Evidence of N-Acetylcysteine in pulmonary disease

 

Antioxidant property
Direct antioxidant properties
free thiol gr. interaction with ROS leads to intermediate formation of NAC thiol, with NAC disulphide as a major end product
Indirect antioxidant properties
GSH precursor

Glutathione
Mainly synthesis in the lung and liver
Central factor in protecting against
internal toxic agent (cellular aerobic respiration and metabolism of phagocytes)
external agents (NO, SO2, and other components of cigarette smoke and pollution)

Pharmacokinetic(PK/PD)
NAC is a thiol (sulfhydryl-containing) compound = chemical formula C5H9NO3S, MW 163.2
rapidly absorbed following an oral dose
1st pass metabolism results in the incorporation of NAC into protein peptide chains and the formation of a variety of metabolites of NAC
small percentage of the intact NAC molecule arrives in the plasma, and subsequently in tissue
Pharmacokinetic(PK/PD)
3% of radioactively-labeled NAC is excreted in the feces following oral administration,
Peak concentrations of NAC typically appear in the plasma in less than one hour following oral administration.
The plasma T1/2 of free NAC is estimated to be about 2.15 hours, and no NAC is detectable 10 -12 hrs post-administration
Mechanism of action
Mucolytic agent
Expectorant : stimulating both ciliary action and the gastro-pulmonary vagal reflex, thereby clearing the mucus from the airways
Ability to reduce extracellular cystine to cysteine, or to act intracellularly as a source of -SH groups
stimulates GSH synthesis, enhances glutathione-S-transferase activity, promotes liver detoxification by inhibiting xenobiotic biotransformation, and is a powerful nucleophile capable of scavenging free radicals
Mucolytic
Exerts mucolytic action through its free sulfhydryl group which opens up the disulfide bonds in the mucoproteins thus lowering mucous viscosity
Indices (biochemical markers) of increased oxidative stress in COPD
Elevated breath hydrogen peroxide and 8-isoprostane levels
Decreased plasma antioxidant capacity
Elevated plasma lipid peroxide (TBARS) levels
Plasma protein sulphydryl oxidation
Increased exhaled CO
Release of ROS from peripheral blood neutrophils and AMs
Increased urinary isoprostane F2a-III levels

NAC (Antioxidant and anti-inflammatory effect)
Effects on cigarette smoke-induced changes
tendency towards normalisation of the cell composition, with increase lymphocyte conc.
improve phagocytic activity of AM
increase LB4
reduced production of O2 free radical and ECP, lactoferrin and antichymotrypsin
Effect of elastase activity : decrease
NAC (Antioxidant and anti-inflammatory effect)
Modulatory effect on genes
inhibit activation of NF-κB and activation protein1,VCAM-1
Effects on oxidative stress induced by viruses
attenuated virus-induced NF-κB and IL-8 release
Effect on exhaled biomarkers of oxidative stress
decrease H2O2
Mucolytic effect : destroying disulphide brideges of mucoprotein macomolecules after inhalation
inhibited smoke-induced goblet cell hyperplasia and associated mucus hypersecretion

Clinical Efficacy of NAC in COPD

Clinical symptoms
1,392 patients demonstrated the efficacy of NAC at a dose of 600 mg/day
viscosity of expectorations:promoting expectoration + severity of cough
After 2 months of treatment with NAC
viscosity of expectorations improved in 80% of cases
difficulty in expectorating improved in 74%
severity of cough improved in 71%.
Bronchial bacterial coloniztion
Open cross-sectional study
22 smokers with non-obstructive chronic bronchitis
19 smokers with chronic bronchitis and COPD
14 healthy non-smokers

 

 

 

To examine the effect of NAC 1200 mg/day on lung hyperinflation at rest and after exercise in patients with moderate and severe COPD
Randomized, double-blind, cross-over study that included 24 eligible patients over 40 years of age with a diagnosis of COPD
FEV1 < 70% of predicted, FVC ratio < 0.70, and FRC > 120% of predicted. Patients were randomized to placebo or NAC twice daily for 6 weeks , 2 weeks’ washout, and then patients were crossed over to alternate therapy for a further 6 weeks
Results: IC and FVC were higher especially after exercise after NAC treatment compared to placebo. RV/TLC was reduced in a similar pattern. Endurance time was longer after NAC treatment compared to placebo.
Conclusions: NAC treatment of stable, moderate and severe COPD patients has a beneficial effect on physical performance, probably due to a reduction in air trapping

 
Studies were select randomized trials comparing oral NAC with placebo in patients with chronic bronchitis was performed
Total 11 studies: NAC 400 -600 mg 12-24 weeks
Outcome :prevention of exacerbation, improvement of symptoms
Clinical outcome of NAC
No effect on FEV1
Reduced exacerbation in COPD
Reduced air trapping
Take home message
Clear Evidence(+)
Mucolytic (Oral)
COPD
Exacerbation
Improve physical performance : decreased air trapping

ชาทีมิกซ์

Posted on กุมภาพันธ์ 24, 2014, in บทความ. Bookmark the permalink. ใส่ความเห็น.

ใส่ความเห็น

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / เปลี่ยนแปลง )

Twitter picture

You are commenting using your Twitter account. Log Out / เปลี่ยนแปลง )

Facebook photo

You are commenting using your Facebook account. Log Out / เปลี่ยนแปลง )

Google+ photo

You are commenting using your Google+ account. Log Out / เปลี่ยนแปลง )

Connecting to %s

%d bloggers like this: