Medicinal Chemistry and Pharmacology of Diuretics

Question 1

What are the functions of the kidneys

Answer 1

maintain homeostatic balance of electrolytes and water, excrete water-soluble end products of metabolism

Question 2

What is the functional unit of the kidney

Answer 2

Nephron

Question 3

What are the two important physical processes in urine formation

Answer 3

osmosis and active transport

Question 4

What are the five parts of the Nephron

Answer 4

Glomerulus, Proximal Tubule, Loop of Henle, Distal Tubule, Collecting Duct

Question 5

Filtrated plasma provided by glomerular capillary network into the Bowman’s capsule becomes what, what is a key difference

Answer 5

Luminal fluid, change in osmotic concentration

Question 6

What are the most important molecules reabsorbed in the proximal tubule, what is the other important molecule absorbed

Answer 6

sodium chloride and bicarbonate, water

Question 7

What enzyme is responsible for transcellular reabsorbption of sodium and bicarbonate

Answer 7

Carbonic anhydrase

Question 8

How does carbonic anhydrase work

Answer 8

Water binds to the enzyme and grabs carbon dioxide to become carbonic acid, carbonic acid is unstable and dissociates to protons and bicarbonate, the protons and sodium are exchanged through an antiporter system to keep electrostatic equilibrium, bicarbonate and sodium are put into the interstitial fluid through a symporter system

Question 9

What enzyme is the driving force to create an osmotic gradient, what is the result

Answer 9

Na+/K+ ATPase, creates Na+ deficit in luminal cell and draws sodium from luminal fluid

Question 10

How are other ways sodium enters the cell or anti-luminal membrane

Answer 10

transcellular transport (passive to luminal membrane, active to anti-luminal membrane), paracellular transport (diffusion)

Question 11

What part of the nephron is most responsible for absorbing Sodium, how much sodium does it reabsorb

Answer 11

proximal tubule, 60%

Question 12

What are the two portions of the loop of Henle

Answer 12

Descending limb, ascending limb

Question 13

Which part of the Loop of Henle water permeable, is it active or passive

Answer 13

Descending limb, osmosis (passive)

Question 14

Which part of the Loop of Henle is water impermeable, what is usually reabsorbed at what ratio

Answer 14

Ascending limb, NaCL (1:2)

Question 15

What percentage of the reabsorbed sodium is reabsorbed by the loop of Henle, which part

Answer 15

30%, Ascending Limb

Question 16

How does sodium and chloride get into the cell in the ascending limb

Answer 16

symporter system

Question 17

What part of the nephron is hormone driven, what hormones drive it

Answer 17

Distal Tubule,ADH and Renin

Question 18

Where is potassium is more likely to enter the urine

Answer 18

Collecting duct

Question 19

How does the nephron react to hypovolemia/ dehydration

Answer 19

decreased renal blood flow and GFR, increased renin secretion, increased secretion of ADH, increased water re-absorption

Question 20

How do diuretic agents work

Answer 20

promote urination by increasing the rate of renal excretion of water and electrolytes

Question 21

T/F: Most diuretics work by inhibitng Na+ transport at one or more of the four mayjor anatomical sites

Answer 21

True

Question 22

What will influence how much diuretic enters the luminal fluid by the filtration process

Answer 22

GFR. plasma concentration of diuretic agent, fraction of the drug that is bound to unfiltrable plasma proteins

Question 23

How do the diuretics get to their site of action

Answer 23

travel through the blood stream and bind to OATs (acids) or OCTs (bases) where they are secreted

Question 24

What is the driving force of the glomerular filtration process

Answer 24

hydraulic pressure (pumping heart)

Question 25

What is the role of the Na+/K+ ATPase in the anti-luminal membrane

Answer 25

driving force of sodium re-absorption and creates a sodium deficit in the luminal cell

Question 26

T/F: Water is reabsorbed throughout the entire Loop of Henle

Answer 26

False- the ascending Loop of Henle is not water-permeable

Question 27

Where is the salt (osmotic) concentration is higher

Answer 27

Medulla

Question 28

What are the classes of diuretics

Answer 28

osmotics, carbonic anhydrase inhibitors, thiazides, loop, potassium sparing

Question 29

What are properties of osmotic dieuretics

Answer 29

highly water soluble, with minimal re-absorption by the renal tubule that are freely filtered through the Bowman's capsule into the renal tubules

Question 30

What are the osmotic diurectics

Answer 30

Mannitol, isosorbide, and sorbitol

Question 31

What is MOA of osmotic diuretics

Answer 31

artificially concentrate the urine causing less sodium absorption and water reabsorption

