Cimetidine blocks antacid-induced hypergastrinemia

The effects on fasting serum gastrin concentrations of hourly doses of magnesium and aluminum hydroxide antacid, with and without intravenous cimetidine, were determined in 8 patients with duodenal ulcer disease. Gastrin levels rose significantly over 10 h when antacid was given either as a bolus of 30 ml every hour or as a constant infusion of 0.5 ml/min (36 +/- 5 pg/ml and 33 +/- 6 pg/ml to 108 +/- 32 pg/ml and 109 +/- 22 pg/ml, respectively, p less than 0.05). This effect was specific for some component of the antacid and not for neutralization of acid per se, inasmuch as sodium bicarbonate, infused to keep gastric pH at levels at or above those of antacid, produced no significant rise in serum gastrin concentration. When intravenous cimetidine was administered simultaneously with intragastric antacid, gastrin levels did not rise. This occurred even though intragastric pH levels were actually higher with cimetidine plus antacid than with antacid alone. The ability of intravenous cimetidine to block antacid-induced hypergastrinemia was counteracted by infusing simultaneously both hydrochloric acid and antacid into the stomach. Since hydrochloric acid reacts with magnesium and aluminum hydroxide to form ionic magnesium and aluminum chloride, cimetidine most likely blocks antacid-induced hypergastrinemia by reducing acid secretion from the stomach and thereby limiting the generation of ionic magnesium and aluminum.     

Absence of in vivo and in vitro interactions of an aluminum hydroxide, magnesium hydroxide containing antacid with cimetidine in patients with peptic ulcer

In view of contradictory reports on the bioavailability of cimetidine in the presence of concomitantly administered antacids we studied the areas under the plasma concentration time curves (AUC) of cimetidine, the maximal concentrations (cmax) and the time, at which cmax was reached (tmax) in eight patients (five patients with duodenal ulcer, three patients with gastric ulcer) with and without the administration of an aluminum hydroxide magnesium hydroxide containing antacid (Maaloxan). No significant effects of the antacid on AUC, cmax and tmax of cimetidine were found. In vitro studies also showed no adsorption of cimetidine to aluminum hydroxide, magnesium hydroxide or the antacid.     

The hypocholesterolemic effect of an antacid containing aluminum hydroxide.

STUDY OBJECTIVE: To evaluate the efficacy, safety, and hypocholesterolemic effect of an aluminum hydroxide-containing antacid in hypercholesterolemic individuals. DESIGN: A prospective, randomized, double-masked, placebo-controlled phase of 2 months' duration, followed by an open-design treatment phase of 2 months' duration and a washout phase of 2 months' duration. SETTING: Family practice clinics of two rural communities (kibbutzim) in Israel. PATIENTS: Fifty-six men and women with hypercholesterolemia (type IIa or IIb). Fifty individuals completed the study. INTERVENTION: After 2 months of dietary modification (low-fat, low-cholesterol diet), the participants were randomized into two matched groups. Group 1 (28 participants) was treated for 2 months with a chewable antacid tablet containing simethicone, magnesium hydroxide, and 113 mg of aluminum hydroxide per tablet, at a dose of two tablets four times daily. Group 2 (22 participants) was given a similar number of placebo tablets for 2 months. During the following 2 months, both groups received the antacid at the above dose. MEASUREMENTS AND MAIN RESULTS: Lipoprotein levels were evaluated at baseline and every 2 months thereafter for 6 months. Compared with pretreatment levels, Group 1 experienced a decrease in low-density lipoprotein cholesterol (LDL-C) of 9.8% after 2 months (p less than 0.001) and 18.5% after 4 months (p less than 0.001). Compared with Group 2, the decrease in LDL-C in Group 1 was 6.2% at the end of the 2-month double-masked, placebo phase. Although the high-density lipoprotein cholesterol (HDL-C) was also reduced in Group 1 at the end of 4 months of therapy (10.2%), the HDL-C/LDL-C ratio increased by 13% during the same interval (p less than 0.05). The treatment was well tolerated, with minimal side effects. CONCLUSIONS: An aluminum hydroxide-containing antacid reduces LDL-C in hypercholesterolemic individuals. Although HDL-C was also reduced to a lesser extent, the overall atherogenic index was improved. Further studies should be conducted to evaluate the long-term safety and efficacy of antacids containing aluminum hydroxide in hypercholesterolemic patients.     

