PEPTIC DISORDER
& DRUG THERAPY

H2 receptor Antagonists Posted on 28/2/2008

Nowadays, H2 receptor antagonists have been replaced by Proton Pump Inhibitors in clinical practice.

The H2 receptor antagonist drugs available are:
- Cimetidine
- Ranitidine
- Famotidine
- Nizatidine

Introduction

Pharmacology
The H2 receptor antagonist inhibits acid production by reducing the basal acid secretion and pepsin production but they do not produce complete suppression of acid secretion. Four different H2 receptor antagonists are different in their pharmacokinetic. H2 receptor antagonists are less potent than proton pump inhibitors but still suppress 24 hours gastric acid secretion by about 70%. 

 

Therapeutic Uses
The major therapeutic indications for H2 receptor antagonist are to promote healing of gastric and duodenal ulcers, to treat uncomplicated GERD and to prevent the occurrence of stress ulcers.

 

Dosage form
Oral dosage form
All four H2 receptor antagonists are available as prescription and over-the-counter formulations for oral administration.

Parenteral dosage form (injection)
Intravenous and intramuscular preparation of cimetidine, ranitidine and famotidine are available. This is useful when oral and nasogastric routes are not an option.

Intravenous doses of H2 receptor antagonist:

 

 

Pharmacokinetic
The H2 receptor antagonists are rapidly absorbed after oral administration, with peak serum concentrations within 1 to 3 hours.

Only a small percentage of H2 receptor antagonists are protein-bound. The kidney excretes these drugs and their metabolites by filtration and renal tubular secretion and it is important to reduce the doses of H2 receptor antagonist in patient with decreased creatinine clearance.

 

Adverse Effect
Side effects are usually minor and include diarrhea, headache, drowsiness, fatigue, muscular pain and constipation. Less common side effect includes those affecting the CNS (confusion, hallucination and slurred speech).

Long term use of cimetidine at high doses will decrease testosterone binding to the androgen receptor and inhibit a CYP that hydroxylates estradiol. Clinically, these effects can cause galactorrhea in women, reduced sperm count and impotence in men.
H2 receptor antagonists can cross the placenta and excreted in breast milk. It should take these drugs with care for patient who suffers from renal failure, kidney failure, pregnant women and breastfeeding mother.

 

Example of H2 Receptor Antagonist

Brand name: TAGAMET
Manufacturer: GlaxoSmithkline
Distributor: [Zuellig Pharma]
Content: Cimetidine
Indication: Listed in dosage form
Dosage: Active peptide ulcer, 800mg at bedtime. NSAID-induced lesions 800mg/day. Oesophageal reflux disease 400mg four time a day for 4-8 week.
Special precaution: Impaired liver function, gastric malignancy, pregnancy, lactation and elderly.
Adverse effect: Mild and transient diarrhea, fatigue, dizziness and rash.
Drug interaction: May affect metabolism of Walfarin-type anticoagulants, phenytoin and theophlline.

 

Brand name: ZANTAC
Manufacturer: GlaxoSmithkline
Distributor: [Zuellig Pharma]
Content: Ranitidine HCI
Indication: Listed in dosage
Dosage: Adult and children more than 16 years old, 150mg and 300mg in tablet, syrup or granule. Duodenal ulcer and benign gastric ulcer 150mg twice a day or 300g at bedtime. Prophylaxis of NSAID-induced duodenal damage 150mg twice a day. Reflux esophagitis 150mg twice to four times a day for up to 8 week.
Special precaution: GI malignancy, dyspeptic symptoms, severe kidney and liver impairment, pregnancy, lactation and patient on NSAID.
Adverse effect: Reversible hepatitis, agranulocytosis, acute pancreatitis, arthralgia myaglia, hypersensitivity, skin rashes and dizziness.
Drug interaction:-

 

Brand name: Apo-cimetidine
Manufacturer: Apotex
Distributor: [Pharmaforte]
Content: Cimetidine
Indication: Treatment of duodenal ulcer, prophylaxis of recurrent duodenal ulcer; non-malignant gastric ulcer; gastroesophageal reflux disease; management of upper GI hemorrhage; control of gastric hypersecretion and peptic ulceration in the Zollinger-Ellison syndrome; prophylaxis of stress ulceration.
Dosage: Adult Duodenal ulcer, non-malignant gastric ulcer and gastroesophageal reflux disease 800mg once daily or 400mg twice a day. Zollinger-Ellison syndrome 300mg four times a day or 200mg three times a day and 400mg at night. Maximum 2.4g/day.
Special precaution: Gastric malignancy. Renal impairment. Haemodialysis. Elderly. Pregnancy, lactation, children.
Adverse effect: Diarrhea, myaglia, dizziness and rash. Reversible confusional states. Gynaecomastia. Hematological disturbance.
Drug interaction: Oral anticoagulant, diazepam, chlordiazepoxide. Bind to cytochrome P450.

 

Brand name: APO-RANITIDINE
Manufacturer: Apotex
Distributor: [Pharmaforte]
Content: Ranitidine HCl
Indication: Listed in dosage
Dosage: Duodenal ulcer, benign gastric ulcer 300mg at bedtime or 150mg twice a day. Maintenance: 150mg at bedtime. Pathological hypersecretion condition (eg. Zollinger-Ellison syndrome) 150mg twice a day, up to 6g/day. Gastroesophageal reflux disease 150mg twice a day.
Special precaution: Gastric malignancy. Renal impairment. Pregnancy, lactation.
Adverse effect: Headache, rash, dizziness, constipation, diarrhea, hepatitis, anaphylactoid reactions.
Drug interaction:-

 

Brand name: ARNETIN
Manufacturer: Medochemie
Distributor: [Komedic]
Content: Ranitidine HCl
Indication: Treatment of duodenal ulcer, benign gastric ulcer, post-op ulcer, GERD and Zollinger-Ellison syndrome. Conditions where reduction of gastric secretion and acid output is desirable eg prophylaxis of GI hemorrhage from stress ulceration in serious ill patients, prophylaxis of recurrent hemorrhage in patients with bleeding peptic ulcers, prior to general anaesth in patients during labour (Mendelson’s syndrome).
Dosage: Adult 50mg via slow IV injection, may be repeated 6-8 hourly; OR 25mg/hour for 2 hour as an intermittent IV infusion, may be repeated 6-8 hourly; OR 50mg IM6-8 hourly. Prevention of GI hemorrhage from stress ulceration in severe ill patients, initially 50mg via slow IV injection, then 0.125-0.25mg/kg/hour via continuous IV infusion. Prevention of gastric aspiration 50mg IM or via slow IV injection 45-60 minutes before induction of general health.
Special precaution: Stomach carcinoma, severe renal impairment. History of porphyria, pregnancy and lactation.
Adverse effect: Occasionally, reversible hepatitis. Rarely, agranulocytosis, acute pancreatitis, arthralgia, myaglia, hypersensitivity reaction, reversible mental confusion, depression and hallucinations in severely ill/ elderly patients, rash, reversible leucopenia and thrombocytopenia, headache, dizziness.
Drug interaction: -

 

Brand name: CIMETIDINE
Manufacturer: Hovid
Distributor: [Hovid]
Content: Cimetidine
Indication: prophylaxis and treatment of duodenal ulcer, short term treatment of active benign gastric ulcer, treatment of pathological gastric hypersecretion state eg Zollinger-Ellison syndrome, treatment of acute GERD, treatment of upper GI bleeding.
Dosage: Adult Duodenal ulcer or benign gastric ulcer 800mg as single bedtime dose OR 400mg twice a day OR 400mg four times a day. To be given for minimum.4 week( 6 week in benign gastric ulcer) GERD 400 mg four times a day. Maximum: 2.4g daily. Children more than 1 year old 25-30 mg/kg/day in divided doses.
Special precaution: Cirrhosis, history of portal systemic encephalopathy, hepatic and renal impairment, history of peptic ulcer. Pregnancy. Elderly.
Adverse effect: Diarrhea, dizziness, fatigue, rash, reversible confusional states.
Drug interaction: Theophylline, phenytoin, lidocaine, anti-arrhythmic, benzodiazepines, anticoagulants, certain B-blocker and vosodilators.

 

Brand name: CIMULCER
Manufacturer: Biolab
Distributor: [Medispec]
Content: Cimetidine
Indication: Duodenal and gastric ulcer, Zollinger-Ellison syndrome.
Dosage: Gastric and Duodenal ulcer Adult 200mg three times a day after meals and 400mg at bedtime; or 400mg twice a day at breakfast and at bedtime; 800mg once daily at bedtime. Continue treatment for at least 4 week. Hypersecretion condition eg Zollinger-Ellison syndrome Adult 200-400 mg three times to four times a day after meals and 400mg at bedtime.
Special precaution: Pregnancy, lactation. Renal impairment.
Adverse effect: Mild diarrhea, muscle pain, dizziness, rash.
Drug interaction: Increases plasma concentration of coumarin anticoagulants, phenytoin, propranolol, some benzodiazepines, lindocaine, theophylline, metronidazole and trimterene.

