Pertemuan 2 Spesialit Obat Dan Alkes Obat Gastrointestinal 2023 N
Pertemuan 2 Spesialit Obat Dan Alkes Obat Gastrointestinal 2023 N
Pertemuan 2 Spesialit Obat Dan Alkes Obat Gastrointestinal 2023 N
Gastrointestinal drugs
GI
Disorder
• Gastroesophageal
Reflux Disease (GERD)
• Peptic Ulcer Disease
(PUD)
• Duodenal Ulcer
• Nausea
• Emesis
• IBS
• Diarrhea
• Constipation
Stomach Lining
Basics
Gastric Mucosal
Barrier
• Surface mucosa cells in
the
pyloric region secrete a
thick,
alkaline-rich mucus
that
protects
lumen. the epithelium of
• the
These cells are stimulated
stomach
mechanical and duodenum
and from
chemical
by
harsh
irritation acid
and conditions of
parasympathetic
the
inputs.
• This protective mucus
barrier
can be damaged by
bacterial
and viral infection,
certain
drugs, and aspirin.
Parietal Cell: Gastric Acid Secretion
H+
Chief Cell: Synthesis and Activation of
Pepsin
+HCl
Pepsin
Serotonin in the Gut
• Serotonin is one of
neurotransmitters our
responsible
that for our mood.are
• Serotonin is produced in the
enterochromaffin cells (EC)
in the intestinal mucosa
• Once serotonin
released,
the it
is
system to increase intestinal
activates
motility (Cammilleri, 2009).
our
Serotonin Dysfunction in the
Gut
Stimulation of gastric acid secretion
Stimulation of gastric acid secretion
Acid-Controlling
Agents
•Promote gastric mucosal defense mechanisms
• Secretion of :
• Mucus: protective barrier against HCl
• Bicarbonate: helps buffer acidic properties of
HCl
• Prostaglandins: prevent activation of proton
pump which results in HCl production
Summary of Acid Reduction therapeutics
Antacids
H+
Cl-
Strategies for Protecting the Gastric Mucosa
from Acid Exposure
Mechanisms Example
H2 Antagonist
Inhibit PPI
H+ secretion Prostaglandins
Muscarinic antagonists
Preven Sucralfate
H+ t
contact
Neutralize Antacids
H+ acid
A N TACIDS: MECHANISM OF ACTION
◾Antacids D O NOT
prevent the over-
production of acid
◾Antacids D O neutralize
the
acid once it’s in the
Drugs for peptic ulcers-----antacids
Action
Neutralize secreted acid
Reduce gastric acidity
Pepsin inactive
Reduce destroy factors
Antacids
Nonsystemic Antacid:
Aluminum Hydroxide + Magnesium Hydroxide Combinations (Maalox and Mylanta)
Contraindicated in patients with impaired renal function
Magnesium may cause diarrhea
◾ Highly soluble
◾ Buffers the acidic properties of HCl
◾ Q uick onset, but short duration
◾ May cause metabolic alkalosis
◾ Sodium content may cause problems in patients with HF, hypertension,
or renal insufficiency (fluid retention)
Major constituents of antacids
Salt
Neutralizing Solubility
Constituent Formed in Adverse Effects
Capacity of Salt
Stomach
Hypercalcemia,
CaCO3 Moderate CaCl2 Moderate nephrolithiasis, milk-alkali
syndrome
Constipation,
hypophosphatemia; drug
Al(OH)3 High AlCl3 Low adsorption reduces bio-
availability
Diarrhea, hypermagnesemia
Mg(OH)2 High MgCl2 Low (in patients with renal
insufficiency)
A N TACIDS: DRUG INTERACTIONS
Misoprostol (Cytotec):
Synthetic Analog of Prostaglandin E1
Anti-acid secretory
0.1 to 0.2 mg results in 85% to 95% acid reduction
Prevention of NSAID gastric ulcers
