Histamine H2 Antagonists include- 
Cimetidine, Famotidine, Nizatidine, Ranitidine, Roxatidine

Refer - Cimetidine

Interacting drugs - summary

 Cimetidine/ Ranitidine  + Procainamide
 cimetidine increase plasma levels of procainamide and  its cardioactive metabolite.(NAPA). Ranitidine decrease renal clearance and increase AUC  of procainamide
                                                                     
Ranitidine + Diazepam
diazepam pharmacologic effects decreased GI absorbution by ranitidine. Staggering administration times may avoid this interaction  
                                                                                                                                          
Ranitidine + Sulfonylureas
ranitidine increase the hypoglycemic effect of glipizide, Glypizide dosage adjustments may be needed.
                                                                       
Ranitidine + Theophylline
theophylline plasma levels may be increased by ranitidine increasing pharmacologic and toxic effects. The interaction is rare
                                                                       
Ranitidine + Warfarin
 ranitidine  interfere with warfarin clearance- significance  not established.Hypoprothrombic effects increase, May  need dosage adjustment

H2 antogonists + Ethanol 
concurrent use increase plasma ethanol levels and AUC. This interaction  have minimal clinical importance
-                                                                       
Antacids /  Anticholinergics/ Metoclopramide + H2 antogonist
 these agents decrease  absorption of cimetidine   
 Ranitidine absorption decreased by concurrent antacids  Avoid simultaneous administration. Bioavailability of famotidine   and nizatidine may be slightly decreased. No special precautions   necessary.
                                                                                                                                                                                                                                                                                                    
Cigerette smoking + Cimetidine
 cigarette smoking reverses cimetidine  inhibition   of nocturnal gastric secretion and ulcer healing. Cigarette   use is closely related to ulcer recurrence    
 
       

Duodenal ulcer, benign gastric ulcer. 

Histamine H2 Antagonists include-

Cimetidine, Famotidine, Nizatidine, Ranitidine, Roxatidine

Refer - Cimetidine 

        Patent Expiry Date of drugs (Ref - IDMA Publication)   

Adverse Reactions-
    
Ranitidine-

Cardiovascular -
 Rrare reports of arrhythmias  sucu as tachycardia, AV block, and  premature  ventricular  beats

CNS -
Rarely malaise, and vertigo. rare case of revesible mental confusion, agitation,
depression and hallucinations reported

Dermatological -
 Rare cases of vasculitis

Hepatic-
Ocassional reports of hepatacelluar , cholestatic or mixed hepatitis with or  without jaundice.  In such cases immediately discontinue ranitdine

Musculoskeletal -
Rare reports of myalgia

Miscellaneous-
Rare cases of hypersensitivity reactions eg. bronchospasm, fever, rash,
eosinophilia,   anaphylaxis, angioneurotic edema and small increase in
serum creatinine.  Transcient pain at the site of IM injection has been reported

Lab test abnormalities-
Small increase in serum creatinine and elevated ALT levels
(at least pretreatment levels) occurred  with ranitidine. Small possibly dose
related increases in plasma creatinine and serum transaminase occurred
with cimetidine. These are not common and do not signify deteriorating renal function.
Elevated AST, ALT, and alkaline phosphatase levels occur with nizatidine

Known hypersens.Children below 8 years.

Special Precautions:
Exclude malignancy before treating gastric ulcer.

Patients with severe renal failure.

Use in pregnancy and lactation  only if essential.

Approved by  FDA  in June 1983

Indications:
Duodenal ulcer,benign gastric ulcer,pathological  hypersecretory conditions

Dosage:
150md orally twice a day, or 300 mg once daily at bed time.
Parentral- IM 50mg(2ml) every 6 to 8 hours.
IV 50 mg(2ml)  every   6 to 8 hours.Dilute  50 mg in 0.9% Sodium  Chloride or compatible  IV soln to a total volume of 20 ml. Inject over 5 minutes.

