pharma

1. Drugs in peptic ulcer disease
(H2 blockers and proton pump inhibitors)
Elgilani Zaher

2. Peptic ulcer
 a localized lesion of the mucous membrane of the
stomach (gastric ulcer) or duodenum (duodenal
ulcer), typically extending through the muscularis
mucosa.
What is different between peptic ulcer & duodenal
ulcer?

3. Pathophysiology:
is imbalance between aggressive factors (acid &
Pepsin & NSAIDs & smoke , H.pylori) and
defensive factors(prostaglandins, very thick layer of
mucus & bicarbonate layer , Good blood flow).
Helicobacter pylori is the major etiological factor in peptic
ulcer disease (PUD) (95% in duodenal and 70% in gastric
ulcer).
Drugs induced such as NSAIDs (aspirin, naproxen )
on long term use .

4. Pathophysiology:
1. HCl and pepsin destroy gastric and
duodenal mucosa.
2. Mucus and HCo3 ion secretions protect
mucosa
3. Prostaglandins protect mucosa by
enhancing mucus and bicarbonate
production and by enhancing mucosal
blood flow

5. Etiology:
H. pylori infection
Alcohol
Smoking
Caffeine
Genetic factors
Diet
Hypersecretory states (Zollinger Ellison syndrome)
Drugs : NSAIDs

6. Gastric secretions
1. HCl and intrinsic factor (Parietal cells).
2. Pepsinogens (Chief cells).
3. Mucus, bicarbonate (mucus-secreting cells)
(secretory cells)

7. Regulation of gastric secretions
Parietal cells secrete acid in response to:
1. Histamine : H2 receptors
2. Gastrin : CCK2 receptors
3. Ach : M3 receptors
4. Proton pump (H+/ K+ ATPase)

9. Gastric secretion by parietal cells

11. Treatment of peptic ulcer
 Eradication of H. pylori infections
 Hyposecretory drugs.
 H2 receptor blockers
 Antimuscarinic drugs
 Proton pump inhibitors
 Mucosal cytoprotective agents.
 Prostaglandin analogues
 Neutralizing agents (antacids).

12. Gastric hyposecretory drugs
Include:
 H2 receptor blockers
 Proton pump inhibitors
 Antimuscarinic drugs
 Hyposecretory drugs decrease gastric acid
secretion Promote healing & relieve pain.

13. Proton Pump Inhibitors (PPIs)
Omeprazole – Lansoprazole
Pantoprazole -Raprazole
Acts by irreversible inhibition of proton pump
(H+/ K+ ATPase) that is responsible for final step
in gastric acid secretion from the parietal cell.

14. Pharmacodynamics
 They are the most potent inhibitors of acid
secretion available today.
 Produce marked inhibition of basal & meal
stimulated-acid secretion (90-98%).
 Reduce pepsin activity.
 Promote mucosal healing & decrease pain
 Proton pump inhibitors heal faster the ulcers
than H-2 blockers, and have H.pylori inhibitory
properties How?.

15. Pharmacokinetics
 Given orally as enteric coated capsules
(unstable in acidic medium in stomach).
 Are pro-drugs
 rapidly absorbed from the intestine.
 Activated in the acidic medium of parietal
cell .
 Should not be combined with H2 blockers or
antacids.
 Inactivated if at neutral pH.

16.  Have long duration of action (> 12 h-24 h).
 Once daily dose is sufficient
 Given 1 h before meal.
 Bioavailability is reduced by food.
 metabolized in the liver by Cyt-P450.
 Dose reduction is required in severe liver
failure.

17. USES
Eradication of H. pylori (combined with
antimicrobial drugs).
Resistant severe peptic ulcer ( 4-8 weeks).
 Reflux esophagitis.
Hypersecretory conditions as Zollinger Ellison
syndrome and gastrinoma (First choice).

18. Adverse effects
 Headache, diarrhea & abdominal pain.
 Achlorhydria
 Hypergastrinaemia.
 Gastric mucosal hyperplasia.
- increased risk of community-acquired respiratory
infections & nosocomial pneumonia
 Long term use:
 Vitamin B12 deficiency
 increased risk of hip fractures

19. H2 receptor blockers
- Cimetidine - Ranitidine
- Famotidine - Nizatidine
Mechanism of action
 They competitively and reversibly block
H2 receptors on the parietal cells.

20. Pharmacokinetics
 Good oral absorption
 Given before meals.
 Famotidine is the most potent drug.
 Exposed to first pass metabolism (except
nizatidine that has 100 % bioavailability).
 Duration of action (4-12 h).
 Metabolized by liver.
 Excreted mainly in urine.
 Cross placenta & excreted in milk (should
not be given in pregnancy unless it is necessary).

22. Uses:
 GERD ((heartburn/ dyspepsia).
 Acute ulcer healing in moderate cases
 Duodenal Ulcer (6-8 weeks).
 Benign gastric ulcer (8-12 weeks).
 Pre-anesthetic medication (to prevent
aspiration pneumonitis).
 Prevention of bleeding from stress-related
gastritis.
 Post–ulcer healing maintenance therapy.
 Together with NSAIDs to prevent ulcers

23. Adverse effects of H2 blockers
 GIT disturbances (Nausea & Vomiting????).
 CNS effects: Headache - confusion
(elderly, hepatic dysfunction, renal dysfunction).
 Bradycardia and hypotension (rapid I.V.)
 CYT-P450 inhibition (Only Cimetidine)
decrease metabolism of warfarin, phenytoin,
benzodiazepines.

24. Endocrine effects (Only Cimetidine)
 Galactorrhea (Hyperprolactinemia )
 Antiandrogenic actions (gynecomasteia –
impotence) due to inhibition of
dihydrotestosterone binding to androgen
receptors.
Precautions
Dose reduction of H2 blockers in severe renal
or hepatic failure and elderly.

25. Antacids
These drugs are mainly inorganic salts
e.g.: NaHCO3; Ca CO3; Al (OH)3; Mg (OH)2
acts by direct chemical neutralization of HCL and as a
result may decrease pepsin activity.
 used to relief pain of peptic ulcer & for dyspepsia.
 All antacids  absorption of some drugs as
tetracycline, fluoroquinolones, iron.
NaHCO3: Systemic alkalosis; Ca CO3 : milk alkali
syndrome (hypercalcemia, renal failure????)
Al (OH)3 : constipation; Mg (OH)2 : Diarrhea

26. Misoprostol
 Prostaglandin analogues (PGE1 )
  HCL secretion.
  protective measures ( mucous/bicarbonate
& gastric mucosal blood flow).
 Orally, must be taken 3-4 times/day.
 Used for NSAIDS-induced peptic ulcer but H2 blockers
or proton pump inhibition are better.
Adverse effects:
 Abdominal cramps; diarrhea
 Uterine contraction (dysmenorrhea or abortion);
 Vaginal bleeding.

27. If H. pylori infection is diagnosed in the
presence of peptic ulcer disease
 Eradication with most commonly "triple
therapy" with a PPI, clarithromycin,
and amoxicillin +/- metronidazole for 7-14
days (Cure rates of 70% to 90% ).
 Pentaprazole 40 mg
 Amoxicillin 1000 mg
 Tetracyclin 500 mg
 Pepto-Bismol 15 ml
 Clarithromycin 500 mg