Over 99% Purity N-Acetyl-L-cysteine CAS: 616-91-1 for Chronic lung disease 

Description
 

Acetylcysteine, also known as N-acetylcysteine (NAC), is a medication that is used to treat paracetamol (acetaminophen) overdose, and to loosen thick mucusin individuals with cystic fibrosis or chronic obstructive pulmonary disease. It can be taken intravenously, by mouth, or inhaled as a mist.Some people use it as a dietary supplement.

Common side effects include nausea and vomiting when taken by mouth.The skin may occasionally become red and itchy with either form. A non-immune type of anaphylaxis may also occur. It appears to be safe in pregnancy. For paracetamol overdose, it works by increasing the level of glutathione, an antioxidant that can neutralise the toxic breakdown products of paracetamol. When inhaled, it acts as a mucolytic by decreasing the thickness of mucus.

Acetylcysteine was initially patented in 1960 and came into medical use in 1968. It is on the World Health Organization's List of Essential Medicines, which lists the safest and most effective medicines needed in a health system. It is available as a generic medication and is inexpensive.

 

Uses

Intravenous and oral formulations of acetylcysteine are available for the treatment of paracetamol (acetaminophen) overdose.^[13] When paracetamol is taken in large quantities, a minor metabolite called N-acetyl-p-benzoquinone imine (NAPQI) accumulates within the body. It is normally conjugated by glutathione, but when taken in excess, the body's glutathione reserves are not sufficient to deactivate the toxic NAPQI. This metabolite is then free to react with key hepatic enzymes, thereby damaging liver cells. This may lead to severe liver damage and even death by acute liver failure.

In the treatment of acetaminophen overdose, acetylcysteine acts to maintain or replenish depleted glutathione reserves in the liver and enhance non-toxic metabolism of acetaminophen.^[14] These actions serve to protect liver cells from NAPQI toxicity. It is most effective in preventing or lessening hepatic injury when administered within 8-10 hours after overdose.^[14] Research suggests that the rate of liver toxicity is approximately 3% when acetylcysteine is administered within 10 hours of overdose.^[13]

Although both IV and oral acetylcysteine are equally effective for this indication, oral administration is generally poorly tolerated due to the higher dosing required to overcome its low oral bioavailability,^[15] its foul taste and odour, and a higher incidence of adverse effects when taken by mouth, particularly nausea and vomiting. Prior pharmacokinetic studies of acetylcysteine did not consider acetylation as a reason for the low bioavailability of acetylcysteine.^[16] Oral acetylcysteine is identical in bioavailability to cysteine precursors.^[16] However, 3% to 6% of people given intravenous acetylcysteine show a severe, anaphylaxis-like allergic reaction, which may include extreme breathing difficulty (due to bronchospasm), a decrease in blood pressure, rash, angioedema, and sometimes also nausea and vomiting.^[17] Repeated doses of intravenous acetylcysteine will cause these allergic reactions to progressively worsen in these people.

Several studies have found this anaphylaxis-like reaction to occur more often in people given IV acetylcysteine despite serum levels of paracetamol not high enough to be considered toxic.

Lungs

Inhaled acetylcysteine has been used for mucolytic ("mucus-dissolving") therapy in addition to other therapies in respiratory conditions with excessive and/or thick mucus production. It is also used post-operatively, as a diagnostic aid, and in tracheotomy care. It may be considered ineffective in cystic fibrosis.^[22] A 2013 Cochrane review in cystic fibrosis found no evidence of benefit.^[23]

Acetylcysteine is used in the treatment of obstructive lung disease as an adjuvant treatment.^[24][25][26]

Kidney and bladder

Evidence for the benefit of acetylcysteine to prevent radiocontrast induced kidney disease is mixed.^[27]

Acetylcysteine has been used for cyclophosphamide-induced haemorrhagic cystitis, although mesna is generally preferred due to the ability of acetylcysteine to diminish the effectiveness of cyclophosphamide.^[28]

