PENGGOLONGAN OBAT

YANG BEKERJA PADA

SISTEM PENCERNAAN

Fathiyah Safithri - FK UMM 2014

Anti Ulkus Peptik


Anti Konstipasi

Anti Diare
 ULKUS PEPTIK

Faktor yang Faktor yang

meningkatkan keasaman melindungi dari keasaman
 ULKUS PEPTIK
 Faktor yg meningkatkan  Faktor yang melindungi
 H. pylori (Proteksi)
 Produksi mukus
 NSAID
 Buffer
 Acidic agents
 Aliran darah
 Pepsin
 Prostaglandin
 Merokok
Faktor Protektif

(epidermal growth factor)

Pembentukan Ulkus
Tujuan Tx : Pendekatan Tx :
1. Menghilangkan 1. me agresifitas dg
nyeri me  produksi
2. Mempercepat asam
penyembuhan 2. Me faktor
ulkus protektif
3. Mencegah (mukoprotektan)
rekurensi 3. Eradikasi H. pylori
Strategies for Protecting the Gastric Mucosa
from Acid Exposure

Mechanisms Example
Cimetidine
Inhibit Omeprazole
H+ secretion Muscarinic antagonists

Prevent
H+ Sucralfate
contact

Neutralize Antacids
H+ acid
Multiple Mechanisms Regulate Gastric Acid

Neural
Acetylcholine

Hormonal
Gastrin

Paracrine
Histamine
Gastric phase of gastric-acid secretion
Strategies for Inhibiting Parietal Cell Acid Secretion

CCK2
Gastrin
Antagonists
Proton pump
H2 Inhibitors
Histamine ↓cAMP
PP H+
Antagonists

M3 Gastric
Muscarinic Lumen
Antagonists
Histamine H2 Antagonists

 Cimetidine

 Ranitidine

 Famotidine

 Nizatidine
 PPI (proton pump inhibitor)

 H+, K+-ATPase is the final transport pathway for

parietal cell hydrogen ion secretion, located in the
apical membrane of the oxyntic cell along the
secretory canaliculi;
• The pump requires large amounts of energy that is
supplied by intracellular ATP;
• Inhibition of H+, K+-ATPase blocks both basal and
stimulated acid secretion.
• Contoh : Omeprazole, Lanzoprazole.
 MUSKARINIK ANTAGONIS

 Bekerja sebagai antagonis R/ M1 hambat

sekresi asam dan pepsin
 Contoh : pirenzepine (Gastrozepine®)

 Rarely used, primarily as adjunct therapy

(Bukan DOC karena ES >>> )
GASTRIN ANTAGONIS
 Proglumide
 Antasida
 Bekerja dg menetralisir keasaman lambung dengan
cara me  pH lambung
 H+ akan berikatan dg CO32–, HCO3– atau OH–
(komponen antasid)
 Indikasi : ulkus peptik, GERD, dispepsia non ulkus
 Menyembuhkan ulkus lebih lama dp H2 antagonis
 Makanan buffering effect, mk antasid diberikan
di antara makan (mis 1j stl mkn)
 Antasida nonabsorbable lbh dipilih (ES sistemik <<<)
dp antasid absorbable
 Antacids
 Magnesium hydroxide

 Magnesium trisilicate

 Magnesium-aluminum mixtures

 Calcium carbonate

 Sodium bicarbonate (absorbable)

Obat yang Melindungi Mukosa
(Mukoprotektan)

