السلام عليكم و رحمة الله و بركاته ...

لي الشرف بأن يكون هذا أول موضوع في هذا المنتدى الكريم .. و الذي تعرفت عليه بالصدفة و وجدت فيه ما أشتهي من مشروع موقع طبي تفاعلي قوي بإذن الله ...
المهم ...

أما و قد أحدث موضوع الأخت البتول ما أحدثه من نقاش جميل و بنّاء..
الموضوع هنا
فلقد ارتأيت أن أضع ما بجعبتي من معلومات بين أيديكم في موضوع منفصل ..

فعلا الموضوع كبير و متشعّب .. و يحتوي من المعلومات ما قد يفاجئ الكثير من الناس ..
نعم يا اخوتي .. الباراسيتامول اللذي نعرفه هو مادة خطيرة جدا .. اذا أسيئ استعمالها .. أو اخذت بكميات كبيرة ..

أما اذا اردت ان تعرف المزيد فخذ وقتك في قراءة التالي عّلي أؤجر عليه و علّك تنتفع منه ..

عندما يصيبك صداع أو وجع في المعدة أو ألم في يديك أو قدميك .. فما هو اول شيء تعمله ؟؟؟
غالبا ما تأخذ قرصين من الباراسيتامول ..
دعني أقل لك أنك -و حرفيا- تلعب بالنار و تصادق مادّة لا يؤتمن جانبها ..
الباراسيتامول يا عزيزي عندما يؤخذ بغير الشكل الموصّى به فإنه يضرّ اكثر مما ينفع ..

عندما نشر الدواء و لأول مرة في اواخر القرن التاسع عشر , لم يكن علم السموم بذلك العلم اللذي هو اليوم , و بعيدا عن دراسات القطط و تجارب الفئران, فإن القليل من آثاره الجانبية كان معلوما آنذاك و حتى عام 1960 حينما ربط العلماء حالة تسمم كبدي ناتجة عن سمية بالباراسيتامول ...
و بتقدم الزمن, زاد عدد المستعملين للباراسيتامول , و كذا حالات الوفيات الناتجة عنه , ففي عام 1989 قتلت الجرعه الزائدة من الباراسيتامول 186 شخصا في المملكة المتحدة وحدها !!

ما سبب التسمم؟؟
عندما يؤخذ الباراسيتامول بجرعات طبيعية فإنه يستقلب عن طريق الإرتباط بـglucuronic acid أو بـٍSulphate ..
إلا أن كميات صغيرة منه تستقلب عن طريق CYP الى N-acetyl-para-benzo-quinoneimine (NABQI) و التي هي مادة قلوية تتفاعل بســـرعه شديدة مع الGlutathion لتعطي مركبا مؤقتا سرعان ما يستقلب الى مركب غير سام مرتبط الى السيستين و حمض الميركابتوبيوريك ..

الوضع يختلف عندما تؤخذ جرعة زائدة من الباراسيتامول ( و تختلف الجرعه السامة للباراسيتامول و لكنها صغير الى حد ان 10 غ (20 حبه)) تكفي للسمية!!
و الذي يحدث أن مستويات الGlutathion تهبط بسرعه ( بسبب عدم كفايتها لإستقلاب كل الكمية من الباراسيتامول) و ذلك بعد أن تكون كميات الـ glucuronic acid و ـٍSulphate قد استهلكت تماما . . و بعد انتهاء كميات الـGlutathion يبقى مركب NABQI الشديد السمية دون استقلاب , و هنا يبدأ هذا المركب بالارتباط بعضيات الخلية و تعطيل انزيماتها, و هذا يسبب السمية الكبدية و التي تؤدي الى الموت ...

و من هذا المنطلق فإن المادة المضادة للتسمم بالباراسيتامول أو الـAnti-dote هي مادة الـ N-acetyl cysteine (NAC) و التي هي مادة تستطيع خلق الـGlutathion و الذي يستطيع تعطيل الـNABQI السّم ..
و هذه صورة توضيحية ..



