5. DIURETICS Flashcards
kidney function associated with urinary excretion (4)
- stabilize osmolarity and volume of extracellular fluid
- regulate concentration in extracellular fluid
- remove metabolic wastes and foreign substances from blood
- contribute to acid-base balance by varying urinary excretion of hydrogen and bicarbonate ions
other functions of kidneys
-production of renin: enzyme that regulates formation of angiotensin 2
-production of glucose from substances other than carbohydrates (during prolonged starving)
-production of erythropoietin, hormone that stimulates formation and maturation of erythrocytes
-production of calcitrol, active form of vitamin D (important in regulating of Ca metabolism)
basic renal processes: urine formation 3 steps
- filtration
2.reabsorption - secretion
hormones controlling diuresis : hormones of adrenal cortex of adrenal gland
aldosterone, desoxycotricosterone and hydrocortisone
hormone of pituitary gland
antidiuretic hormone (ADH).
causes water retention in distal kidney tubules. it does not cause changes in electrolyte balance in physiological concentration
aldosterone: most important factor in regulation of
urinary excretion of Na
aldosterone total amount of Na in body is most important in determining
blood volume and volume of extracellular fluid
aldosterone amount of Na is regulated by
aldosterone
total lack of aldosterone causes
reduction in blood volume and fatal circulatory shock
ADH produced in
paraventricular nucleus of hypothalamus
ADH released as result of
change in osmolarity of extracellular fluid > ‘‘dilution’’ of extracellular fluid causes decrease in production of ADH
following increase ADH production
-acetylcholine
-general anaesthetics
-histamine
-morphine
-some barbiturates
ADH is reduced by
-diabetes insipidus
-multiple medicinal products
-pain
-psychological disorders
impulses sent by hypothalamic osmoreceptors
regulate production of ADH
in case of blood electrolytes and osmotic pressure increase
-amount of ADH will increase
-reabsorption of water from kidney tubules is enhanced
-osmotic pressure of urine increases
-production of urine is inhibited
renin-angiotensin system (RAS) or renin-angiotensin-aldosterone system (RAAS) is a hormone system that regulates
-blood pressure
-fluid and electrolyte balance
-systemic vascular resistance
…. activates RAS or RAAS
renin
renin released in body as response to physiological stimulus
-hypontension
-hypokalemia
-rapid decrease of blood pressure
-decreased blood volume
-stimulation of beta-receptors
renin catalyses formation of angiotensin 1 from
angiotensinogen (in liver)
angiontesin 1 is converted to angiotensin 2 by
specific enzymes
angiotensin 2 effects
-blood vessels constrict
-blood pressure increases
-synthesis of aldosterone increases
as negative feedback synthesis of renin is
inhibited
production of urine
balance of water and electrolytes in organism is assured
..% of primary urine is reabsorbed
99
reabsorption of electrolytes is active process, occurring
against concentration gradient, ATP energy is consumed
participating enzymes in production of urine
-carbonic anhydrase
-succinate dehydrogenase
with enhancement of blood supply in kidneys, amount of primary urine
increases
diuretics substances that
promote production of urine
diuretics enhance ….and reduce…
enhance secretion of electrolytes and reduce amount of extracellular fluid
diuretics alleviating oedema. oedema typically occurs as
result of retention of sodium in organism and increase in accumulation of extracellular fluid
objective of administration of diuretics - to increase excretion
of water from organism
most diuretics exert their effects by
inhibiting specific enzymes, transport proteins, hormone receptors or ion channels that mediate reabsorption of sodium in kidney tubules
diuretics also impact excretion of
other ions and renal hemodynamics
diuretics primary indications: swelling that is caused by
-heart failure
-liver failure
-kidney failure
> different indications for different diuretics
…. caused by diuretics may occur
hypovolemia
mechanism of swelling
-plasma colloid osmotic pressure is reduced
-intravascular volume depletion occurs and fluid flows to interstitial compartment
-blood plasma volume is lowered > reabsorption of water and salts increases in kidneys
-increased reabsorption of fluid increases plasma volume and plasma hydrostatic pressure, outflow of fluid from capillaries increases and swelling occurs
swelling in case of heart failure
-congestive heart failure reduces outflow of blood from heart> reduces blood supply of kidneys > activation of renin-angiotensin-aldosterone system> followed by reabsorption of salts and water in kidneys
-increase in central venous pressure causes increase in hydrostatic pressure in capillaries > fluid penetrates 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
h2o and osmotic diuretics
-water=more fluid organism contains>more is being excreted. flushing of organism
-pure urea
-mannitol
-sodium chloride
-sodium bicarbonate
osmotic diuretics
osmotic pressure of blood plasma increases > extracellular fluid and sodium flow into blood > excreted via kidneys
-strong tissue dehydration effect
osmotic diuretics cannot be used
when kidney function is impaired > will instead lead to swelling
side effects of osmotic diuretics - mannitol
-nausea , vomiting
-dehydration, hypernatremia
-loss of other electrolytes, incl. K
therapeutic uses of mannitol
-with other diuretics to mobilize edema
-for reduction of intracranial and intraocular pressure
-treatment of renal failure > reduction of swelling of tubular elements
diuretics contraindicated in case of
ongoing cranial hemorrhage, anuric renal failure, severe dehydration, pulmonary edema, heart failure
salts that form acidic solutions
-ammonium chloride
-ammonium nitrate
-salt is dissociated into NaCl and ammonia > diuretic effect is based upon releasing Cl ion, which binds to Na from extracellular fluid > forming NaCl > which in turn causes osmotic diuresis. Na and K are excreted
-acidosis occurs as side effect
salts that form acidic solutions are contraindicated in case of
kidney failure and liver failure
salts that form acidic solutions can be used to
dissolve certain types of bladder stones
> also be used to promote excretion of certain toxins or drugs into urine
salts that form acidic solutions side effects
-vomiting
-increased thirst
-rapid breathing
-drowsiness
-rapid or irregular heart beat
carbonic anhydrase inhibitors
-acetazolamide
-dichlorphenamide
-methazolamide
-carbonic anhydrase promotes reabsorption of sodium and water in kidney tubules > diuresis increase in event of blocking
carbonic anhydrase inhibitors reduce the excretion of
ammonium, toxic effect on liver
carbonic anhydrase inhibitors excrete
K ions
carbonic anhydrase inhibitors mainly used to
reduce internal eye pressure in case of glaucoma in dogs
CA inhibitors are sulfonamide derivatives-side effects occur when
animals are sensitive to sulfonamides
CA inhibitors contraindicated in patients with
electrolyte disturbances and those with metabolic or respiratory acidosis
loop diuretics that act
at loop of Henle
loop diuretics with most potent effect, they inhibit
primary sodium reabsorption mechanism
loop diuretics - Furosemide- most frequently used
diuretic
loop diuretics it is used in case of
oedema caused by heart failure, liver failure or kidney failure
loop diuretics-NSAIDs inhibit
diuretic, natriuretic and chloruretic responses to furosemide
loop diuretics side effects are related to
disorders involving electrolyte balance, K is excreted
loop diuretics- extracellular volume depletion and hyponatremia-reduced
blood pressure, diminished organ perfusion
loop diuretics-hypochloremic … and …
alkalosis and hypokalemia
loop diuretics potential for …toxicity
ototoxicity (sisäkorvan vaurioituminen)
loop diuretics cats are more … than dogs
sensitive
furosemide can be used in case of
heart failure in patients already receiving ACE inhibitors , digoxin, or both
torasemide-loop diuretics-treatment of clinical signs, including
oedema and effusion, related to congestive heart failure
bumetanide (loop diuretic) is indicated for treatment of
edema associated with congestive heart failure, cirrhosis of liver and renal disease including nephrotic syndrome (group of symptoms that include protein in urine, low blood protein levels, high triglyceride levels , and swelling)
renal epithelial sodium channel blockers
