Duodenal ulcer,benign gastric ulcer,gastroesophagal reflux

Histamine H2 Antagonists include-

Cimetidine, Famotidine, Nizatidine, Ranitidine, Roxatidine

Refer - Cimetidine

Cimetidine- Reversible exacerbation of joints symptoms with prexisiting arthiritis, including gouty arthiritis, peripheral neuropathy, delirium, cutaneous vasculitis, phtobezoar formation, galactorrhea, neutropenia, (including agranulocytosis) in patients with serious concomittant illness, receiving drugs or treatment known to produce neutropenia.

Rare-Reversible intertisial nephritis and urinary retention, myalgia, polymyositis, epidermal necrolysis, strongyloidiasis, hyperinfection in immunocompromised patients (extremely rare)

Impotence- Reversible impotence in patients with pathological hypersecretory disorders (eg Zollinger- Ellison syndrome) receiving cemetidine., particularly in high doses for 12 to 79 months (mean 38 months). However in large scale survellience studies the incidence has not exceeded that of general population.

Ranitidine- Vertigo, reversible blurred vision, (suggestive of a change in accommodation) malaise, revesible leukopenia, pancycytopenia (sometimes with bone marrow hypoplasia ) anaphylaxis, angioneurorotic edema (rare). Trancient local burnig or itching may occur with IV admnistration.

Famotidine- Anorexia, dry mouth, musculoskeletal pain, parathesia, grand mal seizure (one report), acne, dry skin, flushing, tiinitus, taste disorder, fever, asthena, palpititaions, orbital edema, conjuctivial injection.

Nizatidine- Sweating, asympatomatic ventricular tachycatdia, hyperuricemia, unassociated with gout or neprolithiasis, eosionophilia, fever.

Lab test abnormalities- Small increase in serum creatinine and elevated ALT levels (at least pretreatment levels) occured with ranitidine.

Small possibly dose related increases in plasma creatinine and serum transaminase occured with cimetidine.

These are not common and do not signify deteriorating renal function.

Elevated AST, ALT, and alkaline phosphatase levels ocur with nizatidine Bollus injection has been associated with cardiac arryhthmias.

Diarrhoea, dizziness, somnolence, rash, headache, CNS disturbance, arthalgia, myalgia, gynaecomastia, alopecia, blood dyscrasis, nephritis, pancreatitis, granulocytopenia.

Hypersensitivity.

Warnings

Hypersensitivity- rare cases of anaphylaxis have occurred as well as rare episodes of hypersensitivity (eg. bronchospasm, larthgeal edema, rash, eosinophillia )

Renal function impairment- since these agents are excreted primarily via the kidneys, decreased clearance may occur, reduced dosage may be necessary.

Hepatic function impairment- observe caution. Decreased clearance may occur. In normal function with uncomplicated hepatic dysfunction, niazatidine disposition is similar to that in healthy individuals

Elderly - safety and efficacy appear to those of younger age, however, elderly may have reduced renal function.

Children- safety and efficacy are not established. Cimetidine is not recommended for children < 16 years old. OTC use is not recommended in children < 12 years of age.

Special Precautions:

Impaired renal function. Excludes malignancy in peptic ulcer. Pregnancy, lactation.

Hypersensitivity- Rare case of anaphylaxis have occured as well as (rare episodes of hypersensitivity (eg bronchospoam, laryngeal edema,rash, eosinophilia)

Renal function impairment- Since these agentsare primarily excreted via the kidneys, decreased clearance amy occur, reduced dosage may be necessary.

Hepatic function impairment- Observe caution. Decreased clearance may occur.These agents are partly metabolised in the liver. In the normal function with uncomplicated renal dysfunction. Nizatidine disposition is similar to that in healthy individuals.

Pregnancy- Use only when needed and when the potential benefits outweigh the potentaial hazards to the fetus.

Lactation- Cimetidine is excreted in breast milk and in plasma ratio of approximately 1:1.to 6.7:1. Do not nurse.

Ranitidine- is excreted in bresat milk with milk:plasma ratio of 1:1 to 6.7:1 . Excercise caution while administering to a nursing mother.

Nizatidine- is excreted in breast milk in a concentration of 0.1% of oral dose in proportion to plasma concentrations.

Decide whether to discontinue nursing or discontinue the drug depending on the importance of the drug to the mother.

Famotidine- is excrteted in breast milk of rats. It is not known wherher it is excreted in human breast. Decide whether to discontinue nursing or discontinue the drug depending on the importance of the drug to the mother.

Indications:

Duodenal ulcer,benign gastric ulcer,gastroesophagal reflux

Dosage:

Short term treatment - 800mg at bed time or 300mg 4 times a day

Overdosage- Symptoms

There is no experience with deliberate overdosage.

Toxic doses in animals are associated with rapid respiration and respiratory failure, tachycardia, muscular tremors,vomiting, restlessness, palor of mucous membranes or redness of mouth and ears, hypotension, collapse, and cholinergic-type effects including lacrimation, salivation, emesis, miosis and diarhea.