هذا و الله أعلى وأعلم...
المصدر: www.chemsoc.org

ملاحظة : اذا تسائل أحدهم يوما ما أمامك, و تبجّح بأنه بلع أكثر من عشرين حبة , و لم يزل واقفا امامك , فلك بأن توجه وجهك نحو القبلة و تدعو الله -صادقا- ان يهدي الصناعة الدوائية الى ما فيه خير مرضى هذا الوطن!!!

ملاحظة2: ترقبوا موضوعي القادم : هل تعلم بأن الفلاجيل(ميترونيدازول) مســـــرطن ؟؟؟!!!
و لا تنسوا تعليقاتك و أسئلتكم ...

و السلام خير ختام ...

موضوع حلو كثير شكرا عليه

أهلا بك عزيزي subah ..
الحمد لله الموضوع اعجبك ... و يا رب تكون استفدت منو .


سلام ..

أخي أليساندرو

في هذا الموقع هناك زر للشكر بدلاً من مشاركات الشكر

لديك 11 شكر في موضوعك

أحببت أن أقول هذا لأنك طلبت منا أن لا ننسى المشاركات

ولكننا تفاعلنا معك بالتشكرات

أهلاً وسهلاً بك وبانتظار المزيد منك

[

FROM WIKIPEDIA

Toxicity

Paracetamol has a narrow therapeutic index – the therapeutic dose is close to the toxic dose. Additionally, paracetamol is contained in many preparations (both over-the-counter and prescription only medications). This means that, despite being one of the safest analgesics available at recommended doses, there is a large potential for overdose and toxicity.[6] Without timely treatment, paracetamol overdose can lead to liver failure and death within days. Because of the wide over-the-counter availability of the drug, it is sometimes used in suicide attempts by those unaware of the prolonged timecourse, and high morbidity (likelihood of a severe or fatal outcome) associated with paracetamol-induced toxicity.

In the UK, sales of over-the-counter Paracetamol in pharmacies are restricted to packs of 32 tablets per customer per occasion (only 16 tablets in non-pharmacy stores). In Ireland, the limits are 24 and 12 tablets respectively.

[edit] Mechanism of toxicity

As discussed above in the section regarding metabolism, paracetamol is mostly converted to inactive compounds via Phase II metabolism by conjugation with sulfate and glucuronide, with a small portion being oxidized via the cytochrome P450 enzyme system. Cytochrome P450 2E1 (CYP2E1) converts paracetamol to a highly reactive intermediary metabolite, N-acetyl-p-benzo-quinone imine (NAPQI).

Under normal conditions, NAPQI is detoxified by conjugation with glutathione. In cases of paracetamol toxicity, the sulfate and glucuronide pathways become saturated, and more paracetamol is shunted to the cytochrome P450 system to produce NAPQI. As a result, hepatocellular supplies of glutathione become exhausted and NAPQI is free to react with cellular membrane molecules, resulting in widespread hepatocyte damage and death, clinically leading to acute hepatic necrosis. In animal studies, 70% of hepatic glutathione must be depleted before hepatotoxicity occurs.

[edit] Toxic dose

The toxic dose of paracetamol is highly variable. In adults, single doses above 10 grams or 150 mg/kg have a reasonable likelihood of causing toxicity.[7] Toxicity can also occur when multiple smaller doses within 24 hours exceeds these levels, or even with chronic ingestion of doses as low as 4 g/day, and death with as little as 6 g/day.

In children acute doses above 200 mg/kg could potentially cause toxicity. This higher threshold is largely due to children having relatively larger kidneys and livers than adults and hence being more tolerant of paracetamol overdose than adults.[8] Acute paracetamol overdose in children rarely causes illness or death with chronic supratherapeutic doses being the major cause of toxicity in children.

