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 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.

1) with the concentration gradient 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+

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

Classifiction of diuretics accordingly to power of action І Strong (slowing down of Na+ reabsorbtion for 10-20%) furosemide, etacrynic acid, clopamide, bufenox ІІ Medial power of action (slowing down of Na+ reabsorbtion for 5-8%) dichlothiaside, oxodoline ІІІ Light (slowing down of Na+ reabsorbtion not more than for 3%) diacarb, spironolactone, amiloride, triamteren, xanthines (theophylline)

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

Brain oedema (in case of maintaining ofHEB permeability) 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

FUROSEMIDE Properties : 1. diuretic action 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

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)

Hypopotassiumaemia, hypopotassiumhystia 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!

Furosemide (diuretic)

Furosemide (diuretic)

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)

Indications Side effects 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

Indapamide (ariphone – sulphamoil benzamide)

Pharmacokinetics of some diuretic drugs Way of administration Latent period Duration of action Sulfonyl derivates Oxololin (chlortalidon, hyhroton) peroral 2-4 hours Till 3 days Clopamide 1-3 hours 8-18 (till 24) hours Bufenox (bumetanide) intravenous 20-40 min. 2-5 min. 4-6 hours Potassium-, magnesium-sparing Spironolactone 2-5 days 2-3 days Triamteren (pterophen) 20-30 min. 6-8 hours Amiloride 2 hours till 24 hour

Spironolactone (aldactone)

Combined administration of diuretics Mannitol + furosemide (etacrynic acid) Dichlotiaside + triamteren (spironolactone) Furosemide + spironolactone Furosemide (excretes Calcium ions) + dichlotiaside (retains Calcium ions)

Triampur (triamteren + hydrochlorthiaside)

Fol. Orthosiphoni – kidney tea

Shots of birch tree (Gemmae Betulae)

Leaves of red bilberries (fol.Vitisidaeae)

Herba Equiseti

Blue corn-flowers (Flores Centaureae cyani)

Juniper berries (Fructus Juniperi)

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