Ranitidine
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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
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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
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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
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Pharmacokinetics
- Oral administration
- absorption virtually complete
- Peak levels 1-3 hours
- Extensive hepatic first pass metabolism
- Half life 2-3 hours
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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
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Indications
- Peptic ulcer
Gastric, Duodenal
- GERD / Reflux Oesophagitis
- Stress ulcers; pre-anaesthetic use to prevent acid aspiration syndrome;
with NSAIDs
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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
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Tolerability
- Well tolerated
- Adverse effects (3% approx.) include skin rash, headache and dizziness
- Avoids problems of gynaecomastia and impotence associated with cimetidine
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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
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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
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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
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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
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