Diuretics

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Diuretics
Lector prof. Posokhova K.A.
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Nephron
Speed of primary urine formation 120127
ml/min There are about 1mln. nephrons in a
kidney, reabsorbtive surface of which is 6-8
m2. Along the nephron 99 of ultrafiltrate is
reabsorbed and 1.2-1.5 l of secondary urine forms
from 150-200 l of primary urine.
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Apical (lumenal) membrane
Na enters a cell 1) with the concentration
gradient 2) with the help of protein transporters
permeases (synthesized under the influence of
aldosterone)
Na
Basal membrane
Na enters interstitial space against
concentration gradient with energy consumption
and with the help of specific transport systems
(K, Na-ATPases, c?MP-adenilatcyclases and
phosphodiesterases, etc.)
Na
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Quantity of diuresis
Filtration
Primary urine
Reabsorbtion
Decreasing of reabsorbtion for 10
( 1 of volume of primary urine) Norm
Increasing of filtration 10more
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Classifiction of diuretics accordingly to power
of action ? Strong (slowing down of Na
reabsorbtion for 10-20) furosemide,
etacrynic acid, clopamide, bufenox ?? Medial
power of action (slowing down of Na
reabsorbtion for 5-8) dichlothiaside,
oxodoline ??? Light (slowing down of Na
reabsorbtion not more than for 3)
diacarb, spironolactone, amiloride, triamteren,
xanthines (theophylline)
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Mannitol
15 solution
rapid intravenous introduction
intravenous dropping introduction
diuretic action
dehydrating action
diuretic action
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• 
  Mannitol
• Indicatoins
• Brain oedema (in case of maintaining ofHEB
  permeability)
• Toxic lung oedema (poisoning with gasoline, gass,
  formaline, skipidar etc.)
• 3. Larynx oedema of allergic or inflammatory
  genesis
• 4. Holding of forced diuresis (poisoning with
  barbiturates, salycylates, sulphonamides, PASA,
  metanole, boric acid, haemolytic poisons,
  antifreezers in case of trasfusing of
  incompatible blood, massive hemoglobinuria etc.
• In oliguric phase of acute nephral insufficiency
• Burns, osteomielitis, peritonitis, sepsys
• Contrainidications
• Acute cardiac insufficiency, skull trauma,
  intracranial hemorrhages, arterial hypertension

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FUROSEMIDE

• High ceiling (loop) diuretic
• Properties
• 1. diuretic action
• 2. dilation of peripheral venous
• 3. decrease left ventricular filling pressure
• 4. potent anti-inflammatory effect (similar to
  indometacine and other NSAID)
• Administration hypertensive emergencies,
  long-term treatment of arterial hypertension
• Adverse reactions dehydration, hypokalemia,
  hearing loss - deafness, hypocalcaemia

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• Furosemide (lazix)
• Effective even in case of decreased
  glomerular filtration less than 10 ml/min. (norm
  127ml/min)
• Indications
• Acute left ventricular insufficiency, lung oedema
• Chronic cardiac insufficiency
• Arterial hypertension, including hypertensive
  crisis
• Brain oedema of any etiology
• Acute nephral insufficiency
• Performing of forced diuresis
• For excretion of Calcium ions (hypervitaminosis
  D)

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• 
  Side effects of furosemide
  
• Hypopotassiumaemia, hypopotassiumhystia
• Hypovolemia, vascular collapse, hyposodiumaemia,
  hypocalciumaemia, hypochloraemia, metabolic
  alkalosis
• Ototoxic action
• Contrinsular action (manifestation of latent
  diabetes mellitus)
• Formation of oxalate and phosphate stones in
  urinary tracts
• Decreasing of secretion of uric acid (acute
  attack of gout)
• It should not be combined with antibiotics,
  aminoglycosides and cephalosporines!

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Furosemide (diuretic)
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Furosemide (diuretic)
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THIAZIDES and RELATED DIURETICS

• Medium efficacy diuretics
• Benzothiadiazines (chlorothiazide,
  hydrochlorothiazide, clopamide), related thiazide
  like (chlorthalidone, indapamide)
• for long-term treatment of arterial hypertesion
  (oral administration)
• Duration of action (6-12 hours for
  hydrochlorothiazide, 12-18 hours for clopamide,
  48-50 hours for chlorthalidone)
• Adverse reactions dehydration, hypokalemia,
  hyperuricaemia (rise of blood urate level)

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• 
  Dichlotiaside (hypothiaside)
• Indications
• Oedema in case of chronic cardiac insufficiency
• Oedema in case of chronic pathology of liver and
  kidneys
• Treatment of arterial hypertension
• Diabetes insipidus
• Side effects
• Hypopotassiumaemia, hypopotassiumhystia
• Hypochloraemic alkalosis
• Retention of uric acid - artralgy, acute attack
  of gout, chronic nephropathy
• Hyposodiumaemia of dilution nausea, vomitting,
  diarrhea, weakness
• Pancreatitis

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Indapamide (ariphone sulphamoil benzamide)
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Pharmacokinetics of some diuretic drugs
Drug Way of administration Latent period Duration of action
Sulfonyl derivates Sulfonyl derivates Sulfonyl derivates Sulfonyl derivates
Oxololin (chlortalidon, hyhroton) peroral 2-4 hours Till 3 days
Clopamide peroral 1-3 hours 8-18 (till 24) hours
Bufenox (bumetanide) intravenous 20-40 min. 2-5 min. 4-6 hours 1-3 hours
Potassium-, magnesium-sparing Potassium-, magnesium-sparing Potassium-, magnesium-sparing Potassium-, magnesium-sparing
Spironolactone peroral 2-5 days 2-3 days
Triamteren (pterophen) peroral 20-30 min. 6-8 hours
Amiloride peroral 2 hours till 24 hour
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Spironolactone
(aldactone)
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• Combined administration of diuretics
• Mannitol furosemide (etacrynic acid)
• Dichlotiaside triamteren (spironolactone)
• Furosemide spironolactone
• Furosemide (excretes Calcium ions)
  dichlotiaside
• (retains Calcium ions)

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Triampur (triamteren
hydrochlorthiaside)
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Fol. Orthosiphoni kidney tea
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Shots of birch tree (Gemmae Betulae)
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Leaves of red bilberries (fol.Vitisidaeae)
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Herba Equiseti
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Blue corn-flowers (Flores Centaureae cyani)
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Juniper berries (Fructus Juniperi)
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Drugs affecting myometrium ? Influence mostly on
myometrium contraction 1. Increase
contractions Oxytocine Dinoprost
(prostaglandine F2a ) Pituitrine Dinoprosto
n (prostaglandine E2 ) Hyphotocine 2.
Decrease contraction (tokolytic substances)
Fenoterol Sodium oxybutyrate
Salbutamol Magnesium sulphate ?? Increase mostly
myometrium tone Ergometrini
maleas Cotarnine chloride Ergotamine
hydrotartrate Ergotal ??? Decrease tone of
uterus cervix Atropine sulphate Dinoprost D
inoproston