Heartburn Md Review

DRUG REVIEW: LANSOPRAZOLE

DRUG REVIEW: LANSOPRAZOLE

Introduction

Proton pump inhibitors (PPIs) are the drugs of choice in the management of gastro-duodenal acid and are more effective than H2 receptor antagonists. PPI – antibacterial therapy based regimens are the gold standard for eradication of Helicobacter pylori which is an important agent in the pathogenesis of acid-related diseases (1).

Chemistry and mechanism of action is Lansoprazole substituted benzimidazole, 2 – [[[3-methyl-4-(2,2,2-trifluoro)-2-pyridyl] methyl] sulfinyl] benzimidazole, a compound that inhibits the secretion of acid stomach. Its empirical formula is C16H14F3N3O2S with a molecular weight of 369.37. (2). Lansoprazole act irreversibly blocking the hydrogen / potassium adenosine triphosphatase enzyme system (H + / K + ATPase, or, more commonly, the gastric proton pump) of the gastric parietal cell. Proton pump is the terminal stage of gastric acid secretion, being directly responsible for secretion of H + into the gastric lumen, making it an ideal target for inhibiting acid secretion. ("Irreversible" refers to the effect on a single copy of the enzyme, the effect on the whole digestive system of man is reversible, as the enzymes are naturally destroyed and replaced by new copies.) Targeting the terminal-step in acid production, and the irreversible nature of inhibition, results in a class of drugs that are much more effective than H2 antagonists and reduce gastric acid secretion up to 99%. The lack of acid in the stomach helps the healing of duodenal ulcers and reduces pain from indigestion and heartburn, which can be exacerbated by acid stomach. However, lack of stomach acid is also known as hypochlorhydria, lack of sufficient hydrochloric acid or HCl. Acid chloride is required for protein digestion and absorption of nutrients, especially vitamin B12 and calcium (3).

Of clinical meta-analysis of 30 mg of lansoprazole showed it was more effective in producing healing at 2 and 4 weeks as ranitidine or famotidine. Lansoprazole also led to a greater reduction in the percentage of patients pain free at 2 weeks. The effectiveness of lansoprazole is not different from that of omeprazole (4). When lansoprazole was used as monotherapy, the mean eradication of Hp was 6% in four studies. When lansoprazole was used in combination with amoxicillin, pooled data from four trials using different dosages showed eradication of H. pylori in 38.9% of patients. When lansoprazole was used in combination with clarithromycin, the eradication rate was approximately 47.7% with lansoprazole 30 mg daily and 69.1% with lansoprazole 30 mg twice a day. When lansoprazole was used in triple therapy, eradication rates of H. pylori ranged from 80% to 96%, with best results obtained with a combination of lansoprazole, amoxicillin, and clarithromycin. Lansoprazole with one or preferably two antibiotics is effective in eradicating Hp. With the new macrolides, which have a lower rate of Hp resistance as metronidazole or tinidazole, we can expect to achieve the eradication of H. pylori in all Patients who are compatible with antibiotic treatment and infected with susceptible strains (5). In general pharmacokinetics, absorption inhibitors proton pump is not affected by co-administration with food. The rate of absorption of omeprazole, however, is diminished by the intake of food. In addition, the absorption of lansoprazole and esomeprazole is decreased and delayed by food. It has been reported these pharmacokinetic effects, however, have no significant impact on efficiency. [6] The half-life of inhibitors of proton pump ranges from 0.5 to 2 hours, but the effect of a single dose on acid secretion usually persists up to 2-3 days. It because of drug accumulation in canaliculi of parietal cells and irreversible inhibition of proton pump. (7)

Drug Interactions: Lansoprazole is less likely than omeprazole to interact with other drugs. The absorption of some medicines may be affected by the acidity of the stomach, and as a result PPIs, lansoprazole and others that reduce stomach acid also reduce the absorption and concentration in the blood of ketoconazole (Nizoral) and increase absorption and blood concentration of digoxin (Lanoxin). This can lead to reduced effectiveness of ketoconazole or poisoning digoxin increased, respectively. (8) Adverse events

In general, inhibitors of proton pump are well tolerated and the incidence short-term adverse effects are relatively rare. The range and occurrence of side effects are similar for all inhibitors, proton pump they were reported more frequently with omeprazole. This may be due to its longer availability and hence clinical experience. Common side effects are headache, nausea, diarrhea, abdominal pain, fatigue, dizziness [9] Few adverse events include rash, itching, flatulence, constipation. anxiety, depression. Decreased absorption of vitamin B12 can occur with long-term use. Reactions "idiosyncratic" [8] Rarely PPI cause such as erythema multiforme, pancreatitis, Stevens-Johnson syndrome, and acute interstitial nephritis. [10]

It was observed that gastric acid suppression, using H2 receptor antagonists and inhibitors of proton pump is associated with an increased risk of community-acquired pneumonia. It is suspected that the results Removal of the acid in the insufficient elimination of pathogenic organisms. Therefore, it was suggested that patients at risk higher pneumonia should be prescribed as inhibitors of proton pump at lower doses and only when necessary. [11] PPI also been shown to increase the risk of Clostridium difficile infection [12].