Effect of antacids on the bioavailability and therapeutic efficacy of cimetidine

Five patients with duodenal ulcer received cimetidine and after an interval of four days cimetidine with antacid. Cimetidine in serum was analysed with high performance liquid chromatography. There was no significant difference in the values of the pharmacokinetic parameters of cimetidine (Cmax, tmax and AUC) when taking cimetidine alone and cimetidine plus antacid. 53 outpatients with endoscopically proven duodenal ulcer were evaluated in a randomized study, so as to compare the therapeutic effect of cimetidine and aluminum hydroxide gel plus cimetidine. 18 of 26 patient taking cimetidine alone (69.2%) and 19 of 27 patients taking cimetidine plus antacid (70.4%) had their ulcer completely healed after 4 weeks. The overall healing rates after 8 weeks for the groups taking cimetidine alone and cimetidine plus antacid were 80.0% and 92.6% respectively with no significant difference. This study indicates: (1) Simultaneous administration of aluminum hydroxide gel does not alter the bioavailability of cimetidine. (2) Combined administration of aluminum hydroxide gel and cimetidine does not alter the therapeutic effect of cimetidine in patients with duodenal ulcer.     

Neutralizing capacity and cost effectiveness of antacids

The prescribing physician is faced with a wide choice of antacid preparations. To provide a guide, we tested the commonly available antacids, both liquid and tablet, for their acid-neutralizing capacity. We calculated the cost effectiveness of antacids and tabulated the cost of 1 month of therapy. The acid-neutralizing capacity and cost effectiveness of liquid antacids are generally better than tablet antacids. The most effective liquid antacids, which are composed of either aluminum and magnesium hydroxide mixtures or calcium carbonate, vary in buffering capacity from 3 to 4.2 meq/mL of antacid and range in monthly cost of therapy from $35 to $74. In contrast, the five least effective liquid antacids vary in acid-neutralizing capacity from 0.3 to 2.3 meq/mL of antacid and in monthly cost of therapy from $78 to $498. Because the monthly cost of therapy is influenced primarily by the acid-neutralizing capacity of the antacid, a high-potency antacid should be prescribed. The taste and sodium content of the antacids should also be taken into account by the prescribing physician.     

Long-term low-dose antacid versus cimetidine therapy in the treatment of duodenal ulcer recurrence

The effect of cimetidine (400 mg at night) and of low-dose antacid (400 mg of aluminum hydroxide plus 400 mg of magnesium hydroxide four times a day) given alone or in combination was assessed in a double-blind double-dummy endoscopic trial on prevention of duodenal ulcer (DU). Seventy-five outpatients with healed DU were followed up clinically for 1 year and were checked endoscopically after 6 and 12 months of therapy or in case of symptomatic relapse. After 6 and 12 months, 25% and 41%, respectively, of patients treated with cimetidine alone experienced a relapse, compared with 42% and 54% of those treated with antacid alone and 25% and 43% of patients treated with the combination therapy. The differences are not statistically significant. No relevant side effects were observed in patients of any group. It is concluded that long-term prophylactic treatment of DU with low-dose antacid is as safe and effective as cimetidine treatment, whereas a combination of the two drugs does not achieve a therapeutic gain.     

Fate of oral neutralizing antacid and its effect on postprandial gastric secretion and emptying.

The fate and neutralizing efficiency of oral antacids (aluminum and magnesium hydroxides) as well as their effect on postprandial gastric function were quantified in 6 patients with duodenal ulcer disease. We employed a double-marker technique for measurement of gastric secretion and emptying and combined this with back-titration of the gastric samples and analysis of aluminum to trace the fate of antacid in the stomach and duodenum. These studies show that: (a) antacid therapy with aluminum and magnesium hydroxides significantly increases gastric secretion; (b) intragastric neutralization of gastric acid produces a significant and substantial decrease in net acid output (acid secreted minus acid neutralized), but the beneficial effects of neutralization are partially offset by incomplete intragastric formation of aluminum trichloride; (c) most but not all of the ingested antacid is utilized in acid neutralization in the stomach (average 78.6% in our 6 patients); and (d) antacid therapy does not modify the absolute rate of postprandial gastric emptying, but increases dilution of gastric contents, expanding the intragastric volume. Thus, the fractional gastric emptying rate declines, and this, in turn, should enhance antacid utilization by delaying its emptying.     

