N-Acetyl-L-cysteine

163.19

163.19

1724426

210-498-3

WYQ7N0BPYC

DTXSID5020021

C200

Crystals from water|WHITE, CRYSTALLINE POWDER

R05CB01|R - Respiratory system|S - Sensory organs|V - Various

29309016

67.4

0.4

White Solid

1.3±0.1 g/cm3

109.5 °C

407.7°C at 760 mmHg

200.4±27.3 °C

1.519

soluble in water, ethanol, methanol, dimethyl sulfoxide, hot isopropyl alcohol, methyl acetate and ethyl acetate. Insoluble in chloroform and ether.H2O: 100 mg/mL with heating

2-8°C

1.1X10-5 mm Hg at 25 deg C /Estimated/

Oral-rat LD50:5050 mg/kg; Oral-Mouse LD50:7888 mg/kg

Decomposes smoke in humid air; burning releases toxic nitrogen oxide and sulfur oxide smoke

-35.1 ºC (c=2,H2O)

SLIGHT ACETIC ODOR

CHARACTERISTIC SOUR TASTE

2 TO 2.75 (1 IN 100 ML)

9.52(at 25 °C)

Henry's Law constant = 1.7X10-13 atm-cu m/mole at 25 °C /Estimated/

9.52 (at 25 °C)|pKa= 3.24 (carboxylic acid moiety)|pKa = 9.52 (SH group)

140.9 Ų [M+Na]+ [CCS Type: DT, Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]|140.9 Ų [M+Na]+

It is stable in ordinary light, nonhygroscopic (oxidizes in moist air), and stable at temperatures up to 120 °C|Hydroxyl radical reaction rate constant = 5.5X10-11 cu cm/molec-sec at 25 °C /Estimated/

NONH for all modes of transport

3

36/37/38

22-24/25

HA1660000

The warehouse is ventilated, low temperature and dry; stored separately from acids, alkalis, oxidants, food additives

Stable. Incompatible with strong oxidizing agents.

P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, P501

H315

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Acetylcysteine is a reducing agent and is incompatible with oxidizing agents. Solutions of acetylcysteine become discolored and liberate hydrogen sulfide upon contact with rubber, some metals, particularly iron and copper, and/or when subjected to autoclaving. ... Solutions containing amphotericin B, tetracyclines, erythromycin lactobionate, or ampicillin sodium. ... Acetylcysteine solutions are also physically imcompatible with iodized oil, trypsin, hydrogen peroxide.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl acetylcysteine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

A REVIEW WITH 55 REFERENCES ON THE BIOCHEMISTRY & PHARMACOLOGY OF ACETYLCYSTEINE.[MCKINNEY GR, SISSON GM; ACETYLCYSTEINE; PHARMACOL BIOCHEM PROP DRUG SUBST 2: 479 (1979)]|A REVIEW WITH 28 REFERENCES OF THE EFFECT OF N-ACETYLCYSTEINE ON THE ANTITUMOR ACTIVITY OF DOXORUBICIN & THE LATTER'S CARDIOTOXICITY.[OLSON RD ET AL; INFLUENCE OF N-ACETYLCYSTEINE ON THE ANTITUMOR ACTIVITY OF DOXORUBICIN; SEMIN ONCOL 10(1) 29 (1983)]|Haddad LM, Winchester JF; Clinical Management of Poisoning and Drug Over Dose 2nd ed (1990). Acetaminophen and the use of N-acetylcysteine in treatment of overdose (review). pp 893-908.

|Warning|H315 (60.71%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 55 companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

practically nontoxic

Single intravenous doses of acetylcysteine at 1000 mg/kg in mice, 2445 mg/kg in rats, 1500 mg/kg in guinea pigs, 1200 mg/kg in rabbits and 500 mg/kg in dogs were lethal. Symptoms of acute toxicity were ataxia, hypoactivity, labored respiration, cyanosis, loss of righting reflex and convulsions.

