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[Micromedex][01] acetylcysteine 適應症整理

[Micromedex][02]Acetylcysteine適應症整理

[Micromedex][04]Acetylcysteine 適應症整理
[Micromedex][05]Acetylcysteine適應症整理

這次是第7～第12

7

Bezoar

BEZOARS are a concretion formed in the alimentary canal (Pollard, 1968). They are generally classified into four different groups (TRICHOBEZOARS, PHYTOBEZOARS, MEDICATION BEZOARS, and MISCELLANEOUS) depending on their composition [1]. Trichobezoars are composed of hair and stomach secretions. Phytobezoars are composed of fruit and vegetable fibers. Those phytobezoars resulting from the ingestion of persimmons are commonly referred to as diospyrobezoars. Trichophytobezoars are composed of a combination of the trichobezoar and the phytobezoar (Dolan, 1979). Medication bezoars results from conglomerations of medicines or medication vehicles [1] and the miscellaneous concretions consist of those bezoars that result from the ingestion of laquers, furniture polish, bismuth, calcium, and sodium carbonate (Dolan, 1979). Lactobezoars are a specific type described in low-birth weight neonates fed a highly concentrated casein-containing formula [2].

Gastric endoscopy is the diagnostic technique of choice. Radiologic detection (barium swallow) is successful in only 25% [2]. Pharmacotherapy, endoscopic extraction, fragmentation and/or surgical therapy is warranted in all patients where a bezoar is diagnosed. If left untreated, bezoars have been associated with gastric ulceration, upper gastrointestinal bleeding, intestinal perforation, intestinal obstruction, and weight loss (Rider, 1984; Klamer, 1983; Lee, 1977; Deal, 1973).

The most common pharmacologic agents utilized in the treatment of postgastrectomy bezoars are PAPAIN and CELLULASE. Products containing a mixture of enzyme activity eg, Gastroenterase(R) (pepsin 150 mg, pancreatic enzymes 100 mg, cellulase 25 mg, and dehydrocholic acid 50 mg per tablet; have been discontinued in the US (Pollard, 1968; Deal, 1973; Wortzel, 1977; Zarling, 1984). Acetylcysteine, and various gastric lavage solutions (0.9% saline; 0.1M hydrochloric acid; sodium bicarbonate; pineapple juice) have also been used [1].

Papain therapy usually consist of mixing a teaspoonful of unseasoned meat tenderizer (e.g., Adolph's Meat Tenderizer(R)) in approximately 8 ounces (250 mL) a clear liquid. This mixture is then administered before each meal or with meals and at bedtime for up to a week [1]; (Rider, 1984; Klamer, 1983). An alternative source of papain is Papase(R) tablets. These tablets can be chewed or pulverized and mixed with a clear liquid and then administered orally with each meal [1]; (Rider, 1984).

Cellulase therapy usually consists of pulverizing a cellulase-containing enzyme preparation or cellulase alone. The dose of cellulase has varied dramatically depending on the source of cellulase used. When cellulase-containing enzyme preparations were used, the dose is usually 2-6 tablets three times daily after meals for 2-3 days (Pollard, 1968; Wortzel, 1977) or up to 4 weeks [1]. When cellulase alone was used the dose has ranged from:

• 7.5 g in 1500 mL water given in several portions throughout the day for 2 days for a total 15 g dose (Bonilla et al, 1999).
• 3 to 5 g in 300-500 ml water. This mixture was then sipped slowly over a 20-30 minute period once daily or infused over 2 hours via a NG tube once daily for 2-5 days (Taylor et al, 1998; Smith, 1980).
• 4 g (4000 U = 1 g) dissolve in 300 mL sterile water administered orally for 5 days (Taylor et al, 1998).
• 0.5 g/dL mixed in 1 L, given over 24 hours for 5 days (Taylor et al, 1998).

As a general rule, both cellulase and papain agents are efficacious in the treatment of phytobezoars. In a review of bezoar therapy, papain was reported successful in between 67% to 77% of cases, acetylcysteine- based treatments in about 50%, and cellulase in 83% to 100% [2]. Table 1 summarizes the results of some of these studies and case reports.

* Resolution of the phytobezoar ** Diospyrobezoars

The lack of efficacy of these agents in the treatment of DIOSPYROBEZOARS is not surprising. The postgastrectomy bezoars, phytobezoars, consists of the fruit and vegetable fibers that the patient has been unable to digest secondary to their relative achlorhydric and hypomotility state. A diospyrobezoar results from the ingestion of persimmons. The shibuol, a tannin composed of phloroglucin and gallic acid, contained in the persimmon forms a glue-like coagulum in the acid medium of the stomach. This gummy sticky mass then entraps the seeds and pulp of the persimmon to form the diospyrobezoar. These bezoars are harder and less easily dissolved than the phytobezoars (Dugan, 1972; Dolan, 1979). Adverse reactions associated with papain and cellulase therapy have been infrequent. In fact, none of the patients treated with cellulase have reported adverse reactions secondary to the medication. Such is not the case with papain therapy. Papain has been reported to cause HYPERNATREMIA (Zarling, 1981), GASTRIC ULCER (Dugan, 1972), and ESOPHAGEAL PERFORATIONS (Holsinger, 1968; Anderson, 1959). However, enzymatic therapy is not without risk. Complete jejunal obstruction secondary to breakup of an estimated 8.5 cm diospyrobezoar after daily treatment with a cellulase-based oral enzymatic treatment is described. Endoscopy at day 14 showed the original mass to have softened and split into small, 4-cm pieces; 3 days later, the 66-year-old woman complained of sudden onset of severe abdominal pain with vomiting; obstruction was relieved by enterotomy [3].

CONCLUSION
The lack of controlled clinical trials comparing papain to cellulase therapy makes it difficult to draw a conclusion on which agent is best for the dissolution of phytobezoars. However, based on the results of the published case reports and studies, it would appear that the cellulase therapy is more efficacious and possibly safer than papain therapy in the treatment of phytobezoars. Total cumulative doses of cellulase have ranged from 2.5 to 15 grams given over a period of 2 to 5 days.
Reference
1. Taylor JR, Streetman DS, & Castle SS: Medication bezoars: a literature review and report of a case. Ann Pharmacother 1998; 32:940-946.

2. Andrus CH & Ponsky JL: Bezoars: classification, pathophysiology, and treatment. Am J Gastroenterol 1988; 83(5):476-478.

3. Nomura H, Kitamura T, Takahashi Y, et al: Small-bowel obstruction during enzymatic treatment of gastric bezoar. Endoscopy 1997; 29(5):424-426.

8

Blepharitis

1) Overview

FDA Approval: Adult, no; Pediatric, no

Efficacy: Adult, Evidence is inconclusive

Recommendation: Adult, Class IIb

Strength of Evidence: Adult, Category B

2) Summary:

Oral acetylcysteine improved tear quantity and quality in patients with posterior blepharitis (Yalcin et al, 2002).

3) Adult:

a) Oral acetylcysteine improved tear quantity and quality in patients with posterior blepharitis. A control group of 18 patients (36 eyes) with posterior blepharitis were treated with topical steroids (prednisolone acetate) 4 times daily for 4 weeks, antibiotic (tobramycin sulfate) 4 times daily for 4 weeks, warm compresses twice daily for 2 months, and artificial tears (polyvidone) 4 times daily for 3 months. The therapy group of 22 similar patients (43 eyes) received the same treatment plus oral N-acetylcysteine 100 milligrams 3 times daily for 8 weeks. In the acetylcysteine group, Schirmer values (a measure of tear quantity) increased in 23 eyes, decreased in 17 eyes, and were unchanged in 3 eyes. In the control group, values increased for 10 eyes, decreased in 23 eyes, and were unchanged in 2 eyes. Improvement in tear quality was significantly greater in the acetylcysteine group, as measured by the fluorescein break-up test (p less than 0.0001) and by the mucous fern test (p=0.0096). The authors believe that acetylcysteine improves tear quality by acting not only as a mucolytic agent but by affecting lipid metabolism (Yalcin et al, 2002).

9

Bronchopulmonary disease, acute, With abnormal, viscid, or inspissated mucous secretions

FDA Labeled Indication
1) Overview

FDA Approval: Adult, yes; Pediatric, yes

Efficacy: Adult, Effective; Pediatric, Effective

Recommendation: Adult, Class IIa; Pediatric, Class IIa

Strength of Evidence: Adult, Category B; Pediatric, Category B

2) Summary:

Acetylcysteine inhalation solution is indicated as adjuvant therapy for patients with abnormal, viscid, or inspissated mucous secretions in several conditions including acute bronchopulmonary disease (pneumonia, bronchitis, or tracheobronchitis) (Prod Info acetylcysteine inhalation solution, 2004).

10

Cancer

1) Overview

FDA Approval: Adult, no; Pediatric, no

Efficacy: Adult, Ineffective

Recommendation: Adult, Class III

Strength of Evidence: Adult, Category B

2) Summary:

Acetylcysteine did not improve survival or reduce time to recurrence in patients with head and neck cancer or lung cancer (van Zandwijk et al, 2000).

3) Adult:

a) Neither vitamin A nor N-acetylcysteine (NAC), singly or together, had a positive effect on outcome in patients with head and neck cancer or lung cancer. Patients (n=2573) (93.5% of whom had smoked at some time in their lives) were randomly assigned to receive retinyl palmitate (300,000 international units (IU) daily for 1 year followed by 150,000 IU for the second year), NAC alone (600 units daily for 2 years), the same doses of retinyl palmitate and NAC together, or no additional treatment. Follow-up continued for 6 years from randomization. At 5 years, 58% of the patients with lung cancer, 83% of patients with cancer of the larynx, and 77% of patients with oral cancer were alive. There were no differences in survival attributable to the treatment compounds. Likewise, there were no statistically significant differences by treatment in time to first event or to the occurrence of a second primary tumor (van Zandwijk et al, 2000).

