| Colon Cancer
Prevention: |
A preliminary double-blind placebo-controlled study of NAC enrolled
62 individuals, each of whom had had a polyp removed from the colon.The
abnormal growth of polyps is closely associated with the development of
colon cancer.
In this study, the potential anticancer benefits of NAC
treatment were evaluated by taking a biopsy of the rectum. Individuals
taking NAC at 800 mg daily for 12 weeks showed more normal cells in the
biopsy of the tissue as compared to those in the placebo group.
An antioxidant drug that may keep cancer cells from developing or reduce
the risk of growth of existing cancer.
|
|
HIV: |
Early human trials, including a double-blind study of 45 people,
suggest that NAC may increase levels of CD4+ cells (a type of immune
cell) in healthy people and slow CD4+ cell decline in people with HIV.
It has been proposed as a supplement for patients with AIDS, who
generally have decreased glutathione levels. However, it does not appear
to be effective in restoring glutathione levels (Witschi et al., 1995). |
| Nephroprotective agent: |
Radiocontrast agents (Contrast agents):
They are compounds used to improve the visibility of internal bodily
structures in an X-ray image.
Some recent studies suggest that Oral N-acetylcysteine protects the
kidney from the toxic effects of the contrast agent (Gleeson &
Bulugahapitiya 2004). This effect is, in any case, not overwhelming.
Some researchers (e.g. Hoffmann et al 2004) even claim that the effect
is due to interference with the creatinine laboratory test itself. This
is supported by a lack of correlation between creatinine levels and
cystatin C levels.
Some studies show that prior administration of acetylcysteine markedly
decreases (90%) radiocontrast nephropathy (Tepel et al 2000), while
others appear to cast doubt on its efficacy (Hoffman et al., 2004; Miner
et al., 2004) Nevertheless, acetylcysteine continues to be commonly used
in individuals with renal impairment to prevent the precipitation of
acute renal failure.
|
| Paracetamol overdose: |
Mechanism of toxicity:
Paracetamol is one of the most commonly available medications. An
overdose of paracetamol or acetaminophen as it is otherwise called, can
have deleterious side effects due to its narrow therapeutic index.
The toxicity of paracetamol is related to its metabolism. In
therapeutic doses, 60-90% of the drug is metabolized by conjugation to
form paracetamol glucuronide and sulphate; 5-10% is oxidized by mixed
function oxidase enzymes to form the toxic and highly reactive
N-acetyl-p-benzoquinoneimine which is immediately conjugated with
glutathione and subsequently excreted as cysteine and mercapturate
conjugates. Only 1-4% of a therapeutic dose of paracetamol is excreted
unchanged in the urine. When a person takes an overdose, larger amounts
of the drug are metabolized by oxidation as saturation of the
conjugation pathway occurs rapidly due to the large amount of the drug
being metabolized. As a result the liver stores of glutathione become
depleted and unable to deactivate the toxic metabolite
N-acetyl-p-benzoquinoneimine, which acts as a potent oxidizing agent
that depletes cellular glutathione and inactivating key enzyme
sulfhydryl groups. Paracetamol is also known to induce renal damage
through N-acetyl-p-benzoquinoneimine.
|
| Acetylcysteine: |
Intravenous acetylcysteine is indicated for the treatment of
Paracetamol (acetaminophen) overdose. Oral acetylcysteine for this
indication is uncommon as it is poorly tolerated owing to the high doses
required (due to poor oral bioavailability), unpleasant taste/odor and
adverse drug reactions (particularly nausea and vomiting).
Acetylcysteine reduce paracetamol toxicity by supplying sulfhydryl
groups (mainly in the form of glutathione, of which it is a precursor to
react with the toxic NAPQI metabolite so that it does not damage cells
and can be safely excreted. It acts to augment glutathione reserves
(depleted by toxic Paracetamol metabolites) in the body and, together
with glutathione to directly bind to toxic metabolites. These actions
serve to protect hepatocytes in the liver from toxicity due to
paracetamol overdose.
If the patient presents less than 8 hours after paracetamol overdose,
then acetylcysteine significantly reduces the risk of serious
hepatotoxicity. If Acetylcysteine is started more than 8 hours after
ingestion, there is a sharp decline in its effectiveness because the
cascade of toxic events in the liver has already begun and the risk of
acute hepatic necrosis and death increases dramatically.
