Diuretics UG Class 11th March 2024pptx.pdf

DIURETICS MBBS UG

1. Physiology of Urine
Formation
Presented by
Dr Arun K Negi
Senior Resident
IGMC, Shimla (H.P.)
Dated: 11
th
March 2024
Mail id: [email protected]

2. Learning objectives
✓Brief overview of Renal physiology & urine
formation
✓Introduction to Diuretics
✓Classification of Diuretics
✓Adverse effects
✓Therapeutic uses
✓Summary
✓Bibliography

3. Important terminology
▪Diuretic: Agent that increases urine volume.
✓Drugs that increase the sodium and water excretion
from body through urine.
▪Natriuretic: It causes an ↑se in renal Na
+
excretion.
▪Aquaretic: It ↑ses excretion of solute free water.
▪Urearetics: these agent blocks urea transport, which
results in ↑sed urine output & urea excretion, but not
increased excretion of electrolytes.

4. Physiology of Urine Formation
▪Three major steps are involved :
1) Glomerular filtration.
2) Tubular Reabsorption &
3) Active tubular secretion.
▪Nephron can be divided into four sites :
-Proximal tubule
-Henle’s loop
-DCT
-Collecting duct.
▪Normal GFR is 125ml/min or 180 litres/day, of which
99% gets reabsorbed Only 1.5 litres is excreted as urine.

6. Structure of Nephron

8. Proximal tubule
✓Freely permeable to water.
✓Water is reabsorbed passively through both
transcellular pathway & paracellular pathway
✓Transcellular transport : AQP1
✓Paracellular pathway : Claudin-2
✓Active absorption of NaCl, NaHCO3, Glucose, Amino
Acids, Organic Solutes in early proximal tubule
✓K
+
ions are reabsorbed by the paracellular pathway
✓This is followed by passive absorption of water.

9. •65-80 % filtrate is reabsorbed &
•Most reabsorption is coupled to Na
+
ion movement
SUBSTANCE % OF FILTRATE REABSORBED IN PCT
(H2O) WATER 60 %
(Na) SODIUM 66 %
NaHCO3 (Sodium
bicarbonate)
85%
K (POTASSIUM) 65%
ORGANIC SOLUTES :
GLUCOSE & AMINO ACIDS
100 %
UREA 50 %
PHOSPHATE 80%

10. Descending Loop of Henle (LH)
✓Descending limb-Permeable to water.
✓Osmolarity increases along the this portion because
of the counter current mechanism, that is responsible
for water reabsorption.
✓This results in tubular fluid with a three fold increase
in Na
+
& Cl
-
concentration

11. Thick ascending loop of Henle
✓Impermeable to water but Permeable to Na
+
, K
+
&
Cl
-
✓Active Reabsorption of Na
+
, K
+
& Cl
-
is mediated by a
Na
+
/ K
+
/2Cl
-
co transporter
✓Both Mg
2+
& Ca
2+
are reabsorbed by paracellular
pathway.
✓About 25% -30% of the filtered sodium is absorbed
here.
✓Loop diuretics act here and blocks the co-transporter.

13. Distal convoluted tubule
✓In the Early distal tubule 10% of NaCl is reabsorbed
by Na-Cl symport transporter mechanism.
✓On reaching the DCT almost 90% of sodium is
already reabsorbed.
✓Calcium reabsorption, under the regulation of
parathyroid hormone, is mediated by
-An apical channel & then transported by Na
+
/ Ca
2+
exchanger into interstitial fluid
✓Thiazidesblock Na-Cl symport transporter
system.
✓Thiazides (moderate efficacy) : block only 10% of Na
reabsorption.

15. Collecting Tubule and Collecting Duct
✓The principal cells of the CT & duct are responsible
for Na
+
, K
+
& water transport
✓Whereas intercalated cells affect H
+
secretion.
✓Aldosterone-On membrane receptor and cause
sodium absorption by Na+/H+/ K+exchange.
✓ADH-(vasopressin) binds to V2 receptors to
promote the reabsorption of water through Aquaporin
2 channels.