Pancreatic enzyme replacement

The effect of the addition of sodium bicarbonate, aluminum hydroxide, magnesium hydroxide, calcium carbonate, or cimetidine to supplemental pancreatic enzyme therapy was investigated in patients with severe exocrine pancreatic insufficiency. Steatorrhea was reduced with the administration of three enzyme tablets with meals (73 vs 29 g/24 hr). The coadministration of enzyme tablets with either sodium bicarbonate (16.6 g/24 hr,P=0.08), or aluminum hydroxide (18.4 g/24 hr,P=0.029) yielded a greater reduction in steatorrhea than enzymes alone (29 g/24 hr). Neither magnesium-aluminum hydroxide (36.3 g/24 hr,P=0.22), nor calcium carbonate (39.0 g/24 hr,P=0.029), improved efficacy of enzyme therapy and, in fact, tended to enhance steatorrhea. With the administration of cimetidine there was no significant effect on steatorrhea compared to enzymes alone (32.1 vs 29 g/24 hr,P>0.3). Intraduodenal lipase activity following test meals was found to be a poor predictor of the effectiveness of antacid therapy in improving the efficacy of supplemental enzymes.This study was supported in part by a NIH grant RRO-0350. Computational assistance was provided by the CLINFO Project, funded by the Division of Research Resources of the NIH (RRO-0350).     

Biliary excretion of aluminum in aluminum osteodystrophy with liver disease

Two patients with chronic liver disease developed elevated serum aluminum concentrations and biopsy-proven osteodystrophy. Neither patient had chronic renal failure but both had received aluminum-containing antacids for long periods. We measured biliary and urinary aluminum excretion during antacid loading in patients with normal liver function. Our studies show that biliary excretion is an important route of elimination of orally absorbed aluminum, and we suggest that long-term antacid therapy in patients with severe liver disease be monitored with periodic serum and urinary aluminum determinations to avoid aluminum osteodystrophy.     

Osteomalacia from Mg-containing antacid: a case report of bilateral hip fracture

Non-prescribed antacid drugs that contain magnesium and aluminum are widely used in the treatment of gastritis and peptic ulcer. One of the side effects of these antacid drugs is that they bind phosphate in the gut and result in its malabsorption. In this paper, a 42-year-old female patient who used magnesium hydroxide (Magnesie calcinee powder 100 g) to benefit from its laxative feature, and developed osteomalacia after losing 90 kg in 2 years will be presented by going through the related literature. She had widespread joint pain and could hardly walk without the help. Ca, P and vitamin D were at lower limit of normal, ALP, Mg and PTH were increased in her laboratory tests. There were stress fractures at the femur neck and at the upper part of the tibia in plane radiographies. The patient was hospitalized with the diagnosis of osteomalacia and she was treated successfully.     

Osteomalacia and osteitis fibrosa in a man ingesting aluminum hydroxide antacid

A 53-year-old man with a history of long-term aluminum hydroxide antacid ingestion reported diffuse bone pain and multiple stress fractures over a two-year period. An undecalcified transiliac bone biopsy specimen revealed osteomalacia with osteitis fibrosa; plasma parathyroid hormone and cyclic AMP levels were normal. Following withdrawal of antacids and treatment with calcium and phosphorus, an initially elevated plasma, 1,25-dihydroxyvitamin D level fell to within the normal range, accompanied by decreased bone pain, healed stress fractures, and increased axial bone mineral content as determined by computed tomography of lumbar trabecular bone. Phosphate deprivation and 1,25-dihydroxyvitamin D excess may contribute to the poor mineralization and exaggerated resorption of bone observed in this syndrome. The clinical, biochemical, radiologic, and histologic features of previously reported cases are reviewed. Early recognition of this syndrome is important, since appropriate therapy promotes skeletal remineralization and prevents morbidity.     

Mineral-metabolic side effects of low-dose antacids

Mineral-metabolic side effects of a low dose of a conventional Al-Mg antacid were examined in 10 healthy volunteers, who were given one antacid tablet after the 3 main meals and at bedtime (buffering capacity, 120 mmol/day) for 4 weeks. Compared with the pre-medication state, the following changes of statistical significance occurred during antacid ingestion: increase in urinary excretion of magnesium, calcium, and aluminum; decrease in urinary excretion of phosphate; increase in maximal renal phosphate reabsorption (Tm PO4/GFR); and increase in serum concentration of aluminum. Most of the changes were normalized 3-4 days after cessation of antacid medication. There was no change in intestinal absorption of calcium. The fact that even this low dose of antacids can provoke measurable changes in mineral metabolism, including aluminum absorption, is noteworthy, although we did not see any clinical symptoms from the biochemical changes.     