Intravenous Acetylcysteine is used as a continuous intravenous infusion
over 20 hours (total dose 300 mg/kg). Recommended administration
involves infusion of a 150 mg/kg loading dose over 15 minutes, followed
by 50 mg/kg infusion over 4 hours; the last 100 mg/kg are infused over
the remaining 16 hours of the protocol. Intravenous acetylcysteine has
the advantage of shortening hospital stay, increasing both doctor and
patient convenience, and it allows administration of activated carbon to
reduce absorption of both the paracetamol and any co-ingested drugs
without concerns about interference with oral Acetylcysteine.
Although Acetylcysteine is most effective if given early, it still has
beneficial effects if given as late as 48 hours after ingestion. In
clinical practice, if the patient presents more than 8 hours after the
paracetamol overdose, then activated charcoal is probably not useful,
and Acetylcysteine is started immediately. In earlier presentations the
doctor can give charcoal as soon as the patient arrives, start giving
Acetylcysteine, and wait for the paracetamol level from the laboratory.
Once it has been determined that a potentially toxic overdose has
occurred,Acetylcysteine is continued for the entire regimen, even after
the paracetamol level becomes undetectable in the blood. If hepatic
failure develops, Acetylcysteine should be continued beyond the standard
doses until hepatic function improves or until the patient has a liver
transplant.
|
| Insulin Resistance Syndrome: |
The most common type of insulin resistance is associated with
metabolic syndrome( is a combination of medical disorders that
affect a large number of people in a clustered fashion. In some studies,
the prevalence in the USA is calculated as being up to 25% of the
population, the end result of which is to increase one's risk for
cardiovascular disease and diabetes).
This was first described in the 1930's by H.P. (Harry) Himsworth
(University College Hospital Medical School, London). He described
results of experiments in an article in 1936, entitled, "Diabetes
Mellitus: Its differentiation into insulin sensitive and insulin
insensitive types." He found that those with diabetes can be
differentiated into two types: those in whom injected insulin produces
an immediate suppression of hyperglycemia; and those in whom the insulin
has little or no effect.
Hyperglycemia itself can lead to insulin resistance, but
N-acetylcysteine and taurine can prevent this effect.
|
| Hepatorenal Syndrome: |
A complex of syndromes due to hepatic and renal failure, including
hyperpyrexia, oliguria, and coma. Also known as Hyde's syndrome.
Other agents used in treatment include Pentoxifylline, Acetylcysteine
and Misoprostol.
|
| Other usages: |
It has been suggested that Acetylcysteine may help sufferers of
Samter's triad (is a medical condition consisting of asthma, aspirin
sensitivity, and nasal polyposis). by increasing levels of glutathione
allowing faster breakdown of salicylates, though there is no evidence
that it is of benefit (Bachert et al., 2003).
|
| Dosage forms: |
| N-Acetylcysteine:
|
An aerosolized mucolytic agent often used
as adjunctive therapy for pulmonary complications of cystic fibrosis
(CF) in combination with vigorous chest physiotherapy.
N-acetylcysteine
acts to split the sulfide bonds linking proteins present in the mucus
(mucoproteins) in the macromolecules thereby decreasing viscosity,
allowing for removal by normal chest physiology. The action of
N-acetylcysteine is pH dependent. Mucolytic action is significant at
ranges of pH 7-9.
►It is also used post-operatively, as a diagnostic aid, and in
tracheotomy care.
►It is considered ineffective in cystic fibrosis (Rossi, 2006).
►Oral acetylcysteine may also be used as a mucolytic in less serious
cases.
|
Acetylcysteine is available in different dosage forms for different
indications:
►Solution for inhalation (Mucomyst, Mucosil) inhaled for mucolytic
therapy or ingested for Nephroprotective effect.
►Intravenous injection (Parvolex) treatment of paracetamol overdose.
►Oral solution (Acetylcysteine
sachets SEDICO)& other various indications.
The IV injection and inhalation preparations are generally prescription
only, while oral solution is available over the counter in many
countries.
|
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