Dose Of Antacid Research Articles

Interactions of fluoroquinolones with other drugs: mechanisms, variability, clinical significance, and management.

Several important interactions of fluoroquinolones with other drugs have been reported in the literature. The absorption of all fluoroquinolones is almost entirely inhibited by concomitant administration of di- and trivalent cations, such as aluminum and magnesium contained in antacids. The inhibition of absorption can be significant and can potentially lead to the failure of treatment, even when fluoroquinolone doses are separated from antacid doses by hours. Certain isozymes of the cytochrome P-450 system are selectively inhibited by some fluoroquinolones. The metabolism of theophylline and caffeine is inhibited by enoxacin and ciprofloxacin such that the dosage of theophylline may need to be reduced in order to avoid toxicity. In contrast, ofloxacin and norfloxacin cause less inhibition of the metabolism of these compounds, and reduction of the theophylline dosage is not routinely required. Evidence regarding the effect of fluoroquinolones on the disposition of other drugs known to be metabolized, such as warfarin and cyclosporine, is inconclusive. In summary, the safe and effective use of fluoroquinolone antibiotics requires careful consideration of concomitant drug therapy.

Elevated Plasma Aluminum Levels in Normal Infants Receiving Antacids Containing Aluminum

Aluminum toxicity is a documented cause of encephalopathy, anemia, and osteomalacia. Excretion is primarily renal; therefore, patients with renal insufficiency are at risk for aluminum accumulation and toxicity. This has been demonstrated in uremic children treated with aluminum-containing antacids. The purpose of this study was to determine whether plasma aluminum levels were elevated in infants with normal renal function during prolonged aluminum-containing antacid use. Ten study infants (mean age = 5.8 months), who had been receiving antacids for at least 1 week, were compared with 16 control infants (mean age = 9.8 months) not receiving antacids. The study patients consumed 123 +/- 16 mg/kg per day (mean +/- SEM) of elemental aluminum for an average of 4.7 weeks. Their plasma aluminum level (37.2 +/- 7.13 micrograms/L) was significantly greater than that of the control group (4.13 +/- 0.66 micrograms/L) (P less than .005). It is concluded that plasma aluminum levels may become elevated in infants with normal renal function who are consuming high doses of aluminum-containing antacids. The safety of antacids containing aluminum should not be assumed and they should be used judiciously in infants, with careful monitoring of the aluminum dose and plasma level.

The emergency department of treatment of dyspepsia with antacids and oral lidocaine

The treatment of dyspepsia in the emergency department often consists of antacid in combination with viscous lidocaine, even though the specific etiology of the pain is frequently unknown. The efficacy of lidocaine as a component of symptomatic therapy was evaluated in a randomized, patient-blinded protocol. Patients presenting to the ED with dyspeptic symptoms were randomized to receive 30 mL of antacid (Mylanta II), or 30 mL of antacid plus 15 mL of 2% viscous lidocaine (GI cocktail). Patients recorded their pain score on an 11-cm linear analog scale prior to and 30 minutes after treatment. Seventy-six patients were enrolled; three were excluded from analysis due to incomplete data. Thirty-four patients were randomized to receive antacid and 39 to receive GI cocktail. Patients rated their baseline pain at 6.4 +/- 2.8 cm in the antacid group and 6.7 +/- 2.7 cm in the cocktail group (P greater than .50). Improvement in pain score with treatment was 0.9 +/- 2.9 cm in the antacid group compared with 4.0 +/- 3.4 cm in the GI cocktail group (P less than .0001). Assessment of pain relief using a five-point rating scale also indicated greater relief with GI cocktail therapy compared with antacid alone (P = .004). No adverse effects were noted with either treatment. We conclude that a single dose of antacid and viscous lidocaine provides a significantly greater degree of immediate pain relief than antacid alone in patients with dyspepsia.

