Download - IV - How Do I Use Them
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DIURETICS
How do they work?What do they do?
When do I use them?HOW DO I USE THEM?
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0.01 0.1 1 10 100 1000 100000
50
100
150
Dose
Response
CONCEPT OF CEILING DOSE
Ceiling [Diuretic]TL
Ceiling Effect
Log [Diuretic]TL
Fra
ctio
nal
Exc
reti
on o
f S
odiu
m (
%)
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CONCEPT OF CEILING DOSE
Dose of Diuretic that Achieves a Ceiling[Diuretic] in the Tubular Lumen.
Said Differently
Dose of Diuretic that Yields a Near-MaximalDiuretic Response.
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CONCEPT OF CEILING DOSE
EFFECT
< Ceiling Effect
Ceiling Effect
Ceiling Effect
ACTUAL DOSE
< Ceiling Dose
Ceiling Dose
> Ceiling Dose
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CONCEPT OF CEILING DOSE
Exceeding Ceiling Dose Yields:
Pointless, and possibly harmful, toexceed ceiling dose of diuretic!!
No AdditionalEffect
Possible Adverse Effects
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DETERMINANTS OF CEILING DOSE
VARIABLE
Ceiling Dose Depends on:•Diuretic•Disease
Increased Potency Decrease
CEILING DOSE
Decreased Tubular Transport(e.g., ARF/CRF) Increase
Increased Binding to UrinaryProteins (e.g., Nephrotic Syndrome) Increase
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CEILING DOSES FOR I.V. LOOP DIURETICS(in mgs)
CIRRHOSIS HEART FAILURE
40 to 80
1 to 2
10 to 20
NEPHROTICSYNDROME
AFR/CRFModerate
AFR/CRFSevere
160 to 200
8 to 10
50 to 100
80 to 160
4 to 8
20 to 50
80 to 120
2 to 3
20 to 50
40 to 80
1 to 2
10 to 20
Furosemide
Bumetanide
Torsemide
Protein BindingIncreases Ceiling
Dose
Impaired DeliveryIncreases Ceiling
Dose
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CONVERTING I.V. DOSING TOORAL DOSING
BIOAVAILABILITY CONVERSION FACTOR
~ 50% (highly variable)
~ 100%
~ 100%
2 or higher
1
1
Furosemide
Bumetanide
Torsemide
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DETERMINANTS OF CEILING EFFECT
VARIABLE
Ceiling Effect Depends on:•Diuretic•Disease
Diuretic Loop > Thiazide > K-Sparing
CEILING EFFECT
DiseaseDiminished Nephron Response
in Nephrotic Syndrome, Cirrhosis,& Heart Failure.
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MECHANISMS OF DIURETIC RESISTANCE
MECHANISM
Patient Counseling
SOLUTION
Patient Counseling
Push to Ceiling Dose
Noncompliance
NSAIDS
Decreased Tubular Transport(e.g., ARF & CRF)
Bed RestDecreased RBF
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MECHANISMS OF DIURETIC RESISTANCE(Continued)
MECHANISM SOLUTION
Bed Rest
More Frequent Dosing or Continuous Infusion
Combination Therapy(Sequential Blockade)
Changes in “Volume Hormones”(SNS, RAS, ADH & ANF)
Compensation by Distal Nephron
Diminished Nephron Response(CHF, Cirrhosis, Nephrotic Syndrome)
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MECHANISMS OF DIURETIC RESISTANCE
Proximal Distal
Na Na
Proximal Distal
Na
Proximal Distal
Na Na
Na
Proximal Distal
Na Na
AcuteLoop
ChronicLoop
ChronicLoop + Thiazide
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MECHANISMS OF DIURETIC RESISTANCE(Continued)
MECHANISM SOLUTION
Bed Rest
More Frequent Dosing or Continuous Infusion
Combination Therapy(Sequential Blockade)
Changes in “Volume Hormones”(SNS, RAS, ADH & ANF)
Compensation by Distal Nephron
Diminished Nephron Response(CHF, Cirrhosis, Nephrotic Syndrome)
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RATIONALE FOR MORE FREQUENT DOSINGOR CONTINUOUS I.V. INFUSION
[Diuretic]TL Ceiling
[Diuretic]TL
[Diuretic]TL
Ceiling
Ceiling
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CEILING DOSES FOR CONTINUOUS I.V.INFUSION OF LOOP DIURETICS
(in mgs per hour)
LOADING DOSE(in mgs)
CrCl < 25
10
0.5
5
10 to 20
0.5 to 1
5 to 10
20 to 40
1 to 2
10 to 20
40
1
20
Furosemide
Bumetanide
Torsemide
CrCl: 25 to 75 CrCl > 75
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WHAT HAPPENS WHEN [DIURETIC]IN TUBULAR LUMEN IS LESS
THAN CEILING??
Postdiuresis Sodium Retention!!
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RATIONALE FOR LOW SODIUM DIET
A low sodium diet attenuates postdiureticsodium retention, thereby lowering diuretic
requirements!!
Major Problem is Compliance
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IMPORTANT DRUG INTERACTIONS
NSAIDSSalt
DecongestantsProbenecid
Hyperkalemia-Induced by K-Sparing
Diuretics
Enhanced Ototoxicityof Loop Diuretic
DiminishedDiureticResponse
ACE InhibitorsBeta-Blockers
K SupplementsK-Sparing Diuretics
Heparin
Ototoxic Drugs
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ARF/CRF Nephrotic Syndrome Cirrhosis Mild CHFSevere/Moderate
CHF
DROP Thiazide &ADD Loop Diuretic:1) Titrate Single Daily Dose to Ceiling2) Optimize Frequency of Ceiling Dose
•Furosemide: up to 4X daily•Bumetanide: up to 6X daily•Torsemide: up to 3X daily
ADD Thiazide Diuretic:•CrCl > 50, use 25 to 50 mg/d HCTZ•CrCl 20 to 50, use 50 to 100 mg/d HCTZ•CrCl < 20, use 100 to 200 mg/d HCTZ
ADD K-Sparing Diuretic:•If CrCl > 75•If Urinary [Na]:[K] ratio is < 1
(Note: May add K-Sparing Diuretic to Loop and/or Thiazide Diuretic at Any Point in Algorithmfor K Homeostasis.)
While Maintaining Other Diuretics, Switch Loop Agent to Continuous Infusion
SpironolactoneTitrated to 400 mgDaily.
ADD Thiazide:•If CrCl > 50•50 to 100 mg/d HCTZ
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