eMedicine Specialties > Gastroenterology > Stomach
Achlorhydria: Treatment & Medication
Updated: Nov 9, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Achlorhydria and the physiologic consequences of this condition have the following treatments.
- Achlorhydria associated with H pylori infection may respond to H pylori eradication therapy, although resumption of gastric acid secretion may only be partial.
- The standard, first-line therapy for gastric H pylori is as follows: PPI (20 mg bid) plus clarithromycin (500 mg bid) plus amoxicillin (1 g bid). For patients who are allergic to penicillin, amoxicillin can be replaced by levofloxacin (250 mg bid).
- There is some minor disagreement on the duration of treatment. US guidelines recommend a 14-day course, while in Europe, a 7-day course is considered to be sufficient. A meta-analysis reveals a 12% advantage for a longer course of treatment, but this is at an added expense and a greater risk of adverse effects. Patient compliance is also more difficult with a longer course of treatment (ie, 14 d vs 7 d).
- In immune-mediated diseases (eg, pernicious anemia), acid secretion cannot be restored after destruction of the gastric secretory mucosa.
- Treatment of gastritis that leads to pernicious anemia consists of parenteral vitamin B-12 injection. It is not clear whether intranasal vitamin B-12 therapy is adequate in individuals who have been diagnosed with pernicious anemia. Parenteral vitamin B-12 treatment may reverse hematologic abnormalities. However, it may have little effect on preexisting neurologic abnormalities. This treatment does not affect the underlying gastric atrophy, inflammation, or the possible development of gastric carcinoma and should be followed with these risks in mind.
- Associated immune-mediated conditions (eg, insulin dependent diabetes mellitus, autoimmune thyroiditis) should also be treated. However, treatment of these disorders has no known effect in the treatment of achlorhydria.
- The normal indigenous intestinal microflora consists of about 1015 bacteria that mainly reside in the lower gut. Bacterial overgrowth implies abnormal bacterial colonization of greater than 100,000/mL in the upper gut.
- Small intestinal bacterial overgrowth can result in recurrent diarrhea with malabsorption, D-lactic acidosis, and an increased risk of endogenous infection.
- Other conditions associated with small bowel bacterial overgrowth include steatorrhea, macrocytic anemia, and, less commonly, protein-losing enteropathy.
- Microecological changes are accompanied by vitamin B-12 deficiency anemia, hypovitaminosis, protein deficiency, translocation of bacteria and their toxins from the intestine into the bloodstream, emergence of endotoxinemia, and possible generalization of infection. Bacterial overgrowth is diagnosed by concentration of hydrogen in expiratory flow (glucose-hydrogen breath test) or by bacteriological study of aspirate from the proximal part of the small intestine.
- Antimicrobial agents, including metronidazole, amoxicillin/clavulanate potassium, ciprofloxacin, and rifaximin, can be used to treat bacterial overgrowth.
- Achlorhydria resulting from long-term PPI use may be treated by dose reduction or withdrawal of the PPI.
Surgical Care
Hypergastrinemia due to achlorhydria secondary to PPI therapy or resection of the gastric fundus is known to cause ECL cell hyperplasia and gastric carcinoids. Surgery is the only potentially curative therapy for carcinoid tumors.5
Surgical antrectomy results in normalization of serum gastrin levels and disappearance of multicentric gastric carcinoids. In a study by Hirschowitz et al, antrectomy resulted in normalization of serum gastrin levels within 8 hours and disappearance of carcinoids in 6-16 weeks.6
Gladdy et al examined the efficacy of endoscopic surveillance versus surgical resection in the treatment of patients with type I GI carcinoid tumors.5 In the study, 46 patients underwent endoscopic surveillance with polypectomy, while 19 patients were treated with gastric resection. (The latter treatment was used in patients with larger-sized tumors, increased depth of invasion, and solitary tumors.) The 5-year recurrence-free survival rate was 75% in the surgical resection patients, but the disease-specific survival rate was 100% in both patient groups. Concomitant adenocarcinoma was found in 4 of the patients who underwent resection, with the detection made through preoperative biopsy in 2 of these individuals. (The carcinoid tumors were bigger and the carcinoid disease was more advanced in all patients with coexisting gastric adenocarcinoma.)
The authors recommended that resection be considered for patients with more advanced carcinoid disease, owing to the increased adenocarcinoma risk associated with the advanced disorder. They also concluded that endoscopic surveillance is appropriate for determining the status of carcinoid tumors and for the assessment of the dysplasia or adenocarcinoma that can arise in association with type I GI carcinoid tumors.
Medication
Achlorhydria may be associated with vitamin B-12 deficiency in the setting of pernicious anemia.
Achlorhydria is associated with thiamine deficiency in the setting of bacterial overgrowth. Bacterial overgrowth is commonly treated with the following antimicrobials: metronidazole, amoxicillin-clavulanate potassium, ciprofloxacin, or rifaximin.
H pylori infection can be treated with 3 drugs: PPI, clarithromycin, and amoxicillin. Levofloxacin can be used in place of amoxicillin for patients who are allergic to penicillin.
Vitamins
Vitamin B-12 (cobalamin) deficiency initially and typically manifests as macrocytic anemia, although neurologic symptoms may be present.
Cyanocobalamin (Crystamine, Cyomin, Crysti 1000)
Deoxyadenosylcobalamin and hydroxocobalamin are the active forms of vitamin B-12 in humans. Vitamin B-12 is synthesized by microbes but not by humans or plants. Vitamin B-12 deficiency may result from intrinsic factor deficiency (pernicious anemia), partial or total gastrectomy, or diseases of the distal ileum.
Adult
100-1000 mcg IM qd for 1-2 wk, followed by 100-1000 mcg IM qmo for life
Pediatric
10-50 mcg/d IM for 5-10 d, followed by 100-250 mcg/dose q2-4wk
None reported
Documented hypersensitivity; hereditary optic nerve atrophy
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Severe hypokalemia may result in possibly fatal vitamin B-12–megaloblastic anemia due to increased cellular potassium requirements when anemia resolves
Thiamine
Used for thiamine deficiency syndromes.
Adult
Severe complication of thiamine deficiency: 150 mg slow IV qd
100 mg IM qd for 3 d or 100 mg PO bid for 3 d, then 100 mg PO qd/bid for maintenance
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Sensitivity reactions can occur (intradermal test dose recommended in suspected sensitivity); deaths have resulted from IV use; sudden onset or worsening of Wernicke encephalopathy, following glucose, may occur in thiamine deficient patients; administer before or together with dextrose-containing fluids in suspected thiamine deficiency
Antibiotics
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
Metronidazole (Flagyl)
Component of drug combination therapy that effectively treats duodenal ulcer or gastric ulcer associated with H pylori infection. Active against various anaerobic bacteria and protozoa. Appears to be absorbed into cells. Intermediate-metabolized compounds formed bind DNA and inhibit protein synthesis, causing cell death.
Antibiotics and other agents are used as adjuvants to treat duodenal ulcer disease associated with H pylori.
Adult
250-500 mg PO qid for 7-14 d
Pediatric
Not established
May increase toxicity of anticoagulants, cyclosporine, lithium, phenytoin, tacrolimus, and carbamazepine; cimetidine may increase toxicity of metronidazole; disulfiram reaction may occur with orally ingested ethanol; coadministration increases amiodarone toxicity (QT prolongation); increases disulfiram toxicity (psychotic symptoms) with concurrent use; phenobarbital and rifampin may increase metabolism of metronidazole
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution with liver impairment, blood dyscrasias, CNS disease; reduce dosage with severe hepatic disease; monitor for seizures and development of peripheral neuropathy with a total dose typically of greater than 100 grams.
Clarithromycin (Biaxin)
Semisynthetic macrolide antibiotic that reversibly binds to P site of 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl t-RNA from ribosomes, causing bacterial growth inhibition.