11

Complication of surgical procedure - Respiratory complication

FDA Labeled Indication
1) Overview

FDA Approval: Adult, yes; Pediatric, yes

Efficacy: Adult, Effective; Pediatric, Effective

Recommendation: Adult, Class IIa; Pediatric, Class IIa

Strength of Evidence: Adult, Category B; Pediatric, Category B

2) Summary:

Acetylcysteine inhalation solution is indicated as adjuvant therapy for patients with abnormal, viscid, or inspissated mucous secretions in several conditions including pulmonary complications associated with surgery (Prod Info acetylcysteine inhalation solution, 2004).

12

Cystic fibrosis, Pulmonary complications; Adjunct

FDA Labeled Indication
1) Overview

FDA Approval: Adult, yes; Pediatric, yes

Efficacy: Adult, Evidence favors efficacy; Pediatric, Evidence favors efficacy

Recommendation: Adult, Class IIa; Pediatric, Class IIa

Strength of Evidence: Adult, Category B; Pediatric, Category B

2) Summary:

Acetylcysteine inhalation solution is indicated as adjuvant therapy for patients with abnormal, viscid, or inspissated mucous secretions in several conditions including pulmonary complications of cystic fibrosis (Prod Info acetylcysteine inhalation solution, 2004).
Reports about efficacy of acetylcysteine in cystic fibrosis are inconsistent (Steil & Niessen, 1980; Benjamin, 1971; Reas, 1964), others have found no effect (Mitchell & Elliott, 1982; Gotz et al, 1980).

3) Adult:

a) General

1) The use of acetylcysteine (NAC) in cystic fibrosis has been generally recommended; however, data are inconsistent. Although some authors have reported improvement in pulmonary function tests (Steil & Niessen, 1980; Benjamin, 1971; Reas, 1964), others have found no effect (Mitchell & Elliott, 1982; Gotz et al, 1980). In other studies, significant improvement is usually seen in patients (with or without chronic Pseudomonas aeruginosa infection) who have an initial forced vital capacity (FVC) below 75% or a peak expiratory flow rate (PEFR) of 70% or lower (Stafanger et al, 1988; Stafanger & Koch, 1989; Steil & Niessen, 1980). Most of the reports provide only subjective evaluations and there are few controlled studies (Denton et al, 1967; Stamm & Docter, 1965; Reas, 1964). In one study, acetylcysteine had a deleterious effect on pulmonary function tests and no beneficial effect on subjective response (Teklin & Holsclaw, 1976).

b) A systematic review of literature between 1966 and 1997 on the use of N-acetylcysteine (NAC) in cystic fibrosis revealed 3 controlled clinical studies with nebulized NAC and 6 with oral NAC. Comparing nebulized NAC with placebo, there was no difference in the proportion of patients showing greater than 20% improvement in lung function. With oral NAC, there was a tendency toward improvement of FEV1, but the effect was small (2.3%) and its clinical relevance is questionable. Follow-up in these studies was limited to 3 months; hence, a beneficial effect with longer use cannot be excluded. Patients reported that NAC treatment eased the elimination of sputum, but there is not good evidence that NAC improves lung function (Duijvestijn & Brand, 1999).
c) The effect of oral acetylcysteine was equivocal in patients with cystic fibrosis and chronic pulmonary Pseudomonas aeruginosa infection. Overall, 52 patients were enrolled in a double-blind, placebo-controlled, cross-over trial of two 3-month durations. Active treatment consisted of acetylcysteine 200 milligrams three times daily (patients weighing less than 30 kg) or 400 milligrams twice daily (greater than 30 kg). Effect was evaluated by a subjective clinical score, weight, sputum bacteriology, blood leucocyte count, sedimentation rate, titers of specific antimicrobial antibodies, lung function parameters and measurement of nasal ciliary function in vitro. Thirty-one patients completed the study. No significant differences in lung function or subjective clinical scores were seen between acetylcysteine and placebo. Patients with PEFR below 70% of predicted normal values showed a significant increase in PEFR, FVC, and forced expiratory volume in one second (FEV-1) during treatment. No effect of acetylcysteine on ciliary activity was observed (Stafanger & Koch, 1989).

4) Pediatric:

a) Acetylcysteine does not appear to improve fat malabsorption in cystic fibrosis. A double-blind, cross-over, placebo-controlled trial was conducted in 12 children with cystic fibrosis and a high fecal fat content despite enzyme therapy (Mitchell & Elliot, 1981). Patients received 200 milligrams of acetylcysteine or placebo 3 times a day, each for a 28-day period. Effectiveness of therapy was based on fecal fat excretion collected over the last 5 days of each treatment period. Mean fecal fat excretion was 19.5 grams/24 hours in the acetylcysteine group and 18.9 g/24 hours in the placebo group, which was not significantly different. The only conclusion which can be made is that the thickened mucus covering the villi is an insignificant factor in fat malabsorption associated with cystic fibrosis or that the dose of acetylcysteine used in this study was insufficient.