17. The relative magnitudes of Na+
reabsorption at sites
❖PT -65%
❖Asc LH -25%
❖DT -9%
❖CD -1%.

18. SEGMENT FUNCTIONS WATER
PERMEABILI
TY
PRIMARY
TRANSPORTE
RS& DRUG
TARGETS
DIURETIC
S WITH
MAJOR
ACTION
GLOMERUL
US
FORMATION OF
GLOMERULAR
FILTRATE
EXTREMELY
HIGH
NONE NONE
PCT REABSORPTION OF
65% OF FILTERED
Na/K/Ca/ Mg
85 % ofHCO3 ; 100
% GLUCOSE, Amino
Acids.
ISOSMOTIC
REABSORPTION OF
WATER
VERY HIGH Na/ H (NHE3),
CARBONIC
ANHYDRASE;
Na/ Glucose
cotransporter
s2
SGLT2
CARBONI
C
ANHYDRA
SE
INHIBITO
RS
PROXIMAL
TUBULE ,
STRAIGHT
SEGMENT
SECRETION &
REABSORPTION OF
ORGANIC ACIDS &
BASES INCLUDING
URIC ACID& MOST
DIURETICS
VERY HIGH ACID (URIC
ACID) AND
BASE
TRANSPORTE
RS
NONE

19. SEGMENT FUNCTION WATER
PERMEABILITY
PRIMARY
TRANSPORTERS
AND DRUG
TARGETS
DIURETIC WITH
MAJOR ACTION
THIN
DESCENDING
LIMB OF LOOP OF
HENLE
PASSIVE
REABSORPTION OF
WATER
HIGH AQUAPORINS NONE
THICK
ASCENDING LIMB
OF LOOP OF
HENLE
ACTIVE
REABSORPTION OF
15-25 % OF
FILTERED Na/K/Cl
Secondary
reabsorption of Ca
& Mg
VERYLOW Na/K/2Cl(NKCC2) LOOP DIURETICS
DISTAL
CONVOLUTED
TUBULE
ACTIVE
Reabsorption of 4-8
%of filtered Na &
Cl; Ca
2+
reabsorption under
parathyroid
hormone control
VERYLOW Na/Cl(NCC) THIAZIDES

20. SEGMENT FUNCTIONS WATER
PERMEABI
LITY
PRIMARY
TRANSPORT
ERS AND
DRUG
TARGETS
DIURETIC
WITH
MAJOR
ACTION
CORTICAL
COLLECTING
TUBULE
Na
+
REABSORPTIO
N (2-5%)
COUPLED TO
K
+
and H
+
SECRETION
VARIABLENa
CHANNELS,
K Channels ,
H
+
Transporter
s,
Aquaporins
K
+
Sparing
Diuretics ;
Adenosine
antagonists
under trial
MEDULLARY
Collecting
Duct
Water
reabsorption
under
VASOPRESSIN
Control
VARIABLESEGMENT Vasopressin
Antagonists

21. Diuretics
Presented by
Dr Arun K Negi
Senior Resident
IGMC, Shimla (H.P.)
Dated: 11
th
March2024

23. Diuretics
❖DrugswhichincreasetheexcretionofNa
+
&
waterfromthebodybyanactiononkidney.
❖(ExceptOsmoticdiureticswhichdonotcause
Natriuresisbutproducediuresis)
✓PrimaryeffectistodecreasethereabsorptionofNa
+
&Cl
-
fromthefiltrate
✓IncreasewaterlossbeingsecondarytotheIncreased
excretionofsalt.

