Renal Flashcards
acetazolamide
Carbonic Anhydrase Inhibitor
Proximal Tubule
Effects on Excretion:
- Increase Na excretion
- Increase Potassium
- Decrease H+ excretion (may contribute to acidosis)
- Increase HCO3 excretion
- Increase H2PO4 excretion
Based on the sulfanilamide chemotherapeutic drugs
Potassium Wasting: due to high Na+ delivery to distal nephron
Indicatoins:
- Open Angle Glaucoma
- Pre surgical relief of glaucoma pressure
- Formerly used in Epilepsy
- Altitude sickness (lowers CO2 in blood) metabolic acidosis partially relieves this
- Counteracting diuretic induced metabolic alkalosis (low efficacy as single agent)
Adverse Reaction:
- Allergic Reaction (sulfonamide in general)
- Metabolic acidosis
- Diversion of renal ammonia into circulation: worsens hepatic encephalopathy
- Kidney stones due to alkaline urine
- Bone marrow depression, paresthesias, tingling
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:
- Increase Na
- INcrease K
- Increase H
- Decrease Ca
- Increase Mg
- Increase Cl
- Increase HCO3
- INcrease H2PO4
- INcrease Uric acid (acute affect if chronic use)
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:
- Hypotension
- Hypokalemia
- Hyponatremia
- Metabolic alkalosis
Corticosteroids and amphotericin B increase risk of significant hypokalemia and cardiac arrthymias
- Hypercalcemia/hyperuricemia
- Contraindicated with sulfonamide sensitivity
- NSAIDS reduce diuretic response
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:
- Increase Na
- INcrease K
- Increase H
- Decrease Ca
- Increase Mg
- Increase Cl
- Increase HCO3
- INcrease H2PO4
- INcrease Uric acid (acute affect if chronic use)
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:
- Hypotension
- Hypokalemia
- Hyponatremia
- Metabolic alkalosis
Corticosteroids and amphotericin B increase risk of significant hypokalemia and cardiac arrthymias
- Hypercalcemia/hyperuricemia
- Contraindicated with sulfonamide sensitivity
- NSAIDS reduce diuretic response
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:
- Increase Na
- INcrease K
- Increase H
- Decrease Ca
- Increase Mg
- Increase Cl
- Increase HCO3
- INcrease H2PO4
- INcrease Uric acid (acute affect if chronic use)
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:
- Hypotension
- Hypokalemia
- Hyponatremia
- Metabolic alkalosis
Corticosteroids and amphotericin B increase risk of significant hypokalemia and cardiac arrthymias
- Hypercalcemia/hyperuricemia
- Contraindicated with sulfonamide sensitivity
- NSAIDS reduce diuretic response
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:
- Renal: 65%
- Metabolized: 35%
High Ceiling diuretic
- Lots of diuresis
- 25 percent Na normal reabsorbed in thick ascending limb but is BLOCKED
- Distal segments do not rescue enough Na reabsorption
- BLock salt transport to macula SO NOT LIMITED BY TGF
Indications:
- Acute Pulmonary Edema
- Congestive Heart Failure
- Hypertension (thiazides preferred)
- Nephrotic syndrome (high flow rates)
- Edema and ascites of cirrhosis (may induce HEPTAORENAL SYNDROME)
- Chronic renal failure
Adverse Reactions:
- Hyponatremia
- Hypokalemia (arrthymias secondary to this)
- Volume depletion (do not use if patient hypovolemic)
- Metabolic alkalosis
- Hyperuricemia
- Ototoxicity (DUE TO INH OF SYMPORTER IN EAR)
- NSAIDS reduce action
- PROBENECID: increase effective dose
- Interacts with anticoagulants, propranolol, lithium, sulfonylurea, cisplatin, amphotericin B
ethacrynic acid
Loop Diuretic
Short Half Life: 1 hour
Elimination:
- Renal: 67%
- Metabolized: 33%
High Ceiling diuretic
- Lots of diuresis
- 25 percent Na normal reabsorbed in thick ascending limb but is BLOCKED
- Distal segments do not rescue enough Na reabsorption
- BLock salt transport to macula SO NOT LIMITED BY TGF
Indications:
- Acute Pulmonary Edema
- Congestive Heart Failure
- Hypertension (thiazides preferred)
- Nephrotic syndrome (high flow rates)
- Edema and ascites of cirrhosis (may induce HEPTAORENAL SYNDROME)
- Chronic renal failure
Adverse Reactions:
- Hyponatremia
- Hypokalemia (arrthymias secondary to this)
- Volume depletion (do not use if patient hypovolemic)
- Metabolic alkalosis
- Hyperuricemia
- Ototoxicity!!!!!! MAINLY THIS ONE (DUE TO INH OF SYMPORTER IN EAR)
- NSAIDS reduce action
- PROBENECID: increase effective dose
- Interacts with anticoagulants, propranolol, lithium, sulfonylurea, cisplatin, amphotericin B
furosemide
Loop Diuretic
Short Half Life: 1.5 hours
Elimination:
- Renal: 65%
- Metabolized: 35%
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
- Lots of diuresis
- 25 percent Na normal reabsorbed in thick ascending limb but is BLOCKED
- Distal segments do not rescue enough Na reabsorption
- BLock salt transport to macula SO NOT LIMITED BY TGF
Indications:
- Acute Pulmonary Edema
- Congestive Heart Failure
- Hypertension (thiazides preferred)
- Nephrotic syndrome (high flow rates)
- Edema and ascites of cirrhosis (may induce HEPTAORENAL SYNDROME)
- Chronic renal failure
Adverse Reactions:
- Hyponatremia
- Hypokalemia (arrthymias secondary to this)
- Volume depletion (do not use if patient hypovolemic)
- Metabolic alkalosis
- Hyperuricemia