 

Brand name: FAMOPSIN
Manufacturer: Remedica
Distributor: [IDS Services]
Content: Famotidine
Indication: Listed in Dosage
Dosage: Duodenal ulcer initially 40mg daily at bedtime for 4-8 week. Prevention of relapses of duodenal ulceration 20mg at night for 4-8 week. Zollinger-Ellison syndrome Initially 20mg 6 hourly. Severe condition: Up to160mg 6 hourly.
Special precaution: Gastric neoplasm, renal dysfunction, pregnancy.
Adverse effect: Headache, dizziness, constipation and diarrhea. Minor: dry mouth, nausea, vomiting, rash, abdominal discomfort or distention, anorexia AND FATIGUE.
Drug interaction: -

 

Brand name: Famotidine
Manufacturer: Hovid
Distributor: Hovid
Content: Famotidine
Indication: Short term treatment of duodenal ulcer, benign gastric ulcer and hypersecretory conditions such as Zollinger-Ellison syndrome. Prevention of relapse of duodenal ulceration, symptomatic relief of GERD and healing of oesophageal erosions or ulceration associated with GERD.
Dosage: Duodenal ulcer 40mg once daily at bedtime or 20mg twice a day. Prophylaxis: 20mg at bedtime. Gastric ulcer 40mg once daily at bedtime. Gastric hypersecretory conditions 20mg 6 hourly.Max:160mg hourly. GERD 20mg twice daily for up to 6 week.
Special precaution: Renal impairment. Pregnancy and lactation. Children.
Adverse effect: confusion, antiandrogenic effect, decrease in sexual desire, drowsiness, dry mouth or skin, joint or muscle pain, loss of appetite, loss of hair, nausea or vomiting, ringing or buzzing in ears.
Drug interaction: Antacid may decrease absorption. Bone marrow depressant may increase risk of neutropenia and other blood dyscrasias. May cause decrease in absorption of ketoconazole.

 

Brand name: HISTAC
Manufacturer:  Ranbaxy
Distributor: [Pharmaniaga Logistics]
Content: Ranitidine HCl
Indication: 150mg/300mg tab duodenal ulcer and benign gastric ulcers. Prevention of NSAID associated duodenal ulcers. Treatment of post-op ulcer, Zollinger-Ellison syndrome and esophageal reflux disease, and conditions where reduction of gastric secretion and acid output is desirable. EVT tab duodenal and gastric ulcer, Zollinger-Ellison syndrome, treatment adjunct in rheumatoid arthritis for relief of GI symptom associated with NSAIDs, reflux oesophagitis, stress ulcers, short-bowel (anastomosis) syndrome, prophylaxis of GI hemorrhage from stress ulceration in seriously ill patients, prophylaxis of recurrent hemorrhage in patients with bleeding peptic ulcers and before GA in patients at risk of acid aspiration.
Dosage: 150mg/300mg tab Adult 150mg twice a day. Duodenal ulcer, gastric ulcer, gastric oesophageal reflux Single bedtime dose of 300mg. Maintenance: 150mg at bedtime or for oesophageal reflux disease 150mg twice a day or 300mg at bedtime for 8-12 week. Severe oesophagitis 150mg four times a day for up to 12 week. Zollinger-Ellison syndrome 150mg three times a day. Max: 6g/day. Chronic episodic dyspepsia 150mg twice a day for up to 6 week. Patients at risk of acid aspiration syndrome 150mg 2 hour before induction of general anaesth and also 150mg the previous evening. EVT tab duodenal/gastric ulcer 150mg twice a day for at least 4 week. Maintenance: 150mg at night. Prophylaxis against duodenal ulceration 150mg twice a day during therapy with NSAIDs. GERD 150mg twice a day or max 8 week. Zollinger-Ellison syndrome initially 150mg two or three times a day.max: 6g daily. Prophylaxis of recurrent hemorrhage in patients with bleeding peptic ulcer 150mg two times a day.
Special precaution: Severe cirrhosis and severe renal impairment, hepatic impairment. Pregnancy and lactation.
Adverse effect: Hepatic with or without jaundice. Acute pancreatitis, leucopenia, thrombocytopenia, agranulocytosis, pancytopenia. Bradycardia and atrio-ventricular block. Headache, dizziness, rare cases of reversible mental confusion, depression and hallucinations. Rash, arthralgia and myaglia, gynaecomastia.
Drug interaction: Phenytoin, Warfarin, theophylline, nifedipine and alcohol. Antacid, procainamide.