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Antidotes, SystemicMucolyticsSupplemental Dietary Agents
N-acetyl derivative of L-cysteine, abbreviated as NAC; possesses a strong odor, often described as rotten eggsUsed orally or parenterally as an antidote for acetaminophen overdose to prevent hepatotoxicityUsed via inhalation as a mucolytic agent to treat and reduce COPD exacerbations
Acetadote, Mucomyst, Mucosil Acetylcysteine
Acetadote/Acetylcysteine Intravenous Inj Sol: 1mL, 200mgAcetylcysteine/Mucomyst/Mucosil Acetylcysteine Oral Sol: 10%Acetylcysteine/Mucomyst/Mucosil Acetylcysteine Respiratory (Inhalation) Sol: 10%, 20%
NOTE: Consider infusions beyond 21 hours when the absorption and/or half-life of acetaminophen (APAP) may be prolonged (e.g., suspected massive overdose, concurrent ingestion of other substances, persons with preexisting liver disease). In these cases, measure ALT/AST, INR, and APAP concentrations before the end of the 21-hour infusion. If the APAP concentration is still detectable, ALT/AST are still increasing, or the INR remains elevated, continue the infusion. If the infusion is extended beyond 21 hours, contact either the regional poison center (1-800-222-1222) or a special health professional assistance line for APAP overdose (1-800-525-6115) for assistance with dosing recommendations.
150 mg/kg (Max: 15 g) over 1 hour, followed by 50 mg/kg (Max: 5 g) IV over 4 hours, followed by 100 mg/kg (Max: 10 g) IV over 16 hours. Increase the third dose to 200 mg/kg for massive ingestion (e.g., acetaminophen concentration more than 300 mg/L at 4-hour nomogram line).
200 mg/kg IV over 4 hours, followed by 100 mg/kg IV over 16 hours. Increase the second dose to 200 mg/kg for massive overdose (e.g., acetaminophen concentration more than 300 mg/L at 4-hour nomogram line).
100 mg/kg IV over 2 hours, followed by 200 mg/kg IV over 10 hours. Repeat the second dose for massive overdose (e.g., acetaminophen concentration more than 300 mg/L at 4-hour nomogram line).
150 mg/kg IV over 1 hour, then 12.5 mg/kg/hour continuous IV infusion for 20 hours.
140 mg/kg/dose (Max: 15.4 g/dose) PO loading dose, followed by 70 mg/kg/dose (Max: 7.7 g/dose) PO every 4 hours for 17 doses starting 4 hours after the loading dose. Repeat any dose vomited within 1 hour of administration.
3 to 5 mL of 20% solution or 6 to 10 mL of 10% solution inhaled via nebulization 3 to 4 times daily is the usual dosage for most patients. Dosage range: 1 to 10 mL of 20% solution or 2 to 20 mL of 10% solution via nebulization every 2 to 6 hours. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, in COPD patients not receiving inhaled corticosteroids, regular treatment with mucolytics such as acetylcysteine may reduce COPD exacerbations and modestly improve health status.
1 to 2 mL of 10% or 20% solution, administered by direct instillation into the trachea as often as every hour. Tracheostomy patients, instill direct into the tracheostomy.According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, in COPD patients not receiving inhaled corticosteroids, regular treatment with mucolytics such as acetylcysteine may reduce COPD exacerbations and modestly improve health status.
Safety and efficacy have not been established; off-label use reported for COPD. Dosages used include 200 mg PO 2 to 3 times daily; 300 mg PO twice daily; or 600 mg PO once daily, twice daily or three times per week. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, in COPD patients not receiving inhaled corticosteroids, regular treatment with mucolytics such as acetylcysteine may reduce COPD exacerbations and modestly improve health status.
1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution administered 2 to 3 times prior to the procedure via nebulization or by intratracheal instillation.
3 to 5 mL of 20% solution or 6 to 10 mL of 10% solution, administered via nebulization 3 to 4 times daily is the recommended dosage for most patients; however, the dosage range is 1 to 10 mL of 20% solution or 2 to 20 mL of 10% solution administered every 2 to 6 hours. Dosages at the lower end of the range (e.g., 1 to 2 mL of 20% or 2 to 4 mL of 10%) may be most appropriate for infants. Administration of a bronchodilator 10 to 15 minutes prior to dose may reduce the incidence of bronchospasm.