Acetylcysteine is a simple modified amino acid and appears to be hepatoprotective. In the many studies of acetylcysteine use with acetaminophen overdose as well as with other conditions such as contrast media nephropathy, pulmonary fibrosis, cystic fibrosis and ulcerative colitis, it has not been associated with serum enzyme elevations during therapy or with episodes of clinically apparent liver injury. Since approval of the oral and intravenous forms of acetylcysteine, there have been no published reports of hepatotoxicity and the product label does not mention liver injury as an adverse event. Indeed, acetylcysteine may be beneficial in treating liver diseases in general, although its current indications are limited to acetaminophen overdose or acetaminophen related acute liver injury.

Guinea pigs were treated with daily drug injections as follows: 1 group received 200 mg kanamycin/kg, sc, 1 group received n-acetylcysteine (300 mg/kg, ip) & the 3rd group received n-acetylcysteine followed by kanamycin 1 hr later. After 7-day recovery, thresholds for detection of the compound action potential were measured. N-acetylcysteine alone had no detectable effect on hearing thresholds. Kanamycin alone produced a moderate (10-20 db) hearing loss below 10 khz & a more severe loss above 10 khz. Animals receiving both n-acetylcysteine & kanamycin had severe hearing losses (40-60 db) at all frequencies between 3 & 30 khz. These data indicate that n-acetylcysteine exerts a strong synergistic effect on kanamycin in producing severe hearing loss & cochlear damage.|The major side effect of photodynamic therapy (PDT) using photofrin enhanced skin sensitivity for sunlight which persists for 3-8 weeks after injection. Formation of singlet oxygen and radicals is believed to be involved in the basic mechanism of inducing skin damage. Reducing this side effect would make PDT more widely acceptable particularly for palliative use. Hairless dorsal skin patches of mice injected with 10 mg/kg photofrin ip 24 hr before illumination were used to evaluate the effect of increasing light doses. The light was obtained from a halogen lamp and transmitted via a fiber optic to illuminate a field of 2.5 sq cm. After establishing a dose response relationship for single or fractionated light dose illumination of the skin, drugs known to scavenge radicals, quench singlet oxygen or interfere with histamine release were tested for their protective effect. N-Acetylcysteine, a radical scavenger admin ip (1,000 and 2,000 mg/kg) 1 hr before illumination produced a significant decr in skin damage at light doses > 50 J sq cm (protection factor of 1.3-1.8). When N-acetylcysteine was administered in a dose of 500 mg/kg no protection was observed. Fractionated illumination experiments in combination with multiple injections of N-acetylcysteine (1000 mg/kg) also failed to show any protection. The addition of ranitidine, a histamine blocking agent (25-100 mg/kg) given prior to illumination resulted in a limited protection at higher light doses. From this study /results suggest/ that N-acetylcysteine could be of value in amelioration of the photosensitivity in patients with PDT.|The influence of acetylcysteine on cisplatin nephrotoxicity was investigated in female Wistar rats. Admin of 0.6 mg cisplatin/100 mg bw was followed by oliguria and proteinuria, as well as a significant incr of blood urea nitrogen concn. The ip admin of 0.6 mg cisplatin/100 g body wt concomitantly with 100 mg acetylcysteine/100 g body wt sc completely abolished the nephrotoxic effects of cisplatin. However, following this, the platinum concn in the kidney was decr significantly by acetylcysteine treatment. This was caused by a enhanced urinary excretion of platinum. The same effect on cisplatin nephrotoxicity appeared when cisplatin and acetylcysteine were dissolved together in a soln prior to injection. It could be shown that in this soln a ligand exchange reaction of cisplatin by acetylcysteine started immediately, resulting in incr renal excretion and decr platinum concn in the kidney. ... /Results show/ that the protective effect of acetylcysteine on cisplatin nephrotoxicity is based on the formation of a complex unsuitable for tubular resorption. ...|... Studies have shown that the in utero admin of alcohol alters the activity of gamma-glutamyl transpeptidase, the major enzyme involved with the break down of glutathione. The implication is that the in utero admin of alcohol interferes with gamma-glutamyl cycle and ultimately alters glutathione levels. ... The in utero admin of alcohol results in a decr in brain and liver glutathione levels in the developing fetus. ... N-Acetylcysteine ... was given to pregnant mothers throughout gestation in a liquid diet concomitantly with a dose of alcohol which produces a decr in body and brain weights. ... N-Acetylcysteine antagonized the effects of alcohol in the developing fetus.

LD50 Dog oral 1 g/kg|LD50 Rat oral 3 g/kg|LD50 Mouse oral > 3 g/kg|LD50 Rat oral > 6 g/kg|LD50 Dog ip 700 mg/kg

Asthma is a risk factor for adverse reactions to N-acetylcysteine and special caution should be exercised in its use in brittle asthmatic patients.

83%

Acetylcysteine's production and use as a mucolytic, in the treatment of chronic bronchitis(1), cancer(1), paracetamol intoxication(1), acetaminophen overdose(2), corneal damage(2), and in veterinary application as an expectorant(2) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that acetylcysteine is expected to have very high mobility in soil(SRC). The pKa of the thiol group is 9.52(3) and the pKa of carboxylic acid moiety of acetylcysteine is 3.24(4), indicating that this compound will primarily exist as an anion in the environment and will not volatilize from moist soil surfaces. Acetylcysteine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-5 mm Hg(SRC), determined from a fragment constant method(5). Growth of 10 different bacteria strains were inhibited by acetylcysteine(6), suggesting that biodegradation is not an important environmental fate process in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 10(SRC), determined from a structure estimation method(2), indicates that acetylcysteine is not expected to adsorb to suspended solids and sediment(SRC). The pKa of the thiol group is 9.52(3) and the pKa of carboxylic acid moiety of acetylcysteine is 3.24(4), indicating that this compound will primarily exist as an anion in the environment and anions will not volatilize from water surfaces. According to a classification scheme(6), an estimated BCF of 3.2(SRC), from an estimated log Kow of -0.66(7) and a regression derived equation(8), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Growth of 10 different bacteria strains were inhibited by acetylcysteine(9), suggesting that biodegradation is not an important environmental fate process in water(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), acetylcysteine, which has an estimated vapor pressure of 1.1X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase acetylcysteine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 7 hours(SRC), calculated from its rate constant of 5.5X10-11 cu cm/molec-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase acetylcysteine may be removed from the air by wet and dry deposition(SRC). Acetycysteine does not absorb UV light at wavelengths >290 nm; therefore, acetylcysteine is not expected to be susceptible to photolysis(SRC).

The rate constant for the vapor-phase reaction of acetylcysteine with photochemically-produced hydroxyl radicals has been estimated as 5.5X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 7 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions(2). Acetycysteine does not absorb UV light at wavelengths >290 nm; therefore, acetylcysteine is not expected to be susceptible to photolysis(SRC).

An estimated BCF of 3.2 was calculated for acetylcysteine(SRC), using an estimated log Kow of -0.66(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc for acetylcysteine can be estimated to be 10(SRC). According to a classification scheme(2), this estimated Koc value suggests that acetylcysteine is expected to have very high mobility in soil. The pKa of acetylcysteine is 3.24(3), indicating that this compound will primarily exist as an anion in the environment anions generally do not adsorb more strongly to organic carbon and clay than their neutral counterparts(4).

The pKa of the carboxylic acid moiety of acetylcysteine is 3.24(1), indicating that this compound will primarily exist as an anion in the environment and will not volatilize from moist soil or water surfaces. Acetylcysteine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-5 mm Hg(SRC), determined from a fragment constant method(2).

Occupational exposure to acetylcysteine may occur through inhalation and dermal contact with this compound at workplaces where acetylcysteine is produced or used. Exposure to the drug among the general population may be limited to those administered the acetylcysteine (a mucolytic). (SRC)

Acetylcysteine is used mainly as a mucolytic and in the management of paracetamol (acetaminophen) overdose.|FDA Label|Treatment of upper respiratory tract infections

Acetylcysteine, also known as N-acetylcysteine (NAC), is a modified amino acid that is used as an antidote for acetaminophen overdose to prevent hepatic injury. Acetylcysteine is a hepatoprotective agent and has not been linked to significant serum enzyme elevations during therapy or to instances of clinically apparent acute liver injury.

