Acetylcysteine (NAC) is a widely used pharmaceutical drug with multiple clinical applications. It has antioxidant and anti-inflammatory properties. NAC is beneficial for COPD by reducing oxidative stress, inflammation, and mucus viscosity. It can slow lung function decline and reduce exacerbations. NAC may also slow disease progression in IPF by reducing fibrosis. In bronchiectasis, NAC helps clear mucus as a mucolytic and can reduce exacerbations. NAC can also reduce the severity and duration of influenza episodes. Some research indicates NAC may help protect normal cells from chemotherapy and radiation used to treat cancers like lung cancer.

2. Acetylcysteine ,also known as N-acetylcysteine or N-acetyl-L-
cysteine (abbreviated NAC), is a pharmaceutical drug widely used in
clinical medicine.
Acetylcysteine
Acetylcysteine is a derivative of cysteine; an
acetyl group that is attached to the nitrogen
atom.
Chemical formula : C5H9NO3S
Molecular weight : 163.2 g/mol
Only L-NAC is active; L-NAC is metabolized to
cysteine and then GSH.

3. It is on the WORLD Health
Organization’s list of Essential
Medicines and an important
medication needed in a basic
health system.

4. Multiple Clinical Applications Of NAC
Respiratory medicine
-COPD
- ILD
- Bronchiectasis
- Influenza
- Lung cancer
Paracetamol poisoning
- Contrast induced nephropathy - Neurological illness
- Psychiatric illness - Addictive behavior

5. NAC in COPD

6. Oxidative stress has been implicated in the pathogenesis and
progression of COPD.

7. Structural changes to essential components of the lung are caused by
oxidative stress, contributing to irreversible damage of both
parenchyma and airway walls.
Both reactive oxidant species (ROS) from inhaled cigarette smoke and
those endogenously formed by inflammatory cells constitute an
increased intrapulmonary oxidant burden.

8. How does NAC offer benefit in COPD patients ?
1. Anti-oxidant effects
2. Anti-inflammatory effects
3. Mucolytic effects

9. N-acetylcysteine –
1. Reduces clinical symptom
2. Reduces severity and no. of exacerbations and
3. Reduces the accelerated lung function decline.

10. Effects on Clinical symptoms
The efficacy of NAC at a dose of 600 mg/day –
1. Reduces the viscosity of sputum
2. Reduces the nature of sputum
3. Reducing the severity of cough
0
20
40
60
80
100
Before 100 100 100
After 20 41 26
Viscosity of
Sputum
Nature of
Sputum
Severity of
Cough
Improvement after 2 months NAC therapy

11. Non-smokers
healthy
Smokers
without COPD
Smokers with
COPD
Bacterial colonies
Before After
Treatment with NAC: Bacterial colonization
Effects on bacterial colonization

12. Before 1
year
after 1
year
Effects on Annual decline of FEV 1
ml/yr
Healthy
With NAC Without
NAC
The decline in FEV1 in
COPD patients who takes
NAC for 2 yrs is less than
that in a reference group
receiving usual care.
After 5 yrs, the reduction
in FEV 1 in the NAC
group was less than that
in the reference group.

13. Effects on no. of exacerbations

14. Q. What doses of NAC is advised in COPD patients ?
Ans. A dose of 600 mg once daily
Q. How long NAC can be prescribed in COPD patients ?
Ans. At least 2-3 years.
Q. Is all COPD patients is suitable for NAC prescription ?
Ans. Moderate to very severe COPD patients can be given NAC
as adjunct therapy.
Q. Which points are to be considered in COPD patients receiving
NAC?
Ans.
1. Side effects.
2. Cost effectiveness.

15. COPD
Diagnosis often made at advanced stages
 >50% of patients have moderate/severe COPD on initial presentation
40%
6%
42%
12%
Stage 1 Stage 2 Stage 3 Stage 4

17. NAC in ILD

19. Treatments for Idiopathic Pulmonary Fibrosis
There’s still no proven effective treatment for IPF, except for lung
transplant.
Lung transplant is the only therapy known to prolong survival in IPF, but
the 5 year survival after transplant is only 44%.
Lung transplant is the only therapy known to prolong survival in IPF, but
the 5 year survival after transplant is only 44%.