24. Classifications of Diuretics
❖Thiazide Diuretics:
a) Thiazides: Hydrochlorothiazide, Benzthiazide
b) Thiazide like: Chlorthalidone, Metolazone, Xipamide,
Indapamide, Clopamide
❖Loop Diuretics: Frusemide, Bumetanide, Torasemide,
Ethacrynic acid
❖Potassium Sparing Diuretics:
➢Aldosterone Antagonist:Spironolactone, Canrenone,
Eplerenone
➢Directly Acting (Inhibition of Na+ channel):
Triamterene, Amiloride
❖Carbonic anhydrase inhibitors: Acetazolamide,
Brinzolamide, Dorzolamide
❖Osmotic Diuretics: Mannitol, Glycerine, Urea,
Isosorbide.

26. Thiazides Diuretics
✓Firstdiscoveredin1957(chlorothiazide)whiletrying
tosynthesizemorepotentcarbonicanhydrase
inhibitors
✓Somemembersofthisgroupretainsignificant
CarbonicanhydraseinhibitoractivityE.g.
Chlorthalidone
✓NoteffectiveinverylowGFRof<30ml/min,may
reduceGFRfurther
✓Metolazone→additionalactiononPT,effectiveat
lowGFR,canbetriedinrefractoryedema.

27. Thiazide diuretics
✓Thethiazidesarethemostwidelyuseddiuretics
becauseoftheirantihypertensiveeffects
✓Withlongtermuse,thesedrugsreduceperipheral
vascularresistance.
✓ThiazidesactatearlyDCT;calledlowceilingbecoz
,increasingthedoseabovenormaltherapeuticdoses
doesn’tproduceextradiureticeffect.

28. ThiazideDiuretics-MOA
✓ThiazidediureticinhibitsNaClsymportintheearly
DCT.
✓Proximaltubuleactassecondarysiteofaction
✓InhibitNa
+
-Cl
-
symporterandreabsorption
✓IncreaseNaClexcretion(5-10%Mediumefficacy)
✓Na
+
exchangeswithK
+
intheDT→K
+
loss
→Hypokalaemia.
✓MutationsintheNa
+
-Cl
-
symportercauseaformof
inheritedhypokalemicalkalosiscalledGitelman
syndrome.

30. Therapeutic uses of Thiazide Diuretics
❖Hypertension:clinicallythiazidesaremainstayof
antihypertensivetreatment
✓HydrochlorothiazideandChlorthalidoneisconsidered
becozoflongerhalflife(50Hrs)
❖CongestiveHeartfailure:Loopdiureticsare1
st
choiceinreducingextracellularvolumeinHeart
failure.
✓InpatientsresistanttoLoopdiuretics,thiazidesmay
beaddedwithcarefulmonitoringforhypokalaemia
e.g.Metolazoneisused.

31. Therapeutic uses of Thiazide diuretics
❖Hypercalciuria:useful in treating idiopathic
hypercalciuria and
✓calcium oxalate stones in urinary tract, because they
inhibit urinary Ca
2+
excretion.
❖Diabetes Insipidus: as thiazides have unique ability
to produce a hyperosmolar (concentrated) urine
✓Used in nephrogenic diabetes insipidus
✓Urine volume may drop from 11L / Day to about
3L/day ,when treated with thiazides.

33. Adverse effects
I.Hypokalemia:because thiazide increase the Na
+
in
the filtrate arriving at the distal tubule
•More K
+
is also exchanged for Na
+
, resulting in a
continual loss of K
+
from body.
•Therefore K
+
levels should be measured periodically.
•K
+
supplementation or combination of K
+
sparing
diuretic may be used .
2. Hypomagnesaemia: due to urinary loss of
magnesium (normal level is 1.5-2.5 mEq/ L)

34. 3.Hyponatremia:itdevelopduetoelevationofADH;
duetodiminisheddilutingcapacityofthekidney
4.Hyperuricemia:increasedserumuricacidlevelby
decreasingtheamountofacid
✓excretedthroughcompetitionintheorganicacid
secretorysystem.
✓Beinginsolubleuricaciddepositsinthejoints
✓Thereforetobeusedwithcautioninpatientswith
goutorhighlevelsofserumuricacid.
5.Hypovolemia:Itcancauseorthostatichypotension
&lightheadedness.

