GASTROINTESTINAL

DISEASES & IT'S DRUGS

RAYMUND N. TAPAOAN, RPH
D. INTRODUCTION
REFLUX DISEASE
In this picture the common factors in g
astro-oesophageal reflux disease are
shown.
These include a lack of saliva, poor pe
ristaltic movement through the oesoph
agus, decreased lower oesophageal s
phincter (LES) pressure, transient epis
odes of LES relaxation, delayed gastri
c emptying, and increased gastric acid
. However, therapy is aimed at decrea
sing gastrointestinal gastric acid, incre
asing gastric motility or increasing LE
S tone.
H2 ANTAGONISTS
FOR REFLUX
H2-antagonists were originally introd
uced for the treatment of peptic ulcer
s (see H2-antagonists for ulcers ).
However, due to the high relapse rat
e of reflux patients taking antacids,
maintenance therapy with H2-recept
or antagonists (or PPI's) is often indi
cated. Tolerance can occur and patie
nts chronically using the H2-antagoni
sts may require higher than normal d
osages.
PROTON PUMP INHIBITORS F
OR REFLUX
Acid inhibitory therapy is effective in healing re
flux-oesophagitis and treating symptoms of refl
ux disease.
With the powerful acid inhibition induced by P
PI's (see proton pump inhibitors for ulcers), ov
er 95% of patients with reflux disease are cure
d after 12 weeks therapy.
However, within one year after stopping therap
y, over 75% of patients who had grade 2 endo
scopic oesophagitis or higher, will relapse.
Therefore maintenance therapy with PPI's or
H2 receptor antagonists is indicated in those p
atients. In case of severe reflux symptoms, the
amount of reflux should be evaluated by 24-ho
ur pH metry or by mucosal inflammation durin
g endoscopy.
MUCOSA PROTECTIV
E
Sucralfate can be used for ulcers and for refl
ux disease because of its various actions. To
gether with bismuth, sucralfate belongs to th
e group of mucosa protectives.

In the treatment of ulcers, sucralfate is helpfu

l in protecting the surface of the ulcer. In the
acidic environment of the stomach (pH < 4) it
reacts with hydrochloric acid to form a cross-
link with tissue proteins at the surface of ulce
rs and other lesions. This complex protects t
he tissue from further damage by acid and p
epsin. In this role, the mechanism of action o
f sucralfate is similar to that of bismuth.
MUCOSA PROTECTIV
E
Sucralfate can be used for ulcers an
d for reflux disease Sulcralfate also h
as an indirect role in decreasing acid
production. It has been shown to sti
mulate prostaglandin E2 production.
Prostaglandin E2 inhibits the acid pr
oduction by the parietal cell.

Side effects include constipation, na

usea, allergic skin reactions, and bez
oar (a mass found trapped in the GI
system).
5-HT4 AGONISTS
5-HT4-agonists such as cisapride (Pre
pulsid®) may increase the efficacy of t
herapy in reflux disease when combine
d with PPI's or H2-receptor antagonists
.
Cisapride increases LES pressure, imp
roves oesophageal body motility (more
rapid clearance of acid) and accelerate
s gastric emptying.
Cisapride has no effect on colonic motil
ity, and thus is not used as a laxative.
However, another 5-HT4-agonist (pruc
alopride) is.
INTRODUCTION GALLB
LADDER
The gallbladder, localized under the right liver lobe,
serves two major functions: bile storage and bile m
odification. The bile produced by the liver is concen
trated and stored in the gallbladder. Without food in
the stomach the sphincter of Oddi is closed and the
bile remains in the gallbladder.
Upon arrival of food (containing lipids) in the duode
num (1), the cells in the wall of the duodenum relea
se cholecystokinin (CCK) (2,3). Via the circulation
(4) CCK reaches the gallbladder and stimulates co
ntraction of the bladder (5). CCK also relaxes the s
phincter of Oddi (6), which results in secretion of bil
e in the duodenum.
Bile salts break fat droplets; this is called emulsifica
tion (7). The bile salts also facilitate the interaction
between pancreatic lipid-digesting enzymes and lip
ids and absorption by the intestine.
E. CHOLELITHIASIS
When bile becomes too concentrated, crysta
ls can be formed. Bile salts and phospholipid
s keep cholesterol in a micelle solution. Whe
n there is a shortage of bile salts or a surplu
s of cholesterol, gall stones can be formed.
In cholelithiasis the crystals/stones are small
enough to pass through the bile duct. If the c
rystals and stones become too large, they c
an damage the wall of the gallbladder and bl
ock the bile duct.
Since the bile cannot be released, the press
ure in the bladder elevates and causes pain.
In severe cases the gallbladder can become
infected (cholecystitis).
CHOLECYSTECTOM
Y
Surgical treatment is the best option in case of seve
re damage or inflammation of the gallbladder by gall
stones. Surgical removal of the gallbladder (1, chole
cystectomy by laparoscopy) has no severe impact o
n the digestive process. Bile production continues, h
owever, it is no longer concentrated and its release i
n the duodenum is not closely tied to food arrival in t
he stomach. The circulation of bile salts is quicker a
nd more fat is excreted via the digestive tract.
ERCP (endoscopic retrograde cholangiopancreatog
raphy) is a diagnostic method which can be used to
remove gallstones as well.
Another non-pharmacological option to treat gallsto
nes is the non-invasive method lithotripsy (2). In this
case the gallstones are shattered by focused sound
waves. The fragments of the stones become small e
nough to pass through the duct. Lithotripsy is not ve
ry effective and therefore infrequently used.
BILE SALTS
In people with a functioning gallbladder, bile s
alts (which act by desaturating cholesterol in t
he bile) taken orally may dissolve gallstones
containing cholesterol. However, the process
may take 2 years or longer, and stones may r
eturn after the therapy is ended.
Medical dissolution, using ursodeoxycholic ac
id is successful in 40% of cases. This bile salt
is used for the dissolution of gall stones and f
or various liver disorders. It suppresses hepat
ic bile acid synthesis and secretion. Furtherm
ore, it solubilizes cholesterol in micelles and c
auses dispersion of cholesterol as liquid cryst
als.
For the treatment of liver disorders other prop
erties of ursodeoxycholic acid are useful: it re
duces the toxic bile acids in bile, and it has im
munomodulating effects on the hepatocellular
membranes.
INTRODUCTION-PAN
CREAS
The pancreas, localized in the retroperitoneum
, plays an important role in digestion and uptak
e of food. The endocrine pancreas is formed b
y the islets of Langerhans which secrete insuli
n and glucagon. The exocrine pancreas includ
es the acinar cells which secrete pancreatic jui
ce. This juice contains a variety of enzymes:
• buffer solution with bicarbonate and phospha
te buffers which restore the pH
• alpha-amylase which breakdown carbohydra
te chains
• pancreatic lipase which breaks down lipids in
to fatty acids
• nuclease which breaks down nucleic acids
• proteolytic enzyme for the digestion of protei
ns
INTRODUCTION-PAN
CREAS
Upon arrival of food containing lipid
s, proteins and glucose in the duod
enum (1),
the cells in the wall of the duodenu
m release cholecystokinin (CCK) an
d gastric inhibitory peptide (GIP) int
o the circulation (2).
CCK stimulates the release of panc
reatic enzymes into the intestine (3)
.
GIP stimulates the secretion of insul
in by the pancreatic islets into the ci
rculation (4).
INTRODUCTION-PAN
CREAS
Upon arrival of food containing lipid
s, proteins and glucose in the duod
enum (1),
the cells in the wall of the duodenu
m release cholecystokinin (CCK) an
d gastric inhibitory peptide (GIP) int
o the circulation (2).
CCK stimulates the release of panc
reatic enzymes into the intestine (3)
.
GIP stimulates the secretion of insul
in by the pancreatic islets into the ci
rculation (4).
F. PANCREATITIS
Depending on the cause and severity of the
pancreatitis, the pancreatic enzymes can af
fect their own environment. Especially the p
roteases secreted by the pancreas which a
re released and activated upon arrival of fo
od in the duodenum.
When these enzymes cannot be released i
nto the duodenum, they can cause damage
and destruction of the pancreatic tissue itse
lf (autolysis). The decreased function of the
pancreas can cause fatty diarrhea and incr
eased glucose levels (like in diabetes). Pan
creatitis is accompanied by severe abdomi
nal pain.
An inflammation of the pancreas can have
various causes. In acute pancreatitis, gallst
ones and alcohol account for 70 % of case
s. Many drugs may give rise to pancreatitis.
F. PANCREATITIS
The following drugs are well-known to cau
se acute pancreatitis:
• diuretics like furosemide and hydrochloro
thiazide
• antimicrobial drugs: tetracyclines, sulpho
namides, rifampicin, and metronidazole
• immunosuppressants: corticosteroids, az
athioprine and mercaptopurine
• estrogens
• selective serotonin reuptake inhibitors (S
SRIs)
• 5-acetylsalicylic acid agents (mesalazine
and olsalazine)
• miscellaneous: indomethacin, enalapril,
methyldopa, simvastatin, sodium valproa
te
TREAMENT OF PANC
REATITIS
Treatment of pancreatitis depends on the pa
thogenesis. When the pancreatic enzymes a
re released too early by acid activation in th
e duodenum (already in the pancreas itself),
this activation can be prevented by fasting.
When there is no acid production by the sto
mach, there will be no activation of pancreati
c juice secretion by CCK nor GIP. Keeping a
way stomach acid from the duodenum to pre
vent pancreatic secretory stimulation can als
o be reached by treatment with octreotide or
protease inhibitors.
In case of pancreatic exocrine insufficiency, t
reatment with pancreatic enzymes can be st
arted in order to supply the lacking enzymes
and allow proper digestion.
TREAMENT OF PANC
REATITIS
Pancreatin is a mixture of:
fat dissolving enzyme, lipase, which catalyzes t
he hydrolysis of fats into glycerol and fatty acids
protein enzymes such as protease, that convert
protein into peptides and amino acids
enzymes like amylase that break down starch a
nd complex sugar molecules into smaller carbo
hydrates like dextrins and glucose
Pancreatin tablets are prescribed for patients w
ho are unable to digest food properly because o
f an insufficient amount of natural pancreatic se
cretions. This deficit may be caused by disorder
s of the pancreas, for example, pancreatitis or c
ystic fibrosis.
When also the endocrine function of the pancre
as is disturbed, suppletion with insulin might be
required as well.
 THANK YOU
RNTER TEXT

MEDICAL EXPERTS TO LECTURE