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Flashcards in Renal Deck (20)
1

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

2

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

3

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

4

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

5

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



6

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

7

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

8

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

9

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

10

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

11

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

12

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

13

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

14

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

15

chlorpropamide

Sulfonylurea previous used for diabetes type II

ALso increases ADH secretion

16

desmopressin

Antidiuretic

Synthetic analog of vasopressin

Little V1 activity

Primary effects through V2 receptors (mostly in kidney)

V2 effects:
- stimulate water reabsorpition in distal tubule and collecting duct by stimulating production of aquaporins in epithelium
- More aquaporins due to increased cycling

More permeability of distal duct to urea

Increased activity of Na, K, and Cl symporter in thick ascending limb

17

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:
- Coronary artery occlusion
- Water intoxication

18

probenecid

Uricosuric Agent

Indications: GOUT

Adverse effects:
- Well tolerated
- Increased risk for renal stones
- Interferes with renal excretion of MANY drugs
- Interferes with diuretics (primarily loop and thiazide diuretics) by preventing them access to tubule lumen

19

allopurinol

Uricosuric Agent

Reduce uric acid and inflammation

Inhibits Xanthine oxidase (converts xanthine to uric acid)

Increase renal excretion of uric acid

Biphasic effect:
- Decreased excretion of uric acid
- Once in lumen urate reabsorption is inhibited resulting in increased urate excretion

20

colchicine

Uricosuric Agent

Reduce uric acid and inflammation

Reduces Neutrophil activity

Increase renal excretion of uric acid

Biphasic effect:
- Decreased excretion of uric acid
- Once in lumen urate reabsorption is inhibited resulting in increased urate excretion