Specific dosage is dependent on the available equipment and patient need. Use a sufficient volume of 10% or 20% solution to provide a heavy mist for the desired period of time. Very large volumes (e.g., up to 300 mL) may be required. Intermittent or continuous administration for prolonged periods (e.g., overnight) may be desirable.
1 to 2 mL of 10% or 20% solution administered by direct instillation into the trachea as often as every hour is the general dosing for direct instillation.
1 to 2 mL of 10% or 20% solution directly into the tracheostomy every 1 to 4 hours for routine tracheostomy care. For instillation through percutaneous intratracheal catheter, 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours may be given by a syringe attached to the catheter.
2 to 5 mL of 20% solution administered via a syringe connected to a small catheter that has been placed directly into the desired segment of the bronchopulmonary tree (under local anesthesia and direct vision).
Off-label use described. 600 mg PO twice daily, given the day prior to and the day of administration of the contrast agent (i.e., for 2 days total) has been successful in reducing the risk for radiocontrast-induced nephropathy. Saline hydration is used concurrently in the 12 hours before and after contrast administration.
Off-label use described. 150 mg/kg in 500 mL 0.9% Sodium Chloride IV over 30 minutes immediately before contrast; then, 50 mg/kg in 500 mL 0.9% Sodium Chloride IV over the next 4 hours has been studied in patients with stable renal dysfunction (CrCl less than 50 mL/minute or serum creatinine (SCr) more than 1.36 mg/dL) undergoing cardiac catheterization in addition to usual IV hydration. In this rapid protocol comparing IV acetylcysteine (n = 41) to IV hydration alone (n = 39), 5% of patients in the IV acetylcysteine group compared to 21% of patients in the hydration group developed radiocontrast-induced nephropathy (increase in SCr of 25% at 2 or 4 days after contrast administration; p = 0.045; RR, 0.28; 95% CI, 0.08 to 0.98).
Off label use described. In 354 patients with acute myocardial infarction undergoing angioplasty, a dose of 1,200 mg IV bolus before angioplasty followed by 1,200 mg PO twice daily for the 48 hours following angioplasty significantly reduced the incidence of contrast-induced nephropathy (defined as a 25% increase in creatinine over baseline within 72 hours after angioplasty) compared to a lower dose of acetylcysteine (600 mg IV bolus prior to angioplasty followed by 600 mg PO twice daily for 48 hours after angioplasty) or placebo. The incidence of acute renal failure was 8% in the high-dose acetylcysteine group, 15% in the low-dose acetylcysteine group, and 33% in patients receiving placebo (p less than 0.001). Furthermore, the incidence of death, acute renal failure requiring temporary renal replacement therapy, and the need for mechanical ventilation was also reduced vs. placebo. Patients also received 0.9% Sodium Chloride hydration at a rate of 1 mL/kg/hour for 12 hours after angioplasty; if the patients had overt heart failure, a lower rate of 0.5 mL/kg/hour for 12 hours was used.
A 1—2% solution can be prepared by mixing in artificial tears. Administer topically to the affected eye 4—6 times per day.
Limited data are available; the ideal dosage has not been established. For the acute treatment of moderate DIOS episodes, some experts recommend a "Mucomyst cocktail", which consists of a phosphosoda enema followed by a clear liquid diet for 24 hours. During that 24-hour period, give 3 doses of 10% acetylcysteine 60 mL PO mixed with cold soda or orange juice. For recurrent DIOS, 10 mL of the 20% solution PO 4 times per day in combination with acetylcysteine enemas has also been used; most patients experienced some relief within 24 hours. For recurrent DIOS refractory to other therapies, 5 to 30 mL of the 10% solution PO 1 to 3 times daily may be used.
Limited data are available; the ideal dosage has not been established. For the acute treatment of moderate DIOS episodes, some experts recommend a "Mucomyst cocktail", which consists of a phosphosoda enema followed by a clear liquid diet for 24 hours. During that 24-hour period, give 3 doses of 10% acetylcysteine 30 mL PO mixed with 30 mL of cold soda or orange juice. For recurrent DIOS, 10 mL of the 20% solution PO 4 times per day in combination with acetylcysteine enemas has also been used; most patients experienced some relief within 24 hours. For recurrent DIOS refractory to other therapies, 5 to 30 mL of the 10% solution PO 1 to 3 times daily may be used.
Limited data are available; some experts consider rectal enemas of acetylcysteine to be ineffective. One study used 50 mL of the 20% solution mixed with 50 mL of water as an enema administered 1 to 4 times per day in combination with oral therapy.
