Choleretics, cholelitholytics
= drugs for enhancement of billiary secretion or for
dissolving of gallstones respectively
•
© Oldřich Farsa 2012
Functions of bile (gall): emulsifies fats and facilitates their enzymatic hydrolysis
Enterohepatal circulation of billiary acids
Billiary acids
•derivatives of cholan or cholan-24-oic acid respectively
CH3
R
7
CH3
CH3
OH
OH
O
H
H
H
H
R
12
3
7
12
24
R7
R12
α-OH -OH cholic acid – the most frequent one, raw material for synthesis of
other ones
α-OH -H chenodeoxycholic acid syn. chenodiol [USAN]
β-OH -H ursodeoxycholic acid syn. ursodiol [USAN] – drug for cholesterol
cholelithiasis Ursofalk®
, Ursosan®e
A
7
D
cis/trans/trans
3
12
12
3
7
A
D
OH
OH O
OH
OH
H
OHHO
H
OH
OH
O
H
Cholic acid and its stereochemistry
3α -OH, e: easily esterificable 7α -OH and 12α -OH a: easily oxidable
cholic acid
3α, 7α, 12α-trihydroxycholan-24-oic acid
Billiary acids conjugates
CH3
CH3
CH3
O
O
H
H
H
H
OH
OH
S
O
O
O
CH3
OH
CH3
CH3
OH
O
H
H
H
H
OH
NH
R
Cunjugates formed by reaction of carboxyl
with amino group of a suitable amino acid are
effective as fats emulsifiers in the form of Na+
salt
R = -COOH glycocholic acid (conjugate with
glycine)
R = -CH2SO3H taurocholic acid (conjugate
with taurine, i.e. 2-aminoethanesulfonic acid)
•other billiary acids are coonjugated similarly
lithocholic acid 3-sulfate – methabolic endproduct of cholic acid
Synthetic choleretics

stimulate secretion of billiary acid conjugates
OH
CH3
O
CH3
OOH
7-hydroxy-4-methyl-2H-chromene-2-on1-phenylpentane-1-ol
fenipentol
•stimulates also secretion of pancreatic enzymes
Febichol®
cps.
hymecromone
• also spasmolytic
Isochol®
drg.