35. Adverse effects
6.Hypercalcemia:thiazides inhibit the secretion of
Ca
2+
, leading to elevated levels of Ca
2+
in blood.
7. Hyperglycaemia: can lead to mild elevation of
serum glucose ; this effect is:
✓Due to impaired pancreatic release of insulin &
diminished tissue utilization of glucose.
✓Due to hyperpolarization of beta cells ,thereby
inhibiting insulin release.
✓Should monitor glucose levels if thiazides initiated

36. Adverse effects
8.Hyperlipidaemia:thiazides causes a 5-15 %
increase in total serum cholesterol & LDL.
✓These levels may return toward baseline after
prolonged use
9.Allergic reactions (rare ones): photosensitivity,
generalised dermatitis, haemolytic anaemia etc
10.Other toxicities: weakness , fatigability and
✓impotence(reversible) probably due to volume
depletion.
✓casesofacuteangleclosureglaucomadueto
hyponatremiacausedbythiazidehasbeenreported.

37. Thiazide drugs
❖Chlorthalidone: Used only for hypertension, long
acting (t1/2 –approximately 50 hr)
❖Metolazone: Active even in low GFR. Additive with
furosemide.
✓Used in CHF patients.
✓Used mainly for edema, occasionally for hypertension.
❖Xipamide: More strong diuretic.
✓Used for edema and hypertension
✓More incidence of hypokalaemia and ventricular
arrhythmia.
❖Indapamide: Extensively metabolized ; Very less
amount reach kidney. (Favoured in NICE guidelines
2011)
✓Used only as antihypertensive.

38. Loop diuretics
✓Sulphonamide derivative
✓Most popular powerfuldiuretic.
✓Generally cause greater diuresis than thiazides
✓Can enhance Ca
+2
and Mg
+2
excretion
✓Entertubularlumenviaproximaltubularsecretion
(unusualsecretionsegment)becausebodytreats
themasatoxicdrug
✓Drugs that block this secretion reduces efficacy
(e.g. probenecid)

39. Mechanism of action
✓LoopdiureticsblockstheNa
+
,K
+
,2Cl
-
symporterin
thethickascendinglimboftheLH.
✓It also prevent the reabsorption of Ca
+2 &
Mg
+2
✓From the loop, they come to DCT where some
sodium & chloride are reabsorbed.
✓WhentheycometoCD,Nagoesout&K
compensatesalongwithH
+
✓ThispumpiscalledROMK;Renaloutermedullary
potassiumchannel&forH
+
,itisknownasthe
ATPasepump.
✓ALoopdiureticpatientwillhaveHypokalemia&
metabolicalkalosis.

42. High ceiling diuretics (Loop diuretics)
❖Furosemide–Rapid and short acting, Can be given
IM, IV and oral; plasma T ½ 1-2 hours.
✓Given Intravenously (10 mg) acts in 2-5 minutes;
✓Orally (40 mg) it takes 20-40 minutes, Can produce
upto 10 L of urine/day
✓Effective even in patients with severe renal failure
✓Cause peripheral venous dilation and relieves LVF
✓Cause Ca
+2
and Mg
2+
excretion through urine
✓Hyperuricemia and Hypokalemia
✓May cause ototoxicity
✓Dose: 20 –80 mg

43. ❖Edema -20-80 mg od
-Hypertension -40mg BD
➢Acute pulmonary edema –0.5-1mg/kg iv over
1-2 min. (40-80 mg iv)
➢Maximum dose in renal insufficiency : 200 mg
6 hrly

44. High ceiling diuretics (Loop diuretics)
❖Bumetanide–similar to furosemide.
✓40 times more potent, Can respond in patients
resistant to furosemide
✓Can be used in patients allergic to furosemide
✓Bettertoleratedbecausetheadverseeffectslike
hypokalaemia,ototoxicityhyperglycaemiaand
hyperuricaemiaaremilderbutmaycause
myopathy.
✓Used in CHF and pulmonary edema
✓Dose: 1 –5 mg OD in morning.