Overdosage-     Symptoms                                                

No experience of deliberate overdosage.                     
Toxic doses in animals are associated with rapid respiratory failure, tacyhcardia,
 muscular tremors,  vomiting, restlessness, pallor of mucous membranes  or redness
 of mouth or ears, hypotension,collapse and  cholinergic-type effects including
lacrimation, salivation, emesis, miosis, and diarrhea                                              
                                                                                      
Reported ingestion of up to 20g cimetidine have been associated with transcient
adverse effects  similar to those encountered in normal clinical experience.
Two deaths have occured in adults who  reportedly ingested > 40g on a single
occassion.

Famotidine doses upto 640mg/day have been given to patients with pathological
hypersectory conditions with no serious adverse effects.

                                  Treatment

 1. Symptomatic and supportive
  2. Remove unabsorbed material from the GI tract, monitor the patient and employ
     supportive therapy
  3. With nazatidine renal dialysis for 4 to 6 hours increased plasma clerance by
      approximately by 84%.
  4. Physostigmine has been reported to arouse obtunded  patients with evidence
       of cimetidine-induced.      CNS toxicity; data  insufficient to recommend this use.

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 

Gastro Osephageal Reflux Disease (GORD)

Evidence Based Medicine (MIMS- March 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) 

Refer - Cimetidine

1.For patients taking one dose a day- take it at bed time unless otherwise directed
2.For patients taking two doses a day- take one in the morning and and one at bed time.
3.For patients taking several  doses a day- take them with meals and one at bed time
4.Take the medicines for the full course of treatment, even if you  begin to feel better.
5.Tell your doctor if you had any previous allergic  reaction to the medicine. 

Histamine H2 receptor Antagonists -systemic

1. Allergy- Tell you doctor if you ever had allergic reaction to cimetidine, famotidie, nizatidine, ranitidine

2. Pregnancy- In animal studies famotidine and ranitidine have not been shown to 
   cause birth  defects     or other  problems. Make sure that  your doctor kows if you
    are pregnant or you may become  pregnant before taking  H2 blockers

3.Breast feeding- Cimetidine, famotidine, nizatiidine and ranitidine  pass into te breast milk
   and may cause unwanted effects. It may be necessary to take anothermedicine or stop
   breast feeding during treatment. Make sure that you  discuss the risks and benefits
   of the medicine with your doctor.

4. Children- This medicine has been tested  in effective doses , and has not shown to
   cause different    side effects or  problems than it does in adults when used for
   short periods of time.

5. Older patients- Confusion and dizziness may be respecially likely to occur in elderly
    patients who are more sensitive than younger adults to the effects of H2 blockers.

6. Other medicines- Certain medicines should not be used together at all-  It is important that your
    doctor know if you  are taking any of the following medicines-
   

7. Other medical problems- Presence of other medical problems may affect the use
     H2  blockers-     Tell your Doctor about other medical problems
   

8. Dosing- Dosing of H2 receptor antagonists will be different for different patients.
   If your is different  do not change  unless the doctor tells you to do so.
    Do not take the maximun daily dose contonously for more than 2 weeks unless
    directed by your    doctor.
    If you have trouble in swallowing or persistent abdominal pain, see your doctor
    promptly. These  may signs of a serious condition that need different treatment.
    One dose a day- take it at bed time unless otherwise directed
    Two doses a day- take one in the moring and and one at bed time.
    Several doses  a day-take them with meals and at bedtime for best results.

9. Missed  dose- if you miss a dose take it as soon as possible
    However, ift is almosttime for next dose, skipthe dose and and go back to your schedule.
    Do not double doses.

Pharmacology:

Ranitidine competitively and reversibly inhibits the action of histamine at histamine H2 receptors, including receptors of gastric cells. It is not an anticholinergic agent.

Pharmacokinetics:

Absorption of Ranitidine is not significantly impaired by the administration of food. Concurrent administration of antacids may reduce its adsorption.Propantheline slightly delays and increases peak levels,probably by delaying gastric emptying and transit time. Metabolism/excertion: Hepatic metabolism results in three metabolites.Elimination half-life is 2 to 3 hours and duration of action 8 to 12 hours. Prinipal route of excretion is urine and active tubular excretion. About 30 to 35% of the drug is excreted unchanged in 12 to 24 hours. Ranitidine is removed by hemodialysis and peritoneal dialysis

None

Pregnancy-

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

Lactation-

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