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Culture Documents
Obat Git 2009
Obat Git 2009
Gastrointestinal Medicine
SJARIF ISMAIL
Lab. Farmakologi FK-UNMUL
1
PATHOGENESA PEPTIC ULCER
H. PYLORI
ZES NSAIDs
ALTERED
MUCOSAL
DEFENCE
ACID &
PEPSIN
MUCOSAL DAMAGE
ULCER
Pathogensis of peptic ulcer
2
Defensive factors:
Mucus: forms barriers and protect underlying
cells from attack of acid and pepsin
Bicarbonate: secreted by epithelial cells of
stomach and duodenum; neutralize any
hydrogen ions that penetrate the mucus
Blood flow: sufficient blood flow to cells
maintain mucosal integrity
Prostaglandins: stimulate secretion of mucus
and bicarbonate, promote vasodilation which
help submucosal blood flow, suppress
secretion of gastric acid.
5
Aggressive factors:
H. pylori- bacteria that colonize in the
stomach and duodenum
NSAIDs- inhibit biosynthesis of PG;
- decrease submucosal blood flow;
- promote gastric acid secretion.
Gastric acid: form peptic ulcer by :
1) injuring cells of GI mucosa, and
2) activating pepsin (a proteolytic enzyme)
Pepsin: injure unprotected cells.
3
HP contributes
to gastric mucosal
injury by:
1. Direct mechanism.
2. Alteration in the
immune /
inflammatory
response.
3. Hypergastremia
leading to increased
acid secretion.
NORMAL
Hypergastremia
leading to
increased acid
secretion
4
Membrane phospholipids
PLA2
Arachidonic acid
COX-1 COX-2
Constitutively expressed Induced at inflam.
inflam. site
NSAIDs
5
Drug therapy: Goals
1. To alleviate symptoms
2. To promote healing
3. To prevent complications
4. To prevent recurrences
6
Food
13
7
H2-RECEPTOR ANTAGONISTS
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H2-RECEPTOR ANTAGONISTS
IN PEPTIC ULCER
A single dose of H2 blocker is
seldom adequate.
In the treatment of duodenal
ulcer, it is the suppression of
overnight gastric acidity that
is most closely correlated
with the therapeutic effect of
H2 blockers.
9
Cimetidine exerts a weakly
antiandrogen effect and has rarely
been associated with
gynecomastia and diminished
libido in male patients. Reduction
in sperm counts and reversible
impotence (in long term use of
cimetidine)
Aman untuk wanita hamil
Mechanism of action:
Suppress acid secretion by inhibiting
noncompetitif & irreversible proton
pump H+, K+- ATPase
10
Proton Pump Inhibitors
These medications are similar agents
which are a reversible inhibitor of the
H+K+-ATPase which is found in the
secretory canaliculi of the parietal
cells.
Unlike the H2 blocker, the proton
pump inhibitor effectively inhibits
meal-stimulated acid secretion during
the day as well as basal secretion
overnight.
11
Pharmacokinetics:
Unstable at a low pH enteric coated
granule/tablet
Prodrug, requiring activation in an acid
environment (parietal cell) with or
before meal
Side effects:
Cyt P450 inhibitor
Hypergastrimenia: promote tumor
rebound hypersecretion
of gastric acid
12
Classes of Antiulcer Drugs
Antisecretory agents
Drugs:
3. Muscarinic antagonists
Pirenzepine (gastrozepine®)
Price Rp. 4.000/25mg tab
Mechanism of action:
Suppress acid secretion by blocking
muscarinic cholinergic receptors
13
Misoprostol
is the only synthetic prostaglandin derivative to
have been introduced into clinical practice for
management of acid-related disorders.
The structure comes from a prostaglandin–E1
The synthetic prostaglandin-E derivative has
been shown to be inferior to ranitidine in
maintenance treatment of patients with healed
duodenal ulcers.
SE : It is associated with a high incidence of
diarrhea. The diarrhea is usually mild.
Contraindicated during pregnancy
Pharmacokinetics Misoprostol
14
Other Antiulcer Drugs
Mucosal protectants
Drugs:
Sucralfate (Musin®
Musin® Price: Rp.900/500mg tab,
tab,
Syrup: Rp.26.500/120ml 500mg/5ml;
Ulsanic®
Ulsanic® Rp.
Rp. 1.700/500mg tab, Rp.3.000/1g tab;
Ulsidex®
Ulsidex® Rp.1.000/500mg tab, Rp. 1.500/1g tab;
Ulsicral®
Ulsicral® syrup Rp.
Rp. 27.500/ 100ml, 500mg/5ml)
Mechanism of action:
Forms a barrier over the ulcer crater that
protects against acid and pepsin
Sucralfate
Complex synthetic salt of sucrose and aluminum
octasulfate.
In the presence of acid, sucralfate forms an insoluble
amorphous complex that has the ability, in animal
studies, to adhere to ulcerated tissue.