Question 32

Where do the osmotics usually work at

Answer 32

Proximal tubule and descending limb

Question 33

Where do carbonic anhydrase inhibitors do most of the action at

Answer 33

Proximal tubule

Question 34

What is the MOA of carbonic anhydrase

Answer 34

inhibiton of renal carbonic anhydrase decreases sodium carbonate reabsorption leading to increased volume of luminal fluid

Question 35

What do all carbonic anhydrase drugs have in common

Answer 35

Sulfanilamide lead compound (unsubstituted sulfamoyl group and aromatic system)

Question 36

T/F: Carbonic anhydrase are competitive inhibitors that block the binding of water and carbon dioxide

Answer 36

True

Question 37

What are carbonic anhydrase usually used for

Answer 37

Glaucoma

Question 38

Where do thiazide diuretics work

Answer 38

Distal tubule

Question 39

T/F: Thiazide have a strictly diuretic activity

Answer 39

False: Thiazide diuretics posses a diuretic activity along with CA inhibitory activity due to its sulanilamide moeiry

Question 40

What occurs in the distal tubule, how do thiazides change this

Answer 40

Symporter system that carries sodium and chloride in the luminal cells, inhibit the sodium and chloride symporter leading to an increase in water excretion

Question 41

What is basic in thiazide structure in order for them to work

Answer 41

Six membered aromatic phenyl ring attached to a cyclic six membered ring, a free sulfonilmide and one in the cyclic ring

Question 42

What is essential for diuretic activity in thiazides

Answer 42

an electron withdrawing group at C-6, free sulfonamide at C-7

Question 43

T/F: Substituation with a lipophilic group at C-3 increases diuretic potency and/or its duration of action

Answer 43

True

Question 44

What is the most apparent adverse effect of using thiazide diuretics, why

Answer 44

Hypokalemia, Due to high Sodium in lumen due to thiazide there is increased K+ secretion in the collecting duct when sodium is reabsorbed

Question 45

What is another electrolyte disorder caused by thiazide diuretics, why

Answer 45

hypercalcemia, long-term thiazide treatment is known to trigger an increase in proximal tubule reabsorption of fluid, uric acid, and electrolytes (such as calcium)

Question 46

How do thiazides lead to hyperuricemia

Answer 46

Both thiazides and uric acid are weak organic acids that compete for OATs

Question 47

Which diuretics are used in emergencies, where do they work

Answer 47

Loop diuretics, thick ascending loop

Question 48

What is the most potent Loop diuretic, which is mostly prescribed to patients, which lacks the CA inhibitor activity due to lacking the sulfamoyl group

Answer 48

Bumetanide, Furosemide, Torsemide

Question 49

Which Loop diuretics not only inhibit the luminal Na+/K+/2Cl- symporter system but also the Na+/K+ATPase, what do they lack from other Loop diuretics

Answer 49

Etacrynic acid and Indacrinone, Lack CA inhibition due to no sulfamoyl group

Question 50

What is MOA of potassium sparing diuretics

Answer 50

competitive inhibition of aldosterone receptor or blockade of sodium channels at the luminal membrane

Question 51

What are potassium sparing diuretics that selectively block sodium channels, where do they work, what is their ionic state

Answer 51

Amiloride and Triamterene, collecting duct, positive (basic)

Question 52

What is aldosterone, what does it do

Answer 52

endogenous mineralocoricoid with antidiuretic hormone action through binding mineralocorticoid receptor leading to more Na+/K+ATPase and more Na+ channels

Question 53

What are potassium sparine diuretics that are aldosterone receptor antagonists,

Answer 53

spironolactone, canrenone, and eplerenone

Question 54

Which aldosterone receptor antagonists is a active metabolite of spironolactone, which is more selective for the aldosterone receptor

Answer 54

canrenone and eplerenone

Question 55

T/F: Both potassium sparing diuretics bind to Na channels directly leading to potassium sparing

Answer 55

False: Amiloride and triamterene block these channels directly while spironolactone, canrenone, eplerenone are used to reduce the concentration of these channels

Question 56

What is the mutual effect of all diuretics

Answer 56

increase in osmotic concentration of the luminal fluid and resulting in reduced water re-absorption

Question 57

How do diuretics increase the risk of gout

Answer 57

Uric acid is built up in the body and crystallizes, this happens because Uric acid must now competes with diuretics that also use the enzyme OATs in order to get to the urine

Question 58

Which class diuretics work on the proximal tubule and descending loop of henle, which work on just the proximal tubule, which work on the ascending loop of henle, which work on the distal tubule

Answer 58

osmotic, carbonic anhydrase, Loop, thiazides and potassium sparing