Effects of Antacids on the Clinical Pharmacokinetics of Drugs

Since a previous review by Hurwitz was published in 1977 a large number of reports on drug interactions with antacids have appeared, few of which are of clinical relevance. Tetracyclines form insoluble complex molecules by metal ion chelation with various antacids; tetracycline absorption may be decreased by more than 90% by this interaction. Of the new class of quinolone antibiotics, the absorption of ciprofloxacin and ofloxacin is reduced by 50 to 90% in the presence of aluminium- and magnesium hydroxide-containing antacids. In contrast to early work showing inhibition of the absorption of beta-adrenergic blocking drugs by antacids, subsequent studies did not confirm a reduction in the bioavailability of either atenolol or propranolol during antacid treatment; indeed, they showed an increase in the plasma concentrations of metoprolol when the drug was coadministered with an antacid. The bioavailability of captopril was significantly reduced in the presence of an antacid, and lower plasma concentrations of this angiotensin-converting enzyme inhibitor were accompanied by a reduction of its effect on the systolic blood pressure of the patients. The absorption of the cardiac glycosides digoxin and digitoxin is not inhibited by antacids to a significant degree, although earlier studies had shown a positive effect when the dissolution of the glycoside preparations was relatively poor. Antacids reduce the bioavailability of the H2-receptor antagonists cimetidine and ranitidine only when high antacid doses are used and when the drugs are administered simultaneously. The bioavailability of famotidine was not significantly altered by a potent antacid preparation, although a trend towards reduced absorption was observed. Iron absorption is significantly decreased in the presence of sodium bicarbonate and calcium carbonate, but is nearly complete when coadministered with aluminium-magnesium hydroxide. Nonsteroidal anti-inflammatory drugs such as naproxen, tenoxicam, ketoprofen, ibuprofen and piroxicam are not affected in their absorption by antacid treatment. Theophylline bioavailability is unchanged when the drug is given together with antacids, although its rate of absorption may be altered, leading to a reduction or an increase in the time of the occurrence of peak plasma drug concentrations.

Clinical Efficacy of Low Dose Antacids in the Treatment of Peptic Ulcer

Duodenal ulcer has generally been considered an acid-related disease. The original concept of therapy aimed to reduce acid secretion as much and for as long as possible. In several studies, a low dose antacid regimen has been reported to be superior to placebo and as effective as H2-receptor antagonists in the treatment of both duodenal and gastric ulcers. Similarly, a low dose antacid regimen has been shown to be as effective as H2-receptor antagonists in preventing duodenal ulcer recurrence.

Effect of antacid treatment on endogenous prostaglandin synthesis in human antral and duodenal mucosa.

Using 14C-labeled arachidonic acid as precursor for in vitro prostaglandin synthesis, the effect of an antacid containing Al (OH)3, Mg(OH)2 and CaCO3 on endogenous prostaglandin synthesis was investigated in antral and duodenal mucosa of healthy volunteers. After three weeks of treatment with a high-dose antacid, there was no detectable change in the total capacity of the mucosa for prostaglandin synthesis, but the prostaglandin profile was markedly altered. The relative amounts of PGE2 and PGF2 alpha synthesized by antral and duodenal mucosa increased at the expense of the prostaglandins A2/B2, thromboxane A2, and prostacyclin. In a short-term study, this change was not observed following a single antacid dose within 1 hr after application. It is concluded that long-term antacid treatment may alter the prostaglandin pattern formed by gastroduodenal mucosa and this may be related to its therapeutic effect.

Sodium bicarbonate as a single dose antacid in obstetric anaesthesia

Gastric pH and volumes were measured in 84 women who had general anaesthesia for emergency Caesarean section. Forty-eight received only 20 ml 8.4% sodium bicarbonate immediately before induction of anaesthesia and 36 ranitidine 150 mg 6-hourly during labour in combination with NaHCO3. Gastric pH was less than 2.5 in four women who received only bicarbonate. All aspirates from the ranitidine plus bicarbonate group had a pH greater than 2.5. Mean volumes of gastric content aspirated were 87 (SD 87.4) and 60 (SD 46.3) ml for the bicarbonate alone and bicarbonate plus ranitidine series respectively. These differences were not significant. Twenty millilitres of 8.4% NaHCO3 cannot be recommended as a single dose antacid for emergency Caesarean section. Ranitidine plus bicarbonate is considered a reliable antacid regimen to ensure elevation of gastric pH to safe levels.