 Sukralfat
 Prostaglandin analog
 SUKRALFAT
 Stl pemberian oral, molekul sukralfat
mengalami cross-linking dengan
gastric juice, membentuk suatu pasta
yg melekat pd defek mukosa &
melindungi lapisan yg lebih dalam.
 Sucralfate menghambat H+
protektif thd asam & juga thd
pepsin, trypsin & bile acids  defek
mukosa dpt sembuh lebih cepat
 Diminum saat lambung kosong ( 1
jam sblm makan dan sebelum tidur)
 Well tolerated, tapi mengand sejml
residu Al(OH) shg dpt menyebabkan
konstipasi
 Prostaglandin Analog
 Bekerja sebagai analog PG E1, lebih stabil dp PG endogen
 PG E1 dan PG I2 endogen  menstimuli prod mukus & menghamb
sekresi asam  penting utk memelihara integritas barier mukosa
gastroduodenal
 Sintesa PG melalui jalur yang melibatkan enzim COX1
 NSAID spt Aspirin hamb COX 1 sintesa PG oleh sel parietal 
sekresi asam  & erosi  ulkus
 misoprostol (Cytotec®)
 Terbukti dpt mencegah dan menyembuhkan ulkus peptik akibat
pemakaian NSAID jangka panjang
 Lebih efektif dp H2 antagonis utk ulkus peptik akibat NSAID
 ES : diare, kontraksi uterus pd ibu hamil
 Eradikasi H. pylori
 50-80% mns terinfeksi H.
pylori dan 10-20%nya menj
ulkus peptik / neoplasma
 Hampir semua pasien
gastritis &ulkus duod, 80-
90% ulkus gaster alami inf
H.pylori di anthrumnya
 Rekkurensi ulkus duod 80%
jk H. pylori tdk dieradikasi &
5% jk dieradikasi
 Eradikasiissue penting
saat ini : perkembangan
resistensi thd AB sgt cepat
 Dual Tx : PPI + oral AB (dulu)
 Tripple Tx : PPI+ metro / amox +
clarithromicin 14 hr
 Quadriplle Tx (kasus resisiten) :
PPI+ metro + amox +
clarithromicin
 Komb PPI menguntungkan : me
pH lambung, perbaiki stabilitas &
absorbsi AB  kemamp eradikasi
 bismuth (Pepto-Bismol®)
- sbg Tx tunggal: kemamp eradikasi
hanya 20%
- dpt mengikat dasar ulkus spt
sukralfat
H. pylori Eradication Rates with Either Dual,
Triple or Quad Therapy (1999)

Treatment Pooled Eradication

Rate
Dual Therapy 72%

Triple Therapy 85%

Quad Therapy 90%

 H. pylori Eradication Rates with Either Dual, Triple
or Quad Therapy (1999)

GENERIC NAME DOSING DURATION CURE RATE (%)

Dual therapies

omeprazole 500 mg TID 14 days 70-80

amoxycillin 1,000 mg TID 14 days

ranitidine 400 mg BID 28 days 73-84

clarithromycin 500 mg TID 14 days

lansoprazole 30 mg TID 14 days 66-77

amoxycillin 1,000 mg TID 14 days
 H. pylori Eradication Rates with Either Dual,
Triple or Quad Therapy (1999) Cont.

GENERIC NAME DOSING DURATION CURE RATE (%)

Triple therapies

lansoprazole 30 mg BID 14 days 86-92

amoxycillin 1,000 mg BID 14 day
clarithromycin 500 mg BID 14 days
 H. pylori Eradication Rates with Either Dual, Triple
or Quad Therapy (1999) Cont.

GENERIC NAME DOSING DURATION CURE RATE (%)

Quad therapies
bismuth subsalicylate Two tablets 7 days 85-95
525 mg QID
metronidazole 250 mg QID 7 days
tetracycline 500 mg QID 7 days
omeprazole 20 mg BID 7 days
or
lansoprazole 30 mg BID 7 days
OBAT ANTIKONSTIPASI
 Stool Formation

Kolon : absorbsi air ~90%

 Absorbsi berlebihan
 Konstipasi: keras, dehydrated stool
 Perlu usaha keras untuk defekasi (mengejan)
 Berbahaya utk pasien dengan :
Recent episiotomy, colostomy, hemorrhoids,
cardiovascular disease
 Absorbsi Inadekuat
 Diare: lunak, tidak berbentuk, cair
Peristaltik : Aktivasi intramural
mekanoreceptor
 Peristalsis Produced by Coordinated
Contraction and Relaxation of Muscle Coats
Myenteric plexus
Longitudinal muscle
(Auerbach’s)
***** ***** *****
*****

