SPESIALITE OBAT:

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

Systemic Antacid: Sodium Bicarbonate

Nonsystemic Antacid:
Aluminum Hydroxide + Magnesium Hydroxide Combinations (Maalox and Mylanta)
Contraindicated in patients with impaired renal function
Magnesium may cause diarrhea

Calcium Carbonate (Tums)

Calcium may cause constipation
A N TACIDS: DRUG EFFECTS

◾Reduction of pain associated with

acid- related disorders
◾ Raising gastric pH from 1.3 to 1.6 neutralizes
50% of the gastric acid
◾ Raising gastric pH 1 point (1.3 to 2.3)
neutralizes 90% of the gastric acid
◾ Reducing acidity reduces pain
A N TACIDS: ALUMINUM SALTS

◾ Forms: carbonate, hydroxide

◾ Have constipating effects
◾ Often used with magnesium to counteract constipation
◾ Examples
◾ Aluminum carbonate: Basaljel
◾ Hydroxide salt: AlternaGEL
◾ Combination products (aluminum and magnesium): Gaviscon, Maalox, Mylanta, Di-
Gel
A N TACIDS: MAGNESIUM SALTS

◾ Forms: carbonate, hydroxide, oxide, trisilicate

◾ Commonly cause diarrhea; usually used with other agents to counteract
this effect
◾ Dangerous when used with renal failure —the failing kidney cannot
excrete
extra magnesium, resulting in hypermagnesemia
◾ Examples
◾ Hydroxide salt: magnesium hydroxide (MOM)
◾ Carbonate salt: Gaviscon (also a combination product)
◾ Combination products such as Maalox, Mylanta (aluminum and magnesium)
A N TACIDS: C ALCIUM SALTS

Forms: many, but carbonate is most common

◾ May cause constipation

◾ Their use may result in kidney stones

◾ Long duration of acid action may cause increased gastric acid

secretion (hyperacidity rebound)

◾ O ften advertised as an extra source of dietary calcium

◾ Example:Tums (calcium carbonate)

A N TACIDS: SODIUM BICARBONATE

◾ 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

Systemic alkalosis, fluid

NaHCO3 High NaCl High retention

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

◾ Adsorption of other drugs to antacids

◾ Reduces the ability of the other drug to be
absorbed into the body
◾ Chelation
◾ Chemical binding, or inactivation, of another drug
◾ Produces insoluble complexes
◾ Result: reduced drug absorption
A N TACIDS: NURSING IMPLICATIONS

◾ Assess for allergies and preexisting conditions

that may restrict the use of antacids, such as:
◾ Fluid imbalances – Renal disease – HF
◾ Pregnancy – GI obstruction
◾ Patients with HF or hypertension should use
low- sodium antacids such as Riopan, Maalox,
or Mylanta II
A N TACIDS: NURSING IMPLICATIONS

◾Use with caution with other

medications due to the many drug
interactions
◾Most medications should be given 1 to
2 hours after giving an antacid
◾Antacids may cause premature dissolving
of enteric-coated medications, resulting
in stomach upset
A N TACIDS: NURSING IMPLICATIONS

◾Be sure that chewable tablets are chewed

thoroughly, and liquid forms are shaken
well before giving
◾Administer with a full glass of water to
ensure absorption (except for the
“rapid dissolve” forms)
A N TACIDS: NURSING IMPLICATIONS

◾Monitor for side effects

◾Nausea, vomiting, abdominal pain,
diarrhea
◾With calcium-containing
products: constipation, acid
rebound
◾Monitor for therapeutic
response
◾Notify heath care provider if symptoms
 Mucosal Protective Agents

