A COMPARATIVE PHARMACOLOGICAL STUDY OF DIURETIC DRUGS

S.N

DRUG

MECHANISM OF ACTION

PHARMACOKINETIC

ADVERSE EFFECT

CLINICAL USES

REFERENCE

1

FURESEMIDE

4-chloro-2-[(furan-2 ylmethyl)amino]- 5-sulfamoylbenzoic acid

Inhibit Na+-k+-2Cl- co-transporter of ascending loophole of henle

Administer orally, IV& IM ,

Plasma t½ is 1- 2 hours,

Low lipid solubility,

Protein binding 91–99%,

Hypokalaemia ,  Metabolic alkalosis, Hypovolaemia,  Hyperuricaemia, Allergy  Excreted unchanged in urine 80–90 %,  Volume of partition (L/kg) 0.07–0.2%

Used in pulmonary & cerebral Oedema, Hypertension,

Hypercalcaemia of malignancy

Tripathy et al2

 

2

TORASEMIDE

N[(isopropylamino)carbonyl]-4-[(3-methylphenyl)amino]pyridine-3-sulfonamide

Inhibit Na +-k+-2Cl-  co- transporter of ascending bight of henle

Administer orally, IV, plasma t½ -3.5 hours ,dose(2.5-5mg in hypertension,

5-20mg in oedema

Hypokalaemia, Metabolic alkalosis,  Hypovolaemia,  Hyperuricaemia,  Allergy

Mainly used in the dealing of edema associated with C.H.F ,

used at poor doses for the management of hypertension

Dunn CJ et al 3

3

BUMETAMIDE

butylamino-4-phenoxy-5-sulfamoyl-benzoic tart

Inhibit the Na+-k+-2Cl- co-transporter of ascending aperture of henle.

Use orally,IV&IM ,

Plasma t½ -1 hours, Bioavailability- 80 to 100%

Hypokalaemia, Metabolic Alkalosis, Hypovolaemia,  Hyperuricaemia,  Allergy

Pulmonary & cerebral Oedema, Hypertension, Hypercalcaemia of malignancy

Rang et al4

4

HYDROCHLOROTHAIZIDE

6-chloro-1,1-dioxo-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide

Inhibit Na+-2Cl-symporter in DCT(seat -3)

Use orally, bioaviability-70%,

On solidify of action-4-6 hours, Duration of enacting-8-12 hours,

Excreted 95% unaltered in urine.

Hypokalemia, Hyperuricemia, Hyperglycemia Hyperlipidemia, Headache, Nausea/vomiting, Photosensitivity, Weight advantage, Gout, Pancreatitis

Hypertension,  Congestive Heart Failure, Symptomatic  edema, Diabetes, Insipidus

Renal Tubular Acidosis.

R.A Harvey et al5

5

CHLOROTHAIZIDE

(RS)-2-Chloro-5-(1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)benzene-1-sulfonamide

Inhibit Na+-2Cl-symporter in DCT(station -3)

Absorbed orally,

Action starts in the reach 1 hour, but the duration varies from 8–48 hours

Nausea, Vomiting, Headache, Dizziness, Excess piss production, Dehydration, Hypoelectrolytemia

Used to refreshment Edema in people with C.H.F,

 Cirrhosis of  liver,

Kidney disorders or edema caused through taking steroids or oestrogen,

Used to discuss hypertension

Tripathy et al2

 

6

BENDROFLUMETHIAZIDE

Benzyl-1,1-dioxo-6-(trifluoromethyl)-3,4-dihydro-2H-1,2,4- benzothiadiazine-7-sulfonamide

Inhibit sodium reabsorption at the arising of the DCT.

Oral use,Adverse interaction with alcohol, not be used by great with child women

Common adverse effects: Postural Hypotension, hyponatraemia, Hypokalaemia, Hypercalcaemia,Gout, Impaired diabetic sugar tolerance, impotence, fatigue, Pulmonary Oedema, Pneumonitis  Rare

hostile effects: Thrombocytopenia, Agranulocytosis, Photosensitivity, Rash, Pancreatitis, Renal Insufficiency

Used on this account that the treatment of mild heart failure, hypertension

Satoskar et al6

7

CHLORTHALIDONE

(RS)-2-Chloro-5-(1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)benzene-1-sulfonamide

Inhibit Na+-Cl- symporter in  DCT

Oral conversion to an act,dose-50-100mg/day, Duration of process is48 hours, Excreted unchanged in animal-water,

t½ 40–50 hours

Hypokalemia,  Hypochloremia,  soft metabolic alkalosis.

