Ranitidine is a histamine H2-receptor antagonist that inhibits stomach acid production.
It is commonly used in treatment of peptic ulcer disease and gastroesophageal reflux
disease.
Ranitidine is also used alongside fexofenadine and other antihistamines for the treatment
of skin conditions such as hives.
Ranitidine is also known to give false positives for methamphetamine on drug tests.
It is on the World Health Organization's List of Essential Medicines, a list of the most
important medication needed in a basic health system.
Medical use Relief of heartburn, acid indigestion, and
sour stomach.
Short-term and maintenance therapy of gastric and duodenal ulcers
Ranitidine can also be coadministered with NSAIDs to reduce the risk of ulceration.
Proton-pump inhibitors are more effective for the prevention of NSAID-induced ulcers.
Pathologic GI Hypersecretory Conditions such as Zollinger-Ellison Syndrome
Gastroesophageal Reflux erosive esophagitis
Part of a multidrug regimen for H. pylori eradication to reduce the risk of duodenal
ulcer recurrence.
Recurrent postoperative ulcer Upper GI bleeding
Prevention of acid-aspiration pneumonitis during surgery: Ranitidine can be administered
preoperatively to reduce the risk of aspiration pneumonia.
The drug not only increases gastric pH, but also reduces the total output of gastric juice.
In a 2009 meta-analysis comparing the net benefit of proton pump inhibitors and ranitidine
to reduce the risk of aspiration before anesthesia, ranitidine was found to be more effective
than proton pump inhibitors in reducing the volume of gastric secretions.
Ranitidine may have an antiemetic effect when administered preoperatively.
Prevention of stress-induced ulcers in critically ill patients.
Preparations Certain preparations of ranitidine are available
over the counter in various countries.
In the United States, 75-mg and 150-mg tablets are available OTC.
Zantac OTC is manufactured by Boehringer Ingelheim.
In Australia, packs containing seven or 14 doses of the 150-mg tablet are available in
supermarkets, small packs of 150-mg and 300-mg tablets are schedule 2 pharmacy medicines.
Larger doses and pack sizes still require a prescription.
Dosing For ulcer treatment, a night-time dose is
especially important - as the increase in gastric/duodenal pH promotes healing overnight
when the stomach and duodenum are empty.
Conversely, for treating reflux, smaller and more frequent doses are more effective.
Ranitidine used to be administered long term for reflux treatment, sometimes indefinitely.
However, PPIs have taken over this role.
In addition, a fairly rapid tachyphylaxis can develop within 6 weeks of initiation of
treatment, further limiting its potential for long-term use.
People with Zollinger-Ellison syndrome have been given very high doses without any harm.
Contraindications Ranitidine is contraindicated for patients
known to have hypersensitivity to the drug.
Adverse effects The following adverse effects have been reported
as events in clinical trials Central nervous system
There have been rare reports of malaise, dizziness, somnolence, insomnia, and vertigo.
In severely ill, elderly patients, there have been rare cases of reversible mental confusion,
agitation, depression, and hallucinations.
Ranitidine causes fewer CNS adverse reactions and drug interactions compared to cimetidine.
Cardiovascular There have been rare reports of arrhythmias
such as tachycardia, bradycardia, atrioventricular block, and premature ventricular beats.
Gastrointestinal All drugs in its class have the potential
to cause vitamin B12 deficiency secondary to a reduction in food-bound vitamin B12 absorption.
Elderly patients taking H2 receptor antagonists are more likely to require B12 supplementation
than those not taking such drugs.
H2 blockers may also reduce the absorption of drugs that require an acidic stomach.
In addition, multiple studies suggest the use of H2 receptor antagonists such as raniditine
may increase the risk of infectious diarrhoea, including traveller's diarrhoea and salmonellosis.
Finally by suppressing acid-mediated breakdown of proteins, ranitidine may lead to an elevated
risk of developing food or drug allergies, due to undigested proteins then passing into
the gastrointestinal tract, where sensitisation occurs.
Patients who take these agents develop higher levels of IgE against food, whether they had
prior antibodies or not.
Even months after discontinuation, an elevated level of IgE in 6% of patients was still found
in this study.
Hepatic There have been rare, reported cases of cholestatic
hepatitis, hepatic failure, hepatitis, jaundice.
These symptoms require immediate discontinuation of the drug.
Respiratory Ranitidine and other histamine H2 receptor
antagonists may increase the risk of pneumonia in hospitalized patients.
They may also increase the risk of community-acquired pneumonia in adults and children.
Hematologic Thrombocytopenia is a rare but known side
effect.
Drug-induced thrombocytopenia usually takes weeks or months to appear, but may appear
within 12 hours of drug intake in a sensitized individual.
