Diuretics Flashcards
The kidney functions associated with urinary excretion: (4)
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.
Functions of the kidneys besides urinary excretion and osmolarity of body fluids. (4)
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).
Urine formation is composed of 3 processes:
Filtration
Reabsorption
Secretion
Hormones controlling diuresis (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.
Aldosterone is the most important factor in the regulation of
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.
ADH is produced in the
paraventricular nucleus of the hypothalamus.
ADH is released as a result of a change in
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.
The following increase ADH production: (5)
acetylcholine,
histamine,
general anesthetics,
morphine,
some barbiturates.
ADH may be decreased in what sorts of instances: (4)
Diabetes insipidus,
several medicinal products,
pain,
psychological disorders, etc.
If blood electrolytes and osmotic pressure increase, what occurs in regard to ADH: (4)
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.
Therenin–angiotensin–aldosterone system(RAAS), is a
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.
Renin is released in the body as a response to physiological stimulus such as: (5)
Hypotension
Hypokalemia
Rapid decrease of blood pressure
Decreased blood volume
Stimulation of β-receptors
Renin catalyzes the formation of
angiotensin I from angiotensinogen (in liver)
Angiotensin II effects: (3-4)
blood vessels constrict,
blood pressure increases,
secretion of aldosterone increases
As a negative feedback – synthesis of renin is inhibited.
?% of primary urine is reabsorbed.
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.
Diuretics are
Substances that promote the production of urine.
They enhance the secretion of electrolytes and reduce the amount of extracellular fluid.
The objective of the administration of diuretics is to
increase the excretion of sodium and the consequent excretion of water from the organism.
Most diuretics exert their effects by
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.
Primary indications of diruretics
Swelling/edema caused by heart failure, liver failure or kidney failure.
Different indications for different diuretics!
NB Hypovolemia can occur!
Mechanism of swelling in general
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.
Swelling in the case of heart failure
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.
Classification of diuretics (9)
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
Name substances that belong to the Water and osmotic diuretics-group (5)
Water (the more fluid the organism contains, the more is being excreted. Flushing of organism.)
Pure urea
Mannitol
Sodium chloride
Sodium bicarbonate
Osmotic diuretics mechanism of action
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.
mechanism of action of mannitol
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.
Water and osmotic diuretics-group
Side effects (of mannitol):
Nausea, vomiting
Dehydration, hypernatremia
Loss of other electrolytes, incl. K
Therapeutic uses of mannitol:
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.
Salts that form acidic solutions (2)
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.
Carbonic anhydrase inhibitors do what?
Give some examples.
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
Loop diuretics act where?
Name one.
Side effects?
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.
Furosemide can be used in case of heart failure in patients already receiving
ACE inhibitors, digoxin, or both.
Name a loop diuretic alternative to furosemide. (2)
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.
Name 3 loop diuretics.
furosemide
torsemide
bumetanide
Renal epithelial sodium channel blockers
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.
Thiazide diuretics
explain them and give examples
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
Aldosterone – hormone of the adrenal cortex of the adrenal glands, mineralocorticoid, participates in water and electrolyte metabolism by way of enhancing the
reabsorption of sodium and water and the excretion of potassium.
Aldosterone antagonists as diuretics
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.
Substances reducing tissue hydrophilicity include: (4)
Caffeine (the weakest diuretic)
Theophylline (the most potent diuretic)
Euphyllin
Theobromine
Substances reducing tissue hydrophilicity (such as caffeine) have what types of effects on water balance in the body?
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.
Plant diuretics
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.
Substances with a diuretic effect but do not have direct effects on the kidneys, include: (2)
Cardiac glycosides (digitalis compounds)
ACE inhibitors
Telmisartan (Semintra) is used in vet med for
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.
Benazepril + spironolactone (Cardalis)
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.
Spironolactone inhibits aldosterone-induced…?
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.
Benazepril is a potent and selective
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.
