Diuretics Flashcards by Brooke Thornburg

Diuretics

-agents that help the body get rid of sodium and water
-natriuresis (sodium excretion)
-diuresis (water excretion)

How well did you know this?

Not at all

Perfectly

Diuretics and blood pressure

-dec blood pressure by decreasing plasma volume
-less burden on cardiovasc disease

How well did you know this?

Not at all

Perfectly

Diuretic indications

-edematous states
-HTN
-Heart failure
-Acute renal failure

How well did you know this?

Not at all

Perfectly

Is caffeine a diuretic?

-doses in drinks don’t have diuretic action

How well did you know this?

Not at all

Perfectly

Membrane transporters

-convective flow
-simple diffusion
-channel-mediated diffusion
-carrier-mediated diffusion
-ATP-mediated transport (active)
-Symport (active)
-Antiport (active)

-which are likely tarets of diuretics

How well did you know this?

Not at all

Perfectly

Classification of Diuretics

-sites of action
-efficacy
-structure
-effect on potassium excretion
-MOA

How well did you know this?

Not at all

Perfectly

Classification of diuretics based on MOA

inhibitors of carbonic anhydrase
Osmotic Diuretics
Inhibitors of Na-K-2Cl symport
Inhibitors of NaCl symport
INhibitors of renal Na channels
5b. Mineralcorticoid receptor antagonists

How well did you know this?

Not at all

Perfectly

Transport of diuretics into proximal tubule

-high protein binding
-not filtered through Bowman’s (only unbound is filtered)
-transport/secretion into proximal tube

How well did you know this?

Not at all

Perfectly

Active secretion in Proximal Tubule

-Organic Anion Transporter (OAT)
-Organic Cation Transporter (OCT)

How well did you know this?

Not at all

Perfectly

Drugs secreted by Organic Anion Transport in proximal tubule

-Furosemide
-thiazides
-penicillin
-cephalosporin
-probenecid
-NSAIDs

How well did you know this?

Not at all

Perfectly

Drugs secreted by Organic Cation Transport in proximal tubule

-Amiloride
-Cimetidine
-Digoxin
-Metformin
-Morphine
-Procainamide
-Quinidine
-Ranitidine
-Triamterene
-Trimethoprim
-Vancomycin

How well did you know this?

Not at all

Perfectly

Active secretion in Prox tube mech (OAT and OCT)

Diffusion out of capillary space into interstitial space
Transport across basolateral membrane
secretion across luminal membrane

-non-selective = competition

How well did you know this?

Not at all

Perfectly

Active secretion depends on

-plasma protein binding
-rate of delivery of drug
-transporter saturation
-competing drugs

How well did you know this?

Not at all

Perfectly

Probenecid

-secreted by OAT
-treats gout
-inc uric acid secretion
-competes w penicilin = slow excretion = prolong PCN activity (doubles blood concentration and exposure)

How well did you know this?

Not at all

Perfectly

Penicillin

-secreted by OAT
-inhibit transpeptidase
-block crosslinking of peptidoglycans
-dec cell wall synthesis
-mostly cleared by kidneys unchanged
-was extracted and reused during WWII
-competition by probenecid at OAT to slow penicillin excretion and prolong activity

How well did you know this?

Not at all

Perfectly

Inhibitors of Carbonic Anyhydrase

-inhibit cytoplasmic and membrane bound CA
-inhibit NaHCO3 reabsorption
=inc NaHCO3 excretion

How well did you know this?

Not at all

Perfectly

Carbonic Anhydrase INhibitors SAR

-sulfanilamide derivatives
-high partition coefficient and lowest pKa have greater potency
-Sulfamoyl group essential
-sulfamoyl N unsubstituted to reatin activity

How well did you know this?

Not at all

Perfectly

Carbonic Anhydrase Inhibitor Drugs

-Acetazolamide
-Dichlorphenamide
-Methazolamide

How well did you know this?