Alimentary tract and pancreas. Stimulation of mucosal prostaglandin synthesis in human stomach and duodenum by antacid treatment.

The effect of a low dose antacid treatment on mucosal prostaglandin metabolism was studied in 15 healthy volunteers. A daily dose of 46 mmol (= 138 mval) Al(OH)3 and 42 mmol (= 84 mval) Mg(OH)2 with a titrated in vitro neutralising capacity of 272 mval of H+ was given for three weeks. Total prostaglandin formation and the prostaglandin profile as well as the degradation of PGE2 were assayed by incubating homogenates of endoscopic biopsies from antral and duodenal mucosa with the precursor (14C)arachidonic acid. Total prostaglandin synthesis in antrum (623 (110) pmol/mg protein) and duodenum (432 (72) pmol/mg) was stimulated after three weeks administration of low dose antacids by 176% (p less than 0.05) and 154% (p less than 0.05), respectively. An untreated control group exhibited no significant changes. In contrast, the prostaglandin profile showed only a small increase of the prostacyclin metabolite 6-keto PGF1a (p less than 0.05) at the expense PGD2. PGE2 catabolism was unaffected. This enhanced activity of mucosal prostaglandin cyclooxygenase might represent one possible mechanism of action of a low dose antacid treatment.

Risk factors for healing of duodenal ulcer under antacid treatment: do ulcer patients need individual treatment?

In order to identify the risk factors affecting the healing of duodenal ulcer, a clinical trial with effective dose of antacid was carried out in 53 patients. Duration of ulcer history, number of relapses, duration of the last and present relapse, number, duration and severity of pain attacks in the present ulcer relapse, pain radiation to back, vomiting, appetite, smoking habit, intake of analgesics and previous haemorrhage were registered. Number of ulcers, ulcer depth, bublar narrowing, erosions, duodenitis at initial endoscopy and healing of ulcer were assessed by one endoscopist. Basic and peak acid output were measured. The extent of duodenitis on the site opposite the ulcer was determined by histological examination. Sixty per cent of the duodenal ulcers were healed after three weeks. By univariate analysis, the following factors affect the healing; pain radiation to back and pain duration during treatment (p less than 0.001), multiple or deep ulcers, narrowing of duodenal bulb (p less than 0.01), number of pain attacks and poor appetite (p less than 0.05). By the stepwise logistic regression model, the following factors were selected as predictors for healing of duodenal ulcer with 76% correct classification: pain radiation to back (p = 0.002), deep ulcer (p = 0.013), multiple ulcers (p = 0.028). Number of cigarettes/day (p less than 0.007) and male sex (p = 0.036). By this model, the prediction of healing could be accurately assessed in 78% in a new sample. Individual treatment should be carried out on the basis of these factors.

ANTACID AND FORMULA EFFECTS ON GASTRIC ACIDITY IN INFANTS WITH GASTROESOPHAGEAL REFLUX

A variety of peptic diseases are treated with antacids. Antacid dose requirements for young children have not been extensively evaluated. Moreover, the effects of formula feedings on antacid requirements are also unknown. We have investigated the effects of antacids and formula feedings on gastric acidity in infants less than 1 year of age. Small formula feedings of 15 mL/kg per feeding significantly improve antacid buffering of 0.5 mL/kg per dose of standard magnesium-aluminum hydroxide antacids.

Combination Treatment with Ranitidine and Sodium Bicarbonate Prior to Obstetric Anaesthesia

Summary The gastric pH and volume were measured in 175 patients undergoing elective, and 313 undergoing emergency, obstetric procedures. Ranitidine 150 mg was administered orally every 6 hours in labour and at least 2 hours before elective Caesarean section. Patients received20 ml of8.4% sodium bicarbonate orally immediately prior to induction of anaesthesia. The combination of ranitidine and sodium bicarbonate produced marked alkalinisation of gastric contents (mean pH 8.9). The administration of sodium bicarbonate pre-operatively in patients who received ranitidine less than 2 hours before operation led to satisfactory elevation of gastric pH. Only four patients had a gastric pH < 2.5, one patient refused any medication, two received only ranitidine and one patient had a long interval from administration of bicarbonate to aspiration of gastric contents. Gastric volumes were high in labouring patients (mean 84 ml) despite administration of ranitidine. The effectiveness of sodium bicarbonate as a single dose antacid therapy prior to obstetric anaesthesia requires further study.