Since paracetamol is often included in combination with other drugs, it is important to include all sources of paracetamol when checking a person's dose for toxicity. In addition to being sold by itself, paracetamol may be included in the formulations of various analgesics and cold/flu remedies as a way to increase the pain-relieving properties of the medication. To prevent overdoses, one should read medication labels carefully for the presence of paracetamol and check with a pharmacist before using over-the-counter medications.

[edit] Risk factors for toxicity

Chronic excessive ethanol (alcohol) consumption can induce CYP2E1, thus increasing the potential toxicity of paracetamol.[9] For this reason, other analgesics such as aspirin or ibuprofen are sometimes recommended for hangovers.

Fasting is a risk factor, possibly because of depletion of hepatic glutathione reserves.

It is well documented that concomitant use of the CYP2E1 inducer isoniazid increases the risk of hepatotoxicity, though whether CYP2E1 induction is related to the hepatotoxicity in this case is unclear.[10][11] Concomitant use of other drugs which induce CYP enzymes such as antiepileptics (including carbamazepine, phenytoin, barbituates, etc) have also been reported as risk factors.

[edit] Natural history

Individuals who have overdosed on paracetamol generally have no specific symptoms for the first 24 hours. Although nausea, vomiting, and diaphoresis may occur initially, these symptoms generally resolve after several hours. After resolution of these symptoms, individuals tend to feel better, and may believe that the worst is over. If a toxic dose was absorbed, after this brief feeling of relative wellness, the individual develops overt hepatic failure. In massive overdoses, coma and metabolic acidosis may occur prior to hepatic failure.

Damage generally occurs in hepatocytes as they metabolize the paracetamol. Rarely, acute renal failure also may occur. This is usually caused by either hepatorenal syndrome or Multiple organ dysfunction syndrome. Acute renal failure may also be the primary clinical manifestation of toxicity. In these cases, it has been suggested that the toxic metabolite is produced more in the kidneys than in the liver.[12]

The prognosis of paracetamol toxicity varies depending on the dose and the appropriate treatment. In some cases, massive hepatic necrosis leads to fulminant hepatic failure with complications of bleeding, hypoglycemia, renal failure, hepatic encephalopathy, cerebral edema, sepsis, multiple organ failure, and death within days. In many cases, the hepatic necrosis may run its course, hepatic function may return, and the patient may survive with liver function returning to normal in a few weeks.

[edit] Diagnosis

Evidence of liver toxicity may develop in 1 to 4 days, although in severe cases it may be evident in 12 hours. Right upper quadrant tenderness may be present. Laboratory studies may show evidence of massive hepatic necrosis with elevated AST, ALT, bilirubin, and prolonged coagulation times (particularly, elevated prothrombin time). After paracetamol overdose, when AST and ALT exceed 1000 IU/L, paracetamol-induced hepatotoxicity can be diagnosed. However, the AST and ALT levels can exceed 10,000 IU/L. Generally the AST is somewhat higher than the ALT in paracetamol-induced hepatotoxicity.

A drug nomogram was developed in 1975 which estimated the risk of toxicity based on the serum concentration of paracetamol at a given number of hours after ingestion.[13] To determine the risk of potential hepatotoxicity, the paracetamol level is traced along the standard nomogram. A paracetamol level drawn in the first four hours after ingestion may underestimate the amount in the system because paracetamol may still be in the process of being absorbed from the gastrointestinal tract. Delay of the initial draw for the paracetamol level to account for this is not recommended since the history in these cases is often poor and a toxic level at any time is a reason to give the antidote.

[edit] Treatment

[edit] Initial measures

The initial treatment for uncomplicated paracetamol overdose, similar to any other overdose, is gastrointestinal decontamination. In addition, the antidote, acetylcysteine plays an important role. Paracetamol absorption from the gastrointestinal tract is complete within 2 hours under normal circumstances, so decontamination is most helpful if performed within this timeframe. Absorption may be somewhat slowed when it is ingested with food. There is considerable room for physician judgement regarding gastrointestinal decontamination, activated carbon administration is the most commonly used procedure, however, gastric lavage may also be considered if the amount ingested is potentially life threatening and the procedure can be performed within 60 minutes of ingestion.[14] Syrup of ipecac has no role in paracetamol overdose because the vomiting it induces delays the effective administration of activated carbon and oral acetylcysteine.