Oral ***** Bolus Anal

***** ***** *****

Contracted
Relaxed Circular muscle Submucous plexus
(Meissner’s)
 Laxatives

 Bulk forming (Pembentuk massa)

 Surfactants (Pelicin & Pelunak)

 Stimulants / Irritant (Perangsang)

 Osmotics (Menambah volume cairan)

 Bulk Forming Laxatives
 Mengabsorbsi air
 Melunakkan dan menambah besar ukuran
faeces
 Ukuran faecal yang menggembung distensi

dind usus  menstimuli peristalsis

 Uncleaned rice (brown rice), Bran, Seaweed
(tangle), Methylcellulose (Citrucel®), Psyllium
(Metamucil®), Polycarbophil, Makanan kaya
serat lain
Bulk Forming Laxatives
 Surfactant Laxatives

 Menurunkan tegangan permukaan (spt

detergen)
 Fecal softener

Memfasilitasi
penetrasi cairan
 Docusate salts (Colace®, Modane Soft®)

• Castor oil

• Mineral oil

• Dehydrocholic acid
 Stimulant Laxatives

 Menstimuli peristalsis
 Me sekresi air dan elektrolit ke lumen usus.

 Me  reabsorbsi air dan elektrolit

 Polyphenol or diphenylmethane

 Phenolpthalein(Ex-Lax®, Feen-a-Mint®, Correctol®)

 Bisacodyl (Ducolax®)

 Anthroqiunon
 Senna, Cascara
 Aloe, Casanthranol
Stimulant / irritant Laxatives
 Osmotic Laxatives
 Berupa garam / glukosa yang tidak / sulit diabsorbsi, sehingga tetap berada
sebagai salah satu komponen faekal
 me volume cairan di lumen usus kecil dan usus besar secara osmotik me
 peristaltik
 Mg me  sintesa kolesistokinin me  motilitas kolon
 Salts laxatives
 Magnesium hydroxid (Milk of Magnesia®)

 Sodium phosphate (Solin oral ®)

 Hyperosmolar laxatives
 Laktulosa (Duphalac ®)

 Sorbitol, Glycerin

 Lactitol (Ctri-lactitol ®)

 PEG (Colit , Colyte ®)

 Prokinetic Drugs

• Substances which enhance transit of

materials through the GI tract;

 Increase neuromuscular transmission

 Prokinetic Drugs Act on Enteric Nerves to Increase
Cholinergic Stimulation
Muscarinic M2 (stimulated by Bethanechol)
Dopamine D2 (Blocked by Metoclopramide and Domperidone)
Dopaminergic
Neuron 5HT4 Stimulated by
Metoclopramide
Cisparide

Smooth (-) (+)

Ach

(+) (+)

Ach
Muscle
Cell (+) Cholinergic
Motilin Neuron

(+) Stimulated by Erythromycin

Motilin

• Indirect effects are mediated by M2 muscarinic receptors

• Metoclopramide crosses the blood-brain barrier
 Prokinetic Drugs - Cholinomimetics (Carbachol;
Bethanechol)

Actions
Muscarinic receptor agonist
Increase force of contraction
Little effect on intestinal transit
 Prokinetic Drugs – Metoclopramide (Reglan)

•Metoclopramide is an antiemetic
and improves gastric emptying –
indirectly releases acetylcholine
• Actions
Dopamine D2 receptor antagonist
5-HT4 receptor agonist
Ganglionic stimulant
Prokinetic Drugs – Domperidone (Motilium)

•Domperidone is an antiemetic
and improves gastric emptying –
Not very effective for GERD
• Actions
Dopamine receptor antagonist
Ganglionic stimulant
 Prokinetic Drugs - Cisapride (Propulsid)

Actions
5-HT4 agonist; other unknown actions.
 Prokinetic Drugs - Additional Compounds

Erythromycin
Motilin agonist
Antibacterial
Diarrhea
Motilin (22 amino acid active
peptide)
Agonist for the Motilin receptor
Stimulates gastric emptying
 Comparison of Gastric Prokinetic Drugs