The effect of sodium bicarbonate versus aluminum-magnesium hydroxide on postprandial gastric acid in duodenal ulcer patients

When ingested 1 hour after a meal, conventional liquid antacids have a buffering effect of approximately 2 hours, while in the fasting state their effect is brief, lasting less than 1 hour. We tested the hypothesis that equal doses of antacid, one water soluble (sodium bicarbonate) and the other water insoluble (aluminum hydroxide plus magnesium hydroxide, MaaloxR), would have similar durations of postprandial buffering if the water soluble antacid regenerates the particulate protein buffer of the meal that leaves the stomach more slowly than liquids. Tests were conducted in random order on three separate days in 10 patients with duodenal ulcer. The effects of 30 ml of 2.39 M sodium bicarbonate (6.17 g, about 1 teaspoonful), the aluminum-magnesium antacid, each equivalent to 71.7 mmol of in vitro buffer, and water as a control on pH, hydrogen ion activity, and titratable acidity were compared. Thirty milliliters of each was swallowed 1 and 3 hours after ingestion of a standard solid plus liquid. Compared to the water control each dose of sodium bicarbonate significantly increased intragastric pH and decreased hydrogen ion activity and titratable acidity for only 1 hour. Each dose of the aluminum-magnesium antacid significantly buffered intragastric contents for 2 hours. These findings indicate that sodium bicarbonate transiently buffers postprandial intragastric contents. Therefore, sodium bicarbonate fails to reconstitute the protein buffer of the meal effectively, and the observations suggest that it leaves the stomach rapidly with the liquid phase of the meal. However, the water insoluble, aluminum-magnesium antacid has a longer duration of buffering, probably because it leaves the stomach more slowly, largely with the solid portion of the meal.     

Mucosal protective activity of activated aluminum complex

The antacid ES Riopan was acidified ex vivo to pH 2.5 to completely eliminate its buffering capacity and was then tested as a mucosal protective agent. The pH 2.5 acidified antacid solution was named activated aluminum complex. Activated aluminum complex was 8.2 times more potent than its parent antacid in protecting against acidified aspirin-induced gastric lesions in the rat. Activated aluminum complex had a duration of action greater than 10 h in the ethanol-induced gastric lesion model, while ES Riopan was active for 6 h. Activated aluminum complex was able to inhibit both acid- and nonacid-mediated ulcers in the stomach and intestine. Its mucosal protective activity was not blocked by pretreatment with indomethacin. These results demonstrate that the nonbuffering antacid activated aluminum complex exerted a more potent and longer-lasting mucosal protective activity than its parent antacid. The activity was probably due to the presence of a hexaaquoaluminum cation and supports the argument that antacids possess mucosal protective effects independent of their acid-neutralizing capacity.     

Antacid action of the aluminum cation: comparison of the in vitro effect of hydroxide and phosphate in open and closed systems

Antacid capacity of two aluminium containing-antacid drugs was evaluated in vitro; the first drug contained aluminium hydroxide (Alternagel), the second, aluminium phosphate (Phosphalugel). The antacid evaluation was performed 1) in a closed system by measuring antacid activity by down titration, 2) by a dynamic evaluation simulating acid secretion and gastric emptying. The results were reported both to the recommended therapeutical dose and to 100 mg aluminium. In static conditions, without gastric emptying, it was shown that aluminium hydroxide and phosphate acted by their buffer capacity in pH range less than or equal to pH 1.5. The therapeutical dose of aluminium phosphate displayed greater antacid activity than aluminium hydroxide, this fact being due to the empiric choice of the doses. With regard to aluminium content, aluminium phosphate activity remained greater than that of aluminium hydroxide although the difference decreased with decreasing pH values. The antacid capacities were related to the emptying outputs. Antacid activity corresponding to 100 mg aluminium was similar in both antacids less than pH 1.5. This effect was dependent on emptying rates. It can be suggested that Al was responsible for antacid activity in both preparations, and that the buffering capacity was supported by the change of aluminium cation in hydrolysis intermediary compounds.     