†Indicates off-label use
NOTE: Maximum dosage may vary based upon indication and route of administration. Specific maximum dosage information is not available; however, commonly used maximum doses for IV acetylcysteine are 150 mg/kg (Max: 15,000 mg) for the loading dose, 50 mg/kg (Max: 5000 mg) for the second dose, and 100 mg/kg (Max: 10,000 mg) for the third dose. Specific maximum dosage information is not available for oral or inhalational dosing.
Maximum dosage is not well defined.
Specific guidelines for dosage adjustments in hepatic impairment are not available; it is not known if dosage adjustments are needed. Although there was a 3-fold increase in acetylcysteine plasma concentrations in patients with hepatic cirrhosis, the published medical literature does not indicate that the dose of acetylcysteine in patients with hepatic impairment should be reduced.
Specific guidelines for dosage adjustments in renal impairment are not available. Some experts have recommended the following adjustment for adult patients receiving systemic therapy of 140 mg/kg load then 70 mg/kg every 4 hours x 17 doses :CrCl 10 ml/minute or greater or CRRT: no dosage adjustmentCrCl less than 10 ml/minute or peritoneal dialysis: 75% of recommended dose
For storage information, see specific product information within the How Supplied section.
Oral solution (Mucomyst):Oral acetylcysteine has very poor taste and a strong sulfur-like odor. Diluting the solution with a very cold beverage (e.g., soda, orange juice), serving in a cup with a lid, and drinking the solution through a straw may help to increase palatability and lower the risk of vomiting.Dilution of 10% solution: 1 mL of diluent for every 1 mL of solution.Dilution of 20% solution: 3 mL of diluent for every 1 mL of solution.If the patient cannot drink, the solution may be administered via a nasogastric tube.Use diluted solutions within 1 hour of preparation.If the patient vomits within 1 hour of administration, repeat dose.Storage: Remaining undiluted solutions in opened vials can be stored in the refrigerator up to 96 hours.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.The color of the IV formulation may turn from colorless to a slight pink or purple color after the stopper is punctured; however, the quality of the product is not affected.
DilutionThe IV formulation is hyperosmolar (2,600 mOsm/L) and must be diluted prior to administration.Compatible diluents include: 5% Dextrose Injection, 0.45% Sodium Chloride Injection, and Sterile Water for Injection. If Sterile Water for Injection is used, carefully consider the osmolarity of the resultant solution; some concentrations would be too hypo-osmolar for safe administration (see osmolarity content below).For the 3-bag regimen, the standard volume of diluent to be used is dependent on patient weight as follows:Patients weighing 41 kg or more:Loading dose: dilute in 200 mL diluentSecond dose: dilute in 500 mL diluentThird dose: dilute in 1,000 mL diluentPatients weighing 21 to 40 kg:Loading dose: dilute in 100 mL diluentSecond dose: dilute in 250 mL diluentThird dose: dilute in 500 mL diluentPatients weighing 5 to 20 kg:Loading dose: dilute in 3 mL/kg diluentSecond dose: dilute in 7 mL/kg diluentThird dose: dilute in 14 mL/kg diluentFor the 1-bag regimen, dilute 30 g of acetylcysteine in 1 L of 5% Dextrose Injection.For patients requiring fluid restriction, reduce the dilution volume as clinically appropriate; however, carefully consider the osmolarity of the resultant solution and avoid infusion of a hyper- or hypo-osmolar solution.Acetylcysteine diluted to a concentration of 7 mg/mLOsmolarity in 0.45% Sodium Chloride Injection: 245 mOsmol/LOsmolarity in 5% Dextrose Injection: 343 mOsmol/LOsmolarity in Sterile Water for Injection: 91 mOsmol/L (below recommended osmolarity for administration)Acetylcysteine diluted to a concentration of 24 mg/mLOsmolarity in 0.45% Sodium Chloride Injection: 466 mOsmol/LOsmolarity in 5% Dextrose Injection: 564 mOsmol/LOsmolarity in Sterile Water for Injection: 312 mOsmol/LThe manufacturer provides a Dosage Guide and Preparation Chart in relation to body weight in the product label.Storage: The commercially available vials are intended for single-dose use and are preservative-free. Diluted solutions are stable for 24 hours at controlled room temperature. IV InfusionAdminister the portions of a multi-bag or multi-step regimen sequentially as a continuous infusion with no significant time between doses.Acetylcysteine reacts with certain materials (e.g., iron, nickel, copper, rubber); any part of the IV equipment that comes in contact with acetylcysteine should be made of plastic or glass.
