SlideShare a Scribd company logo
1
DIURETICS
Dr. Hiwa K. Saaed
PhD Pharmacology & Toxicology
Diuretics:
• mainly promotes the excretion of the
(Na+), (Cl-) or (HCO3-) and water,
• the net result being:
– Increase the urine flow,
– change urine pH
– change the ionic composition of the urine and
blood.
Drugs used in renal disorders
I. drugs that modify salt excretion:
A. PCT: carbonic anhydrase inhibitors
B. TAL: loop diuretics
C. DCT: thiazides
D. CCT; K-spairing diuretics
E. Osmotic diuretics; manitol
II. Drugs that modify water excretion
A. Osmotic diuretics: manitol
B. ADH agonists: desmopressin
C. ADH antagonists: conivaptan, demeclocycline, lithium
Diuretics:
Diuretics are very effective in the treatment of:
• Edema: CHF, pregnancy, & nutritional
• nephrotic syndrome
• diabetes insipidus
• hypertension
• cirrhosis of liver
• and also lower the intracellular and CSF
pressure.
4
5
Introduction
• Kidney: 1.3 million nephron each
• Glomerular filtration:
– Receive 25% of cardiac output
– Filtration rate: 100-120 ml/minute
– 180 L of glomerular filtrate/day
• Tubular reaborption:
– Reabsorption of 99% of glomerular filtrate  only + 1
ml/min excreted as urine
– 1.5 L/day of urine.
• Tubular secretion
The excretion by kidney is dependent on: glomerular
filtration, tubular reabsorption and tubular secretion.
6
7
8
Introduction
• Proximal tubules:
– Reabsorption of 60-70% Na+
– Permeable to water  isotonic urine
– Isosmotic reabsorption of amino acids, glucose, cations
• Loop of Henle:
– Thin descending limb: most active water reabsorption
– Thick ascending limb:
• Reabsorption of Na+,
• Water impermeable  diluting segment
• Distal tubules:
– Na+ reabsorption
• Collecting duct: selectively water permeable
Diuretic Drug Groups
• the diuretics acting in these segments each have
different MOA ? b the mechanism for reabsorption
of salt & water different in each 4 segments,
• Most diuretics act from the luminal site of the
membrane & must be present in the urine:
– They are filtered at the glomerulus
– some are also sec by the weak acid sec in the proximal
tubule,
– an exception is the aldosterone receptor antagonist
enter CCT from basolateral side.
9
Electrolyte Transport and Site of Action of Diuretics
11
Site and Mechanisms of Actions of Diuretics
Diuretics Site of Action Mechanism
Osmotic Diuretic 1. Proximal tubules
2. Loop of Henle
3. Collecting duct
Inhibition of water and Na+
reabsorption
Carbonic Anhydrase
Inhibitor (CA-I)
Proximal tubules Inhibition of bicarbonate
reabsorption
Loop Diuretic Loop of Henle
(thick ascending limb)
Inhibition of Na+, K+, Cl-
cotransport
Thiazide Early distal tubule Inhibition of Na+, Cl-
cotransport
K+ sparing diuretics Late distal tubule
Collecting duct
Inhibition of Na+
reabsorption and K+ secretion
12
Carbonic Anhydrase Inhibitor
Acetazolamide (S derivatives)
Mechanism of Actions
• Kidney: self limited diuresis 2-3 days
– Carbonic anhydrase catalyzes : CO2+H2O H2CO3
– H+ ion produced by the breakdown of H2CO3, exchanged
for Na+ & is also combined with HCO3
- in the lumen of
the PCT
– Inhibition of Bicarbonate (HCO3
-) reabsorption
– Reduces Na+-H+-exchange  NaHCO3 is excreted along
with H2O
13
Mechanism of Action of CA-I
14
Adverse Effects and Contraindications
• Metabolic acidosis
• Renal stones (Phosphate and Calcium stone)
• Renal potassium wasting; (NaHCO3
- ) enhances K+
secretion
• Diuresis is self limiting within 2-3 days?
• AE: Drowsiness, paresthesia, disorientation, renal stone
(in case of urine alkalinization)
Contraindication
– Liver cirrhosis (CA-I inhibits conversion of NH3 to NH4)
 NH3 increased  encephalopathy
15
Indications of CA-I
• Glaucoma (Eye: not self limiting effect)
– Orally acetazolamide
– Topically dorzolamide, brinzolamide
• Prevent mountain sickness (high altitude) sickness
inhibit sec of bicarbonate by the choroid plexus;
Acidosis of the CSF results in hyperventilation
• Urinary alkalinization: preventing uric acid and
cystine stones
• Used for their diuretic effect only if edema is
accompanied by significant Metabolic alkalosis
16
Thiazides
• Hydrochlorothiazide (prototype), Chlorothiazide,
Bendroflumethiazide, Chlorthalidone, Metolazone,
Indapamide
• All are sulfonamide derivatives, t1/2 6-12 hrs
Mechanism of Actions
– Thiazides are secreted by proximal tubules but works
in DCT
– Inhibit Na+-Cl- symporter from the lumen to tubular
cells  increase Na+, Cl- excretion (and water)
– Some thiazides have weak CA-I effect
17
Mechanism of Action of Thiazide
18
Effects on Electrolytes
• Increases Na+ and Cl- excretion
• Hypokalemic metabolic alkalosis; K+ excretion
also increase associated w/ increased Na+ in
distal tubules.
• Inhibits uric acid secretion hyperuricemia
and gout
• Decreases Ca2+ excretion
 tends to increase plasma Ca++
 Retards osteoporotic process
• Increases Mg2+ excretion
19
– Hypo K+  Increased risk of digitalis toxicity
– Hypo Na+, Hypo Mg++
– Hyperuricemia  caution in gout arthritis
– Hyperglycemia and hypercholesterolemia 
not favorable for DM and dyslipidemia
(although not contraindicated)
– (Indapamid has less effects on lipid and uric acid)
– Hypercalcemia (long-term)  good for elderly
– Sexual dysfunction
Adverse Effects
20
Interactions
• Increases the risk of arrhythmia when combined
w/ digitalis, quinidine and other antiarrhythmias
• Reduces efficacy of anticoagulant and uricosuric
• Reduces the efficacy oral antidiabetics
• NSAID reduce the efficacy of thiazide
21
Indications of Thiazides
• Hypertension (single drug or in combination)
• Chronic, mild- heart failure
• Edema (loop diuretic is preferable)
• Nephrogenic Diabetes insipidus
• Prevention of Ca++ excretion in osteoporosis and
calcium nephrolithiasis
22
Loop Diuretics
• Furosemide, torasemide, bumetanide: Are sulfonamide
derivatives
• ethacrynic acid is a phenoxyacetic acid derivative
• Site of action: thick ascending limb of Henle
• Mechanism:
