2B : DIURETICS - LOOP Flashcards
Acts on the (TAL) thick ascending limb of the loop of henle
LOOP DIURETICS
A full dose produces
Massive NaCl diuresis
mechanism of action of loop diuretics
- 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
- MOA: It selectively block the luminal Na+/K+/2Cl
transporter in the TAL
- Powerful, efficacious diuretics
(‘high ceiling’) - Unlimited by acidosis
LOOP DIURETICS
result of selectively blocking the luminal
Na+/K+/2Cl transporter in the TAL
selective inhibition of NaCl reabsorption
has weak CAI activity (increase the
urinary excretion of HCO3 and phosphate)
Furosemide
blocking NKCC2
halts NaCl transport
inhibits
reabsorption of Ca2+ & Mg2+
prototype of loop diuretics
Furosemide
- phenoxyacetic derivative
- ## same MOA as furosemide
Ethacrynic
acid
Ethacrynic acid is a moderately effective uricosuric drug if blood volume is maintained
Ethacrynic
acid
Organic Mercurial Diuretics
Loop Diuretics
Therapeutic uses of Loop Diuretics
- Acute Pulmonary Edema
- Chronic CHF
- HTN
- forced diuresis
- Edematous conditions
- Hypercalcemia
- Life threatening hypervolemic hyponatremia
8.
major use of loop diuretics
Acute Pulmonary Edema
to rapidly increase in venous capacitance + brisk
natriuresis reduce LV filling pressures
effect of loop diuretics on chronic CHF
to** diminish ECF volume **to minimize venous & pulmonary congestion
significantly reduces mortality & risk of worsening HF, improves exercise capacity
what type of fluid solution to give in combination with loop diuretics in these condtions
- Hypercalcaemia
- Life threatening hypervolaemic hyponatraemia
- Hypercalcaemia give LD + isotonic saline (to prevent volume depletion)
- Life threatening hypervolaemic hyponatraemia– LD + hypertonic saline
how can LD benefit patients with acute pulmonary edema
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)
therapeutic uses
- 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)
Contraindicated to patient with
osteoporosis or hypocacelmic
When LDs are
coadministered with
Aminoglycosides what is the effect
ototoxicity
When LDs are
coadministered with
sulfonylurea what is the effect
hyperglycemia
BUMETANIDE dosage and consideration
0.5 - 2mg OD
- Significant hepatic metabolism and half life may prolonged by liver disease
Ethacrynic acid dosage and consideration
25 - 100 mg OD
* More reliable absorption and heart failure atients have fewer hospitalization and better quality of living
A full dose of loop diuretics produces
massive NaCl
diuresis
Effects of Loop Diuretics
- 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)
Effects on Urinary Excretion
- 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)
Effects on Renal
Hemodynamics
- 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*
Actions of Loop Diuretics
- Acutely increase systemic venous capacitance
- High doses can inhibit electrolyte transport in many tissues
- Synergistic effect on ear (OTOTOXICITY) with
aminoglycosides
how can loop diuretics, especially furosemide Acutely increase systemic venous capacitance
decrease** LV filling pressure** (mediated by
prostaglandins & requires intact kidneys )
benefits pts with pulmonary edema even before diuresis
High doses can
inhibit electrolyte transport in many
tissues
important clinical effect only in the inner ear
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
oral availability~60%, t1/2 ~1.5h,
65% excreted unchanged in urine,
35% conjugated to glucoronic acid in kidney
efficacy of loop diuretics is decreased by
Efficacy decreased by NSAIDs
has 89% oral availabilities; with significant hepatic metabolism, t1/2 prolonged by liver
disease
Bumetanide
& Torsemide
drugs used in HF patients have fewer hospitalizations & better Quality Of Living (because of more reliable absorption)
Torsemide
Postdiuretic Na+ Retention’
Short dosing intervals **cannot maintain
adequate levels **of Loop Diuretics in lumen →
- LD concentration in lumen declines →
- Nephrons avidly reabsorb Na+ →
- LD effect on total body Na+ is nullified
Remedy ‘Postdiuretic Na+ retention’
- Restrict dietary Na+ intake
- Administer Loop Diuretic more frequently
Adverse Effects because
mostly due to
abnormalities of fluid & electrolyte balance
Hyponatremia
Hypokalemia
Overzealous LD use →serious depletion of total
body Na+ depletion
what are the consequences
Hyponatremia and/or ECF volume depletion →
hypotension, reduced GFR, circulatory collapse,
thrombo embolic episode, hepatic encephalopathy
Hypokalemia effect
(may induce arrhythmias esp in pts taking cardiac glycosides) develops if dietary K+ is
insufficient
how Hypokalemia develops
increased urinary excretion of K+, H+ –>arrhythmias (esp pts on glycosides)
effects of Hypomagnasemia
(risk factor for arrhythmias)
why there is Hypocalcemia
from increased Mg+ and Ca2+
excretion
may precipitate DM
Hyperglycemia
Adverse Effects
- Increase plasma levels of LDL chol , TG; decrease HDL
- Ototoxicity due to rapid IV administration; often induced by Ethacrynic acid (use only
when other LDs intolerable to pt) - Skin rashes, photosensitivity, paresthesias , bone marrow depression, GI disturbances
Contraindications
- 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)
Drug
to Drug interactions
When LDs are
coadministered with:
Aminoglycosides
synergism of ototoxicity
Drug
to Drug interactions
When LDs are
coadministered with:
Anticoagulants
increased anticoagulant activity
Drug
to Drug interactions
When LDs are
coadministered with:
Digitalis glycosides
increased digitalis induced
arrhythmias
Drug
to Drug interactions
When LDs are
coadministered with:
Lithium, Propanolol
increased plasma levels
Drug
to Drug interactions
When LDs are
coadministered with:
Sulfonylureas
hyperglycemia
Drug
to Drug interactions
When LDs are
coadministered with:
Cisplatin
increased risk of ototoxicity
mode of action of loop diuretics
Inhibit NaK2Cl transporter in** TAL**
Powerful, efficacious diuretics
(‘high ceiling’)
loop diuretics
uses
HF, PE, HPN, Hypercalcemia, ARF,
Anion overdose
side effects
**Hypokalemic metabolic alkalosis,
Potassium wasting, Hypocalcemia,
Hypomagnesemia by HYPERuricemia
Synergistic ototoxicity with
aminoglycosides
Decreased efficacy if taken with
NSAIDs