Side Effects
Diarrhea
Abortion
Exacerba
te IBD
and
2. Sucralfate
Mechanism:
Polymerization & gelatine barrier
PGE2 Mucus-
HCO3-
Infeksi Helicobacter pylori
Pharmacologic Effects:
Effective in Duodenal Ulcers
Notice:
Acid pH
Empty stomach
SUCRALFATE (CARAFATE) (CONT'D)
Bismuth compounds
Mechanism of Action
cytoprotective effects
compounds bind to the ulcer base, stimulating
mucus and prostaglandin production
antibacterial effect
inhibition of proteolytic, lipolytic, and
urease activities
Coating and protecting the ulcer crater
3. Canabinoids (CBS)
Mechanism:
Pepsin
PGE1 Mucus-
HCO3-
Coating
Infeksi Helicobacter pylori
( disputed )
4. TEPRENONE
MEKANISME AKSI :
1. ANTI ULCER AGENT
2. MENINGKATKAN MUCUS
3. CYTOPROTECTIVE
4.MENINGKATKAN PG DI MUKOSA
SEDIAAN LAZIM : CAPSUL 50 MG
Regulation of gastric acid secretion
Proglumide
SUMMARY OF ACID REDUCTION THERAPEUTICS
Histamine Type 2 (H2)
Antagonists
Histamine Receptors
H1 receptors
Smooth muscle
Nerves
H2 receptors
Parietal cells
H2 Antagonists
CCK2
acid-producing Ca 2+
parietal cells
EP
(-)
3
⚫ Production of cAMP
Protein H+
Histamine
H
2
PP
hydrogen ions is Antagonist
Kinase K+
reduced, resulting in
ATP
decreased production Ca 2+
of HCl
Histamine H2 Antagonists Decrease Acid Output
Histamine
cAMP
Protein
PP H+
Kinase K+
AT
P
Acid Output
Antagonist 30
(mEq/hr)
20
10
Time (hr) 1 2 3 4
H2 Antagonists:
Indications ESO
⚫ Cimetidine (Tagamet)
Binds with P-450 microsomal oxidase system in the liver,
resulting in inhibited oxidation of many drugs and increased
drug levels
All H2 antagonists may inhibit the absorption of drugs that
require an acidic GI environment for absorption
SMOKING has been shown to decrease the effectiveness of
H2 blockers (increases gastric acid production)
Drugs for Acid-Peptic Disorders - Cimetidine (Tagamet)
Rebeprazole
Esomeprazole Pantoprazole
PPI
s
Proton Pump Inhibitors
• Strong inhibitors of gastric acid secretion through irreversible inhibition of
proton pump, preventing “pumping” or release of gastric acid (24 hr action)
• Indicated in PUD, Gastritis, GERD, & Zollinger-Ellison syndrome
• Faster relief and healing than H2 receptor blockers
• Decreases acid secretion by up to 95% for up to 48 hours
• 4-8 week course of treatment
Omeprazole* Lansoprazole
Rebeprazole
Esomeprazole Pantoprazole
Irreversible (forms a covalent bond with the proton pump) - long lasting
inhibition of acid production;
Highly protein bound; Metabolized by CYP2C & CYP3A; plasma half life of
1 to2 hours but long duration of action; Should be taken just prior to a
meal and should NOT be taken with other acid-suppressing agents.
Prototipe H +, K + -ATPase inhibitor; Sebuah prodrug yang
memerlukan pH rendah menjadi aktif;
⚫ Erosive esophagitis
Antacids
H+
Cl-
Antimuscarinic
Agents
Mechanism:
◦Blocking M3-R on Parietal Cell, M-R on ECL cell and G
cell
Pharmacologic
◦
Effects:
HCl spasmolysis
Agents:
◦Atropine , Probanthine
◦Pirenzepine - M1,M2-R selection
Drugs for Acid-Peptic Disorders -
Anticholinergics
Blockade of acetylcholine at muscarinic (M3/M1)
receptors
◦Effectively blocks acid secretion (30 to 40%)
◦Limited by side-effects