- Ototoxicity (DUE TO INH OF SYMPORTER IN EAR)
- NSAIDS reduce action
- PROBENECID: increase effective dose
- Interacts with anticoagulants, propranolol, lithium, sulfonylurea, cisplatin, amphotericin B
torsemide
Loop Diuretic
Short Half Life: 3.5 hours
Elimination: (MAJOR DIFF)
- Renal: 20%
- Metabolized: 80%
High Ceiling diuretic
- Lots of diuresis
- 25 percent Na normal reabsorbed in thick ascending limb but is BLOCKED
- Distal segments do not rescue enough Na reabsorption
- BLock salt transport to macula SO NOT LIMITED BY TGF
Indications:
- Acute Pulmonary Edema
- Congestive Heart Failure
- Hypertension (thiazides preferred)
- Nephrotic syndrome (high flow rates)
- Edema and ascites of cirrhosis (may induce HEPTAORENAL SYNDROME)
- Chronic renal failure
Adverse Reactions:
- Hyponatremia
- Hypokalemia (arrthymias secondary to this)
- Volume depletion (do not use if patient hypovolemic)
- Metabolic alkalosis
- Hyperuricemia
- Ototoxicity (DUE TO INH OF SYMPORTER IN EAR)
- NSAIDS reduce action
- PROBENECID: increase effective dose
- Interacts with anticoagulants, propranolol, lithium, sulfonylurea, cisplatin, amphotericin B
amiloride
K sparing agent
Inhibits renal Na Channel
- Most Common agent of this group
Cause small increase in NaCl excretion
- Used for ability to block K excretion in combo with other diuretics
- Act on Distal Convoluted tubule and Collecting Duct
- POTASSIUM SPARING
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:
- Slightly increased Na excretion
- Strongly increases potassium reabsorption
- Co-administered with thiazide or loop diuretic to enhance effects and reduce K loss
Treat LIDDLEs syndrome (hypokalemia due to increased Na Transport)
- 5percent African Amercians have polymorphism for ENaC Beta subunit making them particulary potent for reducing hypotension in this group
Used as aerosol in cystic fibrosis to clear mucus
Adverse Reaction
- Hyperkalemia: cardiac arrhythmia and death
- Interacts with other potassium sparers
- ACE inhibition
- NSAIDS
- K dietary supplements
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:
- Increase Na
- Decrease K
- Decrease H
- Decrease Ca
- Decrease Mg
- Increase Cl
Clearance significantly decreased by INHIBITORS of CYP3A4
Adverse effects:
- Hyperkalemia
- NSAIDS decrease efficiency
- Cross reaction with other steroid receptors
- Antiadrogen: feminization
- Antiprogesterone: Mentsrual irregularities
- Diarrhea, gastritis, gastric bleeding, contraindicated with peptic ulcers
- CNS symptoms and Rash
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:
- Increase Na
- Decrease K
- Decrease H
- Decrease Ca
- Decrease Mg
- Increase Cl
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:
- Hyperkalemia
- NSAIDS decrease efficiency
- Cross reaction with other steroid receptors
- Antiadrogen: feminization
- Antiprogesterone: Mentsrual irregularities
- Diarrhea, gastritis, gastric bleeding, contraindicated with peptic ulcers
- CNS symptoms and Rash
- Possible malignancies with chronic use
triamterene
Inhibits renal Na Channel
- Most Common agent of this group
Cause small increase in NaCl excretion
- Used for ability to block K excretion in combo with other diuretics
- Act on Distal Convoluted tubule and Collecting Duct
- POTASSIUM SPARING
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:
- Slightly increased Na excretion
- Strongly increases potassium reabsorption
- Co-administered with thiazide or loop diuretic to enhance effects and reduce K loss
Treat LIDDLEs syndrome (hypokalemia due to increased Na Transport)
- 5percent African Amercians have polymorphism for ENaC Beta subunit making them particulary potent for reducing hypotension in this group
Used as aerosol in cystic fibrosis to clear mucus
Adverse Reaction
- Hyperkalemia: cardiac arrhythmia and death
- Interacts with other potassium sparers
- ACE inhibition
- NSAIDS
- K dietary supplements
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:
- Increase Na
- Increase K
- Increase Ca
- Increase Mg
- Increase Cl
- Increase HCO3
- Increase H2PO4
- Increase Uric Acid
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:
- Acute Renal Failure
- Acute tubular necrosis
- Dialysis disequilibrium syndrome due to too rapid removal of solutes from dialysis
- Used for acute glaucoma to reduce intraocular pressure
Adverse Reactions:
- Convert pulmonary congestion to pulmonary edema
- Hyponatremia
- Hyponatremia and dehydration
- Contraindicated in anuria, impaired liver function
Metabolized and may cause hyperglycemia
mannitol
Osmotic Diuretic
Effects on Excretion:
- Increase Na
- Increase K
- Increase Ca
- Increase Mg
- Increase Cl
- Increase HCO3
- Increase H2PO4
- Increase Uric Acid
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:
- Acute Renal Failure
- Acute tubular necrosis
- Dialysis disequilibrium syndrome due to too rapid removal of solutes from dialysis
- Used for acute glaucoma to reduce intraocular pressure
Adverse Reactions:
- Convert pulmonary congestion to pulmonary edema
- Hyponatremia
- Hyponatremia and dehydration
- Contraindicated in anuria, impaired liver function
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