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Diuretics

Diuretics. Nephron. Speed of primary urine formation – 120–127 ml/min There are about 1mln. nephrons in a kidney, reabsorbtive surface of which is – 6-8 m 2 . 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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Diuretics

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  1. Diuretics

  2. Nephron Speed of primary urine formation – 120–127 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.

  3. 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, cАMP-adenilatcyclases and phosphodiesterases,etc.) Na+

  4. Filtration Primary urine Quantity of diuresis (secondary urine) Reabsorbtion ( 1% of volume of primary urine) Norm Decreasing of reabsorbtion for 10% Increasing of filtration for 10%

  5. 1 – vascular glomerulus with capsule; 2 – proximal tubule; 3 – descendent part of loop of Henle; 4 – ascendent part of loop of Henle; 5 – distal tubule; 6 – collective tubules. Classification of diuretics according to place of dominant action I Mostly act on beginning part of distal nephral canalicules : dichlothiasid, cyclomethiasid, clopamid (brinaldix), oxodolin(chlortalidon, hygroton) ІІ Act on ascendent part of loop of Henle (“loop” diuretics) : furosemide (lasix), etacrynic acid (uregit), bufenox ІІІ Act on ending part of distal nephral canalicules and collective tubules (potassium sparing diuretics): triamterene, amiloride, spironolactone ІV Act along the whole nephral canalicules: mannitol, urea (carbamide) V Act on proximal nephral canalicules: euphylline

  6. Classification of diuretics according to power of action І Strong (slowing down of Na+ reabsorbtion for 10 – 20%) – loop diuretics furosemide, etacrynic acid, clopamide, bufenox ІІ Medial power of action (slowing down of Na+ reabsorbtion for5 – 8%) dichlothiaside, oxodoline ІІІ Light (slowing down of Na+ reabsorbtion no more than for 3%) diacarb, spironolactone, amiloride, triamteren, xantines (theophylline)

  7. Mannitol 15 % solution rapid intravenous introduction intravenous dropping introduction diuretic action dehydrating action diuretic action

  8. Mannitol • Indications • 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. Performing of forced diuresis (poisoning with barbiturates, salycylates, sulphonamides, PASA, metanole, boric acid, haemolytic poisons, antifreezers; in case of transfusion of incompatible blood, massive hemoglobinuria etc. • In oliguric phase of acute kidney insufficiency • Burns, osteomielitis, peritonitis, sepsis (to improve elimination out of the organism toxic compounds which formed from destroyed tissues) • Contraindications • Acute cardiac insufficiency, arterial hypertension,skull trauma, intracranial hemorrhages

  9. Furosemide (lazix) • Effective even in a case of decreased glomerular filtration less than 10 ml/min. (norm – 120-127ml/min) • Indications • Acute left ventricular insufficiency, lung oedema • Chronic cardiac insufficiency • Arterial hypertension, especially hypertensive crisis • Brain oedema of any etiology • Acute kidney insufficiency • Performing of forced diuresis • For excretion of Calcium ions (hypervitaminosis D)

  10. Furosemid

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

  12. Furosemide

  13. Furosemide

  14. Furosemide

  15. Dichlothiaside (hydrochlorthiaside) • Indications • Oedema in case of chronic cardiac insufficiency • Oedema in case of chronic pathology of liver and kidneys • Long-term treatment of arterial hypertension • Diabetes insipidus • Retention of Ca ions • 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

  16. THERAPEUTIC EFFECTS Increase Na Excretion to 5% of Filtered Load Treatment for Nephrogenic Diabetes Insipidus Treatment for Hypertension Treatment for Mild Edema Treatment for Calcium Nephrolithiasis Decrease Ca Excretion

  17. ADVERSE EFFECTS Dichlothiaside (hydrochlorthiaside) Hypercalcemia ECFV Depletion Hyponatremia Hypokalemia Hyperuricemia Metabolic Alkalosis Hyperglycemia Hypomagnesemia Impotence Increased LDL (Renal Cell Carcinoma??)

