2B : DIURETICS - LOOP

Question 1

Acts on the (TAL) thick ascending limb of the loop of henle

Answer 1

LOOP DIURETICS

Question 2

A full dose produces

Answer 2

Massive NaCl diuresis

Question 3

mechanism of action of loop diuretics

Answer 3

1. MOA: Selectively inhibits reabsorption of sodium
   and chloride, Ca2+ and Mg2+

(due to loss of lumen (+) from the proximal and distal tubules and ascending limb of the Loop of Henle, leading to a sodium rich diuresis because of great increased of solute to distal parts of nephron (osmotic agents) –> thus increases renal blood flow  eventually renin is activated

2. MOA: It selectively block the luminal Na+/K+/2Cl
   transporter in the TAL

Question 4

• Powerful, efficacious diuretics
  (‘high ceiling’)
• Unlimited by acidosis

Answer 4

LOOP DIURETICS

Question 5

result of selectively blocking the luminal
Na+/K+/2Cl transporter in the TAL

Answer 5

selective inhibition of NaCl reabsorption

Question 6

has weak CAI activity (increase the
urinary excretion of HCO3 and phosphate)

Answer 6

Furosemide

Question 7

blocking NKCC2

Answer 7

halts NaCl transport

inhibits
reabsorption of Ca2+ & Mg2+

Question 8

prototype of loop diuretics

Answer 8

Furosemide

Question 9

• phenoxyacetic derivative
• ## same MOA as furosemide

Answer 9

Ethacrynic
acid

Question 10

Ethacrynic acid is a moderately effective uricosuric drug if blood volume is maintained

Answer 10

Ethacrynic
acid

Question 11

Organic Mercurial Diuretics

Answer 11

Loop Diuretics

Question 12

Therapeutic uses of Loop Diuretics

Answer 12

1. Acute Pulmonary Edema
2. Chronic CHF
3. HTN
4. forced diuresis
5. Edematous conditions
6. Hypercalcemia
7. Life threatening hypervolemic hyponatremia
   8.

Question 13

major use of loop diuretics

Answer 13

Acute Pulmonary Edema

to rapidly increase in venous capacitance + brisk
natriuresis reduce LV filling pressures

Question 14

effect of loop diuretics on chronic CHF

Answer 14

to** diminish ECF volume **to minimize venous & pulmonary congestion

significantly reduces mortality & risk of worsening HF, improves exercise capacity

Question 15

what type of fluid solution to give in combination with loop diuretics in these condtions

• Hypercalcaemia
• Life threatening hypervolaemic hyponatraemia

Answer 15

• Hypercalcaemia give LD + isotonic saline (to prevent volume depletion)
• Life threatening hypervolaemic hyponatraemia– LD + hypertonic saline

Question 16

how can LD benefit patients with acute pulmonary edema

Answer 16

Benefits patients with acute pulmonary edema **even before diuresis (because of rapid increase in venous capacitance leading to
decrease LV filling pressure **mediated by prostaglandins and requires intact kidneys)

Question 17

therapeutic uses

Answer 17

• Acute pulmonary edema
• Indicated for fluid retention associated with
  Chronic CHF and nephrotic syndrome
• Acute CHF
• For HPN-but as effective as Thiazide Diuretics
• Hypercalcemia (give loop diuretic and** isotonic** saline)
• Hypervolemic hyponatremia (SIADH) (diluted–>give loop diuretic + hypertonic saline)

Question 18

Contraindicated to patient with

Answer 18

osteoporosis or hypocacelmic

Question 19

When LDs are
coadministered with
Aminoglycosides what is the effect

Answer 19

ototoxicity

Question 20

When LDs are
coadministered with
sulfonylurea what is the effect

Answer 20

hyperglycemia

Question 21

BUMETANIDE dosage and consideration

Answer 21

0.5 - 2mg OD

• Significant hepatic metabolism and half life may prolonged by liver disease

Question 22

Ethacrynic acid dosage and consideration

Answer 22

25 - 100 mg OD
* More reliable absorption and heart failure atients have fewer hospitalization and better quality of living

Question 23

A full dose of loop diuretics produces

Answer 23

massive NaCl
diuresis

Question 24

Effects of Loop Diuretics

Answer 24

• A full dose produces massive NaCl diuresis
• Rapid excretion of Edema fluid
• Blood volume may be significantly reduced
• Greatly increased quantities of solute delivered to distal parts of nephron
  -solutes act as osmotic agents-
• Reduced diluting ability of nephron
  (LOH is site of significant dilution of
  urine)

Question 25

Effects on Urinary Excretion

Answer 25

* Massive excretion of Na+ and Cl --(s/e: **hyponatremia**) * Significantly increased **Ca2+ and Mg2+ excretion** (s/e: Hypocalcemia & Hypomagnesemia) due to loss of lumen (+) potential * **Increased delivery of Na+ to DT** may result in **increased excretion of K**+ **titratable acids **(s/e:→hypokalaemic alkalosis)

Question 26

Effects on Renal Hemodynamics

Answer 26

* Generally **increase total RBF** & redistribute RBF to midcortex * Effects on RBF variable * Block TGF by inhibiting salt transport into macula densa (can no longer detect NaCl concentration in TF) ** Powerful simulators of renin release*

