Gastroparesis: Controlling with Medication

from Dr. Bernstein’s book “Diabetes Solution”
© 2007 by Richard K. Bernstein, M.D.

Medications That Facilitate Stomach-Emptying
There is no medication that will cure gastroparesis. The only “cure” is months or years of normal blood sugars. There are, however, some pharmaceutical preparations that may speed the emptying of your stomach after a meal if your gastroparesis is only mild or moderate in severity (page 361, footnote). These will help smooth out your blood sugar profiles after that meal. Most diabetics with mild to moderate gastroparesis will require medication before every meal.

When gastroparesis is very mild, it may be possible to get away with medication only before supper. For some reason—perhaps because most people tend not to be as physically active after supper, and may have their largest meal of the day in the evening—digestion of supper appears to be more impaired than that of other meals. It is also likely that stomach-emptying is slower in the evening, even for nondiabetics.

Medications for gastroparesis may take the form of liquids or pills. The question immediately arises that if pills must dissolve in the stomach to become effective, just how effective are they going to be? My experience is that they’re of questionable value unless chewed. The time required for a pill to dissolve in a paretic stomach is likely to be lengthy, and consequently the medication may take several hours to become effective. I generally prescribe only liquid medications or chewed tablets for stimulating gastric (stomach) emptying.

Super Papaya Enzyme Plus has been praised by many of my patients for its rapid relief of some of the physical symptoms of gastroparesis— bloating and belching, for example. Some claim that it also helps to level off the blood sugar swings caused by gastroparesis. The product consists of pleasant-tasting chewable tablets that contain a variety of enzymes (papain, amylase, proteases, bromelain, lipase, and cellulase) that digest protein, fat, carbohydrate, and fiber while they are still in your stomach. You would normally chew 3–5 tablets during and at the end of each meal. The tablets are available in most health food stores and are marketed by American Health, (631) 567-9500, Ronkonkoma, NY 11779. Some of my kosher patients use a similar product called Freeda All Natural Parvenzyme, which is distributed by Freeda Vitamins, 36 East Forty-first Street,New York, NY 10017, (800) 777-3737, and on the Web at freedavitamins.com. The small amount of sorbitol and similar sweeteners contained in these products should not have a significant effect on your blood sugar if consumption is limited to the above dose.

Tegaserod maleate (Zelnorm,Novartis Pharmaceuticals) This medication was developed for the treatment of irritable bowel syndrome. I have found it to be very effective for treating mild to moderate gastroparesis.  It can be used concurrently with other medications listed in this chapter. I prescribe one 6 mg tablet, 1 hour before breakfast and supper. There is a catch, however—for some users this product stops working after about one month.

Domperidone (Motilium, Janssen Pharmaceutica) is not yet available in the United States. It can be purchased in Canada, the U.K., and perhaps some other countries. Pharmacies in Canada are no longer permitted to ship medications to the United States unless they are prescribed by a Canadian physician. It therefore may be necessary to purchase it elsewhere via the Internet.* Since it is not available as a liquid, we ask patients to chew 2 tablets (10 mg each) 1 hour before meals and to swallow with 8 ounces of water or diet soda. I limit dosing to 2 tablets because larger doses can cause sexual dysfunction in men and absence of menses in women. These problems resolve when the drug is discontinued. Since it works by a mechanism different from those of the preceding products, its effects can be additive (that is, useful with other preparations, not addictive). Janssen may market a liquid form of this product in the United States at some time in the future. In the meantime, some gastroenterologists may be able to prescribe it, as an investigational drug.

Metoclopramide syrup may possibly be the most powerful stimulant of gastric emptying. It works in a fashion similar to domperidone, by inhibiting the effects of dopamine in the stomach. Because it can readily enter the brain, it can cause serious side effects, such as somnolence, depression, agitation, and neurologic problems that resemble Parkinsonism. These side effects can appear immediately in some individuals or only after many months of continuous use in others. Because gastroparesis often requires doses high enough to cause side effects, I use this medication infrequently and limit dosing to no more than 2 teaspoons 30 minutes before meals.

If you use metoclopramide, you should keep on hand the antidote to its side effects—diphenhydramine elixir (Benadryl syrup). Two tablespoons usually work. If side effects become serious enough to warrant use of the antidote, the metoclopramide should be immediately and permanently discontinued.

Abrupt discontinuation of metoclopramide has been reported to cause psychotic behavior in two patients after continuous use for more than three months. This information might suggest to your physician that it be gradually tapered off if it is to be discontinued after even two months of continuous use.

Erythromycin ethylsuccinate is an antibiotic that has been used to treat infections for many years. It has a chemical composition that resembles the hormone motolin, which stimulates muscular activity in the stomach. Apparently, when stimulation of the stomach by the vagus nerve is depressed, as with autonomic neuropathy, motolin secretion is diminished. Three papers delivered to the 1989 annual meeting of the American Gastroenterological Association demonstrated that this drug can stimulate gastric emptying in patients with gastroparesis.

In people without gastroparesis, erythromycin can cause nausea, unless taken after drinking fluids. I ask my patients to drink two glasses of water or other fluid before each dose. I prescribe erythromycin ethylsuccinate oral suspension just before meals. We start with 1 teaspoon of the 400 mg/tsp concentration, and increase to several teaspoons if necessary. As each teaspoon of this suspension contains 3.5 grams of sucrose (table sugar), it will be necessary to increase slightly the doses of insulin covering meals to reduce blood sugar elevation while this medication is used.