45. Bumetanide
✓More lipid soluble
✓Oral bioavailability is 80-100 %
✓Preferred for oral use in severe CHF
✓Plasma T ½ is 60 minute but gets prolonged in
renal & hepatic insufficiency
✓1-5 mg oral morning dose.
✓2-4 mg iv/im dose
✓Maximum dose in renal failure : 15mg/ day.

46. Torasemide –aka torsemide / dytor
✓Similar to furosemide –3 times more potent
✓Slightly longer acting
❑Used in edema: dose 5-20 mg/day
❑Hypertension: 2.5-5 mg/day
❑Renal failure: 100mg Bid
▪Oral absorption is more rapid and complete in
Patients with edema of bowels due to CHF
▪Elimination T ½ is 3.5 hrs & duration of action
is 4-8 hrs

48. Etacrynic acidorethacrynic acid
➢Itisaloopdiureticusedtotreathighblood
pressureandtheswellingcausedbydiseases
likeCongestiveheartfailure,liverfailureandkidney
failure
➢Unliketheotherloopdiuretics,etacrynicacidisnot
asulfonamideandthus,itsuseisnotcontraindicated
inthosewithsulfaallergies.
➢Ethacrynicacidisaphenoxyaceticacidderivative
containingaketonegroupandamethylenegroup.

49. Ethacrynic acid
❑T½ -60-90 min
❑Off label Use -glaucoma
❑50-100mg/day –oral
❑50mg iv –single dose
❑Most ototoxic
❑Vestibular function may also be affected
❑Inducing vertigo.

50. Uses -Loop diuretics
✓Edema
✓Acuterenalfailure&inchronicrenalfailure
largedosesareneeded.
✓Acute pulmonary oedema
✓Cerebral oedema
✓Forceddiuresis:Inpoisoningduetofluoride,
iodideandbromiderespondtofurosemidewith
salineinfusion.
✓Hypertension:Withrenalimpairment
✓Thiazidesarepreferreddiureticsinprimary
hypertension.

51. Uses -Loop diuretics
❑Hypercalcemia: loop diuretics along with
hydration
✓areusefulintreatingacutehypercalcemia
becausetheystimulateCa
2+
excretion.
❑In acute Hyperkalemia also used for
management.

52. Loop diuretics: Adverse effects
❑Hypokalaemia and metabolic alkalosis
(Hypokalaemiashouldbeparticularlypreventedinpost
MIpatients)andinpatientswhoarereceivingdigitalis.
❑Hyponatraemia, hypovolemia, hypotension and
dehydration
❑Hypocalcaemia
❑Hypomagnesaemia
❑Hyperuricaemia, Hyperglycaemia.
❑Ototoxicity.
❑Allergic reactions like skin rashes can occur.
✓Remember 6 Hypo, 2 Hyper & 1 O

53. Loop & Thiazide drugs: Interactions
❑Potentiate antihypertensive drugs
❑Hypokalaemiabydiuretics—causedigitalis
toxicity,arrhythmias.
❑Furosemidewithaminoglycosides–Ototoxicity
andnephrotoxicity.
❑Cotrimoxazole with diuretics: thrombocytopenia
❑NSAIDSwithfurosemide—bluntactionof
furosemide

54. ❑Potassium Sparing Diuretics
❖Aldosterone Antagonist: Spironolactone, Canrenone,
Eplerenone.
❖Directly Acting (Epithelial Na
+
channel blocker):
Triamterene, Amiloride.
❑Carbonic anhydrase inhibitors
✓Acetazolamide
✓Brinzolamide
✓Dorzolamide
❑Osmotic Diuretics:Mannitol, Glycerine, Urea,
Isosorbide.