Question 27

Actions of Loop Diuretics

Answer 27

1. Acutely increase systemic venous capacitance 2. High doses can inhibit electrolyte transport in many tissues 3. Synergistic effect on ear (OTOTOXICITY) with aminoglycosides

Question 28

how can loop diuretics, especially furosemide Acutely increase systemic venous capacitance

Answer 28

**decrease**** LV filling pressure** (mediated by **prostaglandins** & requires intact kidneys ) **benefits pts with pulmonary edema** *even before diuresis*

Question 29

High doses can inhibit electrolyte transport in many tissues

Answer 29

important clinical effect **only** in the **inner ear**

Question 30

Absorption and Elimination Furosemide oral availability: t1/2? Elimination how many percent excreted unchanged in urine, how many percent is conjugated to **glucoronic acid** in kidney

Answer 30

oral availability~60%, **t1/2 ~1.5h,** 65% excreted unchanged in urine, 35% conjugated to glucoronic acid in kidney

Question 31

efficacy of loop diuretics is decreased by

Answer 31

Efficacy decreased by ***NSAIDs***

Question 32

has 89% oral availabilities; with significant **hepatic metabolism**, *t1/2 prolonged by liver disease*

Answer 32

**Bumeta**nide & **Torse**mide

Question 33

drugs used in HF patients have fewer hospitalizations & better Quality Of Living (because of more reliable absorption)

Answer 33

Torsemide

Question 34

Postdiuretic Na+ Retention’

Answer 34

**Short dosing** intervals **cannot maintain adequate levels **of Loop Diuretics in lumen → 1. LD concentration in lumen declines → 2. Nephrons avidly reabsorb Na+ → 3. LD effect on total body Na+ is nullified

Question 35

Remedy ‘Postdiuretic Na+ retention’

Answer 35

1. Restrict dietary Na+ intake 2. Administer Loop Diuretic more frequently

Question 36

Adverse Effects because

Answer 36

mostly due to abnormalities of fluid & electrolyte balance Hyponatremia Hypokalemia

Question 37

Overzealous LD use →serious depletion of total body Na+ depletion what are the consequences

Answer 37

**Hyponatremia** and/or ECF volume depletion → **hypotension**, **reduced GFR**, **circulatory collapse,** **thrombo embolic episode**, **hepatic encephalopathy**

Question 38

Hypokalemia effect

Answer 38

(may **induce** **arrhythmias** esp in pts taking cardiac glycosides) develops if dietary K+ is insufficient

Question 39

how Hypokalemia develops

Answer 39

increased urinary excretion of K+, H+ -->arrhythmias (esp pts on glycosides)

Question 40

effects of Hypomagnasemia

Answer 40

(risk factor for arrhythmias)

Question 41

why there is Hypocalcemia

Answer 41

from increased Mg+ and Ca2+ excretion

Question 42

may precipitate DM

Answer 42

Hyperglycemia

Question 43

Adverse Effects

Answer 43

1. **Increase** plasma **levels** of **LDL** chol , **TG**; **decrease HDL** 2. Ototoxicity due to rapid IV administration; often induced by **Ethacrynic acid** (use only when other LDs intolerable to pt) 3. Skin rashes, photosensitivity, paresthesias , **bone marrow depression**, GI disturbances

Question 44

Contraindications

Answer 44

* Severe Na+ or volume depletion * Hypersensitivity to sulfonamides * Anuria unresponsive to LD trial dose * Postmenopausal **osteopenic** women (increased Ca2+ excretion is deleterious to bone metabolism)

Question 45

Drug to Drug interactions When LDs are coadministered with: **Aminoglycosides**

Answer 45

synergism of ototoxicity

Question 46

Drug to Drug interactions When LDs are coadministered with: **Anticoagulants**

Answer 46

increased anticoagulant activity

Question 47

Drug to Drug interactions When LDs are coadministered with: **Digitalis glycosides**

Answer 47

increased digitalis induced arrhythmias

Question 48

Drug to Drug interactions When LDs are coadministered with: **Lithium, Propanolol**

Answer 48

increased plasma levels

Question 49

Drug to Drug interactions When LDs are coadministered with: **Sulfonylureas**

Answer 49

hyperglycemia

Question 50

Drug to Drug interactions When LDs are coadministered with: **Cisplatin**

Answer 50

increased risk of ototoxicity

Question 51

mode of action of loop diuretics

Answer 51

Inhibit **NaK2Cl** transporter in** TAL**

Question 52

Powerful, efficacious diuretics (‘high ceiling’)

Answer 52

loop diuretics

Question 53

uses

Answer 53

HF, PE, HPN, Hypercalcemia, ARF, Anion overdose

Question 54

side effects

Answer 54

**Hypokalemic metabolic alkalosis, Potassium wasting, Hypocalcemia, Hypomagnesemia by HYPERuricemia

Question 55

Synergistic ototoxicity with

Answer 55

aminoglycosides

Question 56

Decreased efficacy if taken with

Answer 56

NSAIDs