Reported ingestions of 20 g cimetidine have been associated with transcient adverse efects similar to those encountered in normal clinical experience .

Two deaths have occured in adults who reportedly ingested > 40g on a single occassion. Famotidine doses of up to 640mg/day have been given to patients with pathological hypersecretory conditions with no serious effects.

Treatment

1. Symptomatic and supportive.

2. Remove unabsorbed material from the GI tract

3. Monitor the patient and employ supportive therapy

 Missed dose

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

For Availability/supplies 

EVIDENCE BASED MEDICINE

Gastro Osephageal Reflux Disease (GORD) (MIMS April 2003)

Beneficial

1. Proton Pump Inhibitors such as omeprazole, Lansoprazole, pantoprazole

2. H-2 Antagonists such as cimetidine, ranitidine, famotidine, (less than proton pump inhibitors)

3. Fundoplication

Likely to be beneficial

1. Medical and surgical tretment of GORD in selected patients with extraoesophageal manifestations.

Unknown effectiveness

1. Medical and surgical treatment of GORD in patients with Barrets oesophagus

2. Surgical treatment for non erosive oesophagitis

Key Points

1. One systemic review of randomised clinical trials has found proton inhibitors to be more effective than H-2 antagonists in both erosive and non-erosive oesophagitis. One trial has found no significant differences in the effectiveness of different proton pump inhibitors

2. Surgical treatment has not been adequately evaluated in controlled clinical trials. Medical and surgical treatments have not been adequately compared

3. It is not clear whether patients with Barretts oesophagitis benefit from medical or surgical treatment of their gastro oesophageal reflux

4. There is limited, conflicting evidence on the basis on the benefits of treating gastro oesophageal reflux in patients with extra oesophageal manifestations (such as asthma)

HISTAMINE H2 ANTAGONISTS- CIMETIDINE, FAMOTIDINE, RANITIDINE, NIZANTIDINE

1.Take with or immediately following a meal

2.Stagger doses of antacids and cimetidine

3.Inform doctor of any cocomittant drug therapy

4.Inform doctor,if diarrhoea,dizziness,somnolence,rash or hallucinatins occur.

5.Inform doctor,if there are any symptoms that suggest bleeding,such as black tarry stools or coffee ground vomitus

6.Allergies- tell your doctor if you have ever had any unusual or allergic reaction to cimetidine ,famotidine, nizatidine or ranitidine. Also tell your doctor if youare allergic to any other substances, such as foods, presrvatives or dyes.

7.Pregnancy - make sure if you are pregnant or you may become pregnant before taking H2 blockers

8.Breast feeding- be sure you have discussed the risks and benefits of this medicine with your doctor

9 Children - medicine has not been been shown to cause different side effects or problems than it does in adults.

10. Elderly- confusion and dizziness may be especially likely to occur in elderly patients

11. Other medicines - Let your doctor know what other medicines you are taking, so that he can advice you accordingly. Aminophylline or Anticoagulants or Caffeine or Metoprolol or Oxytriphylline or Phenytoin or Propranol or Theophylline or Tricyclic antidepressants- use of these medicines with cimetidine has been shown to increase the effects of cimetidine .

 12. Other medical problems - Tell your doctor if you have any other medical problems especially - Kidney disease or Liver disease - H2 blocker may build up in the blood stream which may increase therisk of side effects

13. Missed dose - If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.

14. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places.

15. Outdated medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of reach of children.

Drug Facts And comparisons(2010)

Histamine H2 Antagonists include-

Cimetidine, Famotidine, Nizatidine, Ranitidine

Refer - Cimetidine

Pharmacology:

Cimetidine completely inhibits the action of histamine at the histamine H2 receptors of the perietal cells.It inhibits both daytime and nocturnal basal gastric acid secretion and chemically -induced gastric secretion. Cimetidine is not an anticholinergic agent. It also inhibits gastric secretion stimulated by food, histamine, pentagastrin, caffeine and betazole.

Pharmacokinetics:

Cimetidine is approximately 60% to 70% bioavailable after oral administration.Peak levels occur at 45 to 90minutes.Absorption may be decreased by antacids,but unaffected by food. Metabolism: The principal route of excretion is is urinary. Half-life of cimetidine is approximately 2 hours.Half-life increases in renal inpairment.

Take with food

Pregnancy

Use only when needed and when the potential benefits outweigh the potentaial hazards to the fetus.

Lactation

Cimetidine is excreted in breast milk and plasma ratio of approximately 1:1.to 6.7:1. Do not nurse.

Ranitidine- is excreted in breast milk with milk:plasma ratio of 1:1 to 6.7:1 . Excercise caution while administering to a nursing mother.

Nizatidine- is excreted in breast milk in a concentration of 0.1% of oral dose in proportion to plasma concentrations.

Decide whether to discontinue nursing or discontinue the drug depending on the importance of the drug to the mother.

Famotidine- is excreted in breast milk of rats. It is not known wherher it is excreted in human breast.

Decide whether to discontinue nursing or discontinue the drug depending on the importance of the drug to the mother.