55. Potassium sparing Diuretics
❖Aldosterone Antagonist:Spironolactone,
Canrenone, Eplerenone.
❖Directly Acting (Inhibition of Na+ channel):
Triamterene, Amiloride
✓Mechanism of action
✓Individual drugs
✓Pharmacokinetics
✓Indications
✓Dose
✓Side effects and Precautions

56. K
+
Sparing Diuretics : MOA
❑Acts on cortical segment of distal tubules/Collecting
duct
❑Competitive antagonist of Aldosterone
❑Inhibit ATP → inhibit Na
+
reabsorption.
✓Mild saluretic (natriuresis) 3% of NaCl
✓Causes K
+
retention (K
+
sparing effect)
→ Hyperkalemia
▪Never used alone as diuretic.
▪Useful when combined with thiazide or frusemide.

59. Spironolactone
❑It is a steroid, chemically related to mineralocorticoid
Aldosterone.
❑Oral bioavailability of spironolactone from microfine
powder tablet is 75%
✓Completely metabolized in liver to generate
✓Active metabolite Canrenone ; it is responsible for ½
to 2/3 of its action.
❑Half life of spironolactone is 1-2 hrs & for
Canrenone is approx 18 hrs.
❑Dose 25-50 mg BD-QID ; max dose:400mg/day

60. Spironolactone -uses
❑Oedema: Useful in cirrhotic and nephrotic syndrome.
✓E.g. hepatic cirrhosis (breaks resistance to thiazides
or frusemide in refractory edema)
❑To counteract K
+
loss due to thiazides, frusemide
❑Resistant Hypertension:combined with thiazide
❑CHF: as an adjunctive therapy, it retards disease
progression and reduces mortality.
❑Primary Hyperaldosteronism(Conn’s syndrome)
❑In Polycystic ovary syndrome: used as off label

61. Spironolactone: Adverse Effects
❑Hyperkalemia risk
✓In CRF patients
✓Patients taking ACEI (Enalapril) or ATRB (Losartan)
✓KCl supplement/ K
+
supplements.
❑Related to steroid structure
✓Gynaecomastia, Impotence in males as ADRs.
✓(note * this drug is used to treat Hirsutism & PCOD
menstrual irregularities in females-as this drug ↓ses
production of testosterone.)
❑Misc.: drowsiness, abdominal upset.

62. Drug Interactions
✓May increase plasma digoxin levels in CHF
✓NSAIDs (Aspirin) decreases its effect by Inhibiting
tubular secretion of its active metabolite canrenone.

63. Potassium sparing diuretics
❑Eplerenone
✓More selective aldosterone antagonist
✓Less hormonal adverse effects
✓Hyperkalemia risk similar to spironolactone
❑Uses:
✓Moderate to severe CHF
✓Post MI Left Ventricular dysfunction.
❑Dose: 25-50 mg BD
✓Well absorbed orally, inactivated in liver by CYP3A4
✓T ½ is 4-6 hrs.

64. Potassium sparing diuretics: Preparations
❑Aldosterone Antagonist Dose(mg) Route
✓Spironolactone 25-100 mg oral
✓K canrenoate I.V.
✓Eplerenone 25-100 mg oral
❑Directly Acting
✓Amiloride 5mg Oral, Aerosol
✓Triamterene 50mg oral
✓Fixed dose combinations with thiazides and frusemide
available but not advisable.

65. Carbonic anhydrase inhibitors
✓Acts on Proximal tubule
✓Acetazolamide & Methazolamide
✓Less potent than Loop & Thiazide Diuretics
❑Mechanism of action:
✓Carbonicanhydraseisanenzymethatcatalysesthe
formationofcarbonicacidwhichspontaneously
ionisestoH
+
andHCO3
-
❖Byinhibitingtheenzyme,carbonicanhydrase
inhibitorsblocksodiumbicarbonatereabsorption
andcausesHCO3-diuresis.
✓Theyinducemetabolicacidosiswhichreducestheir
diureticeffectwithin2to4days