1. Derivatives of Prostaglandin: Misoprostol (PGE1),

Enprostil
 Mechanism:
 HCl  ; Pepsin 
 Mucus-HCO3- ;
 Cytoprotective effect
 Pharmacologic Effects:
 Prevention of ulcers induced by NSAIDs
 Doses that are therapeutic enough to treat duodenal ulcers often
produce abdominal cramps, diarrhea
 Contraindication ：
 Women with childbearing
• Act at prostaglandin EP3 receptors on parietal cells &
on epithelial cells
Inhibits: Stimulates:
 Mucus secretion
 Acid secretion
 Bicarbonate secretion
 Gastrin release
 Mucosal blood flow
 Pepsin secretion

These compounds act by both inhibition of acid production and

by increasing defense mechanisms

• These compounds are also effective against direct damage produced by

alcohol, aspirin and NSAIDs, and are therefore termed “cytoprotective”
Drugs for Acid-Peptic Disorders - Prostaglandins

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)

• LITTLE ABSORPTION FROM THE GUT

• MAY CAUSE CONSTIPATION, NAUSEA, AND DRY MOUTH
• MAY IMPAIR ABSORPTION OF OTHER DRUGS,
ESPECIALLY TETRACYCLINE
• BINDS WITH PHOSPHATE; MAY BE USED IN CHRONIC
RENAL FAILURE TO REDUCE PHOSPHATE LEVELS
• DO NOT ADMINISTER WITH OTHER MEDICATIONS
SUCRALFATE (CARAFATE)

• TABLETS FOR ORAL ADMINISTRATION CONTAIN 1 G OF

SUCRALFATE.

• ORAL DOSAGE FOR DUODENAL ULCER IS 1 G FOUR TIMES PER DAY

ON AN EMPTY STOMACH.

• MAINTENANCE THERAPY: THE RECOMMENDED ADULT ORAL

DOSAGE IS 1 G TWICE A DAY.
 Mucosal protective agents

 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

⚫ Reduce acid secretion

⚫ All available OTC in lower dosage forms
⚫ Most popular drugs for treatment of acid-related disorders
 Cimetidine (Tagamet)
 Famotidine (Pepcid)
 Ranitidine (Zantac)
 Nizatidine (Axid)

Cimetidine Famotidine Ranitidine Nizatidine

 H2 Antagonists:
Mechanism of Action

⚫ Block histamine (H2)

at the receptors of

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

Histamine H2 antagonist administered

orally at arrow

Acid Output
Antagonist 30

(mEq/hr)
20
10
Time (hr) 1 2 3 4
 H2 Antagonists:
Indications
⚫ GERD
⚫ PUD
⚫ Erosive esophagitis
⚫ Adjunct therapy in control
of upper GI bleeding
⚫ Pathologic gastric
hypersecretory
conditions (Zollinger-
Ellison syndrome)
ESO
⚫ Overall, less than 3%
incidence of side effects
⚫ Cimetidine may induce
impotence and
gynecomastia
⚫ May see:
 Headaches, lethargy,
confusion, diarrhea, urticaria,
sweating, flushing, other
effects
 H2 Antagonists:
Drug Interactions

⚫ 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)

Side effects include inhibition of the microsomal

metabolism of other drugs
results in higher blood levels and enhancement of their effects

Interactions have been shown with:

Diazepam Chlordiazepoxide
Theophylline Phenytoin
Warfarin Propranolol
Meperidine Pentobarbital
Lidocaine and many others...
 Drugs for Acid-Peptic Disorders - Cimetidine (Tagamet)

Additional Side effects:

⚫In some patients, cimetidine acts as a nonsteroidal
antiandrogen (i.e., interferes with estrogen metabolism).
decrease in male sexual function
gynecomastia (swelling of the breasts and soreness of the
nipples in males)
⚫Can produce confusion and disorientation in elderly
patients;

⚫Diarrhea, rash and miscellaneous other effects in a small

number of patients.
 Drugs for Acid-Peptic Disorders - Ranitidine (Zantac),
Famotidine (pepcid), Nizatidine (Axid)

Same mechanism of action as Cimetidine but a

longer duration of action (8 to 12 hrs);

Can be given less frequently;

150 or 300 mg, 1-2 times daily

Less interactions at P450 than Cimetidine.

