Medical uses of N-acetyle cysteine

.BYHend Abd Elazeem Hayam Goda MosaHayam Fathi Mansour Warda Magdi Elemam

Medical uses of N-Acetyle cysteine Objectives:

Mechanism of action Uses of N-acetyle cysteine in

-Paracetamol toxicity -Co poisoning

-Heart ,lung diseases -Bile duct blockage in infant

Neurodegenerative diseases Cancers-

Addiction- psychiatric disorders Others.………

Mechanism of N-acetyle cystiene

Glutathione substitute or precursorSupply inorganic sulfur altering metabolism

Free radical scavengerMucolytic splits the disulfide bonds of

Mucoproteins Other mechanisms in neurological and psychiatric disorders

Paracetamol poisoning

MECHANISM

NAPQI depletes the liver's natural antioxidant glutathione and directly damages cells in the liver, leading to liver failure.

.the antidote acetylcysteine acts as a precursor for glutathione, helping the body regenerate enough to prevent damage to the liver.[3] N-acetylcysteine can neutralize NAPQI by itself as well.

CO POISONING

Reactive oxygen metabolites mediates neurolgical injury in models of CO poisoningLipid peroxidation is documented in rats after co poisoning ----- sufficient to cause uncosciousness

N-acetylecystiene --- as antioxidant either precurser for glutathione or glutathione substituteVasodilatation by increasing cyclic guanisine monophosphate Inhibit platelet aggregation ,sulphhydryle donor to reginerate

EDRFThus improving tissue hypoxia

Heart disease (angina)The vasodilator effects of nitroglycerin (NTG) are

mediated via activation of guanylate cyclase; this process requires

the availability of free sulfhydryl groups.(NAC )potentiates the systemic and coronary vasodilator

effects of NTG interaction of NTG and NAC lead to the formation of S-

nitroso-.NAC, which inhibits platelet aggregation

Respiratry diaseases

N-acetyl cysteine is sometimes inhaled (breathed into the lungs) or delivered through a tube in the throat to treat certain lung disorders such as pneumonia, bronchitis,emphysema, cystic fibrosis, and others.

Bile duct obstruction Cholestasis

Leads to hepatic injury ,cell membrane and organells damage

Overtime biliary stasis leads to inflammation and free radicals formation

Neurodegenerative diseases

Studuies showed key role of oxidative stress in neurodegenerative diseases. Alzheimer's disease, Parkinson's disease,ALS, myoclonus epilepsy of the Unverricht-Lundborg type, spinocerebellar degeneration, tardive dyskinesia,

Oxidative stress can decrease cellular bioenergetic capacity, which will then increase the generation

of reactive oxygen species resulting in cellular damage and programmed cell death

Mechanism of actionThe chemical properties of NAC include redox

interactions, particularly with other members of the group XIV elements )selenium, etc.( and ebselen, a lipid-soluble seleno-organic compound .

Second, NAC has been shown to protect against oxidative stress-induced neuronal death in cultured granule

neurons  . NAC acts against 4-hydroxynonenal )HNE(-

induced toxicity in cerebellar granule neurons

Cancers Antioxidants protects cells from ROS ,which react with DNA ……cause damage …cancer Some studies showed that they can aggrevate cancer …Martin Bergus team at university of Gothenburg Showed that antioxidant neutralize ROS at tumour cells as well as healthy cells

Psychiatric disorders

Ocd There have been reports of oxidative stress in

populations with OCD, including increased lipid peroxidation; decreased vitamin E, catalase, GPx and selenium; increased superoxide dismutase; and changes in overall oxidative status

Trichotillomania and grooming disorders

SchizophreniaIn populations with schizophrenia, dysfunction in

glutamate metabolism and decreased glutamate levels in the pre-frontal cortex have been reported.

cysteine has been shown to modulate glutamate levels through glutamate–cystine exchange, and GSH has been shown to modulate the binding of glutamate

to N-methyl-d-aspartate receptors .N-acetylcysteine may be beneficial in the treatment of

schizophrenia by targeting both oxidative stress and glutamatergic dysfunction ,

Bipolar disorderAlterations in oxidative metabolism have also been described

in populations with bipolar disorder. Similar to schizophrenia, changes in antioxidant levels, increased markers of lipid peroxidation and protein carbonylation have all been reported. These changes appear to be related to state, particularly in mania, where increased oxidative stress seems to be apparent.

Addiction Dopamine signals originating from VTA targeting

nucleus accumbens modulate glutamate synaptic plasticity and are involved in pathphysiology of addicion

Administration of NAC provide extrasynaptic cysteine that is oxidized into csytine ……………activation og glutamate –cystine exchanger

Cocaine Cocaine modifies the action of dopamine in the

brain… Following 7 days of cocaine exposure and 21subsequent days of withdrawal, decreased basal extracellular glutamate levels in the NAcare recovered following an IP injection of NAC in

rats.……

Others .It is also used for reducing levels of a type of

cholesterol called lipoprotein (a), homocysteine levels (a possible risk factor for heart disease) and the risk of heart attack and stroke in patients with seriouskidney disease.

Allergic reactions to the anti-seizure drug phenytoin( Dilantin,)

and an Eye infection called keratoconjunctivitis

N-acetyl cysteine is also used for preventing alcoholic liver damage

protecting against environmental pollutants including carbon monoxide, chloroform, urethanes and certain herbicides;

-for reducing toxicity of ifosfamide and doxorubicin, drugs that are used for cancer treatment; as a hangover remedy;

Down syndromeGlutathione is commonly deficient in individuals

with Down Syndrome, due to the extra chromosome & overexpression of the SOD-1

gene. Glutathione (GSH) is an important antioxidant. It helps scavenge free radicals, deal with oxidative stress & the pro-oxidant state of

individuals with Down Syndrome.