DiureticsDiuretics

Lector prof. Posokhova K.A.Lector prof. Posokhova K.A.

NephronNephron

Speed of primary urine formation – 120–127 ml/minSpeed of primary urine formation – 120–127 ml/minThere are about 1mln. nephrons in a kidney, reabsorbtive surface of There are about 1mln. nephrons in a kidney, reabsorbtive surface of which is – 6-8 mwhich is – 6-8 m22..Along the nephron 99% of ultrafiltrate is reabsorbed and 1.2-1.5 l of 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.secondary urine forms from 150-200 l of primary urine.

Apical (lumenal) membraneApical (lumenal) membrane

NaNa++ enters a cell enters a cell 1) with the concentration gradient1) with the concentration gradient2) with the help of protein transporters – 2) with the help of protein transporters – permeases (synthesized under the influence of permeases (synthesized under the influence of aldosterone)aldosterone)

Basal membraneBasal membrane

NaNa++ enters interstitial space against enters interstitial space against concentration gradient with energy concentration gradient with energy consumption and with the help of specific consumption and with the help of specific transport systemstransport systems ( (KK++, Na, Na++--ATPases, cАMP-ATPases, cАMP-adenilatcyclases and phosphodiesterases,adenilatcyclases and phosphodiesterases, etc.)etc.)

Na+

Na+

Quantity of Quantity of didiuuresisresis

Increasing of filtration 10%more

( 1% of volume of primary urine)

Norm

Decreasing of reabsorbtion for 10%

Rea

bso

rbti

on

Primary

urine

Filt

rati

on

Classifiction of diuretics Classifiction of diuretics

accordingaccordinglyly to power of action to power of action

ІІ Strong Strong (slowing down of (slowing down of NaNa+ + reabsorbtion forreabsorbtion for

1010--20%)20%)

furosemide, etacrynic acid, clopamide, bfurosemide, etacrynic acid, clopamide, buufenoxfenox

ІІІІ Medial powerMedial power of action (slowing down of of action (slowing down of NaNa++ reabsorbtion for reabsorbtion for 5-8%) 5-8%)

dichlotdichlothhiaside, oxodolineiaside, oxodoline

ІІІІІІ Light Light (slowing down of (slowing down of NaNa+ + reabsorbtion not reabsorbtion not more more than for 3%)than for 3%)

diacarb, spironolactone, amiloride, triamteren, diacarb, spironolactone, amiloride, triamteren, xantxanthhines (theophylline)ines (theophylline)

Mannitol

15 % solution15 % solution

rapid intravenous rapid intravenous introductionintroduction

intravenous dropping intravenous dropping introductionintroduction

dehydrating dehydrating actionaction

diuretic diuretic actionaction

diureticdiuretic actionaction

MannitolMannitol

IndicatoinsIndicatoins

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 genesis4. 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 insufficiency6. Burns, osteomielitis, peritonitis, sepsysContrainidications Contrainidications

Acute cardiac insufficiency, skull trauma, intracranial hemorrhages, arterial hypertension

FUROSEMIDEFUROSEMIDE

• High ceiling (loop) diureticHigh ceiling (loop) diuretic

• Properties :Properties :

1. diuretic action1. diuretic action

2. dilation of peripheral venous2. dilation of peripheral venous

3. decrease left ventricular filling pressure3. decrease left ventricular filling pressure

4. potent anti-inflammatory effect (similar to 4. potent anti-inflammatory effect (similar to indometacine and other NSAID)indometacine and other NSAID)

• Administration:Administration: hypertensive emergencies, hypertensive emergencies, long-term treatment of arterial hypertension long-term treatment of arterial hypertension

• Adverse reactions: Adverse reactions: dehydration, dehydration, hypokalemia, hearing loss - deafness, hypokalemia, hearing loss - deafness, hypocalcaemia hypocalcaemia

Furosemide (lazix)Furosemide (lazix)

Effective even in case of decreased glomerular filtration less than 10 ml/min. (norm – 127ml/min)

IndicationsIndications

1. Acute left ventricular insufficiency, lung oedema2. Chronic cardiac insufficiency 3. Arterial hypertension, including hypertensive crisis 4. Brain oedema of any etiology5. Acute nephral insufficiency6. Performing of forced diuresis7. For excretion of Calcium ions (hypervitaminosis D)

Side effects of furosemideSide effects of furosemide

1. Hypopotassiumaemia, hypopotassiumhystia2. Hypovolemia, vascular collapse, hyposodiumaemia,

hypocalciumaemia, hypochloraemia, metabolic alkalosis3. Ototoxic action4. Contrinsular action (manifestation of latent diabetes mellitus)5. Formation of oxalate and phosphate stones in urinary tracts6. Decreasing of secretion of uric acid (acute attack of gout)

It should not be combined with antibiotics, aminoglycosides and cephalosporines!