Activated carbon adsorbs paracetamol, reducing its gastrointestinal absorption. Administering activated carbon also poses less risk of aspiration than gastric lavage. Previously there was reluctance to give activated carbon in paracetamol overdose, because of concern that it may also absorb acetylcysteine. Studies have shown that no more than 39% of an oral acetylcysteine is absorbed when they are administered together.[15] Other studies have shown that activated carbon seems to be beneficial to the clinical outcome. It appears the most benefit from activated carbon is gained if it is given with 2 hours of ingestion.[16] However, administering activated carbon later than this can be considered in patients who may have delayed gastric emptying due to co-ingested drugs or following ingestion of sustained or delayed release paracetamol preparations. Activated carbon should also be administered if co-ingested drugs warrant decontamination. There are conflicting recommendations[15][17] regarding whether to change the dosing of oral acetylcysteine after the administration of activated carbon, and even whether the dosing of acetylcysteine needs to be altered at all.

[edit] Acetylcysteine

Acetylcysteine works to 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.

If the patient presents less than 8 hours after paracetamol overdose, then acetylcysteine significantly reduces the risk of serious hepatotoxicity. If NAC 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. Although acetylcysteine is most effective if given early, it still has beneficial effects if given as late as 48 hours after ingestion.[18] 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.

In United States practice, intravenous (IV) and oral administration are considered to be equally effective. However, IV is the only recommended route in Australasian and British practice.

Oral acetylcysteine is given as a 140 mg/kg loading dose followed by 70 mg/kg every 4 hours for 17 more doses. Oral acetylcysteine may be poorly tolerated due to its unpleasant taste, odor, and its tendency to cause nausea and vomiting. It can be diluted to a 5% solution, from its marketed 10% or 20% solutions, to improve palatability. Where oral acetylcysteine is required, the inhalation formulation of acetylcysteine (Mucomyst) is often given orally. The respiratory formulation can also be diluted and filter sterilized by a hospital pharmacist for IV use, however this is an uncommon practice. If repeat doses of charcoal are indicated because of another ingested drug, then subsequent doses of carbon and acetylcysteine should be staggered every two hours.

Intravenous acetylcysteine (Parvolex/Acetadote) 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.[19]

Baseline laboratory studies include bilirubin, AST, ALT, and prothrombin time (with INR). Studies are repeated at least daily. 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.

[edit] Prognosis

The mortality rate from paracetamol overdose increases 2 days after the ingestion, reaches a maximum on day 4, and then gradually decreases. Patients with a poor prognosis are usually identified for likely liver transplantation. Acidemia is the most important single indicator of probable mortality and the need for transplantation. A mortality rate of 95% without transplant was reported in patients who had a documented pH of < 7.30. Other indicators of poor prognosis include renal insufficiency, grade 3 or worse hepatic encephalopathy, a markedly elevated prothrombin time, or a rise in prothrombin time from day 3 to day 4. One study has shown that a factor V level less than 10% of normal indicated a poor prognosis (91% mortality) while a ratio of factor VIII to factor V of less than 30 indicated a good prognosis (100% survival).

المشاركة الأصلية بواسطة Bassam AlRihawi

[

FROM WIKIPEDIA

Toxicity

Paracetamol has a narrow therapeutic index – the therapeutic dose is close to the toxic dose. Additionally, paracetamol is contained in many preparations (both over-the-counter and prescription only medications). This means that, despite being one of the safest analgesics available at recommended doses, there is a large potential for overdose and toxicity.[6] Without timely treatment, paracetamol overdose can lead to liver failure and death within days. Because of the wide over-the-counter availability of the drug, it is sometimes used in suicide attempts by those unaware of the prolonged timecourse, and high morbidity (likelihood of a severe or fatal outcome) associated with paracetamol-induced toxicity.