Solutions may be given via nebulization into a face mask, mouth piece, tracheostomy, tent, or croupette; direct instillation intratracheally is also FDA-approved.The 10% solution may be administered undiluted.The 20% solution may be administered undiluted or, if desired, may be diluted in 0.9% Sodium Chloride Injection or Sterile Water for Injection or Inhalation.Most commercially available nebulizers will produce appropriate particle sizes; however, hand bulbs and some hand-operated nebulizers are not recommended for routine use nebulizing acetylcysteine.Do not place acetylcysteine directly into the chamber of a heated nebulizer.For prolonged nebulizations, when 75% of the initial volume of acetylcysteine has been nebulized, a quantity of Sterile Water for Injection approximately equal to the remaining acetylcysteine volume should be added to the nebulizer.Acetylcysteine reacts with certain materials (e.g., iron, nickel, copper, rubber); therefore, any part of the nebulizer equipment that comes in contact with acetylcysteine should be made of plastic or glass.Storage: Opened vials may be stored in the refrigerator and used within 96 hours.
Intratracheal AdministrationIntratracheal instillation: Instill directly into the trachea or tracheostomy.Percutaneous intratracheal catheter: Administer the solution via a syringe attached to the catheter.
Generic:- Store in a cool, dry placeAcetadote:- Discard unused portion. Do not store for later use.- Protect from light- Store at controlled room temperature (between 68 and 77 degrees F)- Store between 36 to 46 degrees F- Store diluted product at room temperature (68 to 77 degrees F) for up to 24 hours- Store in a cool, well ventilated, dry placeCETYLEV:- Protect from moisture- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F- Store in original package until time of useMucomyst:- Store opened container in refrigerator (36 to 46 degrees F)- Store remaining undiluted portion of product in a refrigerator and use within 96 hours- Store unopened product at 77 degrees F; excursions permitted to 59-86 degrees FMucosil Acetylcysteine :- Store opened container in refrigerator (36 to 46 degrees F)- Store remaining undiluted portion of product in a refrigerator and use within 96 hours- Store unopened product at 77 degrees F; excursions permitted to 59-86 degrees F
NOTE: When acetylcysteine is used for acetaminophen overdose, obtain APAP serum concentrations at least 4 hours post-ingestion of regular-release products or at least 8 hours post-ingestion of extended-release products. Predictors of liver injury include acetaminophen dose over 10 g, presentation more than 10 hours after the overdose and chronic ingestion of more than 80 g alcohol per day. Aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT), bilirubin, prothrombin time, creatinine, blood urea nitrogen (BUN), blood glucose, and electrolytes should be also determined at baseline in order to monitor hepatic and renal function and electrolyte and fluid balance in patients receiving acetylcysteine.
Intravenous acetylcysteine is contraindicated in patients who have had a previous anaphylactoid reaction to acetylcysteine, and acetylcysteine solution for oral use or inhalation is contraindicated in patients who have had any type of hypersensitivity reaction to the drug. Serious anaphylactoid reactions, including a fatality in a patient with asthma, have been reported in patients who received intravenous acetylcysteine (see Adverse Reactions). Intravenous and nebulized acetylcysteine should be used with caution in patients with asthma or a history of bronchospasm; when it is necessary to use these products in this population, careful monitoring is necessary. Intravenous administration or inhalation may result in acute bronchospasm or anaphylaxis. To minimize the risk of bronchospasm, inhaled acetylcysteine should be used with or after the administration of a beta-agonist. Nebulized acetylcysteine should be used with caution in patients with respiratory insufficiency, an inadequate cough mechanism, or gag reflex depression. When administered into respiratory tract, either via inhalation or direct administration into a tracheostomy tube, acetylcysteine liquifies pulmonary secretions, and the increased volume produced can occlude the airway if the patient is unable to adequately clear the secretions. If the patient's cough is not adequate to keep the airway open, mechanical suction or endotracheal aspiration may be necessary.
Oral administration of acetylcysteine can exacerbate vomiting that is associated with acute acetaminophen overdose. In patients with esophageal varices or peptic ulcer disease, vomiting may increase the risk of upper GI bleeding or esophageal tears; thus, caution is advised when administering oral acetylcysteine to these patients. The acetylcysteine nebulizer solution has an unpleasant odor and when undiluted, has irritating and sclerosing properties on the GI mucosa. Acetylcysteine must be diluted with a proper solution to mask the odor and limit GI irritation prior to oral administration.