Combination treatment with ranitidine and sodium bicarbonate prior to obstetric anaesthesia.

The gastric pH and volume were measured in 175 patients undergoing elective, and 313 undergoing emergency, obstetric procedures. Ranitidine 150 mg was administered orally every 6 hours in labour and at least 2 hours before elective Caesarean section. Patients received 20 ml of 8.4% sodium bicarbonate orally immediately prior to induction of anaesthesia. The combination of ranitidine and sodium bicarbonate produced marked alkalinisation of gastric contents (mean pH 8.9). The administration of sodium bicarbonate pre-operatively in patients who received ranitidine less than 2 hours before operation led to satisfactory elevation of gastric pH. Only four patients had a gastric pH less than 2.5, one patient refused any medication, two received only ranitidine and one patient had a long interval from administration of bicarbonate to aspiration of gastric contents. Gastric volumes were high in labouring patients (mean 84 ml) despite administration of ranitidine. The effectiveness of sodium bicarbonate as a single dose antacid therapy prior to obstetric anaesthesia requires further study.

Gastrointestinal absorption of aluminium from single doses of aluminium containing antacids in man

Ten subjects with normal renal function were given different single doses of aluminium containing antacids (1, 4, or 8 tablets). The antacid tablets (aluminium content 244 mg tablet-1) were chewed and swallowed either with water, with orange juice, or with citric acid solution. There was a marked increase in serum concentration of aluminium when the antacids was ingested with citric acid (P less than 0.001) or with orange juice (P less than 0.05). When antacids were taken with water, a slight, but significant increase in serum aluminium concentration was seen with 4, but not with 1 or with 8 tablets. Following all doses of antacid, a significant increase in 24 h urinary excretion of aluminium was seen. The estimated absorption of aluminium was 8 and 50 times higher when antacids were taken with orange juice or with citric acid, respectively, than when taken with water. Thus, measurable quantities of aluminium are absorbed from single oral doses of antacids. The absorption is substantially enhanced by concomitant ingestion of citric acid.

Antacid and Formula Effects on Gastric Acidity in Infants With Gastroesophageal Reflux

A variety of peptic diseases are treated with antacids. Antacid dose requirements for young children have not been extensively evaluated. Moreover, the effects of formula feedings on antacid requirements are also unknown. We have investigated the effects of antacids and formula feedings on gastric acidity in infants less than 1 year of age. Small formula feedings of 15 mL/kg per feeding significantly improve antacid buffering of 0.5 mL/kg per dose of standard magnesium-aluminum hydroxide antacids.

Akute Azetylsalizylsäure-Schädigung der menschlichen Magenschleimhaut: Eine endoskopische Studie mit Antazida, H2-Blockern, Prostaglandinen und Omeprazol

The protective action of drugs used in the treatment of peptic and gastric ulcers, against acute doses of acetylsylicalic acid (ASA), was studied in healthy subjects by a double-blind crossover method. The severity of the lesion was determined by endoscopy.In the corresponding placebo experiments, severe lesions of the gastroduodenal mucosa were seen after administration of 1500 mg ASA. These lesions could be prevented only by means of antisecretory doses of the H2 blocker ranitidin (2 × 150 mg daily) as well as by high doses of antacid mixtures.In contrast to the results of animal experiments, no protective action against ASA was seen when administering prostaglandin analogues, the proton pump inhibitor omeprazol, and ranitidin in non-acid inhibiting doses.We conclude from our studies that protective action against ASA can be achieved only if the intragastric pH level is adequately raised above 3,5 and higher.

