Objectives
Fluid compartmentalization
and body water distribution
Volume regulation:
Feedback mechanisms
High-pressure baroreceptors
ADH
Sympathetic outflow
Neurohormonal volume
regulation (RAAS)
Peripheral edema
(initially in right HF)
Pulmonary edema
(initially in left HF)
Diuretics
Other drugs may compete for the secretory pump and reduce diuretic
efficacy eg. NSAIDS, probenecid for acidic (S2 segment) and cimetidine
for basic (S1 and S2 segment) .
Most diuretics must enter the tubular fluid to exert their effects
most of the channels
on the luminal side. since
are on the luminal side
renal blood flow or renal failure reduces therapeutic efficacy.
There are about 1 million per kidney and about 75 miles of tubular length
GFR ~ 180 L/day in 70kg male
Diuretics Classes
(Sites of action)
Generic name
Trade name(s)
Available doses
Acetazolamide
Diamox
Methazolamide
Neptazane
Dichlorphenamide
Daranide
Oral: 50mg
Carbonic Anhydrase
Inhibitors
OVERALL EFFECT:
Pharmacokinetics
Indications
Toxicity
Hypersensitivity reactions
LOOP DIURETICS
Generic name
Trade name(s)
Available doses
Furosemide
Lasix, others
Bumetanide
(40x more potent)
Bumex
Oral: 0.5, 1, 2 mg
Parenteral: 0.5mg/2mL
Torsemide
Demadex
Ethacrynic Acid
Edecrin
Loop of Henle
(Thick ascending limb)
Loop Diuretics
Pharmacokinetics
Indications
Toxicity
Dehydration
THIAZIDES
Generic name
Trade name(s)
Available doses
Chlorothiazide
Diuril, others
Hydrochlorothiazide Microzide,
HydroDIURIL, others
Chlorthalidone
Thalitone, Hygroton,
combination drugs
Indapamide
Lozol, others
Metolazone
Mykrox, Diulo,
Zaroxolyn, others
Oral: 0.5mg
Thiazides
Unsubstituted
Sulfonamide
Cl
H2N-O2S
Pharmacokinetics
Indications
Toxicity
exacerbate gout
cardiac arrhythmias
Hyponatremia
Metabolic alkalosis
Hyperuricemia may
Clinical Evidence to
support treatment
The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure
B Pitt, F Zannad, WJ Remme, R Cody, A Castaigne, A Perez, J Palensky, J Wittes, for the Randomized Aldactone
Evaluation Study Investigators. N Engl J Med 1999; 341:709-717
In a double-blind study, 1663 patients with severe HF and LVEF <35% on ACE inhibitor, loop diuretic, and in most
cases digoxin. 822 randomly assigned to 25 mg of spironolactone daily, and 841 to receive placebo. Primary end point:
Death.
Spironolactone caused:
30% reduction in the risk of death
35% reduction frequency of hospitalization for worsening HF
Significant improvement in the symptoms of HF, assessed by New York Heart Association functional class
Conclusions:
Blockade of aldosterone receptors by spironolactone, in addition to standard therapy, substantially reduces
the risk of both morbidity and death among patients with severe heart failure.
POTASSIUM-SPARING DIURETICS
Generic name
Trade name(s)
Available doses
Spironolactone
Aldactone
Eplerenone
Amiloride
Oral: 5mg
Triamterene
Dyrenium
K+-sparing Diuretics
SPIRONOLACTONE, EPLERENONE
Indications
Mineralicorticoid excess:
Spironolactone: Pharmacokinetics
Spironolactone: Toxicity
Hyperkalemia
Endocrine effects:
secretion
Sub-Class II:
Na+ transport inhibition
Duration of action:
triamterene (7-9hrs)
amiloride (24hrs).
Contraindications:
Hyperkalemia alert
1.
2.
3.
4.
5.
OSMOTIC DIURETICS
Mannitol
Osmotic Diuretics
Osmotic Diuretics
Indications
urine volume
Toxicity
Conclusions