FurosemideFurosemide (diuretic)(diuretic)

Furosemide Furosemide (diuretic)(diuretic)

THIAZIDES and RELATED THIAZIDES and RELATED DIURETICSDIURETICS

• Medium efficacy diureticsMedium efficacy diuretics

• Benzothiadiazines (chlorothiazide, Benzothiadiazines (chlorothiazide, hydrochlorothiazide, clopamide), related hydrochlorothiazide, clopamide), related thiazide like (chlorthalidone, indapamide)thiazide like (chlorthalidone, indapamide)

• for long-term treatment of arterial hypertesion for long-term treatment of arterial hypertesion (oral administration)(oral administration)

• Duration of action (6-12 hours for Duration of action (6-12 hours for hydrochlorothiazide, 12-18 hours for hydrochlorothiazide, 12-18 hours for clopamide, 48-50 hours for chlorthalidone)clopamide, 48-50 hours for chlorthalidone)

• Adverse reactions: dehydration,Adverse reactions: dehydration, hypokalemia, hypokalemia, hyperuricaemia (rise of blood urate level)hyperuricaemia (rise of blood urate level)

Dichlotiaside (hypothiaside)Dichlotiaside (hypothiaside)

IndicationsIndications

1. Oedema in case of chronic cardiac insufficiency2. Oedema in case of chronic pathology of liver and kidneys 3. Treatment of arterial hypertension4. Diabetes insipidus

Side effectsSide effects

1. Hypopotassiumaemia, hypopotassiumhystia2. Hypochloraemic alkalosis3. Retention of uric acid - artralgy, acute attack of gout, chronic

nephropathy 4. Hyposodiumaemia of dilution: nausea, vomitting, diarrhea,

weakness5. Pancreatitis

IndapamideIndapamide (ariphone – sulphamoil (ariphone – sulphamoil

benzamide)benzamide)

Drug Drug Way of Way of administrationadministration

Latent Latent periodperiod

Duration of Duration of actionaction

Sulfonyl derivates

Oxololin (chlortalidon, Oxololin (chlortalidon, hyhroton) hyhroton)

peroralperoral 2-4 hours2-4 hours Till 3 daysTill 3 days

Clopamide Clopamide peroralperoral 1-3 hours1-3 hours 8-18 (till 24) 8-18 (till 24) hours hours

Bufenox (bumetanide)Bufenox (bumetanide) intravenousintravenous 20-40 min.20-40 min.

2-5 min. 2-5 min.

4-6 hours4-6 hours

1-3 hours1-3 hours

Potassium-, magnesium-sparing

SpironolactoneSpironolactone peroralperoral 2-5 days2-5 days 2-3 days2-3 days

Triamteren (pterophen)Triamteren (pterophen) peroralperoral 20-30 min.20-30 min. 6-8 hours6-8 hours

Amiloride Amiloride peroralperoral 2 hours2 hours till 24 hourtill 24 hour

Pharmacokinetics of some diuretic drugsPharmacokinetics of some diuretic drugs

SpironolactoneSpironolactone (aldactone) (aldactone)

Combined administration of diureticsCombined administration of diuretics

1.1. Mannitol + furosemide (etacrynic acid)Mannitol + furosemide (etacrynic acid)2.2. Dichlotiaside + triamteren (spironolactone)Dichlotiaside + triamteren (spironolactone)3.3. Furosemide + spironolactoneFurosemide + spironolactone4.4. Furosemide (excretes Calcium ions) + Furosemide (excretes Calcium ions) +

dichlotiasidedichlotiaside (retains Calcium ions)(retains Calcium ions)

TriampurTriampur (triamteren + hydrochlorthiaside)(triamteren + hydrochlorthiaside)

Fol. Orthosiphoni Fol. Orthosiphoni – kidney tea– kidney tea

Shots of birch tree Shots of birch tree (Gemmae Betulae)(Gemmae Betulae)

Leaves of red bilberries Leaves of red bilberries ((fol.Vitisidaeae)fol.Vitisidaeae)

Herba Equiseti

Blue corn-flowers (Blue corn-flowers (Flores Flores Centaureae cyani)Centaureae cyani)

Juniper berries (Fructus Juniperi)

Drugs Drugs affectingaffecting m myyometriumometrium

ІІ Influence mostly on m Influence mostly on myyometrium contractionometrium contraction

1. Increase contractions1. Increase contractions

Oxytocine Oxytocine Dinoprost (prostaglandine Dinoprost (prostaglandine FF22αα ))

PituitrinePituitrine Dinoproston (prostaglandine Dinoproston (prostaglandine EE2 2 ))

HyphotocineHyphotocine

2. Decrease contraction (tokolytic substances)2. Decrease contraction (tokolytic substances)

FenoterolFenoterol Sodium oxybutyrateSodium oxybutyrate

SalbutamolSalbutamol Magnesium sulphateMagnesium sulphate

ІІІІ Increase mostly m Increase mostly myyometrium toneometrium tone

Ergometrini maleasErgometrini maleas Cotarnine chlorideCotarnine chloride

Ergotamine hydrotartrateErgotamine hydrotartrate

ErgotalErgotal

ІІІІІІ Decrease tone of uterus cervix Decrease tone of uterus cervix

Atropine sulphateAtropine sulphate DinoprostDinoprost DinoprostonDinoproston