Acetaminophen or paracetamol is a widely used over-the-counter

analgesic (pain reliever) and antipyretic (fever reducer).

It is commonly used for the relief of headaches, and other minor

aches and pains, and is a major ingredient in numerous cold and flu
remedies. In combination with opioid analgesics, paracetamol can also be
used in the management of more severe pain (such as in advanced
cancer).

Metabolism
Paracetamol is metabolized primarily in the liver, into non-toxic products.
Three metabolic pathways are notable:
Glucuronidation is believed to account for 40% to two-thirds of the
metabolism of paracetamol.
Sulfation (sulfate conjugation) may account for 20–40%.
N-hydroxylation and rearrangement, then GSH conjugation, accounts for
less than 15%. The hepatic cytochrome P450 enzyme system metabolizes
paracetamol, forming a minor yet significant alkylating metabolite known
as NAPQI (N-acetyl-p-benzo-quinone imine). NAPQI is then irreversibly
conjugated with the sulfhydryl groups of glutathione.
All three pathways yield final products that are inactive, non-toxic, and
eventually excreted by the kidneys.
PREGNANCY: Acetaminophen is used in all stages of pregnancy and is
the drug of choice for short-term treatment of fever and minor pain during
pregnancy.
NURSING MOTHERS: Acetaminophen is excreted in breast milk in
small quantities. However, acetaminophen use by the nursing mother
appears to be safe.

The usual adult dosage is:

Single Doses Maximum 24-

(Range) Hour Dose

Codeine
15 mg to 60 mg 360 mg
Phosphate

Acetaminophen 300 mg to 1000 mg 4000 mg

Doses may be repeated up to every 4 hours.

Acetaminophen and codeine

Codeine is in a group of drugs called narcotic pain relievers.
Acetaminophen is a less potent pain reliever that increases the effects of
codeine.
The combination of acetaminophen and codeine is used to relieve
moderate to severe pain.

An overdose of acetaminophen can damage your liver. Adults should not

take more than 1 gram (1000 mg) of acetaminophen per dose or 4 grams
(4000 mg) per day.

Read more: http://www.drugs.com/mtm/acetaminophen-and-

codeine.html#ixzz0tctapBLj

Inhibition of cytochrome P4502D6 activity

Paroxetine, with a daily dosage from 20 to 40 mg, is an effective tool in
normalizing the metabolic status of CYP2D6 ultrarapid metabolizers.
Treatment
A single or multiple overdose with acetaminophen and codeine is a
potentially lethal polydrug overdose and consultation with a regional
poison control center is recommended.
Immediate treatment includes support of cardiorespiratory function and
measures to reduce drug absorption. Vomiting should be induced
mechanically, or with syrup of ipecac, if the patient is alert (adequate
pharyngeal and laryngeal reflexes). Oral activated charcoal (1g/kg)
should follow gastric emptying. The first dose should be accompanied by
an appropriate cathartic. If repeated doses are used, the cathartic might be
included with alternate doses as required. Hypotension is usually
hypovolemic and should respond to fluids. Vasopressors and other
supportive measures should be employed as indicated. A cuffed endo-
tracheal tube should be inserted before gastric lavage of the unconscious
patient and, when necessary, to provide assisted respiration.
Meticulous attention should be given to maintaining adequate pulmonary
ventilation. In severe cases of intoxication, peritoneal dialysis, or
preferably hemodialysis, may be considered. If hypoprothrombinemia
occurs due to acetaminophen overdose, vitamin K should be administered
intravenously.
Naloxone, a narcotic antagonist, can reverse respiratory depression and
coma associated with opioid overdose. Naloxone hydrochloride 0.4 mg to
2 mg is given parenterally. Since the duration of action of codeine may
exceed that of the naloxone, the patient should be kept under continuous
surveillance and repeated doses of the antagonist should be administered
as needed to maintain adequate respiration. A narcotic antagonist should
not be administered in the absence of clinically significant respiratory or
cardiovascular depression.
If the dose of acetaminophen may have exceeded 140 mg/kg,
acetylcysteine should be administered as early as possible. Serum
acetaminophen levels should be obtained, since levels four or more hours
following ingestion help predict acetaminophen toxicity. Do not await
acetaminophen assay results before initiating treatment. Hepatic enzymes
should be obtained initially, and repeated at 24-hour intervals.
Methemoglobinemia over 30% should be treated with methylene blue by
slow intravenous administration.