66. Acetazolamide
✓Sulphonamide derivative
✓Enhances excretion of sodium , potassium,
bicarbonate and water.
❖Other Actions:
1. Eye-reduces intra ocular pressure.
2. Brain-reduces the formation of CSF
❑Pharmacokinetics:
✓Well absorbed orally
✓Onset of action within 60-90 min
✓Duration of action 8-12 hr.
✓Excreted unchanged by the kidney

67. Acetazolamide: Mountain sickness
•It is DOC for acute mountain sickness or high
altitude sickness
•MOA:whenapersonascendstoahighaltitude
thereishypoxiacausingthepatienttobreathe
faster&toloseCarbondioxide
•This will lead to respiratory alkalosis
•Hence Acetazolamide compensates for that by
producing Metabolic alkalosis.

68. Adverse effects
✓Metabolic acidosis: (due to bicarbonate loss)
✓Anorexia
✓Haematuria
✓Photosensitivity
✓Melena
✓Hypokalemia
✓Drowsiness
✓Paraesthesia
✓Urticaria
✓Renal stones : Ca
+2
is lost with HCO3 resulting in
hypercalciuria.

69. OSMOTIC DIURETICS
❑Mannitol is a pharmacologically inert substance.
✓Mannitol gets filtered by the glomerulus but is
reabsorbed.
✓Itcauseswaterretentionintheproximaltubuleand
descendinglimbofHenle’sloopbyosmoticeffect
resultinginwaterdiuresis.
✓There is also some loss of sodium.
❑Adverseeffects:aredehydration,ECFvolume
expansion,hyponatremia,headache,nausea,
vomitingandallergicreactions.

70. Uses of Osmotic Diuretics
❑Tomaintainurinevolumeandpreventoliguriain
conditionslikemassivehaemolysis,rhabdomyolysis,
shockandseveretrauma.
✓In such situations mannitol prevents renal failure
✓To reduce intracranial and intraocular pressure
❑Contraindicatedinpatientswhohavealreadygone
intorenalfailure,mannitolcanbedangeroussince
itcancausepulmonaryedemaandmayprecipitate
heartfailureduetovolumeexpansion.
❑Glyceroliseffectiveorally:reducesIntraocularand
intracranialpressure
❑Methylxanthinesliketheophyllinehavemilddiuretic
effect.

71. Points to Remember –Clinical Practice
❑Don’t use diuretics overenthusiastically.
(dehydration, hypotension)
❑Brisk diuresis in cirrhosis may precipitate
hepatic coma.
✓Hypokalemia, alkalosis and increased NH
3levels
❑Diuretics not used in Toxaemia of Pregnancy.
✓Blood volume is low despite edema.
✓Diuretics will compromise placental circulation

72. Points to Remember
❑Most of Loop and Thiazide diuretics are
sulphonamide derivatives.
✓Think of allergic manifestations
❑Hypokalemiabydiureticsprecipitatesdigitalis,
quinidinesideeffects.
❑Hypokalemia by diuretics decrease
sulfonylurea action
✓reduced insulin release due to reduced action of ATP
dependent potassium channel

73. ✓High ceiling not given with Amino-glycosides
✓ACE inhibitors with Thiazides reduce the chances of
hypokalaemia (FDC)
✓Probenecid inhibits tubular secretion of Frusemide
and Thiazides and reduce action.
❖Potency of producing hypokalaemia
✓CAsI >Thiazides > Loop
❖NSAIDS reduce diuretic action due to PG inhibition
and affecting glomerular blood flow

74. ✓Acetazolamide action is self limiting
✓Spironolactone breaks the Thiazide resistance
✓Aspirin blocks Spironolactone action by inhibiting
tubular secretion of canrenone
✓Spironolactone can produce dangerous hyperkalaemia
when used along with ACEI and ARBs
✓Spironolactone has antiandrogenic side effects
✓Eplerenone is new potassium sparing diuretics with
less antiandrogenic effects.
✓Osmotic diuretics indicated in impending ARF : Don’t
use if ARF has set in

75. THANKS