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

Table 25–4
Inhibitors of Na + –K + –2Cl – Symport (Loop Diuretics, High-Ceiling Diuretics)
RELATIVE ORAL t 1/2
ROUTE OF
DRUG STRUCTURE POTENCY AVAILABILITY (HOURS) ELIMINATION
Furosemide 1 ~60% ~1.5 ~65% R,
(LASIX)
~35% M b
CI NH-CH
O 2
H 2 NO 2 S
COOH
Bumetanide NH-CH 40 ~80% ~0.8 ~62% R,
2 -CH 2 -CH 2 -CH 3
(BUMEX)
O
~38% M
H 2 NO 2 S
COOH
Ethacrynic acid CI CI
0.7 ~100% ~1 ~67% R,
O
O
(EDECRIN)
~33% M
H 3 C-H 2 C-C-C
O-CH 2 -C-OH
CH 2
Torsemide H
3 ~80% ~3.5 ~20% R,
(DEMADEX)
~80% M
N N
CH 3
H 3 C O 2 S – NH — C – NH – CH
O
CH 3
Axosemide a 1 ~12% ~2.5 ~27% R,
CI
NH-CH 2
S
63% M
N
N
H 2 NO 2 S
N N
H
Piretanide a 3 ~80% 0.6-1.5 ~50% R,
~50% M
N
O
H 2 NO 2 S COOH
Tripamide a H ID ID ID ID
CI
H
H 2 NO 2 S
CONH N
H
H
a
Not available in the United States. b For furosemide, metabolism occurs predominantly in the kidney. Abbreviations: R, renal excretion of intact
drug; M, metabolism; ID, insufficient data.
Na + -K + -2Cl – symporter (Figure 25–7). This symporter captures free
energy in the Na + electrochemical gradient established by the basolateral
Na + pump and provides for “uphill” transport of K + and Cl –
into the cell. K + channels in the luminal membrane (called ROMK)
provide a conductive pathway for the apical recycling of this cation,
and basolateral Cl – channels (called CLC-Kb) provide a basolateral
exit mechanism for Cl – . Luminal membranes of epithelial cells in
thick ascending limb have a large conductive pathway (channels) for
K + ; therefore, apical membrane voltage is determined by the equilibrium
potential for K + (E K
) and is hyperpolarized. In contrast, the
basolateral membrane has a large conductive pathway (channels) for
Cl – , so the basolateral membrane voltage is less negative than E K
;