Gastric and Doudenal

Peptic Ulcer

Dr.Rania Khalil Mostafa

lecturer of medical pharmacology
Objectives

Gastric and Antispasmodic

Doudenal Ulcer
Antiemetic Prokinetic
Peptic ulcer

• Peptic ulcer is a break in the gastric or

duodenal mucosa that arises when the
normal mucosal defensive factors are
impaired or are overwhelmed by aggressive
luminal factors such as acid and pepsin.
• This imbalance results in any degree of
gastrointestinal mucosal irritation,
inflammation or ulceration
• Most common causes are due to H.pylori
infection and NSAIDs
Goals of Therapy:

peptic ulcer

• Relief of pain.
• Promotion of healing.
• Prevention of recurrence.
• Preventing ulcer complications
b. Antisecretory Drugs (Reduction of Acid
Secretion):
1) H2 – Blockers: Cimetidine, ranitidine,
famotidine, nizatidine
Pharmacodynamics:
▪ Selective Competitive Blocker of H2-
receptors.
▪ ↓Gastric acidity (Basal, NOCTURNAL &
Stimulated)
Formation of pepsin → Daily amount NOT its
concentration.
Secretion of Intrinsic Factor (BUT NO
pernicious anemia).
▪ Does Not affect gut motility → Unlike
Parasympatholytic
1) Proton Pump Inhibitor (H+ /K+ ATPase Inhibitors):
Omeprazole. Esomeprazole, Lansoprazole ,Pantoprazole
Pharmacodynamics: ➢

• Prodrugs: Activated in the acid environment of the secretory

canaliculi of the parietal cells of the stomach. ➢ Irreversible inhibitor
of H+ /K+ ATPase enzyme.
• Their effect is prolonged until synthesis of new H+ /K+ ATPase
enzyme. ➢ Basal & Stimulated gastric acidity up to 100%. BUTNO
effect on gastric motility. ➢ increase Gastrin secretion.
1) Proton Pump Inhibitor (H+ /K+ ATPase Inhibitors):
Omeprazole. Esomeprazole, Lansoprazole
,Pantoprazole
Pharmacodynamics: ➢
1) Proton Pump Inhibitor (H+ /K+ ATPase Inhibitors):
Omeprazole. Esomeprazole, Lansoprazole ,Pantoprazole

Therapeutic Uses:
• 1- Peptic ulcer & Zollinger-Ellison syndrome
(Drug of Choice).
• 2- Gastro-Esophageal Reflux Disorder
(GERD).
 1) Proton Pump Inhibitor (H+ /K+ ATPase Inhibitors):
Omeprazole. Esomeprazole, Lansoprazole ,Pantoprazole

Side Effects:
• 1- Hypergastrinemia (an increase in gastrin and
hyperplasia of enterochromaffin cells) may cause gastric
Carcinoid tumors in rats
• 2- May increase the risk of respiratory & enteric infections
• 3- long-term acid suppression leads to atrophic gastritis
and intestinal metaplasia
1) Proton Pump Inhibitor (H+ /K+ ATPase Inhibitors):
Omeprazole. Esomeprazole, Lansoprazole ,Pantoprazole

Side Effects:
• 4- Hypomagnesemia
• 5- Increased risk of osteoporosis and
risk of fracture (hip, wrist, spine)
 1) Proton Pump Inhibitor (H+ /K+ ATPase Inhibitors): Omeprazole.
Esomeprazole, Lansoprazole ,Pantoprazole

Drug interaction
• Clopidogrel and PPIs. : Clopidogrel is a prodrug that requires activation by the hepatic P450 CYP2C19
isoenzyme, which also is involved to varying degrees in the metabolism of PPIs (especially omeprazole,
esomeprazole, lansoprazole, and dexlansoprazole).
• Thus, PPIs could reduce clopidogrel activation (and its antiplatelet action).
 1) Proton Pump Inhibitor (H+ /K+ ATPase Inhibitors):
Omeprazole. Esomeprazole, Lansoprazole ,Pantoprazole
1) Proton Pump Inhibitor (H+ /K+ ATPase Inhibitors): Omeprazole.
Esomeprazole, Lansoprazole ,Pantoprazole

Drug interaction
• ❖Omeprazole decreases metabolism of Warfarin, Theophylline, Diazepam &
Phenytoin.
• ❖Decreases bioavailability of vitamin B12 & digoxin & ketoconazole
2) Potassium competitive acid blockers
(P-CABs) :Vonoprazan