If H pylori is identified as the underlying cause of gastritis, subsequent eradication now is almost generally accepted practice. Protocols for H pylori eradication require a combination of antimicrobial agents and antisecretory agents, such as PPIs, ranitidine bismuth citrate (RBC), or bismuth subsalicylate. Despite the combinatorial effect of drugs in regimens used to treat H pylori infection, cure rates remain, at best, 80-95%.
Adult
250-500 mg PO bid for 7-14 d
Pediatric
<20 months: Not recommended
>20 months: Not established
Toxicity increases with coadministration of fluconazole and pimozide; effects decrease and GI adverse effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, carbamazepine, ergot alkaloids, triazolam, HMG-CoA reductase inhibitors; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increases in QTc intervals occur with disopyramide; coadministration with omeprazole may increase plasma levels of both agents; decreases metabolism of repaglinide, thus increasing serum levels and effects
Documented hypersensitivity; coadministration of pimozide
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Coadministration with ranitidine or bismuth citrate is not recommended with CrCl <25 mL/min; give half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be sign of pseudomembranous colitis; superinfections may occur with prolonged or repeated antibiotic therapies
Levofloxacin (Levaquin)
S (-) enantiomer of ofloxacin. Inhibits DNA gyrase in susceptible organisms thereby inhibits relaxation of supercoiled DNA and promotes breakage of DNA strands.
Adult
250 mg PO bid for 7-14 d
Pediatric
Not established
Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; levofloxacin reduces therapeutic effects of phenytoin; probenecid may increase levofloxacin serum concentrations
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy
Ciprofloxacin (Cipro, Cipro XR)
Fluoroquinolone that inhibits bacterial DNA synthesis and, consequently, growth, by inhibiting DNA gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material. Quinolones have broad activity against gram-positive and gram-negative aerobic organisms. Has no activity against anaerobes. Continue treatment for at least 2 d (7-14 d typical) after signs and symptoms have disappeared.
Adult
250-500 mg PO bid for 7-14 d
Pediatric
<18 years: Not recommended
>18 years: Administer as in adults
None reported
Documented hypersensitivity; coadministration with steroid combinations after uncomplicated removal of a foreign body from cornea
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Dosage adjustments (adult adjustments)
CrCl (mL/min) <10: 50% of PO or IV dose q12h
HD: 0.25-0.5 g PO or 0.2-0.4 g IV q12h
During peritoneal dialysis: 0.25-0.5 g PO or 0.2-0.4 g IV q8h
In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy
Not drug of first choice in pediatrics due to increased incidence of adverse events compared to controls, including arthropathy; no data exist for dose for pediatric patients with renal impairment (ie, CrCl <50 mL/min)
Rifaximin (Xifaxan)
Nonabsorbed (<0.4%), broad-spectrum antibiotic specific for enteric pathogens of the GI tract (ie, gram-positive, gram-negative, aerobic, anaerobic). Rifampin structural analog. Binds to beta-subunit of bacterial DNA-dependent RNA polymerase, thereby inhibiting RNA synthesis. Indicated for E coli (enterotoxigenic and enteroaggregative strains) associated with travelers' diarrhea.
Adult
200-400 mg PO tid for 7 d
Pediatric
<12 years: Not established
>12 years: Administer as in adults
Induces CYP450 3A4 in vitro; limited data exist; no significant interactions shown in single dose studies with midazolam and oral contraceptives
Documented hypersensitivity to rifaximin or rifamycin antimicrobial agents (eg, rifampin)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Discontinue if diarrhea persists more than 24-48 h or worsens; seek immediate medical care if fever and/or bloody stools emerge (tablets not effective); not effective for travelers' diarrhea due to suspected pathogens other than E coli; postmarketing reports include allergic dermatitis, rash, angioneurotic edema, urticaria, and pruritus
Amoxicillin-clavulanate potassium (Augmentin)
Amoxicillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins. Addition of clavulanate inhibits beta-lactamase producing bacteria.