No pediatric-specific concerns have been identified with the use of acetylcysteine in infants or children; however, for any patients weighing < 40 kg or requiring fluid restriction, use caution to avoid fluid overload when administering IV acetylcysteine. To avoid fluid overload, the volume of diluent should be reduced compared to the standard preparation for adult patients (see Dosage). If the volume is not adjusted, fluid overload can occur, potentially resulting in hyponatremia, seizure, and death. Specific dosing recommendations are not available for neonates for any of the formulations; however, the manufacturer of IV acetylcysteine reports its use in 16 premature infants (gestational ages, 25—31 weeks) with no noted adverse effects (see Dosage).
Adequate and well-controlled studies have not been performed in women receiving acetylcysteine during pregnancy; however, acetylcysteine does cross the placenta and has been detected in the cord blood of infants whose mothers received the drug at delivery. Four pregnant women with acetaminophen toxicity received oral or intravenous acetylcysteine at the time of delivery, and all of the women recovered. Three of the four neonates survived with no evidence of acetaminophen toxicity; one neonate (22 weeks gestational age) died shortly after delivery. Also, other limited case reports of pregnant women who received acetylcysteine during various trimesters have not reported adverse maternal, fetal, or neonatal outcomes. Of note, acetaminophen is also known to cross the placenta. Delaying treatment of pregnant women with acetaminophen overdose may increase the risk for maternal and fetal morbidity and mortality.
According to the manufacturer, it is not known whether acetylcysteine is distributed into human milk; use caution when acetylcysteine is administered to a nursing mother. Intravenous acetylcysteine is nearly completely eliminated within 30 hours after administration; therefore, mothers may consider reinitiating breast-feeding 30 hours after administration. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Use intravenous acetylcysteine cautiously in patients who require fluid restriction, such as patients with heart failure. The usual recommended administration technique for intravenous acetylcysteine (Acetadote) involves a significant amount of fluid and could result in volume overload and even hyponatremia, seizures, and death in extreme cases. For patients requiring fluid restriction, the volume of dilution should be reduced as clinically appropriate; however, carefully consider the osmolarity of the resultant solution and avoid infusion of a hyper- or hypo-osmolar solution. For specific treatment recommendations for patients requiring non-standard administration techniques clinicians can contact the US poison center (1—800—222—1222) or a special health professional assistance line for APAP overdose (1—800—525—6115) for assistance. Caution is advised when administering the acetylcysteine effervescent tablets to patients on a sodium restricted diet (i.e., patients with hypertension, heart failure, renal disease). Each 500 mg and 2.5 gram effervescent tablet contains 3.8 meq and 19 meq of sodium, respectively. At the recommended treatment dose, a 60 kg adult would receive 7 grams (304.3 meq) of sodium on day 1, 5.3 grams (230.4 meq) of sodium on day 2, and 4.4 grams (191.3 meq) of sodium on day 3.
anaphylactoid reactions / Rapid / 7.9-17.0bronchospasm / Rapid / Incidence not known
sinus tachycardia / Rapid / 3.0-5.0edema / Delayed / 1.2-1.6hypotension / Rapid / 0.1-0.1erythema / Early / Incidence not knowndyspnea / Early / Incidence not knownstomatitis / Delayed / Incidence not knownhemoptysis / Delayed / Incidence not knownwheezing / Rapid / Incidence not known
urticaria / Rapid / 6.1-7.6flushing / Rapid / 6.1-7.6pruritus / Rapid / 4.1-4.3rash / Early / Incidence not knownrhinorrhea / Early / Incidence not knownpharyngitis / Delayed / Incidence not knownnausea / Early / Incidence not knownvomiting / Early / Incidence not knowndysgeusia / Early / Incidence not knowndrowsiness / Early / Incidence not knownfever / Early / Incidence not known
Charcoal: (Moderate) Administration of activated charcoal and oral acetylcysteine at the same time may cause a reduction in acetylcysteine (NAC) absorption. There are conflicting data as to whether the reduced bioavailability of NAC is clinically significant during the treatment of drug overdoses. In the case of a mixed drug overdose activated charcoal may be indicated for use along with NAC. However, if activated charcoal has been administered, lavage before administering oral NAC treatment. Activated charcoal adsorbs acetylcysteine in vitro and may do so in patients and thereby may reduce its effectiveness.