 H2 Antagonists:
Nursing Implications

⚫ Assess for allergies and impaired renal or liver

function
⚫ Use with caution in patients who are confused,
disoriented, or elderly (higher incidence of CNS side
effects)
⚫ Take 1 hour before or after antacids
⚫ For intravenous doses, follow administration
guidelines
Omeprazole* Lansoprazole

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

*The first in this new class of drugs

 Omeprazole (Prilosec)
Prototype H+, K+-ATPase inhibitor; A prodrug that needs a low pH to be active;

Irreversible (forms a covalent bond with the proton pump) - long lasting
inhibition of acid production;

Profound reduction of gastric acid - elevates gastric pH significantly

(20mg/day for 7days will decrease acid by 95%);

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;

Ireversibel (membentuk ikatan kovalen dengan pompa proton) -

penghambatan tahan lama produksi asam;

Pengurangan mendalam asam lambung - meningkatkan pH

lambung secara signifikan (20mg / hari untuk 7days akan
menurunkan asam dengan 95%);

Sangat terikat protein; Dimetabolisme oleh CYP2C & CYP3A;

paruh plasma dari 1 to2 jam tapi durasi panjang tindakan; Harus
diambil sesaat sebelum makan dan TIDAK harus diambil
dengan agen penekan asam lainnya.
 PPI
Esomeprazole (Nexium)
Simply the S-isomer of
omeprazole; H+, K+-ATPase
inhibitor;
Given orally.
Rabeprazole (Aciphex)
Lansoprazole (Prevecid)
H+, K+-ATPase inhibitor;
Given orally.
Pantoprazole (Protonix)
⚫ H+, K+-ATPase inhibitor;
⚫ An acid-stable form and can be given
by i.v.
 Proton Pump Inhibitors:
Indications

⚫ GERD maintenance therapy

⚫ Erosive esophagitis

⚫ Short-term treatment of active duodenal and benign

gastric ulcers
⚫ Zollinger-Ellison syndrome

⚫ Treatment of H. pylori–induced ulcers

⚫ Safe for short-term therapy

 Proton Pump Inhibitors:
Nursing Implications

⚫ Assess for allergies and history of liver disease

⚫ pantoprazole (Protonix) is the only proton pump

inhibitor available for parenteral administration,
and can be used for patients who are unable to take
oral medications
⚫ May increase serum levels of diazepam,
phenytoin, and cause increased chance for
bleeding with warfarin
 Proton Pump Inhibitors:
Nursing Implications

Instruct the patient taking omeprazole

(Prilosec):
⚫ It should be taken before meals

⚫ The capsule should be swallowed whole, not

crushed, opened, or chewed

⚫ It may be given with antacids

⚫ Emphasize that the treatment will be short term

 ⚫TUGAS DIRUMAH JELASKAN MASING2
MEKANISME OBAT ANTIMUSKARINIK
AGENT
DAN OBAT DIBAWAH INI SESUAI GAMBAR YANG
TERTERA
 Summary of Acid Reduction therapeutics

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

Side-effects are typical of anticholinergics such

as
◦
atropine
Dry mouth
◦ Tachycardia
◦ Blurred vision
◦ Bowel discomfort (constipation)
◦ Difficulty in urination
 Drugs for Acid-Peptic Disorders -
Anticholinergics
◦ General muscarinic receptor antagonists
(block all types of muscarinic receptors)
◦ Atropine
◦ Propantheline (Pro-Banthine)
◦ Dicyclomine (Bentyl)

◦ Selective M1 receptor antagonists

◦Pirenzepine
◦Telenzepine
⑶ Antagonist of G-R
Mechanism:
◦ Competing Gastrin-R on Parietal Cell
Pharmacologic Effects:
◦ HCl Mucosal
Agents:
◦ Proglumide
Adverse Effect: