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PHARMA > 2B : DIURETICS - LOOP > Flashcards

2B : DIURETICS - LOOP Flashcards

1
Q

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

A

LOOP DIURETICS

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2
Q

A full dose produces

A

Massive NaCl diuresis

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3
Q

mechanism of action of loop diuretics

A
  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

  1. MOA: It selectively block the luminal Na+/K+/2Cl
    transporter in the TAL
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4
Q
  • Powerful, efficacious diuretics
    (‘high ceiling’)
  • Unlimited by acidosis
A

LOOP DIURETICS

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5
Q

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

A

selective inhibition of NaCl reabsorption

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6
Q

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

A

Furosemide

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7
Q

blocking NKCC2

A

halts NaCl transport

inhibits
reabsorption of Ca2+ & Mg2+

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8
Q

prototype of loop diuretics

A

Furosemide

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9
Q
  • phenoxyacetic derivative
  • ## same MOA as furosemide
A

Ethacrynic
acid

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10
Q

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

A

Ethacrynic
acid

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11
Q

Organic Mercurial Diuretics

A

Loop Diuretics

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12
Q

Therapeutic uses of Loop Diuretics

A
  1. Acute Pulmonary Edema
  2. Chronic CHF
  3. HTN
  4. forced diuresis
  5. Edematous conditions
  6. Hypercalcemia
  7. Life threatening hypervolemic hyponatremia
    8.
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13
Q

major use of loop diuretics

A

Acute Pulmonary Edema

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

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14
Q

effect of loop diuretics on chronic CHF

A

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

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

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15
Q

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

  • Hypercalcaemia
  • Life threatening hypervolaemic hyponatraemia
A
  • Hypercalcaemia give LD + isotonic saline (to prevent volume depletion)
  • Life threatening hypervolaemic hyponatraemia– LD + hypertonic saline
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16
Q

how can LD benefit patients with acute pulmonary edema

A

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)

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17
Q

therapeutic uses

A
  • 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)
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18
Q

Contraindicated to patient with

A

osteoporosis or hypocacelmic

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19
Q

When LDs are
coadministered with
Aminoglycosides what is the effect

A

ototoxicity

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20
Q

When LDs are
coadministered with
sulfonylurea what is the effect

A

hyperglycemia

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21
Q

BUMETANIDE dosage and consideration

A

0.5 - 2mg OD

  • Significant hepatic metabolism and half life may prolonged by liver disease
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22
Q

Ethacrynic acid dosage and consideration

A

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

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23
Q

A full dose of loop diuretics produces

A

massive NaCl
diuresis

24
Q

Effects of Loop Diuretics

A
  • 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)
25
Q

Effects on Urinary Excretion

A
  • 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)
26
Q

Effects on Renal
Hemodynamics

A
  • 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*
27
Q

Actions of Loop Diuretics

A
  1. Acutely increase systemic venous capacitance
  2. High doses can inhibit electrolyte transport in many tissues
  3. Synergistic effect on ear (OTOTOXICITY) with
    aminoglycosides
28
Q

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

A

decrease** LV filling pressure** (mediated by
prostaglandins & requires intact kidneys )

benefits pts with pulmonary edema even before diuresis

29
Q

High doses can
inhibit electrolyte transport in many
tissues

A

important clinical effect only in the inner ear

30
Q

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

A

oral availability~60%, t1/2 ~1.5h,

65% excreted unchanged in urine,

35% conjugated to glucoronic acid in kidney

31
Q

efficacy of loop diuretics is decreased by

A

Efficacy decreased by NSAIDs

32
Q

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

A

Bumetanide
& Torsemide

33
Q

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

A

Torsemide

34
Q

Postdiuretic Na+ Retention’

A

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
35
Q

Remedy ‘Postdiuretic Na+ retention’

A
  1. Restrict dietary Na+ intake
  2. Administer Loop Diuretic more frequently
36
Q

Adverse Effects because

A

mostly due to
abnormalities of fluid & electrolyte balance

Hyponatremia
Hypokalemia

37
Q

Overzealous LD use →serious depletion of total
body Na+ depletion

what are the consequences

A

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

38
Q

Hypokalemia effect

A

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

39
Q

how Hypokalemia develops

A

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

40
Q

effects of Hypomagnasemia

A

(risk factor for arrhythmias)

41
Q

why there is Hypocalcemia

A

from increased Mg+ and Ca2+
excretion

42
Q

may precipitate DM

A

Hyperglycemia

43
Q

Adverse Effects

A
  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
44
Q

Contraindications

A
  • 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)
45
Q

Drug
to Drug interactions

When LDs are
coadministered with:

Aminoglycosides

A

synergism of ototoxicity

46
Q

Drug
to Drug interactions

When LDs are
coadministered with:

Anticoagulants

A

increased anticoagulant activity

47
Q

Drug
to Drug interactions

When LDs are
coadministered with:

Digitalis glycosides

A

increased digitalis induced
arrhythmias

48
Q

Drug
to Drug interactions

When LDs are
coadministered with:

Lithium, Propanolol

A

increased plasma levels

49
Q

Drug
to Drug interactions

When LDs are
coadministered with:

Sulfonylureas

A

hyperglycemia

50
Q

Drug
to Drug interactions

When LDs are
coadministered with:

Cisplatin

A

increased risk of ototoxicity

51
Q

mode of action of loop diuretics

A

Inhibit NaK2Cl transporter in** TAL**

52
Q

Powerful, efficacious diuretics
(‘high ceiling’)

A

loop diuretics

53
Q

uses

A

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

54
Q

side effects

A

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

55
Q

Synergistic ototoxicity with

A

aminoglycosides

56
Q

Decreased efficacy if taken with

A

NSAIDs

PHARMA (29 decks)

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