Typically, the platelet count falls to 80% of normal, and thrombocytopenia may be associated
with neutropenia and anemia.
Interaugmentary Rash, including rare cases of erythema multiforme.
Rare cases of hair loss and vasculitis.
Warnings and precautions Disease related concerns
With gastric malignancies, relief of symptoms due to the use of ranitidine does not exclude
the presence of a gastric malignancy.
In addition with renal or hepatic impairment, ranitidine must be used with caution.
Finally, ranitidine should be avoided in patients with porphyria as it may precipitate an attack.
Pregnancy Pregnancy Category B.
Lactation Ranitidine enters breast milk, with peak concentrations
seen at 5.5 hours after the dose in breast milk.
Caution should be exercised when prescribed to nursing women.
Children In children, the use of gastric acid inhibitors
has been associated with an increased risk for development of acute gastroenteritis and
community-acquired pneumonia.
A cohort analysis including over 11,000 neonates reported an association of H2 blocker use
and an increased incidence of necrotizing enterocolitis in very low birth weight neonates.
In addition, there was an approximately sixfold increase in mortality, necrotizing enterocolitis,
and infection was reported in patients receiving ranitidine in a cohort analysis of 274 VLBW
neonates.
Pharmacology Mechanism of action
Ranitidine is a competitive, reversible inhibitor of the action of histamine at the histamine
H2-receptors found in gastric cells.
This results in decreased gastric acid secretion and gastric volume, and reduced hydrogen ion
concentration.
Pharmacokinetics Absorption: Oral: 50%
Protein binding: 15% Metabolism: N-oxide is the principal metabolite.
Half-life elimination: With normal renal function, ranitidine taken orally has a half-life of
2.5–3 hours.
If taken intravenously, the half-life is generally 2-2.5 hours in a patient with normal creatinine
clearance.
Excretion: The primary route of excretion is the urine.
In addition, approximately 30% of the orally administered dose is collected in the urine
as non-absorbed drug in 24 hours.
Elderly In the elderly population, the plasma half-life
of ranitidine is prolonged to 3–4 hours secondary to decreased kidney function causing
decreased clearance.
Children In general, studies looking pediatric patients
have showed no significant differences in pharmacokinetic parameter values in comparison
to healthy adults, when correction is made for body weight.
History
Ranitidine was first prepared as AH19065 by John Bradshaw in the summer of in the Ware
research laboratories of Allen & Hanburys Ltd, part of the Glaxo organization.
Its development was a response to the first in class histamine H2-receptor antagonist,
cimetidine, developed by Sir James Black at Smith, Kline and French, and launched in the
United Kingdom as Tagamet in November 1976.
Both companies would eventually become merged as GlaxoSmithKline following a sequence of
mergers and acquisitions starting with the integration of Allen & Hanbury's Ltd and Glaxo
to form Glaxo Group Research in 1979, and ultimately with the merger of Glaxo Wellcome
and SmithKline Beecham in 2000.
Ranitidine was the result of a rational drug-design process using what was by then a fairly refined
model of the histamine H2-receptor and quantitative structure-activity relationships.
Glaxo refined the model further by replacing the imidazole ring of cimetidine with a furan
ring with a nitrogen-containing substituent, and in doing so developed ranitidine.
Ranitidine was found to have a far-improved tolerability profile, longer-lasting action,
and 10 times the activity of cimetidine.
Ranitidine has 10% of the affinity that cimetidine has to CYP450, so it causes fewer side effects,
but other H2 blockers famotidine and nizatidine have no CYP450 significant interactions.
Ranitidine was introduced in 1981 and was the world's biggest-selling prescription drug
by 1988.
It has since largely been superseded by the even more effective proton-pump inhibitors,
with omeprazole becoming the biggest-selling drug for many years.
When omeprazole and ranitidine were compared in a study of 144 people with severe inflammation
and erosions or ulcers of the esophagus, 85% of those treated with omeprazole healed within
eight weeks, compared to 50% of those given ranitidine.
In addition, the omeprazole group reported earlier relief of heartburn symptoms.
Synthesis Dimethylamine.HCl + paraformaldehyde + furfural
alcohol → 5-(dimethylaminomethyl)furfuryl alcohol.
5-(dimethylaminomethyl)furfuryl alcohol + cysteamine.HCl → 2-(((5-((dimethylamino)methyl)furan-2-yl)methyl)thio)ethanamine
Product above step + N-methyl-1-methylthio-2-nitro-ethenamine → Ranitidine.
See also Famotidine, aka Pepcid AC, Pepcidine: another
popular H2-receptor antagonist References
External links Reflux Remedies: ranitidine
Consumer information on Zantac from the manufacturer Zantac official website GlaxoSmithKline
Zantac OTC official website Boehringer Ingelheim