The long-term use of inhibitors of the pump Proton has been less studied. But in a study of 135,000 people 50 or older, those taking high doses of PPIs for more than one year were found 2.6 times more likely to break a hip. These lower doses to take 1 to 4 years were 1.2 to 1.6 times more likely to fracture a hip. The risk of fracture increased with the length of time taking PPIs [13].

Theories about the cause of the increase are the possibility that reducing stomach acid reduces the amount of calcium dissolved in the stomach or PPIs may interfere with the degradation and reconstruction of the bone by interfering with acid production of osteoclasts [14].

In addition, the reduction of vitamin B12 (in increasing homocysteine) may increase bone fragility, an effect that may be offset by consumption, or co-packaging, order 100 mcg of vitamin B12 with the PPI. A recent study also suggested that inhibitors of proton pump significantly reduced the effect of clopidogrel on platelets as tested by VASP phosphorylation. The clinical impact of these results should be evaluated by other investigations, but PPI therapy should not be added to dual antiplatelet therapy without formal indication [15].

Dosage and Administration The dose of lansoprazole (sold under the brand Prevacid ®) prescribed by your health care provider depends on a number of factors, including: • The state health you are being treated for • Other medical conditions you may have • Other drugs you are taking. As always the case, do not adjust your dose unless your healthcare provider to do so.

For people gastroesophageal reflux disease (GERD) symptoms, the recommended dose is 15 mg lansoprazole once daily for eight weeks. If symptoms of GERD do not improve, your doctor may recommend treatment with lansoprazole GERD for eight weeks. The recommended starting dose of lansoprazole for the healing of erosive esophagitis is 30 mg once daily for eight weeks. Once the erosive esophagitis is healed, a daily dose of 15 mg may be recommended to prevent the return of esophagitis erosive. The recommended starting dose of lansoprazole for the healing of duodenal ulcer is 15 mg once daily for four weeks. Once the ulcer is healed, your doctor may recommend a dose of lansoprazole 15 mg once daily to prevent the ulcer from returning.

The recommended starting dose of lansoprazole to reduce the risk of stomach ulcer (gastric ulcer) associated with non-steroidal anti-inflammatory drugs (NSAIDs) is 15 mg once a day for a maximum of 12 weeks. The recommended starting dose of lansoprazole in healing ulcer of the stomach (gastric ulcer) associated with non-steroidal anti-inflammatory drugs (NSAIDs) is 30 mg once daily for eight weeks. Treatment to kill Helicobacter pylori (H. pylori) involves the use of two other drugs in addition to lansoprazole. This treatment is called "triple therapy. "Triple therapy used to kill H. pylori lansoprazole 30 mg twice daily plus 1000 mg of amoxicillin (twice daily) and 500 mg clarithromycin (twice day). The three drugs are taken for 10 or 14 days. In children aged 1 to 17, the recommended dose lansoprazole depends on the weight of the child. Consult your health care provider for children dosage instructions (16).

Lansoprazole is a conclusion tolerated proton pump inhibitor-well. It has been shown to be effective in healing, symptom relief and prevention of relapse of peptic ulcers and gastroesophageal reflux and may be part of effective regimens H. pylori. It is an important alternative to H2 receptor antagonists and a treatment option additional to other proton pump inhibitors in the management of disorders associated with hyperacidity.

References

1. Richardson P, Hawkey CJ, Stack WA. Inhibitors of proton pump: Pharmacology and rationale for use in gastrointestinal disorders. The Drugs 1998; 56:307-335

2. Rx list, the International Index of drugs, pravacid, description of drugs.

3. Cooper BT, Chapman W, CS Neumann, JC Gearty (2006). "Continuous treatment of Barrett's esophagus patients with proton pump inhibitors up to 13 years: observations on regression Cancer incidence and "Aliment Pharmacol There 23 (6 ):…. 727-33.

4. Poynard T, Lemaire M, H. Agostini meta-analysis of randomized clinical trials comparing lansoprazole with ranitidine or famotidine in the treatment of acute duodenal ulcer. : Eur J Gastroenterol Hepatol. 1995 Jul, 7 (7) :661-5.

5. LAMOULIATTE H. Adjuvant therapy for eradication of Helicobacter pylori: the role of lansoprazole in clinical studies. Lippincott Williams & Wilkins, Hagerstown, MD, USA (1979).

About the Author

Nicholas Maxwell, MD, FACS, Heartburn Solutions