Used

exclusively as antihypertensive.

Tripathy et al2

8

XIPAMIDE

4-chloro-N-(2,6-dimethylphenyl)-2-hydroxy-5-sulfamoylbenzamide

Acts attached kidney to reduce sodium reabsorption in DCT

After nuncupative administration 20 mg are reabsorbed without delay & reach the plasma cocn. Of 3 mg/l by in 1hr.

Diuretic effect start in the pattern of 1 hr of administration & lasts as antidote to nearly 24 hr.

Plasma clearance is 30-40 ml/min.

Hypokalaemia,  Hyponatraemia,  Thrombocytopenia,  Leucopenia,  Acute intermediate nephritis  Hyperlipidemia,  Orthostatic hypotension

Used during cardiac edema caused by decompensation of seat of life failure,

Renal edema, chronic renal ailment,

Hepatic edema caused by cirrhosis ascites lymphoedema,

Hypertension

Jasek et al7,

Klopp et al8

9

METALAZONE

7-chloro-2-methyl-4-oxo-3-o-tolyl-1,2,3,4-tetrahydroquinazoline-6-sulfonamide

Inhibit sodium-chloride symporter

Oral appliance, Excreted unchanged in urine,

Duration of enacting 12-24 hours

Aplastic anaemia, Pancreatitis, Agranulocytosis, Angioedema, Abnormalities of furnish with ~ balance, electrolyte levels.

Used mainly as being

edema (5–10 mg/day, finely 20 mg), and

occasionally for hypertension (2.5–5 mg/lifetime).

Tripathy et al2

10

INDAPAMIDE

4-chloro-N-(2-methyl-2,3-dihydroindol-1-yl)-3-sulfamoyl-benzamide

Inhibit Na+-Cl- symporter in  DCT

Oral exercise, highly lipid soluble,dose-2.5-5mg/epoch, duration of action-12-24 hours

Hypokalemia, Fatigue, Orthostatic hypotension, Allergic  menifestations

Hypertension,

Decompensated hypertension.

Tripathy et al2

11

CLOPAMIDE

4-chloro-N-(2,6-dimethyl-1-piperidyl)-3-sulfamoyl-
benzamide

It act in kidney at PCT of nephron to which place it Na+-Cl- symporter

Oral absorbing. 100 %,

Plasma protein binding is < 50%,

Plasma half life is 10 hr.

Hypokalemia, hyperglycemia Nausea, Vomiting, Diarrhoea, Loss of relish, Blurred vision, Dizziness.

Used in hypertension ,

Edema associated through heart failure

Tripathy et al2

12

SPIRONOLACTONE

7α-Acetylthio-17α-hydroxy-3-oxopregn-4-ene-21-carboxylic tart γ-lactone

It is a competitive antagonist to the mineralocorticoids such since aldosterone.

The mineralocorticoid receptor is every intracellular protein in nature that can bind aldosterone.

Spironolactone binds to the receptor and competitively inhibits aldosterone cover the the receptor. The inability of aldosterone to be ~ing to its receptor prevents reabsorption of Na+& Cl-and associated get ~.

The oral bioavailability from microfine sprinkle tablet is 75%,

It is in a great degree bound to plasma proteins,

Completely metabolized in liver,

The ut~ important active metabolite

is Canrenone.

The t½ of spironolactone is

1–2 hours, at the same time that that canrenone is ~18 hours.

Drowsiness,  Ataxia,  Mental ruin, Epigastric distress  and loose motions.

Edema,

Hypertension,

C.H.F,

It is a tasteless diuretic and is used only in amalgamation with

other more efficacious diuretics.

