Diuretic Drugs Flashcards
Basic Actions of Diuretics
Increase rate of urine flow
Act primarily by decreasing Na reabsorption–> decrease
reabsorption of Cl- and water
Except osmotic diuretics: salturetics primarily (increase NaCl excretion), diuretics secondarily (increase water excretion)
Overview: Clinical Use of Diuretics
Decrease ECM volume
Systemic Oedema vs Localised Oedema
Decrease BP
Chronic vs Acute Hypertension
Increase Excretion of Inorganic Ions
Hypercalcaemia
Lithium Intoxication
Bromide Intoxication
Prevent Anuria in Acute Renal Failure
Other Indications
Calcium Nephrolithiasis
Osteoporosis
Epilepsy (decrease CO2 conc in brain)
Metabolic Alkalosis (increase NaHCO3 excretion)
Classification of Diuretics
Based on Intensity of Diuretic Effect
Highly Effective
Loop Diuretics
Mannitol Infusion
Moderately Effective
Thiazide and Thiazide- Like Drugs
Weak Diuretics
Carbonic Anhydrase Inhibitors
Na Channel Inhibitors
Aldosterone Antagonists
Classification of Diuretics
Based on Alteration of K+ Excretion
K+ and H+ Losing Drugs
Loop Diuretics
Thiazide and Thiazide Like Drugs
K+ and H+ Sparing Drugs
Na Channel Inhibitors
Aldosterone Antagonists
Classification of Diuretics
Based on Site and Mechanism of Action
Osmotic Diuretics
Carbonic Anhydrase Inhibitors
Loop Diuretics
Osmotic Diuretics
Act: EC Space (systemic) and Leaky segments (renally)
Doesn’t have target molecule
Decrease IC water space and water reabsorption
Carbonic Anhydrase Inhibitors
Act: Proximal Convoluted Tubule
Target: Carbonic Anhydrase (Luminal and IC)
Decrease H+ section and NaHCO3 reabsorption
Loop Diuretics
Act: Loop of Henle, thick ascending limb
Target: Na/K/2Cl Symporter
Decrease Na, Cl, Mg, Ca reabsorption, increase K and
H secretion in distal convoluted tubule
Classification of Diuretics
Based on Site and Mechanism of Action
Thiazide and Thiazide-Like Drugs
Na Channel Antagonists
Aldosterone Antagonists
Thiazide and Thiazide- Like Drugs
Act: Distal Convoluted Tubule
Target: Na/Cl Symporter
Decrease Na, Cl, Mg reabsorption, increase Ca
reabsorption, Increase K and H secretion in distal
convoluted tubule
Na Channel Antagonists
Act: DCT and Collecting Duct
Target: Epithelial Na Channel
Decrease Na reabsorption and K and H secretion into
the DCT
Aldosterone Antagonists
Act: DCT and Collecting Duct
Target: Mineralocorticoid Receptor
Decrease Na reabsorption and K and H secretion into
the DCT
Why are Loop Diuretics most affective?