-triamterene
-relatively weak-acting diuretic, to certain extent potassium-sparing, used in combination with thiazide diuretics or loop diuretics (generally not commonly used)
inhibit reabsorption of sodium
-side effects are increase in risk of hyperkalemia and kidney dysfunction
thiazide diuretics
-chlorothiazide
-hydrochlorothiazide
-they increase excretion of sodium and potassium from organism
-have been used to treat swelling with different root causes
-part of treatment scheme in treatment of nephrogenic diabetes insipid > diuretic-induced volume contraction leads to increased proximal tubule reabsorption and decrease in urine volume
thiazide diuretics side effects are
hypokalemia, hyponatraemia, hypochloraemia, simultaneously hypercalcemia > several substances from sulfonamide class of drugs, effect is diuretic, also used in human medicine to treat hypertension
aldosterone antagonist-aldosterone hormone of
adrenal cortex of adrenal glands, mineralocorticoid, participates in water and electrolyte metabolism, enhances reabsorption of sodium and water and excretion of potassium
spironolactone-aldosterone antagonist-with steroidal structure, enhances
elimination of sodium, reduces secretion of K and urea (potassium-sparing diuretics)
spironolactone can be used in combination with
other diuretics, primarily furosemide
aldosterone antagonist side effects
hyperkalemia, dehydration, hyponatremia
substances reducing tissue hydrophilicity
-caffeine (weakest diuretic)
-theophylline (most potent diuretic)
-euphyllin
-theobromine
substances reducing tissue hydrophilicity they also have cardiostimulating effect, increase
blood supply of kidneys and cause tissue dehydration. Blood inflow to heart and kidneys increases, reflexive ADH production decrease occurs
plant diuretics
-motly plants containing essential oils
-juniper berries
-bearberry leaves
-field horsetail herb
-parsley root
-lingonberry leaves
-mechanism of action is unclear, probably irritant effect on kidney tissue
substances with diuretic effect
-cardiac glycosides (digitalis compounds)
-ACE inhibitors
telmisartan (semintra) for reduction of proteinuria resulting
from chronic kidney disease in cats
telmisartan is orally active and specific angiotensin 2 receptor (AT1 type) antagonist, which causes
decrease in mean arterial blood pressure, depending upon dosage, in mammal species, including cats
telmisartan clinical study of cats with kidney disease found
reduction in proteinuria within first 7 days from start of therapy
telmisartan forces out angiotensin 2 from its
binding site with AT 1 receptor subtype
telmisartan selectively binds AT 1 receptor and does not
show affinity to other receptors, including AT 2 receptor and other less characterized AT receptors
AT1 reveptor stimulation causes pathological effects of
angiotensin 2 on kidneys and other organs that are linked to angiotensin 2 > example vasoconstriction, sodium and water retention, increase in synthesis of aldosterone and changes in organ shape
telmisartan effects of AT2 receptor stimulation, including vasodilation, natriuresis and inhibition of undesired cell growth
are not suppressed
telmisartan binding receptors of long-term duration due to
slow dissociation of telmisartan from AT1 receptor binding site
telmisartan ‘’’’’ partial agonist activity on AT1 receptor type
DOES NOT HAVE
combinations of active substances : benazepril + spironolactone (Cardalis) treatment of
congestive heart failure caused by chronic degenerative valvular disease in dogs ( with diuretic support, as appropriate)
spironlactone inhibits
aldosterone-induced sodium retention in kidneys > leading to increase in sodium and subsequently water excretion and potassium retention
-accompanying reduction in extracellular volume reduces cardiac preload and left ventricle pressure
benazepril hydrochloride is
prodrug that is hydrolyzed in vivo into active metabolite benazeprilat
benazeprilat is potent and selective
angiotensin-converting enzyme (ACE) inhibitor, preventing inactive angiotensin 1 from being converted into active angiotensin 2
benazeprilat mediated actions of angiotensin 2 are
blocked > including constriction of arteries and veins and retention of sodium and water by kidneys