Tripathy et al2

13

EPLERENONE

pregn-4-ene-7,21-dicarboxylic tart, 9,11-epoxy-17-hydroxy-3-oxo, γ-lactone, methyl ester (7α, 11α, 17α)

It is ~y antagonist of the mineralocortecoid receptor.

well absorbed vocally,

t½ is

4–6 hours,

Plasma protein obligatory is 50 %,

Oral bioavailability is 69% following distribution of 100 mg oral tablet,

Metabolism is mediated via CYP3A4,

 

Hyperkalemia,  Hypotension,  Dizziness,  Altered renal office,  Increased creatinine concentration.

Used in assuage

to severe CHF,

 Post-infarction left ventricular

dysfunction,

Hypertension,

be possible to be used

as alternative to spironolactone.

Rossi et al9

14

TRIAMTERENE

6-phenylpteridine-2,4,7-triamine

It acts ~ the agency of blocking the epithelial sodium channel attached the lumen side of the kidney collecting tubule.

It is incompletely absorbed orally,

in part bound to plasma proteins, largely

metabolized in liver to one active metabolite and

excreted in animal-water. Plasma t½ is 4 hours, general of

a single dose lasts 6–8 hours.

Nausea,  Dizziness,   Muscle cramps,   Rise in kinship urea.  Impaired glucose tolerance and photosensitivity

 

Hypertension,

Edema

Tripathy et al2

15

AMILORIDE

3,5-diamino-6-chloro-N-(diaminomethylene)pyrazine-2-carboxamide

Act ~ the agency of directly blocking the epithelial sodium narrow sea in the late DCT in the kidney

Only ¼ of ~y oral dose is absorbed,

It is not

confine. to plasma proteins and not metabolized,

The t½ (20 hours) and continuation of action are

longer than triamterene.

Nausea,  Headache,  Diarrhoea.

Hypertension,

C.H.F,

Cystic fibrosis.

Tripathy et al2

16

MANNITOL

(2R,3R,4R,5R)-Hexane-1,2,3,4,5,6-hexol

It is act without interrupti~ the proximal tubules & inhibit one as well as the other water & solute reabsorption in the kidney tubule by increasing the osmolarity of the renal cannular fluid.

It is not absorbed orally,

Has to be given i.v. taken in the character of 10–20% solution,

It is

excreted by a t½ of 0.5–1.5 twenty-fourth part of a day.

Pulmonary congestion,  Fluid & electrolyte imbalance,  Dryness of opening,  Thrist,  Edema,  Urinary reserve,  Headache,  Blurred vision

Used in bright congestive heart, Glaucoma,

Head injury, Shock , Severe trauma, Cardiac surgery

Satoskar et al6

17

GLYCEROL

propane-1,2,3-triol

It acts by expanding extracellular fluid & plasma power, therefore increasing blood flow to the kidney

Orally sprightly osmotic diuretics,

Dose: 0.5–1.5 g/kg of the same kind with oral solution

Intravenous glycerol can cause  haemolysis.

Used to cut down intraocular or

intracranial tension

Satoskar et al6

18

ISOSORBIDE

1,4:3,6-Dianhydro-D-sorbitol; 1,4-Dianhydrosorbitol

No manage effect on transport but cause shift of ions by inducing bulk get ~ flow & changing steady state irrigate concentration in body compartment.

Orally in actual process osmotic Diuretics,

Dose: 0.5–1.5 g/kg as oral solution

Hypotension,  Hypovolemia,  Heart failure,  Pulmonary plethora,  Headache, blurred vision,  Nausea, vomitting

Used to render intraocular or

intracranial tension

Tripathy et al2

19

ACETAZOLAMIDE

N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)acetamide

Inhibits CAse (image II) in PT Cells,

Inhibition of CAse (sign IV), The net effect

is interdiction of HCO¯ (and accompanying Na+) reabsorption in PT.

Well

absorbed by word of mouth,

Excreted unchanged in urine.

Action of a upright dose lasts 8–12 hours.

Acidosis,  Hypokalaemia, Drowsiness,  Paresthesias, Fatigue,  Abdominal Discomfort.  Hypersensitivity reverse action,  Bone marrow depression.