Antidotes, Toxicological Emergency

Antiviral Agents; Expectorants; Free Radical Scavengers|... 113 patients entered into the study were reported to be pregnant at the time of /acetaminophen/ overdose. Follow up including appropriate laboratory and pregnancy data outcome data, was available in 60 cases. Of these, 19 overdosed during the first trimester, 22 during the second trimester and 19 during the third trimester of pregnancy. Of the 24 patients with acetaminophen levels above the acetaminophen overdose nomogram line, 10 were treated with N-acetylcysteine within 10 hr postingestion; eight delivered normal infants, two had elective abortions. Of ten patients treated with N-acetylcysteine 10-16 hr postingestion, five delivered viable infants, two had elective abortions, and three had spontaneous abortions. Of four women treated with N-acetylcysteine 16-24 hr postingestion, one mother died, and there was one spontaneous abortion, one stillbirth, one elective abortion, and one delivery. ...|Acetylcysteine is indicated in the treatment of acetaminophen overdose to protect against hepatotoxicity . /Included in US product labeling/|Acetylcysteine is used in current medical practice in conjunction with chest physiotherapy as mucolytic in patients who have viscid or thickened airway mucus. When administered via direct instillation, it is used to loosen impacted mucus plugs during bronchoscopy. Acetylcysteine can irritate the airways and induce bronchospasm when given by inhalation; therefore, it should be administered simultaneously with or following administration of an inhaled beta-adrenergic bronchodilator. /NOT included in US product labeling/|To evaluate the effectiveness and safety of N-acetylcysteine (NAC) in treating chronic hepatitis B patients, 144 patients with chronic hepatitis B (total bilirubin, TBil>170 mmol/L) from several centers were chosen for a randomized and double blind clinical trial. The patients were divided into a NAC group and a placebo group and all of them were treated with an injection containing the same standardized therapeutic drugs. A daily dose of 8 microgram NAC was added to the injection of the NAC group. The trial lasted 45 days. Hepatic function and other biochemistry parameters were checked at the experimental day 0 and days 15, 30, 45. Each group consisted of 72 patients of similar demology and disease characteristics. During the trial, 28 cases of the 144 patients dropped out. In the NAC group, at day 0 and day 30, the TBil were401.7 vs. 149.2 and 160.1+/-160.6. In the placebo group, the TBil on the corresponding days were 384.1+/-134.0 and 216.3+/-199.9. Its decrease in the NAC group was 62% and 42% in the placebo group. At day 0 and day 45 of treatment, the effective PTa increase rate was 72% in the NAC group and 54% in the placebo group. The total effective rate (TBil + PTa) was 90% in the NAC group and 69% in the placebo group. The parameters of the two groups showed a remarkable difference. The rate of side effects was 14% in the NAC and 5% in the placebo groups. NAC can decrease the level of serum TBil, increase the PTa and reduce the time of hospitalization. NAC showed no serious adverse effects during the period of our treatment. We find that NCA is effective and secure in treating chronic hepatitis B patients.

... /Acetylcysteine/ should be used during pregnancy only when clearly needed. ... Since it is not known if acetylcysteine is distributed into human milk, the drug should be used with caution in nursing women.|Anaphylactoid reactions (i.e., acute hypersensitivity reactions such as rash, hypotension, wheezing, and/or dyspnea) have been reported in patients receiving IV acetylcysteine for the treatment of acetaminophen overdosage; in some cases, the anaphylactoid reactions were serious, including death in a patient with asthma. Rash, urticaria, and pruritus are the most frequently reported adverse reactions in patients receiving IV acetylcysteine. Acute flushing and erythema also have occurred; these reactions generally occur 30-60 minutes after initiating the infusion and resolve despite infusion of the drug. Reactions to acetylcysteine that involve manifestations other than flushing and erythema should be considered anaphylactoid reactions and treated as such.|Chest tightness and bronchoconstriction have been reported with acetylcysteine. Clinically overt acetylcysteine-induced bronchospasm occurs rarely and unpredictably, even in patients with asthmatic bronchitis or bronchitis complicating bronchial asthma. Occasionally, patients receiving oral inhalation of acetylcysteine develop increased airway obstruction of varying and unpredictable severity. Patients who have had such reactions to previous therapy with acetylcysteine may not react during subsequent therapy with the drug, and patients who have had inhalation treatments with acetylcysteine without incident may react to subsequent therapy.|Nausea, vomiting, and other GI symptoms may occur following oral administration of acetylcysteine in the treatment of acetaminophen overdosage. The drug may also aggravate vomiting associated with acetaminophen overdosage. Administration of dilute acetylcysteine solutions may minimize the tendency of the drug to aggravate vomiting.|For more Drug Warnings (Complete) data for N-ACETYLCYSTEINE (15 total), please visit the HSDB record page.