Prophylaxis of stress ulcers: antacid titration vs. histamine2-receptor blockade.

The near universal occurrence of stress ulcers in critically ill patients emphasizes the need for early and effective prophylaxis. Intraluminal gastric acidity, ischemic insult to the bowel, and the presence of stress factors are the major precipitants of stress ulcers. The use of H2-receptor antagonists vs. antacid titration for stress ulcer prophylaxis is reviewed. The goals of preventive therapy are to eliminate the stress factors and to maintain intragastric pH greater than 5. Hourly gastric pH monitoring and antacid titration are the mainstay of stress ulcer prophylaxis, with high potency antacids being the preferred agents. H2-receptor antagonists may serve as adjuncts in patients requiring large doses of antacids or having acid-base abnormalities from high gastric output states.

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.

Osteoporosis: calcium, fluoride, and aluminum interactions.

A gradual loss of bone occurs with age. There are indications in the literature that not only calcium but also fluoride may play an important role in maintaining the bone mass. In view of the high incidence of osteoporosis and its complications, and in view of the fact that fluoride is beneficial for the treatment of osteoporosis, studies have been carried out in this research unit to determine the retention and excretion of fluoride both during a normal dietary intake of fluoride and during fluoride supplementation. Another problem to be examined was to delineate whether certain substances interfere with the intestinal absorption of fluoride and of calcium. One such substance is aluminum contained in commonly used antacids. The use of small amounts of aluminum-containing antacids increased fecal fluoride significantly, thereby decreasing the intestinal absorption of fluoride. In addition, the small doses of aluminum-containing antacids also affected the metabolism of calcium and phosphorus, the primary effect being complexation of phosphorus in the intestine leading to phosphorus depletion. This change in phosphorus metabolism was associated with an increase of the urinary and fecal calcium excretion resulting in a negative calcium balance. The dual effect of aluminum, namely in causing calcium loss and inhibition of the intestinal absorption of fluoride, can result in adverse effects on bone which may contribute to bone loss.

Moderate reduction of gastric acid secretion in the treatment of peptic ulcer disease.

Duodenal ulceration is presumed to be induced and maintained by imbalance between aggressive and defensive factors. Development of drugs for correction of this imbalance has recently concentrated on maximum inhibition of acid secretion e.g. via H2-receptor antagonists but has led to re-evaluation of antacids and antimuscarinics. It has been shown that about the same percentage of ulcers can be healed using low antacid doses or antimuscarinics (e.g. pirenzepine) or doses of H2-receptor antagonists which do not inhibit acid secretion maximally as can be healed using higher doses of H2-receptor antagonists. Avoidance of the intragastric bacterial overgrowth and its consequences and the disturbance of the acid-gastrin feedback mechanism which may follow maximum gastric acid suppression could provide a rationale for use of anti-ulcer therapy based on moderate reduction of gastric acid secretion.

Role of Gastric Acid and Bile Acids in the Pathogenesis of Compound 48/80-induced Gastric Lesions in Rats

We studied the effects of various agents, which influence gastric acidity and bile acids, on compound 48/80 (48/80)-induced gastric lesions in rats. 48/ 80-lnduced gastric lesions were produced by repeated intraperitoneal administration of 48/80 at 0.75 mg/kg once daily for 4 days. Test agents were given orally twice daily (30 min before and 9 hr after 48/80 administration) for 4 days. Al(OH)3 and sucralfate at 2000 mg/kg/day, a weak antacid dose, significantly inhibited (about 50–60%) the development of 48/80-induced lesions. Propantheline at 60 mg/kg/day and omeprazole at 60 or 200 mg/kg/day, which reduced gastric secretion for more than 12 hr, also significantly inhibited (about 30–40%) these lesions. Cimetidine at 200 mg/kg/day, which reduced gastric secretion for only 5 hr, had little effect on the lesion formation. Cholestyramine, which is a potent bile acids binding agent, had no effect on 48/80-induced lesions in doses of 600 or 2000 mg/kg/day. These results suggest that gastric acid, but not bile acids, is partly involved in the pathogenesis of 48/80-induced gastric lesions.