Diuretics Lector prof. Posokhova K.A.

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 l of secondary urine forms from l of primary urine.

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) 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 +

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

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

Mannitol 15 % solution rapid intravenous introduction intravenous dropping intravenous droppingintroduction dehydratingactiondiureticaction diuretic action action

Mannitol Indicatoins 1.Brain oedema (in case of maintaining ofHEB permeability) 2.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. 5.In oliguric phase of acute nephral insufficiency 6.Burns, osteomielitis, peritonitis, sepsysContrainidications Acute cardiac insufficiency, skull trauma, intracranial hemorrhages, arterial hypertension

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

Furosemide (lazix) Furosemide (lazix) Effective even in case of decreased glomerular filtration less than 10 ml/min. (norm – 127ml/min) Indications Indications 1.Acute left ventricular insufficiency, lung oedema 2.Chronic cardiac insufficiency 3.Arterial hypertension, including hypertensive crisis 4.Brain oedema of any etiology 5.Acute nephral insufficiency 6.Performing of forced diuresis 7.For excretion of Calcium ions (hypervitaminosis D)

Side effects of furosemide Side effects of furosemide 1.Hypopotassiumaemia, hypopotassiumhystia 2.Hypovolemia, vascular collapse, hyposodiumaemia, hypocalciumaemia, hypochloraemia, metabolic alkalosis 3.Ototoxic action 4.Contrinsular action (manifestation of latent diabetes mellitus) 5.Formation of oxalate and phosphate stones in urinary tracts 6.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 Medium efficacy diuretics Benzothiadiazines (chlorothiazide, hydrochlorothiazide, clopamide), related thiazide like (chlorthalidone, indapamide) Benzothiadiazines (chlorothiazide, hydrochlorothiazide, clopamide), related thiazide like (chlorthalidone, indapamide) for long-term treatment of arterial hypertesion (oral administration) for long-term treatment of arterial hypertesion (oral administration) Duration of action (6-12 hours for hydrochlorothiazide, hours for clopamide, hours for chlorthalidone) Duration of action (6-12 hours for hydrochlorothiazide, hours for clopamide, hours for chlorthalidone) Adverse reactions: dehydration, hypokalemia, hyperuricaemia (rise of blood urate level) Adverse reactions: dehydration, hypokalemia, hyperuricaemia (rise of blood urate level)

Dichlotiaside (hypothiaside) Dichlotiaside (hypothiaside)Indications 1.Oedema in case of chronic cardiac insufficiency 2.Oedema in case of chronic pathology of liver and kidneys 3.Treatment of arterial hypertension 4.Diabetes insipidus Side effects 1.Hypopotassiumaemia, hypopotassiumhystia 2.Hypochloraemic alkalosis 3.Retention of uric acid - artralgy, acute attack of gout, chronic nephropathy 4.Hyposodiumaemia of dilution: nausea, vomitting, diarrhea, weakness 5.Pancreatitis

Indapamide (ariphone – sulphamoil benzamide) Indapamide (ariphone – sulphamoil benzamide)

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

Spironolactone (aldactone) Spironolactone (aldactone)

Combined administration of diuretics 1.Mannitol + furosemide (etacrynic acid) 2.Dichlotiaside + triamteren (spironolactone) 3.Furosemide + spironolactone 4.Furosemide (excretes Calcium ions) + dichlotiaside (retains Calcium ions) (retains Calcium ions)

Triampur (triamteren + hydrochlorthiaside) 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 І Influence mostly on myometrium contraction 1. Increase contractions Oxytocine Dinoprost (prostaglandine F 2α ) Oxytocine Dinoprost (prostaglandine F 2α ) PituitrineDinoproston (prostaglandine E 2 ) PituitrineDinoproston (prostaglandine E 2 ) Hyphotocine Hyphotocine 2. Decrease contraction (tokolytic substances) FenoterolSodium oxybutyrate FenoterolSodium oxybutyrate SalbutamolMagnesium sulphate SalbutamolMagnesium sulphate ІІ Increase mostly myometrium tone ІІ Increase mostly myometrium tone Ergometrini maleasCotarnine chloride Ergometrini maleasCotarnine chloride Ergotamine hydrotartrate Ergotamine hydrotartrate Ergotal Ergotal ІІІ Decrease tone of uterus cervix Atropine sulphateDinoprostDinoproston Atropine sulphateDinoprostDinoproston