2. 2= Slightly toxic. Probable oral lethal dose (human) 5-15 g/kg; for 70 kg person (150 lb) between 1 pint and 1 quart.

Acetylcysteine has been shown to reduce the extent of liver injury following acetaminophen overdose. It is most effective when given early, with benefit seen principally in patients treated within 8-10 hours of the overdose. Acetylcysteine likely protects the liver by maintaining or restoring the glutathione levels, or by acting as an alternate substrate for conjugation with, and thus detoxification of, the reactive metabolite.

Substances that eliminate free radicals. Among other effects, they protect PANCREATIC ISLETS against damage by CYTOKINES and prevent myocardial and pulmonary REPERFUSION INJURY. (See all compounds classified as Free Radical Scavengers.)|Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. (See all compounds classified as Antiviral Agents.)|Agents that increase mucous excretion. Mucolytic agents, that is drugs that liquefy mucous secretions, are also included here. (See all compounds classified as Expectorants.)

Bioavailability is 6–10% following oral administration and less than 3% following topical administration.|Following oral administration (e.g., when used as an antidote for acetaminophen overdosage), acetylcysteine is absorbed from the GI tract.|Oral acetylcysteine is rapidly absorbed, but the bioavailability is low (10-30%) due to significant first-pass metabolism. Intact acetylcysteine has a relatively small volume of distribution (0.5 L/kg). Serum concentrations after intravenous administration of an initial loading dose of 150 mg/kg over 15 minutes are about 500 mg/L. A steady state plasma concentration of 35 mg/L (10-90 mg/L) was reached in about 12 hours following the loading dose with a continuous infusion of 50 mg/kg over 4 hours and 100 mg/kg over the next 16 hours.

Hepatic. Deacetylated by the liver to cysteine and subsequently metabolized.|Following oral inhalation or intratracheal instillation, most of the administered drug appears to participate in the sulfhydryl-disulfide reaction; the remainder is absorbed from the pulmonary epithelium, deacetylated by the liver to cysteine, and subsequently metabolized.|Acetylcysteine undergoes rapid deacetylation in vivo to yield cysteine or oxidation to yield diacetylcystine.

5.6 hours (adults), 11 hours (neonates)|Following IV administration of acetylcysteine, mean elimination half lives of 5.6 and 11 hours have been reported in adults and in neonates, respectively. The mean elimination half life was increased by 80% in patients with severe liver damage (i.e., alcoholic cirrhosis (Child-Pugh score of 7-13) or primary and/or secondary biliary cirrhosis (Child-Pugh score of 5-11)).

