acetazolamide
Carbonic Anhydrase Inhibitor
Proximal Tubule
Effects on Excretion:
Based on the sulfanilamide chemotherapeutic drugs
Potassium Wasting: due to high Na+ delivery to distal nephron
Indicatoins:
Adverse Reaction:
chlorothiazide
Thiazide/thiazide like agent
Sulfonamine analog
Block NaCl symport but not K
Enters urine via organic ion transporters in PROXIMAL TUBULE (OATs)
DISTAL CONVOLUTED TUBULE
Very common
Potassium Wasting
Energy for transporter affected still Na/K ATPase
Effects on Excretion:
Moderately effective due to 90% of Na has already been reabsorbed before DCT
Act distal to macula so are not limited by TGF (tuberoglomerular feedback)
Increase Ca plasma with chronic use
Medullary Salt conc not affected so water retention is preserved
Half Life: 1.5 hours
Indications:
- Hypertension: due to not risking hypovolemia
- Edema associated with CHF
- Daily Dosing
- Safe, but small risk of sudden death and renal cell carcinoma
- Calcium reabsorption is
increased SO CAN BE USED TO TREAT calcium nephrolithiasis, and aid in treatment of osteoporosis
- Unknown reasons drug treats, nephrogenic diabetes insipidus, (reduces urine volume by 50%)
Adverse effects:
Corticosteroids and amphotericin B increase risk of significant hypokalemia and cardiac arrthymias
Probenecid may increase effective dose
May decrease glucose tolerance and unmask diabetes mellitus
Rare CNS and GI effects and ED
hydrochlorothiazide
Thiazide/thiazide like agent
Sulfonamine analog
Block NaCl symport but not K
Enters urine via organic ion transporters in PROXIMAL TUBULE (OATs)
DISTAL CONVOLUTED TUBULE
Very common
Potassium Wasting
Energy for transporter affected still Na/K ATPase
Effects on Excretion:
Moderately effective due to 90% of Na has already been reabsorbed before DCT
Act distal to macula so are not limited by TGF (tuberoglomerular feedback)
Increase Ca plasma with chronic use
Medullary Salt conc not affected so water retention is preserved
Half Life: 2.5 hours
Indications:
- Hypertension: due to not risking hypovolemia
- Edema associated with CHF
- Daily Dosing
- Safe, but small risk of sudden death and renal cell carcinoma
- Calcium reabsorption is
increased SO CAN BE USED TO TREAT calcium nephrolithiasis, and aid in treatment of osteoporosis
- Unknown reasons drug treats, nephrogenic diabetes insipidus, (reduces urine volume by 50%)
Adverse effects:
Corticosteroids and amphotericin B increase risk of significant hypokalemia and cardiac arrthymias
Probenecid may increase effective dose
May decrease glucose tolerance and unmask diabetes mellitus
Rare CNS and GI effects and ED
HYDROCHLOROTHIAZIDE VERY COMMON FOR ACUTE DIURESIS WITH EDEMA
metolazone
Thiazide like Diuretic
Sulfonamine analog
Block NaCl symport but not K
Enters urine via organic ion transporters in PROXIMAL TUBULE (OATs)
DISTAL CONVOLUTED TUBULE
Very common
Potassium Wasting
Energy for transporter affected still Na/K ATPase
Effects on Excretion:
Moderately effective due to 90% of Na has already been reabsorbed before DCT
Act distal to macula so are not limited by TGF (tuberoglomerular feedback)
Increase Ca plasma with chronic use
Medullary Salt conc not affected so water retention is preserved
Half Life: 20 hours
- Longer acting good for HYPERTENSION
Indications:
- Hypertension: due to not risking hypovolemia
- Edema associated with CHF
- Daily Dosing
- Safe, but small risk of sudden death and renal cell carcinoma
- Calcium reabsorption is
increased SO CAN BE USED TO TREAT calcium nephrolithiasis, and aid in treatment of osteoporosis
- Unknown reasons drug treats, nephrogenic diabetes insipidus, (reduces urine volume by 50%)
Adverse effects:
Corticosteroids and amphotericin B increase risk of significant hypokalemia and cardiac arrthymias
Probenecid may increase effective dose
May decrease glucose tolerance and unmask diabetes mellitus
Rare CNS and GI effects and ED
bumetanide
Loop Diuretic
Short Half Life: 0.8 hours
Elimination:
High Ceiling diuretic
Indications:
Adverse Reactions:
ethacrynic acid
Loop Diuretic
Short Half Life: 1 hour
Elimination:
High Ceiling diuretic
Indications:
Adverse Reactions:
furosemide
Loop Diuretic
Short Half Life: 1.5 hours
Elimination:
MAJOR DRUG OF LOOP
ALSO weak carb anhydrase inhibitor
Acutely increases systemic venous capacitance (useful in heart failure and pulmonary edema)
UNIQUE: Glucoronidated in KIDNEY not liver
High Ceiling diuretic
Indications:
Adverse Reactions:
torsemide
Loop Diuretic
Short Half Life: 3.5 hours
Elimination: (MAJOR DIFF)
High Ceiling diuretic
Indications:
Adverse Reactions:
amiloride
K sparing agent
Inhibits renal Na Channel
- Most Common agent of this group
Cause small increase in NaCl excretion
