Pharmacology: Block 4: Drugs Affecting The Kidney

Front 1

What percentage of CO do the kidneys receive at rest?

Back 1

~20%

Front 2

Acetazolamide: what is it?

Back 2

A carbonic anhydrase inhibitor

Front 3

Acetazolamide: what does it do?

Back 3

Carbonic anhydrase inhibitor

- NaHCO3 reabsorption in PCT down.

- Greatly increases excretion of HCO3 (so that 1/3 of all HCO3 filtered is excreted)

- Decreases H and NH4 excretion in the collecting tubules

- Causes urinary pH to rise to about 8

- Causes metabolic acidosis

- Na and K excretion go up.

Front 4

Acetazolamide: the ceiling effect

Back 4

Carbonic anhydrase inhibitor

?

Front 5

Acetazolamide: other effects

Back 5

Carbonic anhydrase inhibitor

- Dec aqueous humor formation in the eye

- Dec IOP

- Dec seizures

- Dec in mountain sickness

Front 6

Acetazolamide: AE

Back 6

Carbonic anhydrase inhibitor

- Somnolence
- Paresthesias
- Metabolic acidosis
- Inc amine reabsorption --> worsen hepatic encephalopathy
- Inc urinary pH --> renal stones
- Hypersensitivity reactions -- this is a sulfonamide derived medication

Front 7

Acetazolamide: uses

Back 7

Carbonic anhydrase inhibitor

Poor diuretic due to refractoriness

Glaucoma

Mountain sickness (prophylaxis > treatment)

Epilepsy

Front 8

Osmotic diuretics: general

Back 8

Freely filtered
Not reabsorbed
Not metabolized
Pharmacologically inert

Front 9

Osmotic diuretics: site of action

Back 9

PCT and the loop of Henle

Front 10

Osmotic diuretics: M of A?

Back 10

Increase extracellular fluid volume by drawing out intracellular water.

Front 11

Osmotic diuretics: effects of using?

Back 11

RBF: up

Excretion of all ions: up

NaCl concentrating ability in medulla: down

Urine concentrating ability: down

Front 12

Osmotic diuretics: AE

Back 12

Increase in extracellular fluid volume can exacerbate pulmonary edema.

Can mess with plasma ion concentrations.

Contraindicated in anuria

Front 13

Osmotic diuretics: uses

Back 13

Prophylaxis of ARF, ATN prior to ischemia, nephrotoxin (??)

Decreases cerebral edema

Decreases intraocular pressure (IOP)

Mannitol is a free-radical scavenger

Front 14

Loop diuretics: what do they do?

Back 14

Inhibit Na/K/2Cl symporter in the ascending limb.

Front 15

Loop diuretics: effects

Back 15

- Greatly increase NaCl excretion

- Increase K and H excretion due to increased delivery of Na to the distal tubule.

- Decrease medullary tonicity

- Decrease urine concentrating ability

- Ethacrynic acid is the only non-sulfonamide loop diuretic.

Front 16

Furosemide: class

Back 16

Sulfonamide

Front 17

Furosemide: also inhibits?

Back 17

Carbonic anhydrase

Front 18

Furosemide: other effect besides diuresis?

Back 18

Venous dilation

Front 19

Loop diuretics: protein binding, filtration rate.

Back 19

High protein binding, not well filtered.

Front 20

Loop diuretics: secreted where?

Back 20

In the PCT

Front 21

Loop diuretics: oral bioavailability

Back 21

Furosemide: ~60%
Ethacrynic acid: 100%

Front 22

Loop diuretics: metabolism

Back 22

2/3 excreted unchanged
1/3 metabolized

Front 23

Loop diuretics: AE

Back 23

Increased delivery of Na to distal tubule --> increased K, H excretion -->

Hypokalemia
Hypochloremia
Hypomagnesemia
Metabolic alkalosis

Increased Ca excretion in osteoporotic women

Ototoxicity due to altered endolymph --> hearing loss, vertigo (usually reversible)

Front 24

Loop diuretics: rare AE

Back 24

- Hyperuricemia (occasionally causes gout)

- Hyperglycemia (occasionally worsens glycemic control)

- Hypersensitivity cross reaction with other sulfonamides (except ethacrynic acid)

Front 25

Loop diuretics: uses

Back 25

- Acute pulmonary edema
- CHF
- Edema of the nephrotic syndrome
- Edema of cirrhosis
- To increase excretion of some drugs

Front 26

Thiazide diuretics: what do they do?