Psychiatry

Acetylcysteine has been studied a number of psychiatric disorders.^[29][30][31] Several reviews found tentative evidence for N-acetylcysteine in the treatment of Alzheimer's disease, autism, bipolar disorder, drug-induced neuropathy, major depressive disorder, obsessive-compulsive disorder, schizophrenia, specific drug addictions (cocaine), trichotillomania and a certain form of epilepsy (progressive myoclonic).^[29][30][32] Preliminary evidence showed efficacy in anxiety disorder, attention deficit hyperactivity disorder and mild traumatic brain injury although confirmatory studies are required.^{[32][33][34][35]} Tentative evidence also supports use in cannabis use disorder.^[36]

Evidence to date does not support the efficacy for N-acetylcysteine in treating addictions to gambling, methamphetamine, or nicotine, although pilot controlled data are encouraging.^[32] Based upon limited evidence, NAC appears to normalize glutamate neurotransmission into the nucleus accumbens and other brain structures, in part by upregulating the expression of excitatory amino acid transporter 2 (EAAT2), a.k.a. glutamate transporter 1 (GLT1), in individuals with addiction.^[37] While NAC has been demonstrated to modulate glutamate neurotransmission in adult humans who are addicted to cocaine, NAC does not appear to modulate glutamate neurotransmission in healthy adult humans.^[37] NAC has been hypothesized to exert beneficial effects through its modulation of glutamate and dopamine neurotransmission as well as its antioxidant properties.^[30]

Other uses

Acetylcysteine has been used to complex palladium, to help it dissolve in water. This helps to remove palladium from drugs or precursors synthesized by palladium-catalyzed coupling reactions.^[38] N-actelylcysteine can be used to protect the liver.^[39]

Acetylcysteine can be used in Petroff's method i.e. liquefaction and decontamination of sputum, in preparation for recovery of mycobacterium.^[40]

Side effects

The most commonly reported adverse effects for IV formulations of acetylcysteine are rash, urticaria, and itchiness.^[14] Up to 18% of patients have been reported to experience anaphylaxis reaction, which are defined as rash, hypotension, wheezing, and/or shortness of breath. Lower rates of anaphylactoid reactions have been reported with slower rates of infusion.

Adverse effects for inhalational formulations of acetylcysteine include nausea, vomiting, stomatitis, fever, rhinorrhea, drowsiness, clamminess, chest tightness, and bronchoconstriction. Although infrequent, bronchospasm has been reported to occur unpredictably in some patients.^[41]

Adverse effects for oral formulations of acetylcysteine have been reported to include nausea, vomiting, rash, and fever.^[41]

Large doses in a mouse model showed that acetylcysteine could potentially cause damage to the heart and lungs.^[42] They found that acetylcysteine was metabolized to S-nitroso-N-acetylcysteine (SNOAC), which increased blood pressure in the lungs and right ventricle of the heart (pulmonary artery hypertension) in mice treated with acetylcysteine. The effect was similar to that observed following a 3-week exposure to an oxygen-deprived environment (chronic hypoxia). The authors also found that SNOAC induced a hypoxia-like response in the expression of several important genes both in vitroand in vivo.

The implications of these findings for long-term treatment with acetylcysteine have not yet been investigated. The dose used by Palmer and colleagues was dramatically higher than that used in humans, the equivalent of about 20 grams per day.^[42][43] Nonetheless, positive effects on age-diminished control of respiration (the hypoxic ventilatory response) have been observed previously in human subjects at more moderate doses.^[44]

Although N-acetylcysteine prevented liver damage when taken before alcohol, when taken four hours after alcohol it made liver damage worse in a dose-dependent fashion.

Packaging and transportation 

Packing: this product is double-packed: the inner layer is sealed with edible polythene plastic bags, and the outer packaging is in cardboard boxes.The net content of each case is 25kg. It can also be packed according to customers' needs.

Transportation: light loading and unloading.Prevent the sun, rain, can not be mixed with toxic, harmful goods, this product is not dangerous goods, can be transported according to the general chemicals.
Storage: it should be stored in a dry, clean and dark environment. It is strictly prohibited to mix with toxic substances to avoid pollution.The shelf life is two years.


Packaging