Good alternative antibiotic for patients allergic or intolerant to the macrolide class. Usually is well tolerated and provides good coverage to most infectious agents. Not effective against mycoplasmal and legionella species. The half-life of oral dosage form is 1-1.3 h. Has good tissue penetration but does not enter cerebrospinal fluid.
For children >3 months, base dosing protocol on amoxicillin content. Due to different amoxicillin/clavulanic acid ratios in 250-mg tab (250/125) vs 250-mg chewable tab (250/62.5), do not use 250-mg tab until child weighs >40 kg.
Adult
500-875 mg PO q12h or 250-500 mg PO q8h for 7-10 d
Pediatric
<3 mo: 125 mg/5mL PO susp; 30 mg/kg/d (based on amoxicillin component) divided bid for 7-10 d
>3 mo: If using 200 mg/5 mL or 400 mg/5 mL susp, 45 mg/kg/d PO divided q12h; if using 125 mg/5 mL or 250 mg/5 mL suspension, 40 mg/kg/d PO divided bid for 7-10 d
>40 kg: Administer as in adults
Coadministration with warfarin or heparin, increases risk of bleeding; may act synergistically against selected microorganisms when coadministered with aminoglycosides; coadministration with allopurinol may increase incidence of amoxicillin rash; may decrease efficacy of oral contraceptives when administered concomitantly
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Hepatic impairment may occur with prolonged treatment in the elderly; diarrhea may occur; adjust dose in renal impairment; cross allergy may occur with other beta-lactams and cephalosporins
Proton Pump Inhibitors
Inhibit gastric acid secretion by inhibition of the H+/K+/ATP-ase enzyme system in the gastric parietal cells. These agents are used in cases of severe esophagitis and in patients not responding to H2-antagonist therapy.
Esomeprazole magnesium (Nexium)
S-isomer of omeprazole. Inhibits gastric acid secretion by inhibiting H+/K+-ATPase enzyme system at secretory surface of gastric parietal cells.
Used in severe cases and in patients not responding to H2 antagonist therapy.
Used for up to 4 wk to treat and relieve symptoms of active duodenal ulcers; may be used up to 8 wk to treat all grades of erosive esophagitis.
Adult
40 mg PO qd or 20 mg bid for 7-14 d; combine with antibiotics
Pediatric
Not established
Amoxicillin or clarithromycin may increase plasma levels of esomeprazole when used concurrently; may reduce absorption of dapsone; may increase levels of diazepam and GI absorption of digoxin; may decrease absorption of iron, ketoconazole, and itraconazole
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Symptomatic relief with PPIs may mask symptoms of gastric malignancy
More on Achlorhydria |
| Overview: Achlorhydria |
| Differential Diagnoses & Workup: Achlorhydria |
 Treatment & Medication: Achlorhydria |
| Follow-up: Achlorhydria |
| References |
| Further Reading |
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References
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Further Reading
Clinical guidelines
pH testing. Laboratory medicine practice guidelines: evidence-based practice for point-of-care testing.
National Academy of Clinical Biochemistry - Professional Association. 2006. 6 pages. NGC:005646
American Gastroenterological Association medical position statement: evaluation of dyspepsia.
American Gastroenterological Association Institute - Medical Specialty Society. 1997 Nov 8 (revised 2005 Nov). 3 pages. NGC:004711
Clinical trial
Clinical Experiment of H. Pylori Transmission
Related eMedicine topics
Diarrhea
Pernicious Anemia
Somatostatinomas
VIPomas
WDHA Syndrome
Keywords
achlorhydria, adenocarcinoma, pernicious anemia, gastric carcinoma, carcinoid tumor, carcinoid tumors, adenocarcinomas, hypochlorhydria intragastric pH, parietal cell, hypergastrinemia, mucolipidosis type IV, proton pump inhibitors, basal acid secretion, stimulated acid secretion, gastric atrophy, gastric polyps, atrophic gastritis