Acetylcysteine protects against acetaminophen overdose-induced hepatotoxicity by maintaining or restoring hepatic concentrations of glutathione. It does this by producing the glutathione precursor L-cysteine. Glutathione is required to inactivate an intermediate metabolite (N-acetyl-p-benzoquinoneimine or NAPQI) of acetaminophen that is thought to be hepatotoxic. In acetaminophen overdose cases, excessive quantities of this metabolite are formed because the primary metabolic (glucuronide and sulfate conjugation) pathways become saturated. Acetylcysteine may act by reducing the metabolite to the parent compound and/or by providing sulfhydryl for conjugation of the metabolite. Experimental evidence also suggests that a sulfhydryl-containing compound such as acetylcysteine may also directly inactivate the metabolite. The mechanisms of action for acetylcysteine’s well-known mucolytic effects are different. In particular, when inhaled, acetylcysteine (and its metabolic byproduct cysteine) exerts its mucolytic action through its free sulfhydryl group, which reduces the disulfide bonds in the mucus matrix and lowers mucus viscosity. This action increases with increasing pH and is most significant at pH 7 to 9. The mucolytic action of acetylcysteine is not affected by the presence of DNA. Acetylcysteine is also an antioxidant and reduces oxidative stress. Acetylcysteine serves as a prodrug to L-cysteine which is a precursor to the biologic antioxidant, glutathione and hence administration of acetylcysteine replenishes glutathione stores. L-cysteine also serves as a precursor to cystine which in turn serves as a substrate for the cystine-glutamate antiporter on astrocytes hence increasing glutamate release into the extracellular space. This glutamate in turn acts on mGluR2/3 receptors, and at higher doses of acetylcysteine, mGluR5. Glutathione also modulates the NMDA receptor by acting at the redox site. These effects on glutamate and NMDA signaling appear to explain some of the positive neuropsychotropic effects associated with NAC. Acetylcysteine also possesses some anti-inflammatory effects possibly via inhibiting NF-κB through redox activation of the nuclear factor kappa kinases thereby modulating cytokine synthesis.|Acetylcysteine exerts its mucolytic action through its free sulfhydryl group, which opens the disulfide bonds and lower the viscosity of the mucus. This action increases with increasing pH and is most significant at pH 7 to 9. The mucolytic action of acetylcysteine is not affected by the presence of DNA.|Acetylcysteine may protect against acetaminophen overdose-induced hepatotoxicity by maintaining or restoring hepatic concentrations of glutathione. Glutathione is required to inactivate an intermediate metabolite of acetaminophen that is thought to be hepatotoxic. In acetaminophen overdose, excessive quantities of this metabolite are formed because the primary metabolic (glucuronide and sulfate conjugation) pathways become saturated. Acetylcysteine may act by reducing the metabolite to the parent compound and/or by providing sulfhydryl for conjugation of the metabolite. Experimental evidence also suggests that a sulfhydryl-containing compound such as acetylcysteine may directly inactivate the metabolite.

Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

/SIGNS AND SYMPTOMS/ The features of n-acetyl-l-cysteine overdose are similar to the anaphylactoid reactions but more severe. Cardiovascular collapse and death were temporally assocated with the administration of intravenous n-acetyl-l-cysteine in a 4 year old with subtoxic plasma acetaminophen levels. Several fatalities occurred following intravenous n-acetyl-l-cysteine administration, but the contribution of fulminant hepatic failure to mortality limits conclusions about n-acetyl-l-cysteine effects.|/CASE REPORTS/ A case of serum sickness like illness assoc with acetylcysteine therapy in a 29 yr old man who was admitted with an acetaminophen overdose is reported. Acetylcysteine was started at 5 g orally every 6 hr. Three days after admission, the patient developed fever, diffuse abdominal tenderness, and bilateral, symmetric swelling of the knee and elbow joints. Had a discrete erythematous maculopapular eruption on the chest, abdomen, back and extremities with a few erythematous macules on the palms and face. The platelet count was 233 x 109/l. Twelve hr after antibiotic admin for suspected intraabdominal abscess, his temperature was 40 °C and he had tender, palpable cervical, axillary and inguinal lymph nodes. a hypersensitivity reaction to acetylcysteine was suspected and the drug was discontinued. ...|/CASE REPORTS/ A healthy 30-month-old girl allegedly ingested acetaminophen at 418 mg/kg. Because the emergency physician feared the time of ingestion might not be accurate, he decided to start the 20.5-hour intravenous N-acetylcysteine protocol 8 hours after ingestion. He mistakenly prescribed the maximum milliliter-per-kilogram volume of the dextrose 5% diluent for the milliliter-per-kilogram volume of N-acetylcysteine 20% to be administered. Five hours after the error was detected (19.5 hours postingestion), the patient started developing myoclonus on the left side of her body, with left eye deviation. This condition persisted intermittently for 3 hours despite treatment with diazepam, lorazepam, and phenytoin. A first computed tomographic scan result was normal. A few hours later, she sustained shorter recurrences of the myoclonus. At 30 hours after ingestion, she started to have irregular breathing and became unresponsive to pain. A repeated computed tomographic scan showed diffuse cerebral edema. A postmortem examination showed the presence of acute anoxic encephalopathy with marked cerebral edema and the beginning of uncal herniation that confirmed the clinical diagnosis of intracranial hypertension and brain death. A cumulative intravenous dose of 2,450 mg/kg of N -acetylcysteine was associated with status epilepticus, intracranial hypertension, and death in a child.|/CASE REPORTS/ Paracetamol overdose is a common reason for presentation to the emergency department and N-acetylcysteine is frequently used in the treatment of toxic paracetamol ingestions. Adverse reactions to N-acetylcysteine are common though usually mild and easily treated. Serious reactions to N-acetylcysteine however, are rare and there have been no previous reported fatalities with its therapeutic use. This report describes the case of a 40 year old brittle asthmatic patient who died after treatment with intravenous N-acetylcysteine. Asthma is a risk factor for adverse reactions to N-acetylcysteine and special caution should be exercised in its use in brittle asthmatic patients.|/CASE REPORTS/ Marked elevations in liver function test results (eg, AST (SGOT) and ALT (SGPT), occurred on 2 occasions following administration of high doses (total doses: 106 and 250 g over 3-4 days) of acetylcysteine rectally and via nasogastric tube in a 3 year old by with cystic fibrosis; these abnormalities were noted within a few days of initiation of acetylcysteine therapy and resolved gradually following discontinuance of the drug.