In the UK, sales of over-the-counter Paracetamol in pharmacies are restricted to packs of 32 tablets per customer per occasion (only 16 tablets in non-pharmacy stores). In Ireland, the limits are 24 and 12 tablets respectively.

[edit] Mechanism of toxicity

As discussed above in the section regarding metabolism, paracetamol is mostly converted to inactive compounds via Phase II metabolism by conjugation with sulfate and glucuronide, with a small portion being oxidized via the cytochrome P450 enzyme system. Cytochrome P450 2E1 (CYP2E1) converts paracetamol to a highly reactive intermediary metabolite, N-acetyl-p-benzo-quinone imine (NAPQI).

Under normal conditions, NAPQI is detoxified by conjugation with glutathione. In cases of paracetamol toxicity, the sulfate and glucuronide pathways become saturated, and more paracetamol is shunted to the cytochrome P450 system to produce NAPQI. As a result, hepatocellular supplies of glutathione become exhausted and NAPQI is free to react with cellular membrane molecules, resulting in widespread hepatocyte damage and death, clinically leading to acute hepatic necrosis. In animal studies, 70% of hepatic glutathione must be depleted before hepatotoxicity occurs.

[edit] Toxic dose

The toxic dose of paracetamol is highly variable. In adults, single doses above 10 grams or 150 mg/kg have a reasonable likelihood of causing toxicity.[7] Toxicity can also occur when multiple smaller doses within 24 hours exceeds these levels, or even with chronic ingestion of doses as low as 4 g/day, and death with as little as 6 g/day.

In children acute doses above 200 mg/kg could potentially cause toxicity. This higher threshold is largely due to children having relatively larger kidneys and livers than adults and hence being more tolerant of paracetamol overdose than adults.[8] Acute paracetamol overdose in children rarely causes illness or death with chronic supratherapeutic doses being the major cause of toxicity in children.

Since paracetamol is often included in combination with other drugs, it is important to include all sources of paracetamol when checking a person's dose for toxicity. In addition to being sold by itself, paracetamol may be included in the formulations of various analgesics and cold/flu remedies as a way to increase the pain-relieving properties of the medication. To prevent overdoses, one should read medication labels carefully for the presence of paracetamol and check with a pharmacist before using over-the-counter medications.

[edit] Risk factors for toxicity

Chronic excessive ethanol (alcohol) consumption can induce CYP2E1, thus increasing the potential toxicity of paracetamol.[9] For this reason, other analgesics such as aspirin or ibuprofen are sometimes recommended for hangovers.

Fasting is a risk factor, possibly because of depletion of hepatic glutathione reserves.

It is well documented that concomitant use of the CYP2E1 inducer isoniazid increases the risk of hepatotoxicity, though whether CYP2E1 induction is related to the hepatotoxicity in this case is unclear.[10][11] Concomitant use of other drugs which induce CYP enzymes such as antiepileptics (including carbamazepine, phenytoin, barbituates, etc) have also been reported as risk factors.

[edit] Natural history

Individuals who have overdosed on paracetamol generally have no specific symptoms for the first 24 hours. Although nausea, vomiting, and diaphoresis may occur initially, these symptoms generally resolve after several hours. After resolution of these symptoms, individuals tend to feel better, and may believe that the worst is over. If a toxic dose was absorbed, after this brief feeling of relative wellness, the individual develops overt hepatic failure. In massive overdoses, coma and metabolic acidosis may occur prior to hepatic failure.

