Diuretics

Question 1

The kidney functions associated with urinary excretion: (4)

Answer 1

Stabilizes the osmolarity and the volume of extracellular fluid.

Regulates the concentration of the extracellular fluid.

Removes metabolic waste and foreign substances from the blood.

Contributes to acid-base balance by varying urinary excretion of hydrogen and bicarbonate ions.

Question 2

Functions of the kidneys besides urinary excretion and osmolarity of body fluids. (4)

Answer 2

Production of renin: an enzyme that regulates formation of angiotensin II.

Production of erythropoietin, a hormone that stimulates formation and maturation of erythrocytes.

Production of calcitriol, the active form of vitamin D (important in regulation of Ca metabolism).

Gluconeogenesis from substances other than carbohydrates (during prolonged starving).

Question 3

Urine formation is composed of 3 processes:

Answer 3

Filtration
Reabsorption
Secretion

Question 4

Hormones controlling diuresis (4)

Answer 4

Hormones of the adrenal cortex of the adrenal glands:
aldosterone,
deoxycorticosterone and
hydrocortisone.

Hormone of the pituitary gland:
antidiuretic hormone (ADH).

It causes water retention in the distal kidney tubules. It does not cause changes in electrolyte balance in physiological concentration.

Question 5

Aldosterone is the most important factor in the regulation of

Answer 5

urinary excretion of Na.

The total amount of Na in the body is most important determinant for blood volume and volume of extracellular fluid.

The amount of Na present is regulated by aldosterone.

A total lack of aldosterone causes reduction in blood volume, loss of Na+ and fatal circulatory shock.

Question 6

ADH is produced in the

Answer 6

paraventricular nucleus of the hypothalamus.

Question 7

ADH is released as a result of a change in

Answer 7

osmolarity of extracellular fluid.

The “dilution” of extracellular fluid causes the decrease in the production of ADH (negative feedback).

Impulses sent by hypothalamic osmoreceptors regulate the production of ADH.

Question 8

The following increase ADH production: (5)

Answer 8

acetylcholine,
histamine,

general anesthetics,
morphine,
some barbiturates.

Question 9

ADH may be decreased in what sorts of instances: (4)

Answer 9

Diabetes insipidus,
several medicinal products,
pain,
psychological disorders, etc.

Question 10

If blood electrolytes and osmotic pressure increase, what occurs in regard to ADH: (4)

Answer 10

ADH concentrations will increase,

the reabsorption of water from kidney tubules is enhanced,

the osmotic pressure of urine increases,

the production of urine is decreased or inhibited.

Question 11

Therenin–angiotensin–aldosterone system(RAAS), is a

Answer 11

hormone systemthat regulatesblood pressure,fluid andelectrolytebalance, and systemicvascular resistance.

Renin activates the system cascade;
angiotensin I from angiotensinogen;
angiotensin II from angiotensin I
(angiotensin-converting enzyme);
aldosterone secretion stimulated.

Question 12

Renin is released in the body as a response to physiological stimulus such as: (5)

Answer 12

Hypotension
Hypokalemia

Rapid decrease of blood pressure
Decreased blood volume

Stimulation of β-receptors

Question 13

Renin catalyzes the formation of

Answer 13

angiotensin I from angiotensinogen (in liver)

Question 14

Angiotensin II effects: (3-4)

Answer 14

blood vessels constrict,
blood pressure increases,
secretion of aldosterone increases

As a negative feedback – synthesis of renin is inhibited.

Question 15

?% of primary urine is reabsorbed.

Answer 15

99% of primary urine is reabsorbed.

The reabsorption of electrolytes is an active process, occurring against the concentration gradient, ATP energy is consumed.

Participating enzymes:
carbonic anhydrase, succinate dehydrogenase.

Question 16

Diuretics are

Answer 16

Substances that promote the production of urine.

They enhance the secretion of electrolytes and reduce the amount of extracellular fluid.

Question 17

The objective of the administration of diuretics is to

Answer 17

increase the excretion of sodium and the consequent excretion of water from the organism.

Question 18

Most diuretics exert their effects by

Answer 18

inhibiting specific enzymes, transport proteins, hormone receptors or ion channels that mediate the reabsorption of sodium in kidney tubules.

They also impact the excretion of other ions and renal hemodynamics.

Question 19

Primary indications of diruretics

Answer 19

Swelling/edema caused by heart failure, liver failure or kidney failure.

Different indications for different diuretics!

NB Hypovolemia can occur!

Question 20

Mechanism of swelling in general

Answer 20

Plasma colloid osmotic pressure is reduced.

Intravascular volume depletion occurs when the fluid flows into the interstitial compartment.