Ascending Limb of Loop of Henle has very high absorptive capacity
Osmotic Diuretics
Chemical and Pharmacokinetic Properties: Mannitol
Mechanism of Action
Chemical and Pharmacokinetic Properties: Mannitol
Small water soluble molecule: sugar alcohol
Inert compound–> can be given in large doses
Not permeable across the cell membrane, therefore:
Not absorbed orally: Given IV
Distributed in EC space
Not reabsorbed in tubule
Mechanism of Action:
EC Space: increase osmolarity of plasma and EC water:
Extracts water from IC space–> increase EC volume
Increases renal blood flow–> increase GFR and blood
flow of vasa recta
–> washing out of NaCl in interstitium of medulla–>
decrease corticomedullary gradient–> decrease
water reabsorption from leaky descending limb
LOH–> diuresis
–> Primarily diuretics and secondarily salturetics (due to dilution of tubular flow and increased tubular flow)
Indication of Osmotic Diuretic Treatment
Prevention of Anuria in Acute Renal Failure
Give test dose first, if diuresis is produced–> continue
If ineffective: stop as to prevent over-expansion of ECV
Treatment of Acute Cerebral Oedema and Glaucoma
Extraction of water–> lower intracranial and IO
pressure (example pre and post OP)
Treatment of Dialysis Disequilibrium Syndrome
Aggressive haemodialysis–> removal of solutes from
ECV–> water flows into cell–> water intoxication like
symptom: IC pressure increase, EC hypovolemia
Treatment of Cystic Fibrosis
Inhalation of dry mannitol powder–> dilution of viscous
bronchial fluid–> promote mucociliary clearance
Side Effects and Contraindications of Osmotic Diuretics
Side Effects:
Overdose Induced Overexpansion of EC Fluid
Increase load on heart + pulmonary oedema
–> furosemide would be better
Contraindications:
Not given in anuria and HF: due to overloading danger
Urea: Not in cirrhosis as may inhibit arginase–> impairs
elimination of NH3 in Urea Cycle
Glycerin: Not in diabetes: is a gluconeogenic substance
Mannitol and Urea: not in IC bleeding: may cause
increase intravascular volume –> worsening
bleeding
Osmotic Diuretics and their Characteristics
Mannitol
Urea: IV
Brain Oedema, Acute Glaucoma
Excreted renally
Glycerin: Oral
Metabolised in liver too
Isosorbide: Oral
Acute Glaucoma
Excreted Renally
Effects mediated by physiochemical interactions
Carbonic Anhydrase Inhibitors
General Properties
Mechanism of Action
General Properties:
Weak Diuretics
Are organic acids with an aminosulfonic acid group
Mechanism of Action:
H2CO3H2O+CO2
Act on proximal tubule
In the lumen: H+ secreted from cell across the luminal
membrane by Na-H exchanger; HCO3 is filtered at
glomeruli
Spontaneous reaction: H+ + HCO3--> H2CO3 CA catalysed reaction: H2CO3--> H2O + CO2 CO2 then diffused into cell
In the cell:
CA catalysed reaction: H2O+CO2–> H2CO3
Spontaneous reaction: H2CO3–> H+ + HCO3
H+ is excreted (Na/H Exchanger)
Na and HCO3 are reabsorbed (Na/HCO3 symporter)
Net Result of CA and CA Inhibitors
CA: Secretion H, reabsorption Na and HCO3
CA I: Retention H, excretion Na and CO3
Carbonic Anhydrase Inhibitors
Effects of prototype: Acetazolamide
Kidney:
Decreased NaHCO3 reabsorption: weak diuresis
limited because urinary loss of HCO3 depletes EC
HCO3–> less HCO3 filtered in glomeruli
Eye:
H2O+CO2–> H2CO3–> H + HCO3
Secretion of bicarbonate–> formation of aqueous
humor
Decreasing production–> th: open angle glaucoma
RBC:
H2O+CO2--> H2CO3--> H + HCO3
Transport of CO2 by RBC--> Lungs
Acetazolamide--> increases CO2 in tissue incl CNS
In CNS: CO2: weak GA effect
Carbonic Anhydrase Inhibitors
Pharmacokinetics of Acetazolamide
Side Effects
Drug Interactions
Pharmacokinetics of Acetazolamide:
Complete oral bioavailability and GIT absorption
High PPB and low lipid solubility–> low Vd
Elim: unchanged in urine by basolat. OAT and apical
OAT4/MRP4
Side Effects:
Somnolence and parasthesia (effect of CO2 in brain)
Formation of Ca3(PO4)2 containing calculi in UT
due to increased phosphate excretion into urine and
increased phosphate ionisation
Drug Interactions:
Alkalisation of tubular fluid by CA I–>
Tubular reabsorption of weak basic drugs promoted
Amphetamine for example–> delayed elimination
Tubular reabsorption of weak acid drugs decreased
Aspirin for example--> promotes excretion
Indications for CA I use
Often in combo with other diuretics
Open Angle Glaucoma
Epilepsy as adjuvant therapy
Altitude Sickness (symp caused by low CO2–> alkalosis