Mechanism of Action:•Antioxidant effects: Antioxidants such as acetylcysteine may prevent tissue damage to various organs by scavenging oxygen free radicals (e.g., superoxides) or by other poorly understood mechanisms, such as stabilization of cellular signal transduction systems and reduced apoptosis (programmed cell death). Acetylcysteine enhances the effects of nitric oxide (NO) by combining with NO to form S-nitrosothiol, a potent and biologically stable vasodilator. Acetylcysteine may thus compete with the superoxide radical for NO and thus prevent the formation of a damaging perioxinitrite free-radical. Thus, acetylcysteine exhibits multiple potential mechanisms of action that may limit ischemia and promote cellular repair and survival. Studies using acetylcysteine as an antioxidant for organ protection in settings of clinically-relevant heart, lung, liver, and renal ischemia are intriguing and continue to be pursued.•Mucolytic effects: As a mucolytic, it is believed that the free sulfhydryl groups in acetylcysteine react with the disulfide linkages of mucoproteins in bronchial secretions. This, in turn, acts to decrease the hypersecretion and viscosity of mucus secretions of the lungs and aids in the removal of these secretions through coughing, mechanical mechanisms, or postural drainage. Acetylcysteine does not depolymerize proteins and has no action on fibrin or living cells. In COPD, the use of oral acetylcysteine may also promote reductions in bacterial cell counts within the sputum, thus contributing to reduced exacerbation rates.•Prevention of hepatotoxicity secondary to acetaminophen (APAP) overdose: As an antidote, acetylcysteine is used to prevent hepatotoxicity after an acute overdose of acetaminophen. In this role, the sulfhydryl groups of acetylcysteine serve as a substrate for the toxic acetaminophen metabolite in place of glutathione in the liver. It is believed that acetaminophen is hepatotoxic due to the depletion of these glutathione residues. For acetylcysteine to be effective, it must be administered within several hours after the acute ingestion. Benefits are primarily seen in patients treated within 8—10 hours of the overdose.•Proposed prevention of nitrate tolerance: Sulfhydryl groups are also believed to be important in the response to vasodilator nitrates used in the treatment of ischemic heart disease. It is well known that tolerance to nitrates occurs after prolonged use. One proposed mechanism, based on in vitro data, is the decreased conversion of nitrates to nitric oxide, possibly due to depletion of sulfhydryl cofactors. In vivo data do not completely support this sulfhydryl-depletion hypothesis. While supplementation with acetylcysteine does augment nitrate effects in vivo, the mechanism of intracellular sulfhydryl group repletion is inadequate in explaining the reversal of nitrate tolerance; an extracellular thiol/nitrate interaction appears to enhance vasodilation. Acetylcysteine inhibits angiotensin converting enzyme (ACE) in vivo and acts as an antioxidant, two mechanisms that may preserve the function of nitroglycerin-derived nitric oxide (NO). These potential actions indicate that acetylcysteine may protect the neurohormonal or vasoconstrictive responses to nitrates, rather than act as a simple repeller of thiol stores.
Acetylcysteine is administered orally, intravenously, or by inhalation. Once in the systemic circulation, 66% to 87% of the drug is bound to plasma proteins. Any acetylcysteine that is absorbed systemically is deacetylated by the liver and intracellularly in most tissues to cysteine and disulfides. Cysteine is then further metabolized to glutathione, as well as other metabolites. Most of an acetylcysteine dose is expected to be metabolized and incorporated as cysteine into cellular pools. The mean terminal half-life of the intravenous solution is 5.6 hours, while the effervescent tablets have a reported mean terminal half-life of 18.1 hours. Renal clearance accounts for roughly 30% of total clearance. After 24 hours, 13% to 38% of a radioactive dose of S-acetylcysteine is excreted in the urine. No metabolites have been identified in the urine. Only about 3% of acetylcysteine is excreted in feces. Affected cytochrome P450 isoenzymes: none
Acetylcysteine is rapidly absorbed with peak plasma concentrations reached approximately 2 hours (range, 1 to 3.5 hours) after oral administration; however, oral bioavailability is very low (approximately 9%).
The Vdss and protein binding for the IV formulation of acetylcysteine are reported to be 0.47 L/kg and 83%, respectively.
After oral inhalation, the majority of the administered dose undergoes a sulfhydryl-disulfide reaction; only a small portion of the dose is absorbed from the pulmonary epithelium.
Intratracheal RouteAfter intratracheal instillation, the majority of the administered dose undergoes a sulfhydryl-disulfide reaction; only a small portion of the dose is absorbed from the pulmonary epithelium.