20. Commonly used pharmacologic therapy for patients
with idiopathic pulmonary fibrosis
1. Corticosteroids
2. Immunosuppressants
3. Antioxidants
4. Antifibrotic agents

21. Mechanism of action of NAC in treatment of IPF
1. Antioxidant
2. Antifibrotic

22. Azathioprine + prednisone + N-acetylcysteine
versus
azathioprine + prednisolone + placebo
Randomized, double-
blind, placebo-controlled
study outcome

23. What is the clinical benefits of using NAC in treatment of IPF ?
NAC along with
other
recommended
drugs
slow the rate of
disease
progression
Improve the quaProlong the survival
periodlity of life
Improve quality of
life
Prolong the survival
period

24. Stage I II III
Points 0-3 4-5 6-8
Mortality
1-year 5.6 16.2 39.2
2-year 10.9 29.9 62.1
3-year 16.3 42.1 76.8
Predictor Points
Sex Female 0
Male 1
Age (years) ≥60 0
61-65 1
>65 2
FVC (% predicted) >75 0
50-75 1
< 50 2
DLCO (% predicted) >55 0
36-55 1
≤35 2
Cannot
perform
3
Scoring for mortality risk in IPF.
Staging and mortality risk for IPF

25. Other than IPF, N-Acetylcysteine is recommended in ILD
with marked fibrotic changes like –
1. Connective tissue associated interstitial lung diseases,
2. Asbestosis,
3. Sarcoidosis,
4. Hypersensitivity pneumonitis,
5. Drug induced lung disease

26. NAC in Bronchiectasis

27. Bronchiectasis is an abnormal
permanent dilatation of the
bronchi.
Bronchiectasis generally
occurs as a result of infection,
although non-infectious
factors may contribute to the
development of this condition.

28. Accompanying the enlargement of
the bronchi is their decreased ability
to clear secretions.
Failure to clear secretions allows
microbes and particles to collect in
them, which leads to more secretions
and inflammation that further damage
the airways, causing more dilation in
a vicious cycle.

29. Bronchiectasis may occur in a single portion of the lung (localized) or
throughout the lungs (diffuse) and is the major lung abnormality of
cystic fibrosis.

30.  Antibiotic therapy
 Bronchial hygiene
 Bronchodilator therapy
 Anti-inflammatory therapy
 Adjunctive surgical resection
 Lung transplantation.
Treatment modalities

31. Why good bronchial hygiene is required ?
Bronchiectasis
defects in
clearance of
mucus
Mucus plugging
Viscous mucus
formation

32. Mucus plugging
Decline in lung
function
perfect environment for colonization by various less
virulent microorganisms on the airway mucosal
surface
Detoriation of
symptoms
Elimination of
pathogens
Host defense
Pathogenic colonization
Impaired
Host defense

33. Pathogenic colonization
Initial colonization
Intermittent colonization
Chronic colonization
Exacerbation is a clinical situation that can happen during
any of the three scenarios.

34. Antibiotic therapy
Infrequent
exacerbation
Episodic oral
antibiotics.
Episodic
perenteral
antibiotics.
Frequent
exacerbations
Regular antibiotic
regimen

35. Bronchial
hygiene
Postural
Drainage
Mucoactive
drugs
How bronchial hygiene is maintained ?

36. Airway hydration is an important goal in the overall
therapeutic management.
Mucoactive
drugs
Hyperosmolar
agents
Mucolytic
drugs

37. Hyperosmolar
agent
Mannitol
Hypertonic
saline
Dose 400 mg bid 6 or 7% bid
Delivery By an inhaler By nebulizer
Duration of
effect
Sustained (up to
24 h)
Short
Hyperosmolar agents

38. N-acetylcysteine
N-acetylcysteine (NAC) is commonly used in the treatment of BE
patients.
Benefits may come from -
1. It is a mucolytic agent that disrupts the disulfide bonds in mucus
when inhaled.
2. The benefits of this agent may come from its antioxidant properties.
3. NAC has also antibacterial properties by reducing the ability of
bacteria to adhere to epithelial cells.
Q. What doses of NAC is advised in Bronchiectasis patients ?
Ans. A dose of 600-1200 mg once or two divided doses daily

39. NAC in Influenza

40. Evaluation of cell-mediated immunity
showed a progressive, significant shift
from anergy to normoergy following
NAC treatment.
NAC treatment
1. Reduces frequency of influenza-like
episodes
2. Improves both local and systemic
symptoms
3. Severity, and length of time
confined to bed.

41. A total of 262 subjects of both sexes (78% > or = 65 yrs, and 62%
suffering from nonrespiratory chronic degenerative diseases) were
enrolled in a randomized, double-blind trial involving 20 Italian Centres.
They were randomized to receive either placebo or NAC tablets (600 mg)
twice daily for 6 months.
NAC treatment was well tolerated and resulted in a significant decrease
in the frequency of influenza-like episodes, severity, and length of time
confined to bed. Both local and systemic symptoms were sharply and
significantly reduced in the NAC group.
(Attenuation of influenza-like symptomatology and improvement of cell-
mediated immunity with long-term N-acetylcysteine treatment.
ERJ July 1, 2012 vol. 10 no. 7 1535-1541)

42. NAC in Lung Cancer

43. – According to research findings, certain types of cancer
including lung, skin, head and neck, mammary, and liver
can be potentially treated with NAC.
– Results from both cell culture and animal studies indicate
that NAC administration can selectively protect normal
cells, but not malignant ones, from chemotherapy and
radiation toxicity.