Back 26

Inhibit the Na Cl symporter in the distal tubule.

Front 27

Thiazide diuretics: derived from what

Back 27

Sulfonamides

Front 28

Thiazide diuretics: prototype

Back 28

Hydrochlorothiazide

Front 29

Thiazide diuretics: affect on carbonic anhydrase?

Back 29

Weakly inhibits

Front 30

Thiazide diuretics: secreted where?

Back 30

PCT

Front 31

Thiazide diuretics: half-lives

Back 31

HCTZ: ~2.5 hrs
Chlorthalidone (used in the ALLHAT study): ~47 hrs!

Front 32

Thiazide diuretics: AE

Back 32

Increased Na delivery to the DT --> K, H excretion up -->

Hypokalemia
Hypochloremia
Metabolic alkalosis

Hyperuricemia (occasionally gout)
Hyperglycemia (occasionally worsens glycemic control)
Hypersensitivity cross reaction with other sulfonamides

- Erectile dysfunction!

Front 33

Thiazide diuretics: uses

Back 33

HTN
CHF
Edema of the nephrotic syndrome
Edema of cirrhosis

Front 34

Thiazide diuretics: can be used with what for maximum diuretic effect?

Back 34

Metolazone + loop diuretic

Front 35

Spironolactone: what is it?

Back 35

Aldosterone antagonist

Front 36

Spironolactone: what does it do?

Back 36

Increases Na excretion
Increases K, H retention
Also binds to sex hormone receptors!

Front 37

Spironolactone: AE

Back 37

- Hyperkalemia
- Estrogen effects: gynecomastia, impotence
- Androgen effects: hirsutism, deepening of voice
- Increases malignancies?

Front 38

Spironolactone: uses

Back 38

- To increase aldosterone concentrations (??)

- Decrease mortality in CHF

- Used in combination with loop or thiazide diuretics to minimize hypokalemia

- Used for hyperaldosteronism

Front 39

Name two aldosterone antagonists

Back 39

Spironolactone
Eplerenone

Front 40

Name two K sparing diuretics

Back 40

Triamterene
Amiloride

Front 41

K sparing diuretics: what do they do?

Back 41

Block ENaC channel in distal tubule and collecting duct

Block Na reabsorption, so block K, H, Ca, Mg excretion

Increase Na excretion (a little)

Increase K reabsorption (a little more)

Front 42

K sparing diuretics: AE

Back 42

Hyperkalemia

Front 43

K sparing diuretics: common useage?

Back 43

In combination with other diuretics

Front 44

ADH: released from where in response to what?

Back 44

Released from the posterior pituitary in response to increased osmolality.

Front 45

ADH: what does it do?

Back 45

Increases water permeability in the collecting duct.

Front 46

ADH: effect on vessels

Back 46

ADH is a potent vasoconstrictor

Front 47

Diabetes insipidus: what is it?

Back 47

An underproduction or lack of ADH

Front 48

Diabetes insipidus: most significant clinical presentation

Back 48

Huge volume of dilute urine (~20 L/day)

Front 49

Diabetes insipidus: treated with what?

Back 49

Treated with long-acting ADH analogue (desmopressin)

Front 50

Desmopressin: what is it?

Back 50

Long-acting ADH analogue

Front 51

Desmopressin: route

Back 51

Nasally, orally, or via long-acting injection.

Front 52

What is a drug combination that can cause nephrogenic DI?

Back 52

Lithium + demeclocyline

Front 53

SIADH: what is it?

Back 53

When there is too much ADH released

Front 54

SIADH: what is the concentration of the urine?

Back 54

Concentrated urine

Front 55

SIADH: often follows what type of injury?

Back 55

Head injury

Front 56

SIADH: resolution

Back 56

Usually resovles spontaneously

Front 57

SIADH: treatment

Back 57

Usually resolves spontaneously

May be treated with loop diuretics

Front 58

Conivaptan: what is it?

Back 58

A V1 and V2 antagonist approved for the treatment of euvolemic and hypervolemic hyponatremia

Front 59

Probenecid: what does it do?

Back 59

- Inhibits the organic acid transporter

- Inhibits tubular secretion of many acids (e.g. penicillin)

- Inihibits tubular reabsorption of uric acid

Front 60

Probenecid: uses

Back 60

Useful in gout because it increases the amount of uric acid excreted.