DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

700
Chronic
renal
failure
Nephrotic
syndrome
Moderate
or
severe
CHF
Cirrhosis
Spironolactone:
Titrate up to 400 mg/d
as needed.
CrCl
<
50
add
Cr
Cl
>
50
Cr
Cl
<
50
add
Mild
CHF
Cr
Cl
>
50
Loop diuretic: Titrate single daily dose up to ceiling dose* as needed
Drop Thiazide
Thiazide:
50 to 100 mg/d HCTZ
Loop diuretic: Increase frequency of ceiling does as needed:
Furosemide, up to 3X daily; Bumetanide, up to 4X daily; Torsemide, up to 2X daily
Add
SECTION III
K + -sparing diuretic:
If CrCl > 75 & urinary [Na]:[K] ratio is < 1
(Note: May add K + -sparing diuretic to loop
and/or thiazide diuretic at any point in algorithm
for K + homeostasis.)
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
MODULATION OF CARDIOVASCULAR FUNCTION
While maintaining other diuretics, switch loop agent to continuous infusion
Figure 25–15. “Brater’s algorithm” for diuretic therapy of chronic renal failure, nephrotic syndrome, congestive heart failure, and cirrhosis.
Follow algorithm until adequate response is achieved. If adequate response is not obtained, advance to the next step. For illustrative
purposes, the thiazide diuretic used in Brater’s algorithm is hydrochlorothiazide (HCTZ). An alternative thiazide-type diuretic
may be substituted with appropriate dosage adjustment so as to be pharmacologically equivalent to the recommended dose of HCTZ.
Do not combine two K + -sparing diuretics because of the risk of hyperkalemia. CrCl indicates creatinine clearance in mL/min, and ceiling
dose refers to the smallest dose of diuretic that produces a near-maximal effect. Ceiling doses of loop diuretics and dosing regimens
for continuous intravenous infusions of loop diuretics are disease-state-specific. In this regard, see Brater (1998) for
recommended dosages. Doses are for adults only.
nephrons may have diminished diuretic responsiveness
because of increased proximal tubular Na + reabsorption,
leading to diminished Na + delivery to distal
nephron segments (Knauf and Mutschler, 1997).
Faced with resistance to loop diuretics, the clinician
has several options:
1. Bed rest may restore drug responsiveness by
improving the renal circulation.
2. An increase in dose of loop diuretic may restore
responsiveness; however, nothing is gained by
increasing the dose above that which causes a nearmaximal
effect (the ceiling dose) of the diuretic.
3. Administration of smaller doses more frequently
or a continuous intravenous infusion of a loop
diuretic (Ferguson et al., 1997) will increase the
length of time that an effective diuretic concentration
is at the active site.
4. Use of combination therapy to sequentially block
more than one site in the nephron may result in a
synergistic interaction between two diuretics. For
instance, a combination of a loop diuretic with a
K + -sparing or a thiazide diuretic may improve therapeutic
response; however, nothing is gained by the
administration of two drugs of the same type.
Thiazide diuretics with significant proximal tubular effects
(e.g., metolazone) are particularly well suited for sequential
blockade when co-administered with a loop diuretic. This
combination should be used with caution and the patient followed
closely in the first few weeks of therapy. Significant
complications may ensue, including severe hyponatremia,
hypokalemia, and volume depletion. The patient should be
warned to stop both drugs and contact his or her physician if
weight loss exceeds 5 pounds per week.
5. Reducing salt intake will diminish postdiuretic Na +
retention that can nullify previous increases in Na +
excretion.
6. Scheduling of diuretic administration shortly before
food intake will provide effective diuretic concentration
in the tubular lumen when salt load is highest.