Damage generally occurs in hepatocytes as they metabolize the paracetamol. Rarely, acute renal failure also may occur. This is usually caused by either hepatorenal syndrome or Multiple organ dysfunction syndrome. Acute renal failure may also be the primary clinical manifestation of toxicity. In these cases, it has been suggested that the toxic metabolite is produced more in the kidneys than in the liver.[12]

The prognosis of paracetamol toxicity varies depending on the dose and the appropriate treatment. In some cases, massive hepatic necrosis leads to fulminant hepatic failure with complications of bleeding, hypoglycemia, renal failure, hepatic encephalopathy, cerebral edema, sepsis, multiple organ failure, and death within days. In many cases, the hepatic necrosis may run its course, hepatic function may return, and the patient may survive with liver function returning to normal in a few weeks.

[edit] Diagnosis

Evidence of liver toxicity may develop in 1 to 4 days, although in severe cases it may be evident in 12 hours. Right upper quadrant tenderness may be present. Laboratory studies may show evidence of massive hepatic necrosis with elevated AST, ALT, bilirubin, and prolonged coagulation times (particularly, elevated prothrombin time). After paracetamol overdose, when AST and ALT exceed 1000 IU/L, paracetamol-induced hepatotoxicity can be diagnosed. However, the AST and ALT levels can exceed 10,000 IU/L. Generally the AST is somewhat higher than the ALT in paracetamol-induced hepatotoxicity.

A drug nomogram was developed in 1975 which estimated the risk of toxicity based on the serum concentration of paracetamol at a given number of hours after ingestion.[13] To determine the risk of potential hepatotoxicity, the paracetamol level is traced along the standard nomogram. A paracetamol level drawn in the first four hours after ingestion may underestimate the amount in the system because paracetamol may still be in the process of being absorbed from the gastrointestinal tract. Delay of the initial draw for the paracetamol level to account for this is not recommended since the history in these cases is often poor and a toxic level at any time is a reason to give the antidote.

[edit] Treatment

[edit] Initial measures

The initial treatment for uncomplicated paracetamol overdose, similar to any other overdose, is gastrointestinal decontamination. In addition, the antidote, acetylcysteine plays an important role. Paracetamol absorption from the gastrointestinal tract is complete within 2 hours under normal circumstances, so decontamination is most helpful if performed within this timeframe. Absorption may be somewhat slowed when it is ingested with food. There is considerable room for physician judgement regarding gastrointestinal decontamination, activated carbon administration is the most commonly used procedure, however, gastric lavage may also be considered if the amount ingested is potentially life threatening and the procedure can be performed within 60 minutes of ingestion.[14] Syrup of ipecac has no role in paracetamol overdose because the vomiting it induces delays the effective administration of activated carbon and oral acetylcysteine.

Activated carbon adsorbs paracetamol, reducing its gastrointestinal absorption. Administering activated carbon also poses less risk of aspiration than gastric lavage. Previously there was reluctance to give activated carbon in paracetamol overdose, because of concern that it may also absorb acetylcysteine. Studies have shown that no more than 39% of an oral acetylcysteine is absorbed when they are administered together.[15] Other studies have shown that activated carbon seems to be beneficial to the clinical outcome. It appears the most benefit from activated carbon is gained if it is given with 2 hours of ingestion.[16] However, administering activated carbon later than this can be considered in patients who may have delayed gastric emptying due to co-ingested drugs or following ingestion of sustained or delayed release paracetamol preparations. Activated carbon should also be administered if co-ingested drugs warrant decontamination. There are conflicting recommendations[15][17] regarding whether to change the dosing of oral acetylcysteine after the administration of activated carbon, and even whether the dosing of acetylcysteine needs to be altered at all.

[edit] Acetylcysteine

Acetylcysteine works to 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.

If the patient presents less than 8 hours after paracetamol overdose, then acetylcysteine significantly reduces the risk of serious hepatotoxicity. If NAC 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. Although acetylcysteine is most effective if given early, it still has beneficial effects if given as late as 48 hours after ingestion.[18] 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.