Blocking the luminal Na channel drops K secretion by blocking depolarization of luminal membrane which drives K secretion
Inhibits H secretion also by raising intra-luminal positive potential
Half Life: 21 Hours
Renal Excretion
Indications:
Treat LIDDLEs syndrome (hypokalemia due to increased Na Transport)
Used as aerosol in cystic fibrosis to clear mucus
Adverse Reaction
Some diffuse CNS, GI, Dermatological, hematological effects
NSAIDS may decrease efficiency
Blocks uptake of Lithium by Na channels in collecting duct
- Used for lithium induced nephrogenic diabetes insipidus
eplerenone
K sparing agent
Mineralcorticoid antagonist
Competitively bind the mineralcorticoid receptor and block function
Secreted by adrenal glands and cause retention of salt and water while increasing excretion of K and Protons
Primary sites of activity are in Distal Convoluted Tubule and Collecting Duct
Compete with Aldosterone
Aldosterone acts in nucleus to change DNA expression of AIP (aldosterone induced proteins)
AIPs activate previously silent Na channels and pumps promoting reuptake of Na and H20
- Induced in response to dehydration
Effects on Excretion:
Clearance significantly decreased by INHIBITORS of CYP3A4
Adverse effects:
spironolactone
K sparing agent
Mineralcorticoid antagonist
- MAJOR REPRESENTATIVE OF CLASS
Competitively bind the mineralcorticoid receptor and block function
Secreted by adrenal glands and cause retention of salt and water while increasing excretion of K and Protons
Primary sites of activity are in Distal Convoluted Tubule and Collecting Duct
Compete with Aldosterone
Aldosterone acts in nucleus to change DNA expression of AIP (aldosterone induced proteins)
AIPs activate previously silent Na channels and pumps promoting reuptake of Na and H20
- Induced in response to dehydration
Effects on Excretion:
Used in treatment of Primary Hyperaldosteronism in ADRENAL ADENOMAS and ADRENAL HYPERPLASIA
With secondary hyperaldosteronism (resulted from Cardiac Failure, cirrhosis, nephrotic syndrome, severe ascites)
Treatment of choice for ascites and edema due to cirrhosis
Adverse effects:
triamterene
Inhibits renal Na Channel
- Most Common agent of this group
Cause small increase in NaCl excretion
Blocking the luminal Na channel drops K secretion by blocking depolarization of luminal membrane which drives K secretion
Inhibits H secretion also by raising intra-luminal positive potential
Half Life: 4 Hours
METABOLIZED
Indications:
Treat LIDDLEs syndrome (hypokalemia due to increased Na Transport)
Used as aerosol in cystic fibrosis to clear mucus
Adverse Reaction
FOLATE ANTAGONIST and may lead to MEGALOBLASTIC ANEMIA in cirrhosis
Some diffuse CNS, GI, Dermatological, hematological effects
NSAIDS may decrease efficiency
Blocks uptake of Lithium by Na channels in collecting duct
- Used for lithium induced nephrogenic diabetes insipidus
glycerin
Osmotic Diuretic
Effects on Excretion:
Act on tissues by drawing water into blood
Act on kidney by increasing renal blood flow and washing out medullary salt gradient
POTASSIUM WASTING
Indications:
Adverse Reactions:
Metabolized and may cause hyperglycemia
mannitol
Osmotic Diuretic
Effects on Excretion:
Act on tissues by drawing water into blood
Act on kidney by increasing renal blood flow and washing out medullary salt gradient
POTASSIUM WASTING
Indications:
Adverse Reactions:
Used preop and postop for neurosurgery to reduce brain swelling
Contraindicated with those with active intracranial bleeding
chlorpropamide
Sulfonylurea previous used for diabetes type II
ALso increases ADH secretion
desmopressin
Antidiuretic
Synthetic analog of vasopressin
Little V1 activity
Primary effects through V2 receptors (mostly in kidney)
V2 effects:
More permeability of distal duct to urea
Increased activity of Na, K, and Cl symporter in thick ascending limb
vasopressin
Antidiuretic Hormone ADH
Binds V1 and V2 receptors
V1: reduce medullary blood flow, thus increasing medullary salt gradient and reabsorption of water
V2:
- Stimulate water reabsorption in distal tubule and collecting duct by stimulating production of aquaporins in epithelium
More aquaporins in apical membrane due to increased recycling
More permeability to urea
INcreased activity of Na, K, and Cl symporter in thick ascending limb
Indications:
- Diabetes insipidus
Adverse Effects:
probenecid
Uricosuric Agent
Indications: GOUT
Adverse effects:
allopurinol
Uricosuric Agent
Reduce uric acid and inflammation
Inhibits Xanthine oxidase (converts xanthine to uric acid)
Increase renal excretion of uric acid
Biphasic effect:
colchicine
Uricosuric Agent
Reduce uric acid and inflammation
Reduces Neutrophil activity
Increase renal excretion of uric acid
Biphasic effect: