H2-RECEPTOR ANTAGONISTS (H2RAs) — Currently available H2RAs are listed in Table 1. These drugs inhibit the action of histamine at the H2-receptor of the gastric parietal cell, decreasing basal acid secretion and, to a lesser degree, food-stimulated acid secretion. All H2RAs are about equally effective for treatment of PUD and GERD. H2RAs are faster acting than PPIs in relieving symptoms of dyspepsia or GERD, but they are not as effective as PPIs in relieving symptoms or in healing erosive esophagitis. Repeated administration of H2RAs leads to pharmacologic tolerance and has been associated with the development of new dyspeptic symptoms. Rebound acid hypersecretion can occur after stopping H2RAs.

Peptic ulcer disease (PUD) is usually caused by nonsteroidal anti-inflammatory drugs (NSAIDs) or by infection with Helicobacter pylori. Gastroesophageal reflux disease (GERD) can be caused by transient lower esophageal sphincter relaxation, reduced lower esophageal sphincter tone, hiatal hernia, delayed gastric emptying or hormonal changes due to pregnancy. Acid suppressive therapy is the cornerstone of management for both PUD and GERD.

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are common causes of peptic ulcer disease. Patients infected with Helicobacter pylori who take aspirin or another NSAID have an especially high risk. Drugs that have been tried for prevention of ulcers in patients taking NSAIDs including H₂-receptor antagonists, proton pump inhibitors (PPIs), aluminum- or magnesium-containing antacids, the prostaglandin misoprostol (Cytotec, and others), and antibiotics to eradicate H. pylori.

Click here to view the free full article.

Inflammatory bowel disease (IBD) is either Crohn's disease or ulcerative colitis. Drug selection is guided by disease type (Crohn's versus ulcerative colitis), severity and location and whether the goal is induction or maintenance of remission. Table 1 on page 66 lists the drugs used to treat IBD with their formulations and cost. Table 2 on page 68 lists the drugs of choice and their doses for different indications. Table 3 on page 71 lists the drugs' adverse effects and recommendations for monitoring. More detailed guidelines are available from the American College of Gastroenterology.

Primary hypothyroidism is usually the result of Hashimoto's thyroiditis, thyroidectomy for hyperthyroidism, goiter or cancer, or radioactive iodine therapy for hyperthyroidism.

Peptic ulcers caused by treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) are mainly gastric ulcers. Most duodenal and other gastric ulcers are caused by the gram-negative bacillus Helicobacter pylori. Gastroesophageal reflux disease (GERD) is caused by gastric acid reflux into the esophagus. Drugs that suppress gastric acid production are the primary treatment for GERD and peptic ulcers.

Most peptic ulcers not caused by nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with infection of the gastric mucosa by the gram-negative bacilli Helicobacter pylori. The majority of NSAID-related ulcers are gastric. H. pylori infection causes both duodenal and gastric ulcers. Eradication of H. pylori promotes healing and markedly decreases recurrence of both duodenal and gastric ulcers (A Shiotamni and DY Graham, Med Clin North Am 2002; 86:1447; FKL Chan and WK Leung, Lancet 2002; 360:933). The first step in the management of peptic ulcers is the diagnosis and treatment of H. pylori.

New drug approvals as well as continuing concerns about drug toxicity and the development of resistance have prompted new antiretroviral treatment guidelines (Panel on Clinical Practices for Treatment of HIV Infection, November 10, 2003, www.aidsinfo.nih.gov).

Cefdinir (Omnicef - Parke-Davis), a third-generation oral cephalosporin, has been approved by the FDA for treatment of acute sinusitis, otitis media, acute exacerbations of chronic bronchitis, pharyngitis, community-acquired pneumonia and skin infections. Other drugs available for these indications are reviewed in The Medical Letter Handbook of Antimicrobial Therapy, 1998.

Risedronate (Actonel - Procter & Gamble), a pyridinyl bisphosphonate, has been approved by the FDA for oral treatment of Paget's disease of bone. Characterized by excessive bone resorption, bony deformity, disorganized bone remodeling and structural weakness, Paget's disease occurs in up to 3% of people older than 55 in Europe and North America (PD Delmas and PJ Meunier, N Engl J Med, 336:558, 1997).

Trovafloxacin (Trovan - Pfizer) and its prodrug alatrofoxacin (Trovan IV) are new fluroroquinolones marketed for an unusually wide variety of infections, including oral and intravenous treatment of nosocomial and community-acquired pneumonia, acute ecerbations of chronic bronchitis, acute sinusitis, complicate intra-abdominal and pelvic infections, diabetic foot infection, uncomplicated urinary tract infection, prostatitis, cervicitis and uncomplicated gonorrhea.

Grepafloxacin (Raxar - Glaxo Wellcome), a once-daily oral fluoroquinolone, is now being marketed for treatment of community-acquired pneumonia, acute bacterial exacerbations of chronic bronchitis, uncomplicated gonorrhea, and nongonococcal urethritis and cervicitis.

The drugs of choice for treatment of deep fungal infections are listed in the table below. Some of the indications and dosages recommended here have not been approved by the FDA.

Most peptic ulcers not caused by nonsteroidal anti-inflammatory drugs (NSAIDs) are now thought to be associated with infection of the gastric mucosa by the gram-negative bacilli Helicobacter pylori. The majority of NSAID-related ulcers are gastric. H. pylori have been associated with both duodenal and gastric ulcers. Eradication of H. pylori promotes healing and markedly decreases recurrence of both duodenal and gastric ulcers (AH Soll, JAMA, 275:622, 1996).

The drugs of choice for treatment of deep fungal infections are listed in the table on page 101. Some of the indications and dosages recommended here have not been approved by the US Food and Drug Administration. More detailed guidelines are available from the Infectious Diseases Society of America (J Sobel et al, Clin Infect Dis, volume 30, April 2000).

Patients may be asking their physicians about use of histamine H2-receptor antagonists for treatment and prevention of heartburn. Cimetidine and famotidine have recently been released for over-the-counter sale and are being heavily advertised on television and in the print media.

Most peptic ulcers not caused by nonsteroidal anti-inflammatory drugs (NSAIDs) are now thought to be associated with infection of the gastric mucosa by the gram-negative bacilli Helicobacter pylori (NIH Consensus Development Panel, JAMA, 272:65, July 6, 1994). NSAID-related ulcers are usually gastric. H. pylori have been associated with both duodenal and gastric ulcers.

Teniposide (ten i poe' side; VM 26; Vumon - Bristol), an anticancer drug that has been under investigation in the USA for 20 years, has now been approved for use in combination induction treatment of refractory acute lymphoblastic leukemia (ALL) in children. A semisynthetic derivative of podophyllotoxin, teniposide is chemically related to etoposide (VePesid - Medical Letter, 26:48, 1984).

Flumazenil (Mazicon - Roche), a benzodiazepine receptor antagonist, has been approved by the US Food and Drug Administration to reverse the sedative effects of benzodiazepines after anesthesia, sedation for brief surgical or diagnostic procedures, or after benzodiazepine overdosage. The drug does not antagonize opioids, non-benzodiazepine sedatives, or anesthetic drugs.

Temafloxacin (Omniflox - Abbott) and lomefloxacin (Maxaquin - Searle) are the latest fluoroquinolone antimicrobial agents to be approved by the US Food and Drug Administration (FDA) for oral treatment of various infections. Previously marketed include norfloxacin (Noroxin - Medical Letter, 29:25, 1987), ciprofloxacin (Cipro - Medical Letter, 30:11, 1988), and ofloxacin (Floxin - Medical Letter, 33:71, 1991). Norfloxacin is marketed only for treatment of urinary tract infections, and lomefloxacin only for treatment of urinary tract infections and bronchitis known to be caused by Haemophilus influenzae or Moraxella catarrhalis. Ciprofloxacin and ofloxacin are also available in parenteral formulations.

Drugs that accelerate healing and prevent relapse or reurrence of peptic ulcers act either by decreasing gastric acidity or by enhancing mucosal defense mechanisms. Risk factors that may cause breakdown of mucosal defenses include the use of aspirinor other nonsteroidal anti-inflammatory drugs (NSAIDs) and the presence of Helicobacter pylori bacterial in the gastric antrum (AH Soll, Engl J Med, 322:909, 1990; WL Peterson, N Engl J Med, 324:1043, 1991).

Idarubicin hydrochloride (Idamycin - Adria), an anthracycline structurally related to daunorubicin (Cerubidine, and others) and doxorubicin (Adriamycin, and others), was recently approved in the USA for treatment of acute myelogenous leukemia (AML) in adults.

Ofloxacin (Floxin - McNeil, Ortho), a new fluoroquinolone antibacterial agent, was recently marketed in the USA for oral treatment of various infections caused by susceptible microorganisms. Ofloxacin is the third fluoroquinolone to become available in this country. Norfloxacin (Noroxin - Medical Letter, 29:25, 1987) is marketed only for treatment of urinary tract infections. Ciprofloxacin (Cipro - Medical Letter, 30:11, 1988), like ofloxacin, is approved for use in a variety of infections.

Nizatidine (Axid - Lilly), a new H2-receptor antagonist similar to cimetidine (Tagamet), ranitidine (Zantac) and famotidine (Pepcid), was recently approved by the US Food and Drug Administration for treatment of active duodenal ulcer and for maintenance therapy after healing. Cimetidine, ranitidine and famotidine are also approved for treatment of pathological hypersecretory conditions such as Zollinger- Ellison syndrome; cimetidine is approved in addition for treatment of gastric ulcers.

The incidence of opportunistic deep fungal infections continues to increase, particularly among patients who have AIDS, are taking immunosuppressive drugs, or are in intensive care units.

Ciprofloxacin hydrochloride (Cipro - Miles), a synthetic antibacterial agent, was recently marketed in the USA for oral treatment of a wide variety of infections. Ciprofloxacin is the second fluoroquinolone to become available in this country; norfloxacin (Noroxin - Medical Letter, 29:25, 1987) is marketed only for treatment of urinary tract infections. Fluoroquinolones are more potent and have a much broader spectrum of activity than older quinolones such as nalidixic acid (NegGram).