– Loop diuretics should be excreted into the
lumen
– Inhibits Na+, K+, 2Cl- symporter  significantly
increases the excretion of Na+, K+, Cl-
– Osmotic gradient for water reabsorption is also
decreased  increasing water excretion
– Ca2+ and Mg2+ are excreted as well.
23
Mechanism of Action of Loop Diuretic
24
Interactions
• Concomitant use w/ aminoglycoside or cisplatin
increases the risk of nephrotoxicity and
ototoxicity
• PGs are important in maintaining GF; NSAID
reduces the effects of diuretics
• Probenecid reduces the effects of diuretics by
inhibiting its secretion into the lumen.
25
Indications
• Congestive heart failure (1st line drug)
• Acute pulmonary edema
• Edema due to renal failure, nephrotic syndrome,
ascites
• Hypercalcemia (that induced by malignancy)
• Severe hypertension
• Force diuresis during drug/chemical intoxication
(drug that excreted through the kidney in active
form)
Adverse effects
• Hypovolemic metabolic alkalosis
• Ototoxicity
• Typical sulfonamide allergy
26
27
Potassium Sparing Diuretics
1. Na+ channel inhibitor (Amiloride, triamterene)
 Inhibit Na+ reabsorption  Na+ excretion
 Reduced K+ secretion  K+ retention
2. Aldosterone antagonist (Spironolactone,
eplerenone) Steroid derivatives
– Aldosterone induces the expression of Na/K-
ATPase and Na+ channel
– Spironolactone and eplerenone blocks aldosterone
receptor  reduces Na+ reabsorption and K+
secretion
Potassium Sparing Diuretics
29
• Potassium sparing diuretic has a weak diuretic
action
• Usually used in combination w/ other diuretic:
– Potentiation of diuretic and antihypertensive effects
– Prevents hypokalemia
• Spironolactone is metabolized to its active
metabolite, canrenone.
• Long term use of spironolactone can prevent
myocardial hypertrophy and myocardial fibrosis
Potassium Sparing Diuretics
30
Adverse Effects
Spironolactone
• Hyperkalemia
• Antiandrogenic effect
» gynecomastia,
» decrease of libido, impotence,
» menstrual disturbance.
• Megaloblastic anemia: Triamterene (folate
antagonist)
31
INDICATIONS
• Antihypertension:
– In combination w/ other antihypertensives
– To increase the effect and to prevent hypokalemia
– Aldosteronism (that occur in cirrhosis)
CONTRAINDICATIONS/PRECAUTIONS
• Conditions that prone to hyperkalemia:
– Renal failure
– Should never be combined with ACE-inhibition, ARB,
NSAID, K+ supplementation
32
Osmotic Diuretics (OD)
• Mannitol (prototype),
• Others rarely used: urea, glycerin, isosorbide
• Properties of osmotic diuretics:
– Freely filtrated by glomerulus
– Negligible tubular reabsorption
– Chemically inert
– Usually non metabolized
33
Pharmacokinetics
• Mannitol and urea: intravenous
• Glycerin and isosorbide: Can be administered
orally
• Metabolism:
– glycerin 80% metabolized
– mannitol 20%
– Urea, isosorbide: not metabolized
• Excretion: renal
34
Mechanism of Action
• OD is filtrated and increases osmotic pressure in
tubular lumen
• Hence, increases excretion of water and
electrolytes (Na+, K+, Ca++, Mg++, HCO3
-,
phosphate) ↑volume of urine & rate of urine flow
through the tubule
• Mannitol can also reduce brain volume and
intracranial pressure by osmotically extracting
water from the tissue into the blood
• A similar effect occurs in the eye
35
Indications
• Glaucoma (rare) ↓IOP
• Brain edema ↓brain volume & pressure
– mannitol and urea are given before and after
brain surgery
• Disequilibrium syndrome after hemodialysis
• Solute overload in sever hemolysis and
rhabdomyolysis
• Prophylaxis of ATN (acute tubular necrosis) due
to contrast media, surgery, and trauma.
– NaCl 0.45% can also be used
36
Adverse Effects
• Removal of water from the I.C compartments 
Initial increase of plasma volume  potentially
dangerous in heart failure and pulmonary
edema  Hypo Na+  headache, nausea,
vomiting
• Water exc.  Hypovolemia  hypernatremia
• Hypersensitivity reaction
• Vein thrombosis, pain if extravasation (urea)
• Hyperglycemia, glycosuria (glycerin)
37
Antidiuretic Hormone (ADH) Agonists and Antagonists
• ADH & Desmopressin are ADH Agonists
• Peptides must be given parenterally(rapid degradation by
trypsin)
• Secretion of ADH increase in response to:
–  Plasma osmolarity
– Hypovolemia, hypotension (bleeding, dehydration)
• Demeclocycline and conivaptan are ADH
antagonists
• Lithium has ADH antagonist effect but never used
for this purpose
38
Mechanism of Action
• Works in ascending limb of Henle’s loop and
collecting ducts
• Two kind of receptors:
– V1: vascular smooth muscle vasoconstriction
– V2: kidney  increase water permeability of
tubular epithelium  water reabsorption
ADH
• ADH facilitates water reabsorption from the
collecting tubule by:
• activation of V2 receptors(coupled to GS,
stimulate AC) increase cAMP
• cause insertion of additional aquaporin AQP2
water channels into the luminal membrane in
this part of the tubule
39
ADH antagonists
• Conivaptan is an ADH inhibitor at V1a and V2
receptors
• Demeclocycline and Li inhibit the action of ADH
at some point distal to the generation of cAMP
and presumably the insertion of water channels
into the membrane.
41
42
Clinical uses of ADH Agonists
• ADH and desmopressin reduce urine volume
and concentrate it, are useful in Pitutary
Diabetes Insipidus (not for nephrogenic DI Rx
by salt restriction, thizides and loop diuretics)
• DI due to head trauma or brain surgery
• Gastrointestinal bleeding due to portal
hypertension (by reducing mesenteric blood
flow)
Clinical uses of ADH Antagonists
• Oppose the actions of ADH and other naturally
occurring peptides (certain tumors; small cell
carcinoma of the lung) that act on the same V2
receptors, significant water retention and
dangerous hyponatremia.
• Syndrome of inappropriate ADH secretion
(SIADH) can be treated with demeclocycline and
conivaptan
43
Adverse effects
• ADH, Desmopressin, water overload,
hyponatremia
• Demeclocycline: bone and teeth abnormalities
• Li: nephrogenic DI
44