Not at all

Perfectly

Carbonic Anhydrase Inhibitor Drug Uses

-low diuretic efficacy
-acute mountain sickness
-metabolic alkalosis
-glaucoma
-urinary alkalinization

How well did you know this?

Not at all

Perfectly

Carbonic Anhydrase Inhibitor Drug Toxicities

-hypercloremic metabolic acidosis
-renal stones
-renal potassium wasting
-drowsiness/paresthesia

How well did you know this?

Not at all

Perfectly

Acute Mountain sickness tx

-acetazolamide prophylactically several days before ascent above 10,000 feet
-metabolic acidosis produced by the drug counteracts the respiratory alkalosis that can result from hyperventilation

How well did you know this?

Not at all

Perfectly

diuretic and sulfonaimde antimicrobials cross-sensitivity

-most pt do with drug allergy don’t react
-Sulfa rash in 5-10% of pt (rare in diuretics)
-withholding sulfamoyl containing diuretics from pt with hx of sulfonamide allergy is not justified

How well did you know this?

Not at all

Perfectly

Osmotic Diuretics

-inc H2O excretion
-renal prox tubule
-descending limb of loop of henle
-pharmacologically inert
-non-reabsorbable substances shifting osmotic flow
-alter renal blood flow

How well did you know this?

Not at all

Perfectly

Osmotic diuretic drugs

-Mannitol (IV)
-Urea (IV)
-Glucose
-Isosorbide
-Glycerine

How well did you know this?

Not at all

Perfectly

Mannitol side effects?

-loss of water -reduced intracellular volume -hypernatremia risk

Osmotic SAR and MOA

Na-K-2Cl symport Inhibitors

-inc Na, K, Cl -loop diuretics and high ceiling diuretics -thick ascending limb

Na-K-2Cl inhibitors

-act on luminal surface symport = must be in lumen for diuretic activity -rapid response after IV admin -most potent class (useful for edema) -some have weak CA inhibitory activity -Chronically reduce uric acid secretion -problems w K, Ca, Mg reuptake

Na-K-2Cl symport inhibitor SAR

-1 position must have acidic substitent (carboxyl best, tetrazole) -sulfamoyl group at 5 is essential -activating group at 4 (Cl, CF3, phenoxy, alkoxy, anilino, benzyl, benzoyl group

Na-K-2Cl symport inhibitor drugs

-Furosemide -Bumetanide -Ethacrynic acid -Torsemide

Na-K-2Cl symport inhibitor drug use

-edema -acute pulmonary edema -HTN, HF -acute hypercalcemia -hyperkalemia -acute renal failure -anion overdose

Na-K-2Cl symport inhibitor drug toxicities

-dehydration -hypokalemic metabolic alkalosis* -Ototoxicity* -hyperuricemia -hypomagnesmia

Ethacrynic Acid (Edecrin)

-Na-K-2Cl symport inhibitor =not derived from sulfonamides -alkylates thiols to give the sulfhydryl-containing conjugates that are diuretics -prodrug? -structure?

NaCl symport inhibitors

-inc NaCl excretion -thiazides -DCT, PCT secondary -enhance potency of CA-I -reduce K reuptake

SAR of thiazides (NaCl inhibitor)

-slide 30 -sulfaniliamide to acetazolamide to dichlorphenamide to chlorothiazide -2 rings

NaCl inhibitor drug classes

-Thiazide (acylating agent) -Hydrothiazide (aldehyde or ketones)

NaCl inhibitor drugs

-Chlorothiazide -Hydrochlorothiazide -Chlorothalidone -Metolazone

NaCl inhibitor drug use

-HTN -HF -nephrolithiasis due to hypercalciuria -nephrogenic diabetes insipidus

NaCl inhibitor drug toxicities

-Hypokalemic metabolic acidosis -hyperuricemia -hyperglycemia -impaired carbohydrate tolerance -hyperlipidemia -hyponatremia

The post-discharge therapy included a substitution of hydrochlorothiazide with furosemide. Which of the following statements best explains why loop diuretics are far more effective than thiazide diuretics?

More sodium is physiologically reabsorbed at the loop of Henle than at the distal convolute tubule.