Acétylcystéine GNR

ESSENTIALLY 100% AS A MUCOLYTIC AGENT

Parenteral: For injection concentrate, for IV infusion: 200 mg/mL Acetadote (Cumberland).|Oral inhalation, intratracheal instillation, and oral: Solution: 100 mg (of acetylcysteine) per mL (10%), Acetylcysteine Sodium Solution, (Abbott, American Regent, Bedford, Dey, Mayne, Roxane); Mucomyst (Sandoz); 200 mg (of acetylcysteine) per mL (20%) Acetylcysteine Sodium Solution (Abbott, American Regent, Bedford, Dey, Mayne, Roxane); Mucomyst (Sandoz). /Acetylcysteine sodium/

L-Cysteine, N-acetyl-: ACTIVE|Information available in 2005 indicated that Acetylcysteine was used in the manufacture of pharmaceutical preparations in the following countries: Algeria, Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Colombia, Croatia, Czech Republic, Denmark, Ecuador, Finland, France, Germany, Greece, Hong Kong, Hungary, India, Indonesia, Ireland, Israel, Italy, Japan, Luxembourg, Malaysia, Monaco, Netherlands, New Zealand, Norway, Poland, Portugal, Romania, Russian Federation, Singapore, Slovenia, South Africa, Spain, Sweden, Switzerland, Thailand, Turkey, United Kingdom, United States, Yugoslavia (1,2)|Information available in 2005 indicated that Acetylcysteine sodium was used in the manufacture of pharmaceutical preparations in the following countries: Australia, Germany, Netherlands, Norway, Poland, Romania, Russian Federation, Switzerland, United States (1,2) /Acetylcysteine Sodium/

THREE N-SUBSTITUTED MALEIMIDES, INCLUDING ACETYLCYSTEINE, WERE TESTED AS DERIVATIZING REAGENTS. N-ACETYLCYSTEINE WAS READILY CONVERTED INTO THE ADDUCT WITH N-(4-ANILINOPHENYL)MALEIMIDE. PICROGRAM LEVELS WERE SEPARATED & QUANTIFIED.|The following methods have been developed for the analysis of free amino acids in blood, food, and feedstocks: (1) Protein hydrolysis, (2) Chromatographic methods that include high performance liquid chromatography (HPLC), gas chromatography (GC) and thin-layer chromatography (TLC), (3) Colorimetric and Fluorimetric Analysis, (4) Spectrometric Analysis, and (5) Enzymatic Determination and Microbial Assay /amino acids/|Analyte: acetylcysteine; matrix: chemical identification; procedure: infrared absorption spectrophotometry with comparison to standards|Analyte: acetylcysteine; matrix: chemical purity; procedure: liquid chromatography with detection at 214 nm and comparison to standards|For more Analytic Laboratory Methods (Complete) data for N-ACETYLCYSTEINE (6 total), please visit the HSDB record page.

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