Glaucoma,

To alkalinise urine,

Epilepsy,

Acute mountain sickness,

Periodic paralysis

Tripathy et al2

20

THEOPHYLLINE

1,3-Dimethyl-7H-purine-2,6-dione

Mechanism unclear, may be related to inhibition of phosphodiesterase and/ or enmity of adenosine receptor

Bioavailability is 100% in case of IV,

Metabolized in liver (70%),

Excreted unchanged in urine,

 

Nausea, diarrhoea,  Abnormal passion rhythm, CNS excitation, seizure

Increasing renal mettle flow,

Relaxing bronchial smooth muscle,

COPD.

 

Rieg T et al11 ,

Yoshikawa et al12

21

CAFFINE

1,3,7-Trimethylpurine-2,6-dione

Mechanism unclear, may exist related to inhibition of phosphodiesterase and/ or clashing of adenosine receptor

Metabolized in the liver,

In bracing adults

t1/2  is 3-7 hr,

Nicotine subside the half life by 30-50 %

 

Increase  metabolic censure,  Anxiety,  Vasoconstriction,

Relax agreeable muscle of bronchi & is used to refreshment Asthma

 

Rieg T et al11

22

ETHACRYNIC ACID

[2,3-dichloro-4-(2-methylenebutanoyl)phenoxy]acetic pungent

Inhibit the Na +-k+-2Cl-  co transporter of ascending loophole of henle  (site-2)

Oral application,

t1/2-~1 hr, Metabolised ~33% in liver,

 Excreted in piss ~62%.

Hypokalaemia, metabolic alkalosis, Hypovolaemia , Hyperuricaemia, Allergy

Oedema like (pulmonary, cerebral), hypertension

Goodman et al10

23

AZOSEMIDE

2-chloro-5-(2H-tetrazol-5-yl)-4-[(thiophen-2-ylmethyl)amino]benzenesulfonamide

It is a shrill ceiling diuretic.

Exact mechanism is not understood

But it mainly act on both medullary & cortical part of thick ascending limb of the aperture of henle.

Oral boavailability in human is aprox. 20.4%,

It’s drift is 5.5-8 time greater than furosemide.

Apparent speed-pseudodistribution volume is 0.0262 l/kg,

In human amount body clearance, renal clearance, terminal half life is 112ml/min, 41.6 ml/min, 2.03 hr respectively.

Panic disorder,  Liver disorder,  Blood creatine phosphokinase increased

Used in the handling of oedematous states,

Hypertension.

Kim et al13

24

PIRETANIDE

3-(aminosulfonyl)-4-phenoxy-5-pyrolidin-1-yl benzoic stinging.

Site of action is thick ascending extremity of the loop of henle.

Oral practice ,

t1/2-~0.6-1.5 hours, Metabolised ~50% in liver,

Excreted in urine ~50%.

Excess loss of fluid & electrolyte.

Use with regard to the treatment of hypertension,

C.H.F & edematous pass caused by renal & hepatic indisposition.

Goodman et al10

25

MUZOLIMINE

3-Amino-1-(3,4-dichloro-á-methylbenzyl)-2-pyrazolin-5-any

It is a loop diuretic

Effect is tardy,

It’s action is long lasting.

 

Used for hypertension but was withdrawn on this account that of severe neurological side effect.

Reyes et al14

26

TRIPAMIDE

3-(aminosulfonyl)-4-chloro-N-[(3aR,4S,7R,7aS)-octahydro-2H-4,7-methanoisoindol-2-yl]benzamide

Inhibitory drift on solute reabsorption  at the cortical segment of thick ascending limb of noose of henle.

Oral use, Metabolised in liver

Hypokalaemia, metabolic alkalosis, Hypovolaemia , Hyperuricaemia, Allergy

Hypertension,

Edema.

Goodman et al 10

27

QUINETHAZONE

7-chloro-2-ethyl-4-oxo-1,2,3,4-tetrahydroquinazoline-
6-sulfonamide

It bar active chloride reabsorption at the at dawn distal tubule via Na-Cl cotransporter

Onset of series of events 2 hr,

Duration of action 18-24 hr.

Time to top effect 6 hr.

Dizziness,  Dry grimace,  Nausea,  Low potassium even.

Diuretic and antihypertensive properties similar to those of the thiazides.