Pharmacological Specific Drugs Mechanism of

Class Action
Cholinergic ethanechol Muscarinic
Receptors M3
Dopamine Antagonist etoclopramide D2
Domperidone
Serotonin Agonist
etoclopramide 5-HT4
Motilin Agonist rythromycin Motilin Receptor
OBAT ANTIDIARE
Diarrhea is Associated with Excessive Flow Through
the Lumen of the Bowel
Normal Diarrhea

Net fluid
Net fluid
absorption
accumulation

Increased
Normal mixing propulsive
and propulsive contractions
contractions
Decreased mixing
contractions

Normal Flow Increased Flow

 The Goals of Antidiarrheal Therapy are to
Correct the Pathophysiology

Goals:
 Eliminate cause;

 Decrease fluid accumulation in lumen;

 Decrease propulsive contractions;

 Increase mixing contractions.

 Opioids and Intestinal Motility
Segmenting Contractions
Normal
Normal Flow
Reduced Contractions
Increased
Flow

Diarrhea
{ Propulsive Contractions
Increased
Flow
Segmenting Contractions

Decreased
Opioids Flow
 Antidiarrheal Agents - Opioids

 Agonist at mu opioid receptors;

 Decreases fluid secretion;

 Increases fluid absorption;

 Decreases propulsive contractions;

 Increases segmenting contractions;

 Delays gastric emptying.

Opioids and Mucosal Transport of Salt and Water

Physiological
Normal
Balance

Net Fluid
Diarrhea Accumulation

Net Fluid
Opioids Absorption
Analgesics that can be used as Antidiarrheal
Agents

 Morphine
 Codeine
 Some Opioid Drugs Act Both in the CNS and on
Enteric Nerves, Others Act Only on Enteric Nerves

Drug Central Nervous Enteric Nerves

System
Morphine +++ +++

Codeine +++ +++

Diphenoxylate + +++

Loperamide 0 +++

Loperamide does not effectively cross the blood-brain barrier

after oral administration and exerts mainly peripheral effects
 Antidiarrheal Agents - Anticholinergics

Muscarinic antagonists
Decrease propulsive contractions
Decrease cholinergic secretions
Side Effects
Produce typical antimuscarinic side-effects
Dry mouth
Tachycardia
Blurred vision
Bowel discomfort (constipation)
Difficulty in urination
 Antidiarrheal Agents - Clonidine (Catapres)

Alpha2 agonist
Decreased release of secretagogues
Action on villus cells
increase fluid and electrolyte absorption

Side Effect
Induces hypotension
 Clonidine Acts at Alpha-2 Adrenergic Receptors
to Decrease Secretion and Increase Absorption
Mucosal
Epithelium Intestinal
Lumen

(+) Villus
Clonidine
(+)
a2

a2
Secretomotor Ach (+) Crypt
Neuron VIP (+)

Clonidine acts at neural a2 receptors to inhibit release of secretory

neurotransmitters and at epithelial a2 receptors to stimulate absorption
 Antidiarrheal Agents - Bismuth Subsalicylate

Bismuth Subsalicylate (Pepto-Bismol)

Binds bacterial toxins
Reduces formation of prostanoids
Antibacterial
 Bismuth Subsalicylate

Blocks?

Bacterial Fluid
Toxins PGs cAMP Accumulation
 Antidiarrheal Agents - Gel Forming Agents

Attapulgite - natural clay

Kaolin - natural clay
Pectin - citrus pulp (Kaopectate)
ineffective

Excessive Increase Viscosity Reduce

Fluid Flow
 Bile Acid Catharsis

Cholestyramine (anion-exchange resin)

Lowers LDL cholesterol

Reduce
binds Bile Acids
Flow

Side Effects
Not well absobed
Constipation
 Antidiarrheal Drugs Act By a Variety of
Mechanisms
Drugs Inhibit Stimulate Decrease Enhance Bind
propulsive nonpropulsive fluid fluid luminal
contractions contractions secretion* absorption secretagogues
Opioids +++ +++ +++ ++

a2 agonists +++ +

Anticholinergics +++ ++

Somatostatin + +++
(Octreotide)
Bismuth +++
subsalicylate
Cholestyramine +++

* Stimulated by secretagogues