Relapse rates of duodenal ulcer healed with concentrated antacid or cimetidine

The incidence of duodenal ulcer relapse after initial therapy with concentrated aluminium-magnesium hydroxide (Maalox 70) or cimetidine (Tagamet) was investigated in a one-year follow-up study. 92.3% (24 out of 26) of the antacid patients and 76.2% (16 out of 21) of the cimetidine patients relapsed. The difference is not statistically significant. With respect to the pattern of onset of relapses, no difference was seen between the two groups. 33% of the recurrent lesions following treatment with antacids and 25% of those following cimetidine therapy were asymptomatic. This difference too is not significant. The results permit the conclusion that the mode of pharmaceutical therapy of ulcers (buffering of gastric acid by way of an antacid or inhibition of acid secretion by an H2-blocker) has no bearing on the further course of the ulcer disease.     

Zollinger-Ellison syndrome in a patient with normal screening gastrin level

A 59-year-old female presented with multifocal peptic ulcer disease and diarrhea. A fasting serum gastrin level obtained while the patient was receiving no antacid therapy was normal. A secretin stimulation test was positive. A small gastrinoma was found in the anterior duodenal wall at exploratory laparotomy. Normal fasting gastrin levels do occur in patients with overt Zollinger-Ellison syndrome and should not deter further investigation if clinical suspicion of this syndrome is high.     

Encephalopathy and seizures induced by intravesical alum irrigations.

Hemorrhagic cystitis is a significant toxic effect of cyclophosphamide therapy. Continuous bladder irrigation of a 1% alum solution is a simple and generally safe method of chemical cautery to treat the bleeding urothelium. We report four cases of encephalopathy coincident with elevated aluminum levels as well as one patient who developed seizures while receiving continuous bladder irrigations with alum. All patients had significant renal insufficiency. We recommend the cautious use of alum irrigation in patients with renal impairment and monitoring of serum aluminum levels to prevent excessive accumulation and toxicity.     

Calcium and acid rebound: a reappraisal.

We review acid rebound, the seemingly paradoxical increase in acid secretion resulting from administration of an antacid. Primarily a laboratory observation, the demonstration of the phenomenon was a major contributing factor to the swift, and possibly unjustified, fall from grace of calcium carbonate in the therapy of peptic ulcer disease despite years of apparently successful use. Calcium, as carbonate or other salts, causes an increase in gastric acid secretion owing, at least in part, to direct ionic stimulation. Another possible mode of action involves antral alkalinization with subsequent gastrin release. Other antacids, notably magnesium hydroxide and aluminum hydroxide, may therefore also cause rebound, but the data in this area are less convincing. Despite the demonstration that acid rebound occurs, no one has thoroughly investigated its clinical import. What limited data actually exist suggest no obvious clinically significant deleterious effect from use of calcium carbonate in peptic ulcer. Because of calcium carbonate's excellent acid-neutralizing capacity, its venerable past record in treating ulcer disease, and recent observations that low-dose antacids heal peptic ulcers, it is appropriate to reevaluate acid rebound, to focus on its clinical significance, if any.     

Thyroid dysfunction during chronic amiodarone therapy

Clinical and laboratory features of 99 patients receiving long-term amiodarone therapy were analyzed to determine which individuals may be at a high risk for developing amiodarone-induced thyroid dysfunction. The group of 68 men and 31 women was followed up for an average of 27 months (range 3 to 60). There were no differences in age, sex, dose of amiodarone, type or severity of underlying heart disease or baseline serum thyroxine levels in patients who developed hypothyroidism (n = 32) or hyperthyroidism (n = 5) or remained euthyroid (n = 62). Baseline serum thyrotropin levels were statistically higher in patients who became hypothyroid, but there was considerable overlap with the other patient groups. Serum reverse triiodothyronine (reverse T3), which has been suggested to be a marker of amiodarone efficacy, correlated directly with serum thyroxine levels, and was not an independent variable. There was no pattern to the time course for development of thyroid dysfunction, which occurred in 49% of those followed up and developed as early as 1 month or, in one individual, as late as after 3 years of amiodarone therapy. There are few guidelines for replacement therapy in patients with amiodarone-induced hypothyroidism. L-thyroxine dosage was adjusted cautiously in these high risk individuals to achieve serum thyroxine levels within the reference range of euthyroid individuals taking amiodarone: the mean dosage required was 136 micrograms/day. Normalization of serum thyrotropin (TSH) would have required doses of L-thyroxine that were judged to be excessively high.(ABSTRACT TRUNCATED AT 250 WORDS)