  18. Post diuresis Sodium Retention!! – ricochet effect

  19. Indapamide (ariphone – sulphamoil benzamide)

  20. Pharmacokinetics of some diuretics

  21. K-Sparing Diuretics Triamterene Spironolactone Amiloride

  22. THERAPEUTIC EFFECTS Used in Combination with Loop & Thiazide Diuretics Enhance Natriuresis Caused by Other Diuretics Prevent Hypokalemia Block Na Channels Treatment for Lithium-Induced Diabetes Insipidus Treatment for Liddle’s Syndromen (pseudoaldosteronism)

  23. ADVERSE EFFECTS Triamterene Amiloride Hyperkalemia Hyperkalemia Renal Stones Interstitial Nephritis Megaloblastosis

  24. MINERALOCORTICOID RECEPTOR ANTAGONISTS • Also Called: • K-Sparing Diuretics • Aldosterone Antagonists Spironolactone Eplerenone

  25. THERAPEUTIC EFFECTS Used in Combination with Loop & Thiazide Diuretics Enhances Natriuresis Caused by Other Diuretics Prevents Hypokalemia Blocks Aldosterone Treatment for Primary Hyper-aldosteronism Treatment for Heart Failure Treatment for Edema of Liver Cirrhosis Treatment for Hypertension

  26. spironolactoneADVERSE EFFECTS Gastritis Hyperkalemia Peptic Ulcers Metabolic Acidosis Impotence Deepening of Voice CNS Side Effects Hirsutism Gynecomastia Menstrual Irregularities

  27. Spironolactone

  28. Combined administration of diuretics • Mannitol + furosemide (etacrynic acid) • Dichlothiaside + triamteren (spironolactone) • Furosemide + spironolactone • Furosemide (excretes Calcium ions) + dichlothiaside(retains Calcium ions)

  29. Triampur(triamteren + hydrochlorthiaside)

  30. IMPORTANT DRUG INTERACTIONS NSAIDS Salt Decongestants Probenecid Diminished Diuretic Response Hyperkalemia- Induced by K-Sparing Diuretics ACE Inhibitors Beta-Blockers K Supplements K-Sparing Diuretics Heparin Enhanced Ototoxicity of Loop Diuretics Ototoxic Drugs

  31. kidney tea Fol. Orthosiphoni

  32. Shots of birch tree (Gemmae Betulae)

  33. Leaves of red bilberries(fol.Vitisidaeae)

  34. Horse-tail Herba Equiseti

  35. Blue corn-flowers (Flores Centaureae cyani)

  36. Juniper berries (Fructus Juniperi)

  37. Drugs effectinguterus contraction І Influence mostly on myometrium contraction 1. Increaserhythmic contraction Oxytocine, Pituitrine, Hyphotocine Dinoprost (prostaglandine F2α), Dinoproston (prostaglandine E2 ), 2. Decrease contractions (tokolytic substances) Salbutamol, Fenoterol, Sodium oxybutyrate, Magnesium sulphate Diazoxide ІІ Increase mostly myometrium tone Ergometrini maleas Cotarnine chloride Ergotamine hydrotartrate Ergotal ІІІ Decrease tone of uterus cervix Atropine sulphate Dinoprost Dinoproston

  38. For labour stimulation (rhythmic contraction of uterus):- i. v. dropply – 1 ml (5 Units) dissolve in 500 ml 5 % glucose- i. m or in cervix of uterus 0,5-2,0Unitsfor single injection For post labor atonic bleeding (it is necessary to provoke spastic contraction of uterus) 1-2 ml i. m.

  39. Dinoprost (prostaglandinF2α)Dinoproston (prostaglandinE2) • They cause rhythmic contractions of uterus • For stimulation of labor, i. v. dropply • Initiate uterus contractions independently of the term of pregnancy • Uses only after hospital admission!

  40. Ergometrini maleas – for stopping after labor atonic (hypotonic) bleedingsAbsolutely contraindicated for labour stimulation !!! Fungi Claviceps purpurea (Ergot) - Secale cornutum

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