Novel potassium -competitive acid

blocker
Pharmacodynamics: Quality
Service
Provide reversible gastric acid
suppression by preventing K+ from
binding to gastric H+ /K+ -ATPase.
2) Potassium competitive acid Therapeutic uses:
blockers (P-CABs) :Vonoprazan

1 Peptic ulcer

2 Gastro-Esophageal Reflux
Disorder (GERD

3 Eradication of H.pylori
2) Potassium competitive acid
blockers (P-CABs) :Vonoprazan
Side Effects

1
GIT upset: diarrhea, nausea,
abdominal distention or
discomfort

2 Hepatic function
abnormalities

Risk of fracture (hip, wrist,

3 spine) after long-term use
or high doses

4
4
Hypersensitivity reaction
( urticaria, anaphylactic
shock)
Advantages and differences of
P-CABs over PPIs are as
follows:

P-CABs are acid stable hence they don't require enteric

coated formulation.

They have a faster onset of action and achieve rapid acid

suppression even at first dose when compared to PPIs
They exert direct inhibitory effect on H+ /K+ ATPase
enzyme without need for activation.

They bind to active and inactive forms of the proton pump while
PPIs block mainly active state of the pumps.

Unlike PPIs, there is no pharmacogenetics variation and

enzymatic inhibition properties in P_CABs
4) Antimuscarinic Drugs: Pirenzepine. Telenzepine

Effectively blocks acid secretion

(30 to 40%)
▪ Moderately reduce gastric acid
and pepsin secretion without
inhibiting smooth-muscle activity
▪ Hasten peptic ulcer healing and
improve the symptoms of reflux
esophagitis
▪ combination with H2-antagonists
they abolish gastric acid secretion
almost completely
D) Eradication of H. pylori:
Triple therapy
consists of:
PPI + Clarithromycin + Amoxycillin or
Metronidazole
Quadruple therapy
consists of:
PPI + Bismuth compounds + Metronidazole +
Tetracyclines
E) Other Drugs:
1. Sedatives or Tranquillizers e.g. Diazepam
→ # Psychic effect on acid secretion.
2. Tricyclic Antidepressants→ Psychic
effects + Anti-cholinergic
Treatment of Colic 1- Parasympatholytics e.g. Atropine and its
antispasmodic substitutes: e.g.
Antispasmodics Propantheline

2- Direct Spasmolytics: Volatile oils

(peppermint), Kheline, papaverine Mebeverine
• Useful in colon spasm
Antiemetics Drugs used in the prevention
& treatment of nausea & vomiting
1- H1 (histamine) receptor blockers
(Antihistaminics):
▪ Block H1-receptor in vomiting center.
▪ Effective in all vomiting including Motion
sickness.
Long acting Useful in sea sickness.
E.g. Dimenhydrinate, Diphenhydramine,
Promethazine, Meclizine & Cyclizine
2- Muscarinic receptor blockers: Hyoscine½ mg
½ hr before the journey po or transdermal patch.
a- Blocks M-receptors in vomiting center.
b- Effective in ALL vomiting including Motion
sickness.
Short acting Useful in air sickness
Antiemetics Drugs used in the prevention
& treatment of nausea & vomiting

3- D2 (Dopamine) receptor blockers:

• Block D2-receptor in CTZ. Effective in all vomiting
EXCEPT motion sickness.
• Include:
Metoclopramide,Domperidone,Phenothiazines,Butyroph
enones - Metoclopramide: Antiemetic acting by:
• Centrally Blocks D2-receptor in CTZ.
• Peripherally --Stimulate 5-HT4 receptors in enteric ganglia-
--increase Release of A.Ch.increase Gastric motility and
Gastric emptying ---Prokinetic agent.
• This action is antagonized by atropine.
Antiemetics Drugs used in the prevention &
treatment of nausea & vomiting

3- D2 (Dopamine) receptor blockers:

Domperidone: antiemetic acting by: -
• Centrally Blocks D2-receptor in CTZ.
• Peripherally increase Gastric motility --- Prokinetic agent.
Phenothiazines: eg Chlorpromazine & Butyrophenones: eg
Droperidol & Haloperidol.➔Block D2-receptor in CTZ. Also,
➔useful in ttt of schizophrenia
Antiemetics Drugs used in the prevention
& treatment of nausea & vomiting
4- 5-HT3 (Serotonin) Receptors
blockers:
e.g.Ondansetron&Granisetron

Block 5-HT3 receptors in CTZ ➢ Used

orally & IV once daily mainly in vomiting
induced by cancer chemotherapy.