More Related Content

What's hot

Loop diuretics
Loop diureticsLoop diuretics
Loop diuretics
Domina Petric
 
Antihypertensive drugs
Antihypertensive drugsAntihypertensive drugs
Antihypertensive drugs
Subramani Parasuraman
 
Antianginal drug
Antianginal drugAntianginal drug
Antianginal drug
pankaj rana
 
Proton pump inhibitors
Proton pump inhibitorsProton pump inhibitors
Proton pump inhibitors
Md. Hayder
 
Antihyperlipidemic drugs
Antihyperlipidemic drugsAntihyperlipidemic drugs
Antihyperlipidemic drugs
Likhita Kolli
 
Potassium sparing diuretics
Potassium sparing diureticsPotassium sparing diuretics
Potassium sparing diuretics
Domina Petric
 
Antidiabetic drugs
Antidiabetic drugsAntidiabetic drugs
Antidiabetic drugs
Dr. Pramod B
 
Antiarrhythmic drugs bds
Antiarrhythmic drugs bdsAntiarrhythmic drugs bds
Antiarrhythmic drugs bds
Naser Tadvi
 
Antiplatelet Drugs
Antiplatelet DrugsAntiplatelet Drugs
Antiplatelet Drugs
Lady Hardinge Medical College
 
Digoxin
DigoxinDigoxin
Anti diuretics drugs
Anti diuretics drugsAnti diuretics drugs
Anti diuretics drugs
SnehalChakorkar
 
Antihypertensive drugs naser
Antihypertensive drugs naserAntihypertensive drugs naser
Antihypertensive drugs naser
Naser Tadvi
 
NSAID'S --ASPIRIN
NSAID'S --ASPIRINNSAID'S --ASPIRIN
NSAID'S --ASPIRIN
Heena Parveen
 
Antiepileptics
AntiepilepticsAntiepileptics
Antiepileptics
Kalaivanisathishr
 
Propranolol
PropranololPropranolol
Propranolol
Md Shohag Hosen
 
Vasodilators
VasodilatorsVasodilators
Vasodilators
Dr. Advaitha MV
 
Drugs used in Congestive heart failure
Drugs used in Congestive heart failure Drugs used in Congestive heart failure
Drugs used in Congestive heart failure
shoaib241087
 
Cardiac glycosides
Cardiac glycosidesCardiac glycosides
Cardiac glycosides
Subramani Parasuraman
 
Fibrinolytics & antiplatelets
Fibrinolytics & antiplateletsFibrinolytics & antiplatelets
Fibrinolytics & antiplatelets
Naser Tadvi
 
Antihypertensive mbbs copy
Antihypertensive mbbs   copyAntihypertensive mbbs   copy
Antihypertensive mbbs copy
Divya Krishnan
 

What's hot (20)

Loop diuretics
Loop diureticsLoop diuretics
Loop diuretics
 
Antihypertensive drugs
Antihypertensive drugsAntihypertensive drugs
Antihypertensive drugs
 
Antianginal drug
Antianginal drugAntianginal drug
Antianginal drug
 
Proton pump inhibitors
Proton pump inhibitorsProton pump inhibitors
Proton pump inhibitors
 
Antihyperlipidemic drugs
Antihyperlipidemic drugsAntihyperlipidemic drugs
Antihyperlipidemic drugs
 
Potassium sparing diuretics
Potassium sparing diureticsPotassium sparing diuretics
Potassium sparing diuretics
 
Antidiabetic drugs
Antidiabetic drugsAntidiabetic drugs
Antidiabetic drugs
 
Antiarrhythmic drugs bds
Antiarrhythmic drugs bdsAntiarrhythmic drugs bds
Antiarrhythmic drugs bds
 
Antiplatelet Drugs
Antiplatelet DrugsAntiplatelet Drugs
Antiplatelet Drugs
 
Digoxin
DigoxinDigoxin
Digoxin
 
Anti diuretics drugs
Anti diuretics drugsAnti diuretics drugs
Anti diuretics drugs
 
Antihypertensive drugs naser
Antihypertensive drugs naserAntihypertensive drugs naser
Antihypertensive drugs naser
 
NSAID'S --ASPIRIN
NSAID'S --ASPIRINNSAID'S --ASPIRIN
NSAID'S --ASPIRIN
 
Antiepileptics
AntiepilepticsAntiepileptics
Antiepileptics
 
Propranolol
PropranololPropranolol
Propranolol
 
Vasodilators
VasodilatorsVasodilators
Vasodilators
 
Drugs used in Congestive heart failure
Drugs used in Congestive heart failure Drugs used in Congestive heart failure
Drugs used in Congestive heart failure
 
Cardiac glycosides
Cardiac glycosidesCardiac glycosides
Cardiac glycosides
 
Fibrinolytics & antiplatelets
Fibrinolytics & antiplateletsFibrinolytics & antiplatelets
Fibrinolytics & antiplatelets
 
Antihypertensive mbbs copy
Antihypertensive mbbs   copyAntihypertensive mbbs   copy
Antihypertensive mbbs copy
 

Viewers also liked

Magement of cataract
Magement of cataractMagement of cataract
Magement of cataract
Thann Watcharapanjamart
 
NurseReview.Org Pharmacology - Kidney Drugs
NurseReview.Org Pharmacology - Kidney DrugsNurseReview.Org Pharmacology - Kidney Drugs
NurseReview.Org Pharmacology - Kidney Drugs
Nurse ReviewDotOrg
 
Cataract surgery
Cataract surgery Cataract surgery
Cataract surgery
Suleman Muhammad
 
NurseReview.Org - Pharmacology Git Drugs
NurseReview.Org - Pharmacology Git DrugsNurseReview.Org - Pharmacology Git Drugs
NurseReview.Org - Pharmacology Git Drugs
Nurse ReviewDotOrg
 
Cataract Surgery Complications for General Practitioners
Cataract Surgery Complications for General PractitionersCataract Surgery Complications for General Practitioners
Cataract Surgery Complications for General Practitioners
presmedaustralia
 
Diuretics by P.Ravisankar
Diuretics by P.RavisankarDiuretics by P.Ravisankar
Diuretics by P.Ravisankar
Dr. Ravi Sankar
 
Diuretic drugs
Diuretic drugsDiuretic drugs
Diuretic drugs
Shirley Garay
 
NurseReview.Org - Study Skills and Test Strategies for the New Nursing Student
NurseReview.Org - Study Skills and Test Strategies for the New Nursing StudentNurseReview.Org - Study Skills and Test Strategies for the New Nursing Student
NurseReview.Org - Study Skills and Test Strategies for the New Nursing Student
Nurse ReviewDotOrg
 
Antihypertensive drugs 2015-16
Antihypertensive drugs 2015-16Antihypertensive drugs 2015-16
Antihypertensive drugs 2015-16
College of Pharmacy University of Sulaimani
 

Viewers also liked (9)

Magement of cataract
Magement of cataractMagement of cataract
Magement of cataract
 
NurseReview.Org Pharmacology - Kidney Drugs
NurseReview.Org Pharmacology - Kidney DrugsNurseReview.Org Pharmacology - Kidney Drugs
NurseReview.Org Pharmacology - Kidney Drugs
 
Cataract surgery
Cataract surgery Cataract surgery
Cataract surgery
 
NurseReview.Org - Pharmacology Git Drugs
NurseReview.Org - Pharmacology Git DrugsNurseReview.Org - Pharmacology Git Drugs
NurseReview.Org - Pharmacology Git Drugs
 