Stimulation of local prostglandin production
Inhibit the hydrolisis of mucosal protein by pepsin
It forms a protective coating of the ulcer that might
prevent further acid peptic digestion, and this might
persist for 12-
12-16 hours after administration.
Common side effect is constipation
Aman untuk wanita hamil
15
Other Antiulcer Drugs
Antacids
Drugs:
Aluminum hydroxide, Calcium
carbonate, Magnesium hydroxide
Mechanism of action:
React with gastric acid to form neutral
salts.
Taking antacids : 2 hours before or after
ingestion of other drugs
Antacids
Composition :
CaCO3 neutralize HCL rapidly ,
unpredictable effects on gastrointestinal
motility, hypercalcemia
AL(OH)3 Sustained neutralizing capacity,
relax gastric smooth muscle (delayed gastric
emptying and constipation), osteoporosis,
encephalopathy. Tidak aman untuk wanita
hamil
Mg(OH)2 sustained neutralizing capacity
but opposed delayed gastric emptying and
constipation)
16
33
Antibiotics
Drugs:
One-Drug regimens eradikasi <40%
Two-Drug Regimens eradikasi <60%
Three-Drug Regimens eradikasi <85%
Four-Drug Regimens eradikasi >90%
Mechanism of action:
Eradication of H. pylori infection
17
The recommendation of the
consensus of the National
Institute of Health was that:
Ulcer patients with H. pylori
infection reguire treatment with
antimicrobial agents in addition
to antisecretory drugs wheter
on first presentation of the
ilness or on recurrence
18
QUADRIPLE THERAPY:
PPI1 + Bismuth2 + Metronidazole6 +
Tetracycline7
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39
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41
Conceptual model of
prokinetic agents
42
21
Classification of prokinetic agents
General
Example of Used
pharm. Mech. Of action
drug medications
class
Dopamine Domperidone
Metoclopramide
D2 antagonism GERD
receptor
5HT4 rec. activation . &
Serotonin Cisapride 5HT3 rec. antagonism
receptor 5HT4 rec. activation . & Gastroparesis
modulation metoclopamid D2 rec. antagonism
PROKINETIC DRUG
(MOTILITY-PROMOTING DRUG)
In GERD, prokinetic drug that increase lower
esophageal sphincter pressure and increase gastric
motility and thus empties the stomach more quickly
may ameliorate the symptoms.
Metoclopamide,
Metoclopamide, domperidone & ondansentron are D2
type receptor antagonist in GIT dopamine
receptor antagonist may potentiate cholinergic
smooth muscle stimulation
Metoclopamide has anticholinergic and CNS, effects
as a result of blocking dopamine receptor and cross
the BBB. Domperidon hasn’
hasn’t anticholinergic
effects not cross the BBB.
22
Cisapride exhibits agonist
activity at 5-HT4 receptors but
hasn’t activity at dopamine
receptors.
Metoklopamid dan ondansentron
aman untuk wanita hamil,
domperiodon tidak ada data untuk
wanita hamil
23
Mayor stimuli of nausea & vomiting:
GIT irritation.
Motion sickness.
Hormon disturbance.
Intracranial pathology.
Metabolic disorder.
Psychogenic factor.
Pain.
Drug & radiation.
Endogenous toxins.
Post operative nausea & vomiting
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49
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Others:
Glucorticoid (dexamethazone) by
supressing prostaglandin production
Benzodiazepines (lorazepam)
reducing the anticipatory of nausea
and vomiting
Subtance P receptor antagonist
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53
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55
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Pharmacology in Gastrointestinal Medicine
Prokinetic
agents
29
Agents used for constipation & diarrhea
Generally mechanism of action of laxatives:
1. Luminal active agents :
bran,physsilum) bulk forming
Hydriphillic colloids (bran,physsilum)
agents
Osmotic agent (MgSO4, Nafosfat, Lactulosa) non
Nafosfat, Lactulosa)
absorbalble in organic salts/sugar
Stool wetting agentas (stool surfactant agents) and
emollients Softeners. Eg:
Eg: glycerin supp, docusate po
2. Non specifec stimulants or irritants (with effects
on fluid secretion and motility)
Diphenylmethanes (bisacodyl)
bisacodyl)
Anthraquinones (senna and cascara)
Castor oil
3. Prokinetic agents (acting primarily on motility)
o 5 HT4 rec antagonist
o Opioid rec antagonist
30
Pharmacology in Gastrointestinal Medicine
Diarrhea :
The mainstay therapy is rehydration.
Another therapy in these patients is :
Intraluminal agents :
Bulk forming and hydroscopic agents
Cholestyramine (binds bile acid & bact. toxin)
Bismuth (antiinflam., antimicrobial effects)
Antimotility and antisecretory agents:
opioids (loperamide, diphenoxylate)
receptor (intestinal motility )
atropin antimuscarinic
Octreotide (analog somastotin) inhibit the
severe secretory diarrhea, hormone,
chemotherapy, diabetic)
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