H-2 Receptor Blockers

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H-2 receptor blockers

Definition

Histamine H-2 receptor blockers act by stopping the pathway that leads to the secretion of stomach acid. There are two kinds of pathways that react to stimulation by histamine. Histamine is produced in the body and released by mast cells in response to some types of injury or to the presence of an antigen. When histamine reaches the H-1 receptors, the reaction results in dilation of capillaries, leading to redness and swelling, along with itching . These reactions can be controlled with traditional antihistamines .

Histamine that reaches the H-2 receptors causes increased secretion of stomach acid.

Purpose

H-2 receptor blockers are used to treat conditions associated with excess amounts of stomach acid, although in some cases they have been replaced by the proton pump inhibitors , which have a greater effect on reducing acid secretions.

H-2 receptor blockers are used to treat the following conditions:

duodenal ulcer, as short term therapy and maintenance
H-2 blockers
Brand name Generic name
(Illustration by GGS Information Services. Cengage Learning, Gale)
Axid nizatidine
Pepcid famotidine
Tagamet cimetidine
Zantac ranitidine
gastric ulcer, as short term therapy and maintenance
gastroesophageal reflux disease (GERD), including endoscopically diagnosed erosive esophagitis
pathological hypersecretory conditions such as Zollinger-Ellison syndrome, systemic mastocytosis, and multiple endocrine adenomas
upper GI bleeding
heartburn, acid indigestion, and sour stomach

**H-2 blockers**
Brand name	Generic name
(Illustration by GGS Information Services. Cengage Learning, Gale)
Axid	nizatidine
Pepcid	famotidine
Tagamet	cimetidine
Zantac	ranitidine

None of the drugs in this class has been approved for use by children under the age of 12 years. However, standard pediatric texts have reported on use by infants and children.

Description

There are four H-2 receptor blockers on the market. Although they all work in the same manner and have similar effects, they are not all approved for the same uses.

Cimetidine (Tagamet) is available in both prescription and over-the-counter forms. The oldest of the group and the most studied, this drug is the least potent of the H-2 receptor blockers, which means that higher dosages are required to provide comparable effects. There is no evidence that higher potency improves therapeutic results.

Cimetidine is the only drug in its class which is approved for prevention of upper gastro-intestinal bleeding. It has been reported on for a number of uses, with varying degrees of success. Cimetidine, like ranitidine, has shown some benefit in treatment of colorectal cancer . Although some claims have been made that cimetidine is useful in treatment of acetaminophen overdose, the evidence for this use is lacking, and cimetidine should not be used. Because cimetidine is a mild antiandrogen, it has been of some use in treatment of hirsutism (abnormal growth of hair on a woman's face and body).

The three other H-2 receptor blockers, famotidine (Pepcid, Pepcid AC), nizatidine (Axid), and ranitidine (Zantac), are similar in their uses. All are approved for treatment of duodenal ulcer both acute treatment and maintenance therapy, gastro-esophageal reflux disease, including erosive esophagitis and gastric ulcer short term treatment, although in this group ranitidine alone is approved for maintenance treatment.

In their over-the-counter (non-prescription) forms, cimetidine and famotidine are approved for treatment of heartburn , acid indigestion, and sour stomach.

Drugs in this class are similar in other respects as well. Although study results vary, cimetidine will usually show its effects within one hour and last for about five hours after a single dose; famotidine and nizatidine also show effects within one hour but may act for up to 12 hours at maximum dosing. Ranitidine has a comparable onset of action and duration in adults but may be slower in the elderly. Onset and duration of action will vary with the individual, the dose of medication, and the presence or absence of food or antacids in the stomach.

When Facts and Comparisons, a widely used online drug information resource, compared the published reports on cure rates for duodenal ulcers, it found that after eight weeks of treatment, all drugs showed healing rates in the range of 82% to 95%. These results were based on comparing separate studies and did not represent comparative trials of the drugs against each other.

Recommended dosage

Cimetidine doses for patients over the age of 12 years, for oral administration.

Short-term treatment of active duodenal ulcer: 800 mg at bedtime. Other dose regimens are sometimes used.
Heartburn, acid indigestion, and sour stomach using the over-the-counter product: 100 to 200 mg with water when symptoms start. The dose may be repeated once in 24 hours.
Prevention of heartburn, acid indigestion, and sour stomach using the over-the-counter product: 100 to 200 mg with water up to one hour before eating food or drinking beverages expected to cause symptoms. Dose should not exceed 400 mg in 24 hours.
Treatment of hypersecretory conditions: 300 mg four times a day, with meals and at bedtime.
Gastroesophageal reflux disease: 800 to 1600 mg a day, divided into smaller doses. Treatment usually lasts 12 weeks.

Famotidine doses for patients over the age of 12 years, for oral administration.

Treatment of duodenal ulcers: 40 mg once a day at bedtime. If necessary, 20 milligrams two times a day may be used.
Prevention of duodenal ulcers: 20 mg once a day at bedtime.
Gastric ulcers: 40 mg once a day at bedtime.
To treat heartburn, acid indigestion, and sour stomach using the over-the-counter product: 10 mg with water when symptoms start. The dose may be repeated once in 24 hours.
Hypersecretory conditions: 20 mg every six hours.
Gastroesophageal reflux disease: 20 mg two times a day, usually for up to six weeks.

Nizatidine doses for patients over the age of 12 years, for oral administration.

Treatment of duodenal or gastric ulcers: 300 mg once a day at bedtime. Alternately, 150 mg two times a day.
Prevention of duodenal ulcers: 150 mg once a day at bedtime.
Prevention of heartburn, acid indigestion, and sour stomach: 75 mg taken thirty to sixty minutes before meals which may cause symptoms. The dose may be repeated once in 24 hours.
Gastroesophageal reflux disease: 150 mg two times a day.

Ranitidine doses for patients over the age of 12 years, for oral administration.

Duodenal ulcers, treatment: 150 mg two times a day. Alternately, 300 mg once a day at bedtime.
Duodenal ulcers, prevention: 150 mg at bedtime.
Gastric ulcers, treatment: 150 mg two times a day.
Heartburn, acid indigestion, and sour stomach, treatment: 75 mg with water when symptoms start. The dose may be repeated once in 24 hours.
Heartburn, acid indigestion, and sour stomach, prevention: 75 mg with water taken thirty to sixty minutes before meals or beverages which may cause symptoms. The dose may be repeated once in 24 hours.
Hypersecretory conditions: 150 mg two times a day.
Gastroesophageal reflux disease: 150 mg two times a day. The dose may be increased as needed.

Precautions

Overall, the histamine H-2 receptor blockers are a safe class of drugs. However, some patients may be particularly susceptible to adverse effects of these drugs. H-2 receptor blockers are metabolized in the liver and excreted through the kidneys. Therefore, patients with kidney or liver problems may require reduced doses in order to maintain safe blood levels of the drugs.

Although the safety and effectiveness of H-2 receptor blockers in patients over the age of 65 appears to be similar to that seen in younger patients, age-associated reductions in kidney function may lead to elevated blood levels.

Allergic reactions to these drugs are rare but have been reported.

The histamine H-2 receptor blockers are Pregnancy category B. There are no adequate and well-controlled studies with these agents in pregnant women. Women should use them only when clearly needed and when the potential benefits outweigh the potential hazards to the fetus. Cimetidine is known to cross the placenta.

All drugs in this class are excreted into breast milk and should not be taken by nursing women. Decide whether to discontinue nursing, or discontinue the drug, taking into account the importance of the drug to the mother.

These drugs may mask the symptoms of stomach cancer .

Side effects

Although side effects due to the H-2 receptor blockers are relatively rare and usually mild, a large number of adverse effects have been reported, in part because of the high use of these drugs. For example, the most common single adverse effect of cimetidine has been a 4% incidence of breast enlargement among males taking the drug in high doses for hypersecretory conditions. Similarly, the incidence of headache among high-dose cimetidine patients was 3.5%. Among patients taking lower doses, the frequency of headache was 2.1% compared to 2.3% in a placebo control group. Decreased white blood cell count was reported in 1 in 1,000,000 patients.

The reported side effects from the H2 receptor blocks are:

abdominal pain
back, leg, or stomach pain
bleeding or crusting sores on lips
blistering, burning, redness, scaling, or tenderness of skin
blisters on palms of hands and soles of feet
changes in vision or blurred vision
coughing or difficulty in swallowing
dark-colored urine
dizziness
fainting
fast, pounding, or irregular heartbeat
fever and/or chills
flu-like symptoms
general feeling of discomfort or illness
hives
inflammation of blood vessels
joint pain
light-colored stools
mood or mental changes, including anxiety, agitation, confusion, hallucinations (seeing, hearing, or feeling things that are not there), mental depression, nervousness, or severe mental illness
muscle cramps or aches
nausea, vomiting, or loss of appetite
pain
peeling or sloughing of skin
red or irritated eyes
shortness of breath
skin rash or itching
slow heartbeat
sore throat
sores, ulcers, or white spots on lips, in mouth, or on genitals
sudden difficult breathing
swelling of face, lips, mouth, tongue, or eyelids
swelling of hands or feet
swollen or painful glands
tightness in chest
troubled breathing, unusually slow or irregular breathing
unusual bleeding or bruising
unusual tiredness or weakness
wheezing
yellow eyes or skin

Less frequently reported are

constipation
decreased sexual ability (especially in patients with Zollinger-Ellison disease who have received high doses of cimetidine for at least 1 year)
decrease in sexual desire
diarrhea
difficult urination
dizziness
drowsiness
dryness of mouth or skin
headache
increased or decreased urination
increased sweating
loss of hair
ringing or buzzing in ears
runny nose
swelling of breasts or breast soreness in females and males
trouble in sleeping

Not all of these adverse effects have been reported with all of the H-2 receptor blockers, and some of the adverse effects may not have been drug related. However, because of the high similarity between drugs in this class, any of the reported adverse effects may be considered a possible result of therapy.

Interactions

Cimetidine and ranitidine are both metabolized in the liver using the cytochrome P450 oxidase enzyme system. Since the same enzymes metabolize many drugs, taking two or more drugs that affect the same group of enzymes may cause one of the drugs to be retained in the body longer than would have been expected. The following is a partial list of drugs which may interact with cimetidine, or to a lesser extent with ranitidine.

benzodiazepines, including Valium, Librium and Xanax
caffeine
calcium channel blockers, including Adalat, Calan, Procadia, and others
carbamazepine
chloroquine
labetolol
lidocaine
metoprolol
metronidazole
phenytoin
propranolol
quinidine
quinine
sulfonylureas (includes many of the drugs used to treat diabetes)
theophyllines (used to treat asthma; Dyphylline, a member of this group, does not interact with cimetidine)
triamterene (a diuretic drug rarely used alone but may be found in fixed combinations, including Dyazide and Maxzide)
tricyclic antidepressants (a group that includes amitriptyline, imipramine, and others)
valproic acid
warfarin

KEY TERMS

Duodenal —Pertaining to the first part of the small intestine.

Gastric —Pertaining to the stomach.

Histamine —A physiologically active compound found in plant and animal tissue and released from mast cells as part of an allergic reaction in humans. It stimulates gastric secretion and causes dilation of capillaries, constriction of bronchial smooth muscle, and decreased blood pressure.

Hypersecretory —Excessive secretions, over production of stomach acid.

Mast cell —A cell found in connective tissue that releases substances such as heparin and histamine in response to injury or inflammation of bodily tissues.

Peptic —Induced by or associated with the action of digestive secretions.

Zollinger-Ellizon syndrome —Severe peptic ulceration from excessive stomach acid production stimulated by one or more tumors that produce a powerful acid secretion.

Additional drugs may also interact with the H2 receptor blockers, particularly those which might have a similar mechanism or action or adverse effects.

Resources

BOOKS

Beers, Mark H., ed. Merck Manual of Medical Information: Home Edition. Riverside, NJ: Simon & Schuster, 2004.

Physicians' Desk Reference 2005. Montvale, NJ: Thomson Healthcare, 2004.

Robertson, Jason, et al. The Harriet Lane Handbook: A Manual for Pediatric House Officers. Orlando, FL: Mosby Inc., 2005.

PERIODICALS

Black, R. A., and D. A. Hill. “Over-the-counter medications in pregnancy.” American Family Physician 67, no. 12 (June 15, 2003): 2517–24.

Chandramouli, J. “What is the most effective therapy for preventing NSAID-induced gastropathy?” Journal of Pain and Palliative Care Pharmacotherapy 16, no. 2 (2002): 23–36.