The drugs are most effective when given

as a single dose by intravenous
injection 30 minutes prior to
administration of chemotherapy
Antiemetics Drugs used in the prevention
& treatment of nausea & vomiting

4- 5-HT3 (Serotonin) Receptors

blockers:

Palonosetron is a newer
intravenous agent that has
greater affinity for the 5- HT3
receptor and a long serum half-life
of 40 hours. ➢ used in
Postoperative and post
radiation nausea and vomiting
5- Neurokinin receptor blockers: e.g.
Aprepitant

• Neurokinin receptors are recently found in vomiting

center where they are stimulated by substance P---
Vomiting & blocked by Aprepitant
Antiemetic Action Aprepitant:
Used orally to prevent vomiting induced by cancer
chemotherapy Netupitant (300 mg) is available only as a
combination product with palonosetron (0.5 mg).
Side Effects:
Fatigue, Dizziness & Anorexia
6- Glucocorticoids:

Dexamethasone
Used in vomiting due to cancer
chemotherapy.
These agents appear to enhance the
efficacy of 5-HT3-receptor
7- Cannabinoids e.g. Dronabinol. Used in
vomiting due to cancer chemotherapy.

Mechanism of action:
Inhibit dopamine release
Side Effects:
1. CNS: Euphoria, uncontrollable laugh, weak
mental concentration, impairment of reflexes.
2. CVS: Vasodilatation and tachycardia Because of
the availability of more effective agents, dronabinol
now is uncommonly used for the prevention of
chemotherapy-induced nausea and vomiting.
Combination therapy with phenothiazines
provides synergistic antiemetic action and appears
to attenuate the adverse effects of both agents.
8- Pyridoxine (Vit B-6):
Effective in vomiting of pregnancy.

9-Benzodiazepine
Benzodiazepines such as lorazepam or
diazepam are used before the initiation of
chemotherapy to reduce anticipatory
vomiting or vomiting caused by anxiety
 Drugs which GIT motility &enhance
Prokinetic Agents transit of materials through the GI tract
e.g. Metoclopramide, Domperidone,
Itopride & Erythromycin.
 1- Antiemetic: mechanism of action:
A- Metoclopramide a- Central: Blocks D2-receptors in CTZ
(Primperan) b- Peripheral - Stimulate 5-HT4 receptors in enteric
Pharmacodynamics: ganglia ---- Release of A.Ch. Gastric motility Gastric
emptying -----Prokinetic agent. This action is blocked by
atropine
A- Metoclopramide 2- Prokinetic agent
Gastric motility & emptying.
(Primperan)
□Therapeutic Uses: 10 mg 3-4 times/day Orally, Rectally, IM & IV.
Pharmacodynamics: 1- All vomiting EXCEPT motion sickness.
2- Gastric Hypomotility e.g. Diabetic gastroparesis.
3- Gastro-Esophageal-Reflux-Disease (GERD, Reflux Esophagitis).
4- Hiccup
A- Metoclopramide
(Primperan)
1- Dizziness & nervousness.
Adverse Effects:
2- Extrapyramidal manifestations e.g.
Parkinsonism & ataxia.
3- Hyperprolactinemia ---- Galactorrhea in females.
5- Absorption of concomitantly administrated drugs
e.g. Paracetamol, BUT NOT Digoxin
Alizapride
• N.B. Alizapride is a dopamine (D2) antagonist with
prokinetic and antiemetic effects
• used in the treatment of nausea and vomiting,
including postoperative nausea and vomiting.
• It is structurally related to metoclopramide.
B-Domperidone
(Motelium)

1- Similar to Metoclopramide --Dual Anti-Emetic &

Prokinetic agent:
a- Central: Block D2-receptors.
b- Peripheral: Block alpha -adrenoceptors in stomach
Motility------Prokinetic agent. This action is NOT
antagonized by atropine.
 C- Itopride
(Ganaton)&Mosapride
(Gasmovac)

5-HT4 receptors in Release of A.Ch. Gastric

enteric ganglia & Colonic motility

Prokinetic agent:
Used in GERD with Proton Pump Inhibitors
D- Erythromycin:

Macrolide antibiotic Stimulates motilin receptors

on GIT

Rapid tolerance to this effect

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