Blood plasma volume is lowered, as a consequence of that, the reabsorption of water and salts increases in the kidneys.

The increased reabsorption of fluid increases the plasma volume and the plasma hydrostatic pressure, the outflow of fluid from capillaries increases and swelling occurs.

Question 21

Swelling in the case of heart failure

Answer 21

Congestive heart failure reduces the outflow of blood from the heart, thereby reducing the blood supply of the kidneys, which causes activation of the renin–angiotensin–aldosterone system, followed by the reabsorption of salts and water in the kidneys.

An increase in the central venous pressure causes an increase in the hydrostatic pressure in the capillaries, the fluid penetrates the capillary walls, swelling occurs.

Question 22

Classification of diuretics (9)

Answer 22

Water and osmotic diuretics
Salts that form acidic solutions

Carbonic anhydrase inhibitors
Loop diuretics

Epithelial sodium channel blockers
Thiazide diuretics

Aldosterone antagonists
Substances reducing tissue hydrophilicity

Essential oils or plant-based substances

Question 23

Name substances that belong to the Water and osmotic diuretics-group (5)

Answer 23

Water (the more fluid the organism contains, the more is being excreted. Flushing of organism.)

Pure urea
Mannitol

Sodium chloride
Sodium bicarbonate

Question 24

Osmotic diuretics mechanism of action

Answer 24

the osmotic pressure of the blood plasma increases, extracellular fluid and sodium flow into the blood, excreted through the kidneys.

A strong tissue dehydration effect (crenation).

Cannot be used when kidney function is impaired - this will instead lead to swelling.

Question 25

mechanism of action of mannitol

Answer 25

osmotic diuretic: Its primary mechanism of action involves altering the osmotic pressure in the renal tubules.

Mannitol is not reabsorbed by the renal tubules in significant amounts.

When administered intravenously, mannitol remains in the renal tubules and draws water into the tubules through osmosis.

This increased osmotic pressure in the tubules prevents water reabsorption, leading to increased urine production.

The osmotic diuretic effect of mannitol leads to the removal of water from the intracellular and interstitial compartments into the intravascular space.

Question 26

Water and osmotic diuretics-group
Side effects (of mannitol):

Answer 26

Nausea, vomiting
Dehydration, hypernatremia
Loss of other electrolytes, incl. K

Question 27

Therapeutic uses of mannitol:

Answer 27

With other diuretics to mobilize edema

For the reduction of intracranial and intraocular pressure

Treatment of renal failure (reduction of swelling of tubular elements)

! Contraindicated in case of ongoing cranial hemorrhage, anuric renal failure, severe dehydration, pulmonary edema, heart failure.

Question 28

Salts that form acidic solutions (2)

Answer 28

Ammonium chloride
Ammonium nitrate

Salt is dissociated into sodium chloride and ammonia. The diuretic effect is based upon the releasing Cl ion, which binds to Na from the extracellular fluid, forming NaCl, which in turn causes osmotic diuresis.

Na and K are excreted.
Acidosis occurs as a side effect.
Contraindicated in the case of kidney failure and liver failure.

For acidification of the urine.
Can be used to dissolve certain types of bladder stones.
It may also be used to promote the excretion of certain toxins or drugs into the urine.

Side effects: vomiting, increased thirst, rapid breathing, drowsiness, a rapid or irregular heart beat.

Question 29

Carbonic anhydrase inhibitors do what?
Give some examples.

Answer 29

Carbonic anhydrase promotes the reabsorption of sodium and water in the kidney tubules. Diuresis increases in the event of blocking.

• They reduce the excretion of ammonium, which has a toxic effect on the liver.
• They excrete K ions.
• They are mainly used to reduce internal eye pressure in the case of glaucoma in dogs.

Contraindicated in patients with electrolyte disturbances and those with metabolic or respiratory acidosis.

e.g. Acetazolamide
Dichlorphenamide
Methazolamide
Carbonic anhydrase

Question 30

Loop diuretics act where?
Name one.
Side effects?

Answer 30

the loop of Henle.

With the most potent effect, they inhibit the primary sodium reabsorption mechanism.

Furosemide, the most frequently used diuretic, is a loop diuretic.

It is used in the case of oedema caused by heart failure, liver failure or kidney failure.

NSAIDs inhibit the diuretic, natriuretic and chloruretic responses to furosemide.

Side effects are related to disorders involving electrolyte balance, K is excreted.

Extracellular volume depletion and hyponatremia – reduced blood pressure, diminished organ perfusion.

Hypochloremic alkalosis, hypokalemia.

Potential for ototoxicity.

Cats are more sensitive than dogs.

Question 31

Furosemide can be used in case of heart failure in patients already receiving

Answer 31

ACE inhibitors, digoxin, or both.

Question 32

Name a loop diuretic alternative to furosemide. (2)

Answer 32

Torasemide - for treatment of clinical signs, including edema and effusion, related to congestive heart failure.

OR

Bumetanide (loop diuretic) is indicated for the treatment of edema associated with congestive heart failure, cirrhosis of the liver and renal disease including nephrotic syndrome (a group of symptoms that includeprotein in the urine, low blood protein levels, high triglyceride levels, andswelling).

In cats, dogs and guinea pigs, bumetanide has been shown to produce ototoxicity.

Question 33

Name 3 loop diuretics.

Answer 33

furosemide
torsemide
bumetanide

Question 34

Renal epithelial sodium channel blockers

Answer 34

Such as Triamterene

A relatively weak-acting diuretic, to a certain extent potassium-sparing, used in combination with thiazide diuretics or loop diuretics (generally not commonly used).

They inhibit the reabsorption of sodium.

Side effects are an increase in the risk of hyperkalemia and kidney dysfunction.

Question 35

Thiazide diuretics
explain them and give examples

Answer 35

increase the excretion of sodium and potassium.

Are Part of treatment scheme in treatment of nephrogenic diabetes insipidus:
- Diuretic-induced volume contraction leads to increased proximal tubule reabsorption and decrease in urine volume.

Side effects are hypokalemia, hyponatraemia, hypochloraemia, simultaneously hypercalcemia.

e.g. Chlorothiazide
Hydrochlorothiazide

Question 36

Aldosterone – hormone of the adrenal cortex of the adrenal glands, mineralocorticoid, participates in water and electrolyte metabolism by way of enhancing the

Answer 36

reabsorption of sodium and water and the excretion of potassium.

Question 37

Aldosterone antagonists as diuretics

Answer 37

Spironolactone is an aldosterone antagonist, with a steroidal structure, it enhances the elimination of sodium, reduces the secretion of K and urea (potassium-sparing diuretics).

Spironolactone can be used in combination with other diuretics, primarily furosemide.

Side effects:
Hyperkalemia, dehydration, hyponatremia.

Question 38

Substances reducing tissue hydrophilicity include: (4)

Answer 38

Caffeine (the weakest diuretic)
Theophylline (the most potent diuretic)
Euphyllin
Theobromine

Question 39

Substances reducing tissue hydrophilicity (such as caffeine) have what types of effects on water balance in the body?

Answer 39

have a cardiostimulating effect, increase the blood supply of kidneys and cause tissue dehydration.

The blood inflow to the heart and kidneys increases, a reflexive ADH production decrease occurs.

Question 40

Plant diuretics

Answer 40

Mostly plants containing essential oils
Juniper berries
Bearberry leaves
Field horsetail herb
Parsley root
Lingonberry leaves

The mechanism of action is unclear, probably an irritant effect on the kidney tissue.

Question 41

Substances with a diuretic effect but do not have direct effects on the kidneys, include: (2)

Answer 41

Cardiac glycosides (digitalis compounds)
ACE inhibitors

Question 42

Telmisartan (Semintra) is used in vet med for

Answer 42

the reduction of proteinuria resulting from chronic kidney disease in cats.

Telmisartan is an orally active and specific angiotensin II receptor (AT1 type) antagonist, which causes a decrease in mean arterial blood pressure, depending upon the dosage, in mammal species, including cats.

AT1 receptor STIMulation causes the pathological effects of angiotensin II on the kidneys and other organs that are linked to angiotensin II, for instance vasoconstriction, sodium and water retention, increase in the synthesis of aldosterone.

A clinical study of cats with chronic kidney disease found a reduction in proteinuria within the first 7 days from the start of therapy.

Question 43

Benazepril + spironolactone (Cardalis)

Answer 43

is a combination of two active substances used in the Treatment of congestive heart failure caused by chronic degenerative valvular disease in dogs (with diuretic support, as appropriate).

Benazepril is an ACE-inhibitor & spironolactone is a Aldosterone antagonist and K+-sparing diuretic.

Question 44

Spironolactone inhibits aldosterone-induced…?

Answer 44

sodium retention in the kidneys, leading to an increase in sodium, and subsequently water, excretion and potassium retention.

The accompanying reduction in extracellular volume reduces cardiac preload and left ventricle pressure.

Spironolactone is a Aldosterone antagonist and K+-sparing diuretic.

Question 45

Benazepril is a potent and selective

Answer 45

angiotensin-converting enzyme (ACE) inhibitor, preventing inactive angiotensin I from being converted into active angiotensin II.

Therefore, the mediated actions of angiotensin II are blocked, including the constriction of arteries and veins and the retention of sodium and water by the kidneys.