In United States practice, intravenous (IV) and oral administration are considered to be equally effective. However, IV is the only recommended route in Australasian and British practice.

Oral acetylcysteine is given as a 140 mg/kg loading dose followed by 70 mg/kg every 4 hours for 17 more doses. Oral acetylcysteine may be poorly tolerated due to its unpleasant taste, odor, and its tendency to cause nausea and vomiting. It can be diluted to a 5% solution, from its marketed 10% or 20% solutions, to improve palatability. Where oral acetylcysteine is required, the inhalation formulation of acetylcysteine (Mucomyst) is often given orally. The respiratory formulation can also be diluted and filter sterilized by a hospital pharmacist for IV use, however this is an uncommon practice. If repeat doses of charcoal are indicated because of another ingested drug, then subsequent doses of carbon and acetylcysteine should be staggered every two hours.

Intravenous acetylcysteine (Parvolex/Acetadote) 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.[19]

Baseline laboratory studies include bilirubin, AST, ALT, and prothrombin time (with INR). Studies are repeated at least daily. 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.

[edit] Prognosis

The mortality rate from paracetamol overdose increases 2 days after the ingestion, reaches a maximum on day 4, and then gradually decreases. Patients with a poor prognosis are usually identified for likely liver transplantation. Acidemia is the most important single indicator of probable mortality and the need for transplantation. A mortality rate of 95% without transplant was reported in patients who had a documented pH of < 7.30. Other indicators of poor prognosis include renal insufficiency, grade 3 or worse hepatic encephalopathy, a markedly elevated prothrombin time, or a rise in prothrombin time from day 3 to day 4. One study has shown that a factor V level less than 10% of normal indicated a poor prognosis (91% mortality) while a ratio of factor VIII to factor V of less than 30 indicated a good prognosis (100% survival).

copying FROM WIKIPEDIA is not the kind of partecipating i was expecting ...
anyways, good thing you stoped by even for a copy and paste action ...
welcome dude ...
--------------
Mr.Bassam AlRihawi ah .. one more thing ..-----> i'm getting bored of my self, but i can't handle it .. gotta talk !!!!

i noticed that you just came in .. copied an pasted .. didn't say your thought about it .. if any??
but i got you an excuse .. look =>
According to a new study .. pressing the THANKS button can cause:1-cancer 2- Parkinson 3-HTN 4-Liver failure ...

so goog thing you didn't !!! ..

Later ..

lol ok
Another nervous guy, got to deal with a lot of them these days.
well I hope that I understand what are you talking about.

ADDING SOME IMPORTANT AND SCIENTIFIC SOURCES IS A GOOD PARTICIPATION I THINK.

you can note that I am the only one who added something to the discussion
finally Neither YOU nor I or anybody of this forum will tell you something that he found Himself about PARACETAMOL beacause it is used from a long time and hase been tested in all directions and cases.
WHAT i COPIED and pasted From wikipedia is a compimentary information for the subject.

thats all

IT is allowed to copy past but you have to list the sources I think I did that pretty clearly.

anyways thank you for the critic it is always constructive.

بسااام شكرا على الافاده اكثر

loooooool ... who`s nervous now ???

i'm so sorry my comment was misunderstood like that .. it was supposed 2 b funny .. :-( .. nothing more
it didn't come out like i hoped after all ...

anyways, i repeat i`m sorry if you felt ensulted by any mean ...
note: you acted really defensive --->shocked me!
but .. all i asked is that befor you add smthin.. just say THANKS at least, am i wrong?



and let us all be happy again ----->



note : Mr.subah ----> what's your post supposed to mean .. ?
if you don't like what i wrote .. say so ..
believe me i won't take it personally :-) -- > i won't care to be more specific

well after reading myself i found that I was really aggressive, plz dont consider this one it was not intented, like i said i got to deal with a lot of nervous men this makes me one of them naturally. lol
Sorry

By the way I ve just discovered the thank you botton