Cataract Surgery Complications for General Practitioners
Cataract Surgery Complications for General PractitionersCataract Surgery Complications for General Practitioners
Cataract Surgery Complications for General Practitioners
 
Diuretics by P.Ravisankar
Diuretics by P.RavisankarDiuretics by P.Ravisankar
Diuretics by P.Ravisankar
 
Diuretic drugs
Diuretic drugsDiuretic drugs
Diuretic drugs
 
NurseReview.Org - Study Skills and Test Strategies for the New Nursing Student
NurseReview.Org - Study Skills and Test Strategies for the New Nursing StudentNurseReview.Org - Study Skills and Test Strategies for the New Nursing Student
NurseReview.Org - Study Skills and Test Strategies for the New Nursing Student
 
Antihypertensive drugs 2015-16
Antihypertensive drugs 2015-16Antihypertensive drugs 2015-16
Antihypertensive drugs 2015-16
 

Similar to Diuretics

Diuretics and antidiuretics detail STUDY
Diuretics and antidiuretics detail STUDYDiuretics and antidiuretics detail STUDY
Diuretics and antidiuretics detail STUDY
NittalVekaria
 
Diuretics
DiureticsDiuretics
Diuretics
Aamna Tabassum
 
Diuretics
DiureticsDiuretics
Diuretics
DiureticsDiuretics
Diuretics : Dr Renuka Joshi MD,DNB, (FNB )
Diuretics : Dr Renuka Joshi MD,DNB, (FNB )Diuretics : Dr Renuka Joshi MD,DNB, (FNB )
Diuretics : Dr Renuka Joshi MD,DNB, (FNB )
Renuka Buche
 
DIURETICS.pptx
DIURETICS.pptxDIURETICS.pptx
DIURETICS.pptx
CarlZoghzoghi
 
Lecture 1 adithan diuretics july 22, 2016 mgmcri
Lecture 1 adithan diuretics july 22, 2016 mgmcriLecture 1 adithan diuretics july 22, 2016 mgmcri
Lecture 1 adithan diuretics july 22, 2016 mgmcri
Mahatma Gandhi Medical College & Hospital
 
4. Cardiovascular and Renal Pharmacology.pptx
4. Cardiovascular and Renal Pharmacology.pptx4. Cardiovascular and Renal Pharmacology.pptx
4. Cardiovascular and Renal Pharmacology.pptx
Fatima117039
 
Diureticss.pdf
Diureticss.pdfDiureticss.pdf
Diureticss.pdf
KookieJun
 
Diuretic_Diksha
Diuretic_DikshaDiuretic_Diksha
Diuretic_Diksha
Lalit Singh
 
Diuretics
Diuretics Diuretics
Pharmacology of diuretics including renal physiology.ppt
Pharmacology of diuretics including renal physiology.pptPharmacology of diuretics including renal physiology.ppt
Pharmacology of diuretics including renal physiology.ppt
Haftom Gebregergs Hailu
 
Diuretics
DiureticsDiuretics
Diuretics
Chintan Doshi
 
Lecture 1 adithan diuretics july 22, 2016 mgmcri
Lecture 1 adithan diuretics july 22, 2016 mgmcriLecture 1 adithan diuretics july 22, 2016 mgmcri
Lecture 1 adithan diuretics july 22, 2016 mgmcri
Mahatma Gandhi Medical College & Hospital
 
Diuretics
DiureticsDiuretics
Diuretics
Sushant Shete
 
2.Diuretics.pptx
2.Diuretics.pptx2.Diuretics.pptx
2.Diuretics.pptx
AmitPandit41
 
Drugs affecting renal excretory function
Drugs affecting renal excretory functionDrugs affecting renal excretory function
Drugs affecting renal excretory function
Prerna Singh
 
Diuretics
DiureticsDiuretics
Diuretics
Sujit Karpe
 
Diuretics new
Diuretics newDiuretics new
CHAPTER 1.pptx
CHAPTER 1.pptxCHAPTER 1.pptx
CHAPTER 1.pptx
mahediabdella
 

Similar to Diuretics (20)

Diuretics and antidiuretics detail STUDY
Diuretics and antidiuretics detail STUDYDiuretics and antidiuretics detail STUDY
Diuretics and antidiuretics detail STUDY
 
Diuretics
DiureticsDiuretics
Diuretics
 
Diuretics
DiureticsDiuretics
Diuretics
 
Diuretics
DiureticsDiuretics
Diuretics
 
Diuretics : Dr Renuka Joshi MD,DNB, (FNB )
Diuretics : Dr Renuka Joshi MD,DNB, (FNB )Diuretics : Dr Renuka Joshi MD,DNB, (FNB )
Diuretics : Dr Renuka Joshi MD,DNB, (FNB )
 
DIURETICS.pptx
DIURETICS.pptxDIURETICS.pptx
DIURETICS.pptx
 
Lecture 1 adithan diuretics july 22, 2016 mgmcri
Lecture 1 adithan diuretics july 22, 2016 mgmcriLecture 1 adithan diuretics july 22, 2016 mgmcri
Lecture 1 adithan diuretics july 22, 2016 mgmcri
 
4. Cardiovascular and Renal Pharmacology.pptx
4. Cardiovascular and Renal Pharmacology.pptx4. Cardiovascular and Renal Pharmacology.pptx
4. Cardiovascular and Renal Pharmacology.pptx
 
Diureticss.pdf
Diureticss.pdfDiureticss.pdf
Diureticss.pdf
 
Diuretic_Diksha
Diuretic_DikshaDiuretic_Diksha
Diuretic_Diksha
 
Diuretics
Diuretics Diuretics
Diuretics
 
Pharmacology of diuretics including renal physiology.ppt
Pharmacology of diuretics including renal physiology.pptPharmacology of diuretics including renal physiology.ppt
Pharmacology of diuretics including renal physiology.ppt
 
Diuretics
DiureticsDiuretics
Diuretics
 
Lecture 1 adithan diuretics july 22, 2016 mgmcri
Lecture 1 adithan diuretics july 22, 2016 mgmcriLecture 1 adithan diuretics july 22, 2016 mgmcri
Lecture 1 adithan diuretics july 22, 2016 mgmcri
 
Diuretics
DiureticsDiuretics
Diuretics
 
2.Diuretics.pptx
2.Diuretics.pptx2.Diuretics.pptx
2.Diuretics.pptx
 
Drugs affecting renal excretory function
Drugs affecting renal excretory functionDrugs affecting renal excretory function
Drugs affecting renal excretory function
 
Diuretics
DiureticsDiuretics
Diuretics
 
Diuretics new
Diuretics newDiuretics new
Diuretics new
 
CHAPTER 1.pptx
CHAPTER 1.pptxCHAPTER 1.pptx
CHAPTER 1.pptx
 

More from College of Pharmacy University of Sulaimani

L7 ans pharmacology 17 18
L7 ans pharmacology 17 18L7 ans pharmacology 17 18
L3 ans pharmacology 2017 2018
L3 ans pharmacology 2017 2018L3 ans pharmacology 2017 2018
L3 ans pharmacology 2017 2018
College of Pharmacy University of Sulaimani
 
L4 ans pharmacology 17 18
L4 ans pharmacology 17 18L4 ans pharmacology 17 18
L6 ans pharmacology 17 18
L6 ans pharmacology 17 18L6 ans pharmacology 17 18
L5 ans pharmacology 17 18
L5 ans pharmacology 17 18L5 ans pharmacology 17 18
L2 ans pharmacology 2017 2018
L2 ans pharmacology 2017 2018L2 ans pharmacology 2017 2018
L2 ans pharmacology 2017 2018
College of Pharmacy University of Sulaimani
 
Heart failure
Heart failureHeart failure
Antiarrythmic drugs
Antiarrythmic drugsAntiarrythmic drugs
Antianginal drugs
Antianginal drugsAntianginal drugs
Hyperlipidemia
HyperlipidemiaHyperlipidemia
L7
L7L7
L2
L2L2
L1: Drugs acting on the ANS
L1: Drugs acting on the ANSL1: Drugs acting on the ANS
L1: Drugs acting on the ANS
College of Pharmacy University of Sulaimani
 
L6: adrenergic neurotransmition/ agonists
L6: adrenergic neurotransmition/ agonistsL6: adrenergic neurotransmition/ agonists
L6: adrenergic neurotransmition/ agonists
College of Pharmacy University of Sulaimani
 
L5: Adrenergic agonists; sympathomimetics
L5: Adrenergic agonists; sympathomimeticsL5: Adrenergic agonists; sympathomimetics
L5: Adrenergic agonists; sympathomimetics
College of Pharmacy University of Sulaimani
 
L 4: Cholinergic antagonists
L 4: Cholinergic antagonistsL 4: Cholinergic antagonists
L 4: Cholinergic antagonists
College of Pharmacy University of Sulaimani
 
L3:cholinomimetics
L3:cholinomimeticsL3:cholinomimetics
L8: B-adrenergic blockers
L8: B-adrenergic blockersL8: B-adrenergic blockers
local anesthetics
local anestheticslocal anesthetics
Week 8 helping patients manage therapeutic regimens
Week 8 helping patients manage therapeutic regimensWeek 8 helping patients manage therapeutic regimens
Week 8 helping patients manage therapeutic regimens
College of Pharmacy University of Sulaimani
 

More from College of Pharmacy University of Sulaimani (20)

L7 ans pharmacology 17 18
L7 ans pharmacology 17 18L7 ans pharmacology 17 18
L7 ans pharmacology 17 18
 
L3 ans pharmacology 2017 2018
L3 ans pharmacology 2017 2018L3 ans pharmacology 2017 2018
L3 ans pharmacology 2017 2018
 
L4 ans pharmacology 17 18
L4 ans pharmacology 17 18L4 ans pharmacology 17 18
L4 ans pharmacology 17 18
 
L6 ans pharmacology 17 18
L6 ans pharmacology 17 18L6 ans pharmacology 17 18
L6 ans pharmacology 17 18
 
L5 ans pharmacology 17 18
L5 ans pharmacology 17 18L5 ans pharmacology 17 18
L5 ans pharmacology 17 18
 
L2 ans pharmacology 2017 2018
L2 ans pharmacology 2017 2018L2 ans pharmacology 2017 2018
L2 ans pharmacology 2017 2018
 
Heart failure
Heart failureHeart failure
Heart failure
 
Antiarrythmic drugs
Antiarrythmic drugsAntiarrythmic drugs
Antiarrythmic drugs
 
Antianginal drugs
Antianginal drugsAntianginal drugs
Antianginal drugs
 
Hyperlipidemia
HyperlipidemiaHyperlipidemia
Hyperlipidemia
 
L7
L7L7
L7
 
L2
L2L2
L2
 
L1: Drugs acting on the ANS
L1: Drugs acting on the ANSL1: Drugs acting on the ANS
L1: Drugs acting on the ANS
 
L6: adrenergic neurotransmition/ agonists
L6: adrenergic neurotransmition/ agonistsL6: adrenergic neurotransmition/ agonists
L6: adrenergic neurotransmition/ agonists
 
L5: Adrenergic agonists; sympathomimetics
L5: Adrenergic agonists; sympathomimeticsL5: Adrenergic agonists; sympathomimetics
L5: Adrenergic agonists; sympathomimetics
 
L 4: Cholinergic antagonists
L 4: Cholinergic antagonistsL 4: Cholinergic antagonists
L 4: Cholinergic antagonists
 
L3:cholinomimetics
L3:cholinomimeticsL3:cholinomimetics
L3:cholinomimetics
 
L8: B-adrenergic blockers
L8: B-adrenergic blockersL8: B-adrenergic blockers
L8: B-adrenergic blockers
 
local anesthetics
local anestheticslocal anesthetics
local anesthetics
 
Week 8 helping patients manage therapeutic regimens
Week 8 helping patients manage therapeutic regimensWeek 8 helping patients manage therapeutic regimens
Week 8 helping patients manage therapeutic regimens
 

Recently uploaded

How to choose the best dermatologists in Indore.
How to choose the best dermatologists in Indore.How to choose the best dermatologists in Indore.
How to choose the best dermatologists in Indore.
Gokuldas Hospital
 
Breast cancer: Post menopausal endocrine therapy
Breast cancer: Post menopausal endocrine therapyBreast cancer: Post menopausal endocrine therapy
Breast cancer: Post menopausal endocrine therapy
Dr. Sumit KUMAR
 
What is Obesity? How to overcome Obesity?
What is Obesity? How to overcome Obesity?What is Obesity? How to overcome Obesity?
What is Obesity? How to overcome Obesity?
Healthmedsrx.com
 
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdfTest bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
rightmanforbloodline
 
Post-Menstrual Smell- When to Suspect Vaginitis.pptx
Post-Menstrual Smell- When to Suspect Vaginitis.pptxPost-Menstrual Smell- When to Suspect Vaginitis.pptx
Post-Menstrual Smell- When to Suspect Vaginitis.pptx
FFragrant
 
Recent advances on Cervical cancer .pptx
Recent advances on Cervical cancer .pptxRecent advances on Cervical cancer .pptx
Recent advances on Cervical cancer .pptx
DrGirishJHoogar
 
NARCOTICS- POLICY AND PROCEDURES FOR ITS USE
NARCOTICS- POLICY AND PROCEDURES FOR ITS USENARCOTICS- POLICY AND PROCEDURES FOR ITS USE
NARCOTICS- POLICY AND PROCEDURES FOR ITS USE
Dr. Ahana Haroon
 
Call Girls In Mumbai +91-7426014248 High Profile Call Girl Mumbai
Call Girls In Mumbai +91-7426014248 High Profile Call Girl MumbaiCall Girls In Mumbai +91-7426014248 High Profile Call Girl Mumbai
Call Girls In Mumbai +91-7426014248 High Profile Call Girl Mumbai
Mobile Problem
 
Pollen and Fungal allergy: aeroallergy.pdf
Pollen and Fungal allergy: aeroallergy.pdfPollen and Fungal allergy: aeroallergy.pdf
Pollen and Fungal allergy: aeroallergy.pdf
Chulalongkorn Allergy and Clinical Immunology Research Group
 
Artificial Intelligence Symposium (THAIS)
Artificial Intelligence Symposium (THAIS)Artificial Intelligence Symposium (THAIS)
Artificial Intelligence Symposium (THAIS)
Josep Vidal-Alaball
 
What are the different types of Dental implants.
What are the different types of Dental implants.What are the different types of Dental implants.
What are the different types of Dental implants.
Gokuldas Hospital
 
NAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdf
NAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdfNAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdf
NAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdf
Rahul Sen
 
“Psychiatry and the Humanities”: An Innovative Course at the University of Mo...
“Psychiatry and the Humanities”: An Innovative Course at the University of Mo...“Psychiatry and the Humanities”: An Innovative Course at the University of Mo...
“Psychiatry and the Humanities”: An Innovative Course at the University of Mo...
Université de Montréal
 
Physical demands in sports - WCSPT Oslo 2024
Physical demands in sports - WCSPT Oslo 2024Physical demands in sports - WCSPT Oslo 2024
Physical demands in sports - WCSPT Oslo 2024
Torstein Dalen-Lorentsen
 
Computer in pharmaceutical research and development-Mpharm(Pharmaceutics)
Computer in pharmaceutical research and development-Mpharm(Pharmaceutics)Computer in pharmaceutical research and development-Mpharm(Pharmaceutics)
Computer in pharmaceutical research and development-Mpharm(Pharmaceutics)
MuskanShingari
 
Know the difference between Endodontics and Orthodontics.
Know the difference between Endodontics and Orthodontics.Know the difference between Endodontics and Orthodontics.
Know the difference between Endodontics and Orthodontics.
Gokuldas Hospital
 
Nano-gold for Cancer Therapy chemistry investigatory project
Nano-gold for Cancer Therapy chemistry investigatory projectNano-gold for Cancer Therapy chemistry investigatory project
Nano-gold for Cancer Therapy chemistry investigatory project
SIVAVINAYAKPK
 
CBL Seminar 2024_Preliminary Program.pdf
CBL Seminar 2024_Preliminary Program.pdfCBL Seminar 2024_Preliminary Program.pdf
CBL Seminar 2024_Preliminary Program.pdf
suvadeepdas911
 
acne vulgaris -Mpharm (2nd semester) Cosmetics and cosmeceuticals
acne vulgaris -Mpharm (2nd semester) Cosmetics and cosmeceuticalsacne vulgaris -Mpharm (2nd semester) Cosmetics and cosmeceuticals
acne vulgaris -Mpharm (2nd semester) Cosmetics and cosmeceuticals
MuskanShingari
 
Histololgy of Female Reproductive System.pptx
Histololgy of Female Reproductive System.pptxHistololgy of Female Reproductive System.pptx
Histololgy of Female Reproductive System.pptx
AyeshaZaid1
 

Recently uploaded (20)

How to choose the best dermatologists in Indore.
How to choose the best dermatologists in Indore.How to choose the best dermatologists in Indore.
How to choose the best dermatologists in Indore.
 
Breast cancer: Post menopausal endocrine therapy
Breast cancer: Post menopausal endocrine therapyBreast cancer: Post menopausal endocrine therapy
Breast cancer: Post menopausal endocrine therapy
 
What is Obesity? How to overcome Obesity?
What is Obesity? How to overcome Obesity?What is Obesity? How to overcome Obesity?
What is Obesity? How to overcome Obesity?
 
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdfTest bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
Test bank for karp s cell and molecular biology 9th edition by gerald karp.pdf
 
Post-Menstrual Smell- When to Suspect Vaginitis.pptx
Post-Menstrual Smell- When to Suspect Vaginitis.pptxPost-Menstrual Smell- When to Suspect Vaginitis.pptx
Post-Menstrual Smell- When to Suspect Vaginitis.pptx
 
Recent advances on Cervical cancer .pptx
Recent advances on Cervical cancer .pptxRecent advances on Cervical cancer .pptx
Recent advances on Cervical cancer .pptx
 
NARCOTICS- POLICY AND PROCEDURES FOR ITS USE
NARCOTICS- POLICY AND PROCEDURES FOR ITS USENARCOTICS- POLICY AND PROCEDURES FOR ITS USE
NARCOTICS- POLICY AND PROCEDURES FOR ITS USE
 
Call Girls In Mumbai +91-7426014248 High Profile Call Girl Mumbai
Call Girls In Mumbai +91-7426014248 High Profile Call Girl MumbaiCall Girls In Mumbai +91-7426014248 High Profile Call Girl Mumbai
Call Girls In Mumbai +91-7426014248 High Profile Call Girl Mumbai
 
Pollen and Fungal allergy: aeroallergy.pdf
Pollen and Fungal allergy: aeroallergy.pdfPollen and Fungal allergy: aeroallergy.pdf
Pollen and Fungal allergy: aeroallergy.pdf
 
Artificial Intelligence Symposium (THAIS)
Artificial Intelligence Symposium (THAIS)Artificial Intelligence Symposium (THAIS)
Artificial Intelligence Symposium (THAIS)
 
What are the different types of Dental implants.
What are the different types of Dental implants.What are the different types of Dental implants.
What are the different types of Dental implants.
 
NAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdf
NAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdfNAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdf
NAVIGATING THE HORIZONS OF TIME LAPSE EMBRYO MONITORING.pdf
 
“Psychiatry and the Humanities”: An Innovative Course at the University of Mo...
“Psychiatry and the Humanities”: An Innovative Course at the University of Mo...“Psychiatry and the Humanities”: An Innovative Course at the University of Mo...
“Psychiatry and the Humanities”: An Innovative Course at the University of Mo...
 
Physical demands in sports - WCSPT Oslo 2024
Physical demands in sports - WCSPT Oslo 2024Physical demands in sports - WCSPT Oslo 2024
Physical demands in sports - WCSPT Oslo 2024
 
Computer in pharmaceutical research and development-Mpharm(Pharmaceutics)
Computer in pharmaceutical research and development-Mpharm(Pharmaceutics)Computer in pharmaceutical research and development-Mpharm(Pharmaceutics)
Computer in pharmaceutical research and development-Mpharm(Pharmaceutics)
 
Know the difference between Endodontics and Orthodontics.
Know the difference between Endodontics and Orthodontics.Know the difference between Endodontics and Orthodontics.
Know the difference between Endodontics and Orthodontics.
 
Nano-gold for Cancer Therapy chemistry investigatory project
Nano-gold for Cancer Therapy chemistry investigatory projectNano-gold for Cancer Therapy chemistry investigatory project
Nano-gold for Cancer Therapy chemistry investigatory project
 
CBL Seminar 2024_Preliminary Program.pdf
CBL Seminar 2024_Preliminary Program.pdfCBL Seminar 2024_Preliminary Program.pdf
CBL Seminar 2024_Preliminary Program.pdf
 
acne vulgaris -Mpharm (2nd semester) Cosmetics and cosmeceuticals
acne vulgaris -Mpharm (2nd semester) Cosmetics and cosmeceuticalsacne vulgaris -Mpharm (2nd semester) Cosmetics and cosmeceuticals
acne vulgaris -Mpharm (2nd semester) Cosmetics and cosmeceuticals
 
Histololgy of Female Reproductive System.pptx
Histololgy of Female Reproductive System.pptxHistololgy of Female Reproductive System.pptx
Histololgy of Female Reproductive System.pptx
 

Diuretics

  • 1. 1 DIURETICS Dr. Hiwa K. Saaed PhD Pharmacology & Toxicology
  • 2. Diuretics: • mainly promotes the excretion of the (Na+), (Cl-) or (HCO3-) and water, • the net result being: – Increase the urine flow, – change urine pH – change the ionic composition of the urine and blood.
  • 3. Drugs used in renal disorders I. drugs that modify salt excretion: A. PCT: carbonic anhydrase inhibitors B. TAL: loop diuretics C. DCT: thiazides D. CCT; K-spairing diuretics E. Osmotic diuretics; manitol II. Drugs that modify water excretion A. Osmotic diuretics: manitol B. ADH agonists: desmopressin C. ADH antagonists: conivaptan, demeclocycline, lithium
  • 4. Diuretics: Diuretics are very effective in the treatment of: • Edema: CHF, pregnancy, & nutritional • nephrotic syndrome • diabetes insipidus • hypertension • cirrhosis of liver • and also lower the intracellular and CSF pressure. 4
  • 5. 5 Introduction • Kidney: 1.3 million nephron each • Glomerular filtration: – Receive 25% of cardiac output – Filtration rate: 100-120 ml/minute – 180 L of glomerular filtrate/day • Tubular reaborption: – Reabsorption of 99% of glomerular filtrate  only + 1 ml/min excreted as urine – 1.5 L/day of urine. • Tubular secretion
  • 6. The excretion by kidney is dependent on: glomerular filtration, tubular reabsorption and tubular secretion. 6
  • 7. 7
  • 8. 8 Introduction • Proximal tubules: – Reabsorption of 60-70% Na+ – Permeable to water  isotonic urine – Isosmotic reabsorption of amino acids, glucose, cations • Loop of Henle: – Thin descending limb: most active water reabsorption – Thick ascending limb: • Reabsorption of Na+, • Water impermeable  diluting segment • Distal tubules: – Na+ reabsorption • Collecting duct: selectively water permeable
  • 9. Diuretic Drug Groups • the diuretics acting in these segments each have different MOA ? b the mechanism for reabsorption of salt & water different in each 4 segments, • Most diuretics act from the luminal site of the membrane & must be present in the urine: – They are filtered at the glomerulus – some are also sec by the weak acid sec in the proximal tubule, – an exception is the aldosterone receptor antagonist enter CCT from basolateral side. 9
  • 10. Electrolyte Transport and Site of Action of Diuretics
  • 11. 11 Site and Mechanisms of Actions of Diuretics Diuretics Site of Action Mechanism Osmotic Diuretic 1. Proximal tubules 2. Loop of Henle 3. Collecting duct Inhibition of water and Na+ reabsorption Carbonic Anhydrase Inhibitor (CA-I) Proximal tubules Inhibition of bicarbonate reabsorption Loop Diuretic Loop of Henle (thick ascending limb) Inhibition of Na+, K+, Cl- cotransport Thiazide Early distal tubule Inhibition of Na+, Cl- cotransport K+ sparing diuretics Late distal tubule Collecting duct Inhibition of Na+ reabsorption and K+ secretion
  • 12. 12 Carbonic Anhydrase Inhibitor Acetazolamide (S derivatives) Mechanism of Actions • Kidney: self limited diuresis 2-3 days – Carbonic anhydrase catalyzes : CO2+H2O H2CO3 – H+ ion produced by the breakdown of H2CO3, exchanged for Na+ & is also combined with HCO3 - in the lumen of the PCT – Inhibition of Bicarbonate (HCO3 -) reabsorption – Reduces Na+-H+-exchange  NaHCO3 is excreted along with H2O
  • 14. 14 Adverse Effects and Contraindications • Metabolic acidosis • Renal stones (Phosphate and Calcium stone) • Renal potassium wasting; (NaHCO3 - ) enhances K+ secretion • Diuresis is self limiting within 2-3 days? • AE: Drowsiness, paresthesia, disorientation, renal stone (in case of urine alkalinization) Contraindication – Liver cirrhosis (CA-I inhibits conversion of NH3 to NH4)  NH3 increased  encephalopathy
  • 15. 15 Indications of CA-I • Glaucoma (Eye: not self limiting effect) – Orally acetazolamide – Topically dorzolamide, brinzolamide • Prevent mountain sickness (high altitude) sickness inhibit sec of bicarbonate by the choroid plexus; Acidosis of the CSF results in hyperventilation • Urinary alkalinization: preventing uric acid and cystine stones • Used for their diuretic effect only if edema is accompanied by significant Metabolic alkalosis
  • 16. 16 Thiazides • Hydrochlorothiazide (prototype), Chlorothiazide, Bendroflumethiazide, Chlorthalidone, Metolazone, Indapamide • All are sulfonamide derivatives, t1/2 6-12 hrs Mechanism of Actions – Thiazides are secreted by proximal tubules but works in DCT – Inhibit Na+-Cl- symporter from the lumen to tubular cells  increase Na+, Cl- excretion (and water) – Some thiazides have weak CA-I effect
  • 17. 17 Mechanism of Action of Thiazide
  • 18. 18 Effects on Electrolytes • Increases Na+ and Cl- excretion • Hypokalemic metabolic alkalosis; K+ excretion also increase associated w/ increased Na+ in distal tubules. • Inhibits uric acid secretion hyperuricemia and gout • Decreases Ca2+ excretion  tends to increase plasma Ca++  Retards osteoporotic process • Increases Mg2+ excretion
  • 19. 19 – Hypo K+  Increased risk of digitalis toxicity – Hypo Na+, Hypo Mg++ – Hyperuricemia  caution in gout arthritis – Hyperglycemia and hypercholesterolemia  not favorable for DM and dyslipidemia (although not contraindicated) – (Indapamid has less effects on lipid and uric acid) – Hypercalcemia (long-term)  good for elderly – Sexual dysfunction Adverse Effects
  • 20. 20 Interactions • Increases the risk of arrhythmia when combined w/ digitalis, quinidine and other antiarrhythmias • Reduces efficacy of anticoagulant and uricosuric • Reduces the efficacy oral antidiabetics • NSAID reduce the efficacy of thiazide
  • 21. 21 Indications of Thiazides • Hypertension (single drug or in combination) • Chronic, mild- heart failure • Edema (loop diuretic is preferable) • Nephrogenic Diabetes insipidus • Prevention of Ca++ excretion in osteoporosis and calcium nephrolithiasis
  • 22. 22 Loop Diuretics • Furosemide, torasemide, bumetanide: Are sulfonamide derivatives • ethacrynic acid is a phenoxyacetic acid derivative • Site of action: thick ascending limb of Henle • Mechanism: – Loop diuretics should be excreted into the lumen – Inhibits Na+, K+, 2Cl- symporter  significantly increases the excretion of Na+, K+, Cl- – Osmotic gradient for water reabsorption is also decreased  increasing water excretion – Ca2+ and Mg2+ are excreted as well.
  • 23. 23 Mechanism of Action of Loop Diuretic
  • 24. 24 Interactions • Concomitant use w/ aminoglycoside or cisplatin increases the risk of nephrotoxicity and ototoxicity • PGs are important in maintaining GF; NSAID reduces the effects of diuretics • Probenecid reduces the effects of diuretics by inhibiting its secretion into the lumen.
  • 25. 25 Indications • Congestive heart failure (1st line drug) • Acute pulmonary edema • Edema due to renal failure, nephrotic syndrome, ascites • Hypercalcemia (that induced by malignancy) • Severe hypertension • Force diuresis during drug/chemical intoxication (drug that excreted through the kidney in active form)
  • 26. Adverse effects • Hypovolemic metabolic alkalosis • Ototoxicity • Typical sulfonamide allergy 26
  • 27. 27 Potassium Sparing Diuretics 1. Na+ channel inhibitor (Amiloride, triamterene)  Inhibit Na+ reabsorption  Na+ excretion  Reduced K+ secretion  K+ retention 2. Aldosterone antagonist (Spironolactone, eplerenone) Steroid derivatives – Aldosterone induces the expression of Na/K- ATPase and Na+ channel – Spironolactone and eplerenone blocks aldosterone receptor  reduces Na+ reabsorption and K+ secretion
  • 29. 29 • Potassium sparing diuretic has a weak diuretic action • Usually used in combination w/ other diuretic: – Potentiation of diuretic and antihypertensive effects – Prevents hypokalemia • Spironolactone is metabolized to its active metabolite, canrenone. • Long term use of spironolactone can prevent myocardial hypertrophy and myocardial fibrosis Potassium Sparing Diuretics
  • 30. 30 Adverse Effects Spironolactone • Hyperkalemia • Antiandrogenic effect » gynecomastia, » decrease of libido, impotence, » menstrual disturbance. • Megaloblastic anemia: Triamterene (folate antagonist)
  • 31. 31 INDICATIONS • Antihypertension: – In combination w/ other antihypertensives – To increase the effect and to prevent hypokalemia – Aldosteronism (that occur in cirrhosis) CONTRAINDICATIONS/PRECAUTIONS • Conditions that prone to hyperkalemia: – Renal failure – Should never be combined with ACE-inhibition, ARB, NSAID, K+ supplementation
  • 32. 32 Osmotic Diuretics (OD) • Mannitol (prototype), • Others rarely used: urea, glycerin, isosorbide • Properties of osmotic diuretics: – Freely filtrated by glomerulus – Negligible tubular reabsorption – Chemically inert – Usually non metabolized
  • 33. 33 Pharmacokinetics • Mannitol and urea: intravenous • Glycerin and isosorbide: Can be administered orally • Metabolism: – glycerin 80% metabolized – mannitol 20% – Urea, isosorbide: not metabolized • Excretion: renal
  • 34. 34 Mechanism of Action • OD is filtrated and increases osmotic pressure in tubular lumen • Hence, increases excretion of water and electrolytes (Na+, K+, Ca++, Mg++, HCO3 -, phosphate) ↑volume of urine & rate of urine flow through the tubule • Mannitol can also reduce brain volume and intracranial pressure by osmotically extracting water from the tissue into the blood • A similar effect occurs in the eye
  • 35. 35 Indications • Glaucoma (rare) ↓IOP • Brain edema ↓brain volume & pressure – mannitol and urea are given before and after brain surgery • Disequilibrium syndrome after hemodialysis • Solute overload in sever hemolysis and rhabdomyolysis • Prophylaxis of ATN (acute tubular necrosis) due to contrast media, surgery, and trauma. – NaCl 0.45% can also be used
  • 36. 36 Adverse Effects • Removal of water from the I.C compartments  Initial increase of plasma volume  potentially dangerous in heart failure and pulmonary edema  Hypo Na+  headache, nausea, vomiting • Water exc.  Hypovolemia  hypernatremia • Hypersensitivity reaction • Vein thrombosis, pain if extravasation (urea) • Hyperglycemia, glycosuria (glycerin)
  • 37. 37 Antidiuretic Hormone (ADH) Agonists and Antagonists • ADH & Desmopressin are ADH Agonists • Peptides must be given parenterally(rapid degradation by trypsin) • Secretion of ADH increase in response to: –  Plasma osmolarity – Hypovolemia, hypotension (bleeding, dehydration) • Demeclocycline and conivaptan are ADH antagonists • Lithium has ADH antagonist effect but never used for this purpose
  • 38. 38 Mechanism of Action • Works in ascending limb of Henle’s loop and collecting ducts • Two kind of receptors: – V1: vascular smooth muscle vasoconstriction – V2: kidney  increase water permeability of tubular epithelium  water reabsorption
  • 39. ADH • ADH facilitates water reabsorption from the collecting tubule by: • activation of V2 receptors(coupled to GS, stimulate AC) increase cAMP • cause insertion of additional aquaporin AQP2 water channels into the luminal membrane in this part of the tubule 39
  • 40.
  • 41. ADH antagonists • Conivaptan is an ADH inhibitor at V1a and V2 receptors • Demeclocycline and Li inhibit the action of ADH at some point distal to the generation of cAMP and presumably the insertion of water channels into the membrane. 41
  • 42. 42 Clinical uses of ADH Agonists • ADH and desmopressin reduce urine volume and concentrate it, are useful in Pitutary Diabetes Insipidus (not for nephrogenic DI Rx by salt restriction, thizides and loop diuretics) • DI due to head trauma or brain surgery • Gastrointestinal bleeding due to portal hypertension (by reducing mesenteric blood flow)
  • 43. Clinical uses of ADH Antagonists • Oppose the actions of ADH and other naturally occurring peptides (certain tumors; small cell carcinoma of the lung) that act on the same V2 receptors, significant water retention and dangerous hyponatremia. • Syndrome of inappropriate ADH secretion (SIADH) can be treated with demeclocycline and conivaptan 43
  • 44. Adverse effects • ADH, Desmopressin, water overload, hyponatremia • Demeclocycline: bone and teeth abnormalities • Li: nephrogenic DI 44
  • 45.