Peptic Ulcers

Description

Alternative Names

Treatment for NSAID-Induced Ulcers

Preventing Ulcers or Rebleeding Induced by NSAIDs. If NSAID-induced ulcers or bleeding are identified, the first steps are the following:

• Test for H. pylori and if infected take antibiotic treatments.
• Try switching to alternative pain relievers. The first choice at this time are coxibs, usually celecoxib (Celebrex). It should be noted, however, that although they have a lower risk for ulcers and bleeding than standard NSAIDs, they are not entirely safe for the GI tract.

People who still need to take NSAIDs may try the following:

• Use the lowest NSAID dose possible.
• Try adding a proton-pump inhibitor (PPIs). Studies suggest they lower the risk for NSAID-induced ulcers but cannot completely prevent them. Brands include omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (Aciphex), and pantoprazole (Protonix).
• Try misoprostol or Arthrotec. If other agents are inappropriate, misoprostol protects against the major intestinal toxicity of NSAIDs. It was the first drug approved for preventing NSAID-induced ulcers. It is equally or even more effective than some of the PPIs, but it does not heal existing ulcers and has more side effects than PPIs. Patients tend to stop using it. Arthrotec is a combination of an ulcer protective agent called misoprostol and the NSAID diclofenac. One study found that patients taking Arthrotec had 65% to 80% fewer ulcers than those who took NSAIDs alone.
• One small study on animals suggested that taking L-arginine (an amino acid found in health stores) may help protect against damage from NSAIDs. As with all alternative agents, this product is not government regulated and more research is needed to confirm its benefits.

A 2002 study compared the coxib Celebrex with an NSAID (diclofenac) plus Prilosec in patients who had NSAID-induced bleeding. Unfortunately, there were no significant differences in rebleeding rates, which were high (about 5% within six months). Pain relief was about equal. More research is needed to determine whether other combinations may prove to be better for these patients.

Healing Existing Ulcers. For healing existing NSAID-induces ulcers, a number of agents are available. Treatment takes about two to six weeks. Proton-pump inhibitors are the most effective drugs. Others that may be beneficial include sucralfate or H2 blockers, such as famotidine (Pepcid AC), cimetidine (Tagamet), ranitidine (Zantac). Sucralfate may also help with dyspepsia caused by NSAIDs, but this agent plays no role in prevention. (Misoprostol, an effective agent used for prevention cannot heal existing ulcers.)

Alternative Medications for People with Chronic Pain

COX-2 Inhibitors (Coxibs). Celecoxib (Celebrex), rofecoxib (Vioxx), and valdecoxib (Bextra) are known as COX-2 (cyclooxygenase-2) inhibitors, or coxibs. They inhibit an inflammation-promoting enzyme called COX-2. Others, such as etoricoxib, are under investigation. Meloxicam (Mobicox) is a related drug known as a COX-2 preferential.

Evidence is increasing that the coxibs are significantly less harmful to the gastrointestinal (GI) tract than common NSAIDs, but they still pose some risk. In an important 2003 study, Celebrex had a significantly better safety record in the GI tract than NSAIDs and had lower rates of ulcers even in patients who needed to also take aspirin prevent heart attacks. Another 2003 study also suggested that rofecoxib was safer for the GI tract than NSAIDs. Some early evidence also suggests that, like NSAIDs, they may be partially protective against colon cancer and possibly even Alzheimer's disease.

In spite of their potential promise, some researchers believe that inhibiting COX-2 may have some negative side effects over the long term. The effects of these drugs on the heart particularly require clarification. The following are possible adverse effects or complications:

• They still pose a risk for gastrointestinal bleeding, although it is lower than with NSAIDs.
• Some studies have reported a higher incidence of heart attacks in patients taking Vioxx than in those taking NSAIDs. There were limitations to these studies, however, and 2003 study of 67,000 elderly patients found no higher risk compared to patients taking NSAIDs or any anti-inflammatory drug. Some (but not all evidence) suggests that the COX-2 inhibitors may increase the risk for blood clots. On the other hand, some studies have suggested that the anti-inflammatory effects, at least in Celebrex and meloxicam (Movicox), may have beneficial effects on blood vessels that would be heart protective.
• Celebrex or Vioxx can increase in blood pressure, with Vioxx having the greater effect.
• A few cases of neurologic side effects (hallucinations) have been observed with higher doses of Celebrex or Vioxx.
• Coxibs may have some adverse effects on kidney function, particularly in elderly people, which is similar to the effects of standard NSAIDs. Liver abnormalities, which are side effects of many drugs, have also been reported with coxibs and need further follow-up.
• They may have negative effects on pregnancy and fertility.
• Some severe allergic reactions have been reported in patients taking valdecoxib (Bextra). People allergic to sulfa drugs may be at particular risk.Anyone who develops a rash after taking these agents should stop taking them immediately.
• Patients who are sensitive to aspirin should discuss coxibs with their physician. Some may be safer for these individuals than others.

Coxibs can interfere with other drugs taken concurrently. Patients taking anticoagulant drugs such as warfarin may experience a higher risk for bleeding with the use of these agents. The use of coxibs can interfere with many other drugs taken concurrently, including lithium, methotrexate, and many others taken for heart disease, high blood pressure, or epilepsy. Patients should discuss all other medications with their physician.

COX-2 inhibitors are also significantly more expensive than traditional NSAIDs, costing about $80 per month, compared to about $15 for an NSAID like naproxen. Although they pose a lower risk for ulcers than NSAIDs, this risk is small for most NSAID users, so choosing coxibs may be justified only in patients with evidence of GI bleeding. More research is needed.

Capsaicin

Capsaicin is a component of hot red peppers and may bring pain relief when used as a skin cream (Zostrix). This is the only skin preparation that does more than just mask pain or reduce it temporarily. Capsaicin seems to reduce a substance in the body, known as substance P, which contributes both to inflammation and the delivery of pain impulses from the central nervous system. A small amount of capsaicin must be applied to the area of inflammation about four times a day. During the first few days of use, the patient will experience a warm, stinging sensation when the cream is applied. This sensation goes away, and pain relief usually begins within one to two weeks.

Arthrotec. Arthrotec is a combination of misoprostol and the NSAID diclofenac that may reduce the risk for gastrointestinal bleeding. One study found that patients taking Arthrotec had 65% to 80% fewer ulcers than those who took NSAIDs alone.

Acetaminophen. Acetaminophen (Tylenol, Anacin-3, Panadal, Phenaphen, Valadol, and other brands) is the most common alternative to NSAIDs. Acetaminophen is inexpensive and generally safe. It poses far less of a risk for gastrointestinal problems than NSAIDs and does not appear to pose a risk for miscarriage, as NSAIDs do, even when used regularly. It does have some adverse effects, however, and the daily dose should not exceed 4 grams (4000 mg). Patients who take high doses of this drug for long periods are at risk for liver damage, particularly if they drink alcohol and do not eat regularly. It may pose a small risk for serious kidney complications in people with preexisting kidney disease, although it is still the drug of choice for people with impaired kidney function. There is some evidence that taking even more than 2 grams (2000 mg) a day for the long term may confer a risk of ulcers and bleeding comparable to that of NSAIDs. This finding needs to be confirmed, however. It also may interact with certain medications, including the blood thinner warfarin.

Tramadol. Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. It has opioid-like properties but is not as addictive. (Dependence and abuse have been reported, however.) It can cause nausea but does not cause severe gastrointestinal problems, as NSAIDs can. Some patients experience severe itching. A combination of tramadol and acetaminophen (Ultracet) is now available and provides more rapid pain relief than tramadol alone and more durable relief than acetaminophen alone. Side effects are the same as for each of these agents.

Experimental Alternatives to COX-2s and NSAIDs. Possible safer alternatives to COX-2s and NSAIDs are also under investigation.

• NO-NSAIDs are drugs that combine NSAIDs and nitric oxide (NO), a substance that enhances blood flow to the stomach and increases levels of protective mucus and bicarbonate. These agents show particular promise in providing pain relief and reducing the risk for GI problems and warrant further investigation.
• Licofelone is drug that inhibits both the COX enzyme plus an inflammatory substance called Lipoxygenase 5. Early trials indicate they may be more effective and safer than either NSAIDs or COX-2 inhibitors, though further study is needed.