Histamine & Gastric Acid

- Histamine involved in allergic reactions and also gastric acid secretion
- In stomach, acetylcholine (from vagal stimulation) and gastrin stimulate the parietal cells, but their efficacy depends upon simultaneous stimulation by histamine

 

Histamine blockers

- H1 receptors are concerned with allergy; conventional antihistamines block H1 receptors
- H2 receptors in the parietal cell of stomach are involved with acid secretion; thus H2 receptor antagonists inhibit acid secretion
- H2 receptor antagonists reversibly and competitively bind to H2 receptors

 

Chemistry

- Cimetidine, the first H2 blocker for clinical use, like histamine, has an imidazole ring
- Ranitidine does not have an imidazole group, but possesses a substituted furan ring

Pharmacokinetics

- Oral administration
- absorption virtually complete
- Peak levels 1-3 hours
- Extensive hepatic first pass metabolism
- Half life 2-3 hours

 

Dosage
Usual dosage150 mg b.d. or 300 mg h.s.

Peptic ulcer
150 mg b.d. or 300 mg h.s., till ulcer is healed (or 4-8 weeks if endoscopic assessment is not possible)
Maintenance
150 mg h.s.

Reflux oesophagitis / GERD
150 mg b.d. or 300 mg h.s. for up to 8 weeks

Zollinger Ellison syndrome
150 mg t.I.d. increased to 900 mg daily

 

Indications

- Peptic ulcer Gastric, Duodenal
- GERD / Reflux Oesophagitis
- Stress ulcers; pre-anaesthetic use to prevent acid aspiration syndrome; with NSAIDs

 

Ranitidine in peptic ulcer

- Inhibits acid secretion, facilitates ulcer healing
- Effective in gastric and duodenal ulcers
- Good healing rates (» 90%)
- Safe on long term administration over many years
- Time tested and widely documented

 

Tolerability

- Well tolerated
- Adverse effects (3% approx.) include skin rash, headache and dizziness
- Avoids problems of gynaecomastia and impotence associated with cimetidine

 

Advantages over cimetidine

- Ranitidine is more potent than cimetidine
- Cimetidine blocks androgen receptors and is associated with gynaecomastia and impotence; ranitidine has no such effects
- CNS adverse effects are less frequent with ranitidine than cimetidine
- Cimetidine binds to cytochrome P-450 causing drug interactions with phenytoin, theophylline, propranolol, diazepam, etc.; these are less with ranitidine

 

 

Advantages over newer H2 blockers

- Newer agents have no major benefits over ranitidine
- Among H2 antagonists, ranitidine has become the standard agent, others may be described as “me-too” agents
- Ranitidine is more extensively tried and documented than newer compounds

 

Status vis-a-vis Proton Pump Inhibitors

- Proton pump inhibitors provide potent acid inhibition; ranitidine may be used in situations where less potency is adequate
- Ranitidine can be employed in patients who cannot be administered proton pump inhibitors

 

Salient Features

- Established as the front line agent amongst H2 receptor antagonists
- Extensively used and documented, i.e., efficacy and safety well established
- Useful in peptic ulcer, GERD, with NSAIDs, to prevent acid aspiration syndrome, stress ulcers, Zollinger Ellison syndrome
- Convenient o.d. dosing