Renal Epithelial Na channel inhibitors

-potassium-sparing diuretics -late DCT and collecting duct -weak diuretics -used in combo w other diuretics

Renal Epithelial Na channel inhibitor drugs

-Amiloride -Triamterene

Renal Epithelial Na channel inhibitor drug use

-adjunctive tx w thiazide or loop diuretic in HF or HTN

Renal Epithelial Na channel inhibitor drug toxicities

-Hyperkalemia* -Hyperchloremic metabolic acidosis

Renal Epithelial Na channel inhibitor drug contraindications

-K+ supplements -ACE inhibitors

Mineralcorticoid Receptor Antagonists (MRA)

-aldosterone antagonists -potassium-sparing diuretics -inc Na excretion -inc K retention -bind to MR but don't stimulate AIP production -only diuretics that do not act within the tubular lumen!

MRA drugs

-spironolactone -canrenone -potassium canrenoate -eplerenone

MRA toxicities

-Hyperkalemia -Hyperchloremic metabolic acidosis -Gynecomastia -impotence -benign prostatic hyperplasia

MRA drug use

-HTN or HF w other diuretics -excess mineralcorticoids -Aldosteronism

MRA drug contraindications

-K supplements -ACE inhibitors -Chronic renal insufficiency

PK and PD determinants of diuretic response

-luminal (not MRAs) -CA-I, furosemide and thiazide are highly bound to plasma protein (secreted not filtered) -secretion is saturable (dose-dependent) -secretion decreases with renal failure (reduced efficacy) -sensitivity to diuretics reduced bc homeostatic responses in CRF (inc hyperaldosteronism)

Diuretic site of action

-luminal -except MRAs

Diuretic secretion

-CA-I, furosemide, thiazide (not filtered bc bound to plasma protein) -saturable (dose-dependent) -dec with renal failure

Braking Phenomenon

-Osmosis (water follows salts) -when Na excretion > Na intake, BW and ECF decrease -activation of RAAS and SNS -BW and ECF stabilize at output=input -BW and ECF rise when output

Diuretic responsiveness in HF

-reduced -diuretics can;t manage pt well as HF progresses

Diuretic responsiveness in CRF

-potency shifts -efficacy can be obtained w increased dose

Combining diuretics w different MOAs

-more effective than dose inc of single agent

Slide 44

CA I Drugs to know

Acetazolamide

Osmotic diuretics to know

Mannitol

Loop diuretics to know

-Furosemide -Bumetanide -Torsemide -Ethacrynic acid

Distal tubule diuretics to know

-Hydrochlorothiazide -chlorthalidone -metolazone

K-sparing diuretics to know

-NaCl I: amiloride and triamterine -Aldosterone Antagonists (MRA): spirinolactone and eplerenone

chart on slide 45

chart on slife 45

A 55-year-old male with kidney stones has been placed on a diuretic to decrease calcium excretion. However, after a few weeks, he develops an attack of gout. Which diuretic was he taking?

-thiazides associated w elevated SUA levels

Question: An 83-year-old man has been effectively treated with hydrochlorothiazide to control his elevated blood pressure. He has had a recent onset of weakness. Blood chemistry analysis reveals hypokalemia. Another drug is added, and 1 month later his serum K+ is normal. Which of the following drugs most likely helped normalize his serum potassium levels?

Amiloride

Question: A patient taking an oral diuretic for about 6 months presents with elevated fasting and postprandial blood glucose levels. You suspect the glycemic problems are diuretic-induced. Which of the following was the most likely cause?

Hydrochlorothiazide

Question: A patient with severe infectious disease is being treated with an aminoglycoside antibiotic. Which of the following diuretics should be avoided, if possible, because of the risk of a serious common and additive adverse effect?

-Furosemide -both the loop diuretics and aminoglycoside are ototoxic (balance and hearing injury) -

aminoglycoside antibiotic

-gentamicin -protein synthesis inhibitor -avoid with loop diuretics -ototoxic and nephrotoxic