, epistaxis
• Systemic Side effects: belching, nausea, vomiting, abdominal cramps, pallor, urge to
defecate, backache in females (uterine contraction)
• Fluid retention, hyponatremia
• Bradycardia, increased cardiac afterload, precipitate angina

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Contraindication:
• In patients with ischemic heart disease, hypertension, chronic nephritis, psychogenic
polydipsia
Sl No Chapter Name Long
Essay
Short
Essay
Short
Answer
Total
Marks
Duration
allotted
1 Pharmacology of
drugs acting on
Renal System
- 01 01 07 04
SHORT ESSAYS
1. What are diuretics? Classify them with examples.
2. Write mechanism of action, adverse effects and uses of loop diuretics.
3. Define diuretic? Write the clinical application of diuretics with emphasis on edema.
4. Write mechanism of action, adverse effects and uses of thiazide diuretics.
5. Enlist potassium sparing diuretics. Write their mechanism of action and uses.
6. Classify weak diuretics. Add a note on mechanism of action and uses of Carbonic
anhydrase inhibitors.
7. Enlist diuretics acting on ascending and descending loop of Henle. Write their adverse
effects and therapeutic uses.
8. What are anti-diuretics? Give examples. Add a note on mechanism of action and uses of
ADH.
9. Write the mechanism action, adverse effect of uses of frusemide.
10. Write the pharmacology action of spironolactone.
SHORT ANSWERS
1. Name four vasopressin analogues?
2. Name any two ADH and its two uses.
3. Define carbonic anhydrase inhibitors? Give two examples
4. What are osmotic diuretics? Write their uses.
5. Classify diuretics showing their site of action in nephron.
6. Write four uses of potassium sparing diuretics.
7. Enlist potassium sparing diuretics.
8. Mention four uses of thiazide diuretics.
9. Give four indications for loop diuretics.
10. Mention four adverse effects of diuretics.
THANKYOU