If the liquid is kept in a refrigerator, the taste begins to deteriorate after 35 days. At room temperature, taste deteriorates after 14 days.

I have seen no side effects from this medication. I insist that patients who use it chronically take 1 probiotic capsule (such as Florastor [saccharomyces boulardii], Culturelle Lactobacillus GG, or Nature’s Way Primadophilus Reuteri) at least 2 hours before or after each dose. This is to restore to the intestine natural bacteria that can be destroyed by this antibiotic. It is also wise to consume one 150 mg fluconazole tablet per month to inhibit growth of fungus in the GI tract. I have not found erythromycin to be especially effective for treating gastroparesis, despite published studies.

Betaine hydrochloride with pepsin is a potent combination that can predigest food in the stomach by increasing acidity and adding a powerful digestive enzyme. It can be procured at most health food stores or at Rosedale Pharmacy. Because of its acidity it should not be used by those with gastritis, esophagitis, or stomach/duodenal ulcers.  Food that has been predigested will more likely pass through the narrowed pyloric valve of gastroparesis.We initially use 1 tablet or capsule midmeal. If no burning is perceived, we increase the dose to 2 and then eventually 3 tablets or capsules spaced evenly throughout subsequent meals. It should never be chewed or taken on an empty stomach.  Since betaine HCl with pepsin, unlike cisapride, does not attempt to stimulate the vagus nerve, it is frequently of value for even severe cases of gastroparesis.

Nitric Oxide Agonists
Although the aforementioned agents can be very effective when gastroparesis is mild, their effectiveness in minimizing blood sugar uncertainty after meals diminishes when this condition is more severe.

My frustration in trying to circumvent this problem has led to my investigation of a class of substances called nitric oxide agonists. Such agents are currently being used to relieve effects of angina in patients with cardiac disease. Since they work by relaxing the smooth muscle in the walls of coronary arteries, I assumed that they could also relax the smooth muscle of the pyloric valve.

My initial trial was with a medication called isosorbide dinitrate. I had it prepared as a suspension in almond oil (with flavoring) so that it could coat the pylorus and work directly upon it. I had it compounded in a concentrate of 5 mg/tsp (1 mg/ml). I was pleased to see that my assumption proved correct—it was very effective for nearly all ofmy patients who used it. Thus far, it appears to be more successful than any of the agents described above. Nevertheless, it is only partially effective for more severe cases of gastroparesis.

This formulation can be prepared by any compounding chemist (see footnote, page 202). The only adverse effect I’ve observed has been headache in about 10 percent of the users. Although the headache usually resolves after several days of use, I try to prevent it by starting with very small doses that can then be gradually increased.

I therefore recommend that initially . teaspoon be taken 30–60 minutes before dinner. After one week, we increase the dose to 1 teaspoon.

If this fails to level off blood sugars at bedtime and the following morning, we continue 1 teaspoon for a week and then increase it to 2 teaspoons. If this is not fully effective, we then increase to 3 teaspoons.  If this dose doesn’t do the trick, I discontinue the treatment, as further increases are unlikely to be effective. If 1–3 teaspoons work, we then use the same dose 30–60 minutes before each meal. It’s been unusual for this formula to be totally ineffective. The liquid must be vigorously shaken before use.

If you have a cardiac condition, isosorbide dinitrate should not be used for gastroparesis unless approved by your cardiologist.

Unfortunately, like tegaserod maleate, isosorbide dinitrate usually stops working after a period of weeks to months. I therefore attempt to increase effectiveness and lower blood sugar levels by applying a chemically similar product to the skin directly over the pylorus. What I prescribe is a nitroglycerine skin patch. These are available by prescription at any pharmacy in strengths of 0.1, 0.2, 0.4, and 0.8 mg. The patch is placed over the pylorus, which is located on the midline of the abdomen above the navel, about 1. inches (37 mm) below the middle of the lowest rib where it forms an inverted V. The patch is applied on arising in the morning and removed at bedtime. We start with the 0.1 mg patch and increase the size each week if there are no adverse effects.  As with isosorbide dinitrate, nitroglycerine should not be used for gastroparesis without your cardiologist’s approval if you have a cardiac condition.

Another alternative is the clonidine adhesive skin patch. This product is sold as Catapres in all pharmacies to lower blood pressure and requires a prescription. It is a powerful smooth muscle relaxant. It can, however, cause somnolence (sleepiness) in some people. We therefore start at the smallest size (1 mg) for the first week and increase it to 2 mg for the second week, then 3 mg for the third week and thereafter.  Although each patch will work for a week on most people, we remove it at bedtime and replace it the next morning. Since the patch’s adhesiveness will be reduced after it’s removed, you can use paper tape to keep it attached after the first day. If it causes tiredness, we lower the patch dosage or discontinue it.

Like the aforementioned nitric oxide agonists, it can stop working eventually. If it has been effective and stops working, we discontinue it and restart it after a couple of months. Some patients find that a patch will stop working after 3–4 days. For these people, we change to a new patch midweek.

The reason we remove the clonidine (or nitroglycerine) patch from the skin at bedtime is to slow down the development of tolerance to its action which eventually occurs. I also recommend alternating daytime skin patches—one week on clonidine and one week on nitroglycerine— alternating over and over.

* A number of Canadian pharmacies for an additional charge of $5 can secure prescriptions for distant foreign patients from Canadian physicians. One of these is Murray Shore Pharmacy, (800) 201-8590.