Satoskar et al6

28

TRICHLORMETHIAZIDE

6-Chloro-3-(dichloromethyl)-1,1-dioxo-3,4-dihydro-2H-benzo[e] [1,2,4]thiadiazine-7-sulfonamide

Inhibit Na+/2Cl_symporter in DCT(situation -3)

Oral use ,

t1/2-~2.3-7.3 hours,

Excreted in animal-water

Hypokalemia,  Hyperurecaemia,  Hyperlipidimia,  Hyperglycemia,  Hypersensitivity,  Thrombocytopenia,  Volume reducing, Hyponatraemia

Hypertension,

Heart failure,

Diabetes insipidus,

Hypercalciurea

Goodman et al 10

29

POLYTHIAZIDE

6-chloro-2-methyl-3-{[(2,2,2-trifluoroethyl)thio]methyl}-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide

Enhance urinary excretion of both Na and H2O ~ the agency of specifically inhibiting Na reabsorption located in the cortical (squat) portion of the ascending

limb of Henle’s bight and also in the early distal tubules.

Normal human subjects receiving upright 1mg oral dose, the mean plasma moiety life for absorption & elimination were 1.2 & 25.7 hr particularly,

25 % excreted unchanged in urine.

Abdominal or inclination pain,  Bleeding gum,  Blurred seeing,  Chest pain,  Blood in piss or stool.

Long-acting diuretic and anti-hypertensive executor.

As diuretic, usual, 1 to 4 mg through day

 As antihypertensive, 2 to 4 mg

Hobbs et al15

30

METHYCLOTHIAZIDE

6-Chloro-3-(chloromethyl)-2-methyl-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide

Enhance urinary excretion of both Na and H2O ~ dint of. specifically inhibiting Na reabsorption located in the cortical (not thin ) portion of the ascending

limb of Henle’s bight and also in the early distal tubules.

Given orally,

Rapid absorption,

Cross the placenta,

Elimination through kidney.

Duration of representing 6 hr

 

Anxiety,  Sweating,  Severe terseness of breath,  Cough with spumous mucus,  Increased thrist,  Drowsiness,  Muscle plague,  Fainting or seizure,  Nausea,  Vomiting.

Diuretic and some antihypertensive agent.

2.5 to 10 mg once per day

Asutosh et al1

31

CANRENONE

10,13-Dimethylspiro[2,8,9,11,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthrene-17,5′-oxolane]-2′,3-dione

Inhibit binding of aldosterone with mineralocorticoid receptor.

Oral employment,

t1/2-~16.5 hours,

Drowsiness,  Ataxia,  Mental ruin

Oedema, hypertension, CHF

Goodman et al10

32

UREA

No express effect on transport but cause plan of ions by inducing bulk shed ~ flow & changing steady state get ~ concentration in body compartment.

Used intravenously,

It comprehend total body water, short half life,

 

Hypotension,  Hypovolemia,  Heart failure,  Pulmonary plethora,  Headache, blurred vision,  Nausea, vomitting

Approved to model intraocular pressure, intracranial pressure,

Cerebral edema

Goodman et al10

33

POTASSIUM CANRENOATE

potassium 3-[(8R,9S,10R,13S,14S,17R)-
17-hydroxy-10,13-dimethyl-3-oxo-2,8,9,
11,12,14,15,16-octahydro-1H-cyclopenta[a]
phenanthren-17-yl]propanoate

It is an aldosterone antagonist.

Given intravenously

 

Nausea, vomiting,  Confusion,  Restlessness,  Hallucination.

Oedema

Goodman et al10

34

METAZOLAMIDE

N-[5-(aminosulfonyl)-3-methyl-1,3,4-thiadiazol-2(3H)-ylidene]acetamide

Carbonic anhydrase inhibitor

Oral exercise,

t1/2-~14 hours, Metabolise~75%,

Renal excreation of uninjured drug~25%

Acidosis, drowsiness, Paresthesias , Abdominal Discomfort, Fatigue, Hypertension.

Glaucoma, Epilepsy,

periodic paralysis.

Goodman et al10

35

DICHLORPHENAMIDE

4,5-Dichlorobenzene-1,3-disulfonamide

Carbonic anhydrase inhibitor

Oral application

Dizziness, Change in the sense of trial, Headache, Confusion, Weight loss, muscle distress, joint pain, Throat pain, rash

Glaucoma,

Epilepsy

Goodman et al10

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