Paracetamol

Paracetamol has a painkiller, as well as antipyretic effect.

[1], [2]

Indications Paracetamol

It is used for therapy in such cases:

• various pain syndromes (tooth or headache, myalgia, algomenorrhea, and in addition, arthralgia, neuralgia and migraine);
• state of fever resulting from the development of infectious diseases.

If the need for rapid elimination of inflammation and pain (for example, after a surgical procedure), and in addition, in cases where oral administration of the drug cannot be performed (suspension or tablets), intravenous administration of the substance can be prescribed.

The drug is prescribed for symptomatic treatment, as well as reducing the intensity of pain and inflammation at the time of its use. It does not affect the progression of pathology.

[3], [4], [5]

Release form

The release of the drug produced:

• in tablets (in the amount of 6 or 10 pieces inside blister or cell-free plates);
• in the form of a 2.4% syrup (inside 50 ml bottles), as well as 2.4% suspension (in 0.1 l bottles);
• in rectal suppositories with a volume of 0.08, 0.17, and 0.33 g (in the amount of 5 pieces inside a blister pack; in a box - 2 blisters).

[6], [7], [8]

Pharmacodynamics

Paracetamol is an analgesic substance of a non-narcotic nature. Its medicinal effects and properties are in the ability to block (mainly inside the CNS) of the elements COX-1, as well as COX-2. At the same time, the substance affects the pain and thermoregulation centers.

The medication does not have anti-inflammatory properties (this effect is extremely small, which allows not to pay attention to it), because its effect on COX is neutralized by enzyme peroxidase inside the inflamed tissues.

Since the drug does not block the binding of Pg inside peripheral tissues, it does not adversely affect the processes of water-electrolyte metabolism inside the body and the mucous membrane of the digestive tract.

[9], [10], [11], [12], [13], [14], [15]

Pharmacokinetics

The drug absorption is quite high, its Cmax values are in the range of 5-20 μg / ml. Paracetamol reaches these indicators after 0.5-2 hours. The active element is able to penetrate the BBB.

When breastfeeding, the drug is excreted with the mother's milk (its concentration does not exceed 1% mark).

The drug is subject to processes of hepatic biotransformation. Metabolism involving microsomal hepatic enzymes leads to the formation of toxic metabolic intermediates (such as N-acetyl-b-benzoquinone imine). These components can lead to damage and necrosis of the liver cells, if there are reduced levels of glutathione in the body. The depletion of stocks of this element is observed when using 10+ g of paracetamol.

Two other metabolic pathways of paracetamol are the process of conjugation with sulfates (often observed in newborns, especially premature), as well as with glucuronides (mostly observed in adults).

Conjugated metabolic products have a weak drug activity (this includes the toxic effect).

Half-life period is within 1-4 hours (for elderly people, this value may be higher). Excretion occurs mainly through the kidneys, in the form of conjugates. Only 3% of used paracetamol is excreted unchanged.

[16], [17], [18], [19], [20], [21]

Dosing and administration

Serving sizes for adolescents (from 12 years old, if their weight is more than 40 kg) and adults make up a maximum of 4 g per day (20 tablets with a volume of 0.2 g or 8 tablets with a volume of 0.5 g).

For 1 use should be taken at 0.5 g of the substance (if necessary, may be 1 g). Tablets drugs are allowed to use up to 4 times per day. The duration of therapy is 5-7 days.

Children’s Paracetamol tablets can be consumed from 2 years old. Younger children are required to take 0.5 tablets with a volume of 0.2 g with 4-6-hour intervals. A child older than 6 years old is allowed to take a whole pill, with the frequency indicated above.

Tablets of 325 mg can be taken from 10 years. Children of the age group of 10-12 years of age are prescribed for oral administration 2-3 times per day (the maximum dose should not be exceeded - in this category of patients, it is 1500 mg per day).

Teenagers from 12 years old and adults should take 1-3 tablets with a 4-6 hour interval. You can not take a day more than 4 g of the drug, and the intervals between use should be at least 4 hours.

The use of suppositories.

Suppositories are administered rectally - into the rectum. Before the procedure is necessary to clean the intestines.

The size of the dosage of drugs in suppositories for the child should be calculated, taking into account the age and weight of the patient. 80 mg suppositories are used for infants from 3 months of age; 170 mg suppositories for children 1-6 years old; 330 mg suppositories for children 7-12 years old.

To enter the suppository should be on the first thing, while adhering to a minimum of 4-hour gap between procedures; 3-4 suppositories are administered per day (the number of suppositories depends on the patient's condition).

Children are often prescribed Paracetamol in suppositories or syrup. When comparing their therapeutic efficacy, it is noted that the syrup has a more rapid, and suppositories have a longer effect.

Because it is safer and more convenient to use the suppository (compared to pills), young children are recommended to prescribe them (for example, for newborns they are considered the optimal dosage form of this medication).

For a child, a toxic dose of drugs is 150+ mg / kg. Thus, a child weighing 20 kg can die from the use of 3 g of substance per day.

Selection of a 1-fold portion is made according to the formula 10-15 mg / kg with 2-3 times daily use (with 4-6-hour intervals). The maximum dosage of medication for a child is 60 mg / kg per day.

Mode of use of the suspension and syrup for children.

Syrup can be prescribed to babies from 3 months old, and the suspension can be applied already from the 1st month of life (because it does not contain sugar).

Sizes of 1-fold portions of syrup for different age groups:

• babies 3-12 months - 0.5-1 teaspoon;
• children 1-6 years old - 1-2 teaspoons;
• children 6-14 years old - 2-4 teaspoons.

The frequency of admission varies from 1-4 times per day (the child must take the drug at least 4-hour intervals).

The dosage of the infant suspension is similar to that used for syrup. The scheme of use of drugs for infants up to 3 months of age is chosen exclusively by the attending doctor.

The sizes of portions of drugs need to be selected, taking into account also the weight of the child. You can prescribe the use of a maximum of 10-15 mg / kg for 1 use and not more than 60 mg / kg per day. Thus, a 3-year-old child with an average weight of 15 kg should be consumed 150-225 mg of medication for 1 dose.

In the absence of a result, if a suspension or syrup is used in the indicated portions, Paracetamol needs to be replaced by some analogue having another active ingredient.

To eliminate the fever, sometimes a combination of paracetamol with analgin is used (if the temperature is between 38.5 ° C and it is difficult to knock it down). The sizes of portions are the following - paracetamol in the dosages indicated above (taking into account age and weight); analgin - 0.3-0.5 mg / kg.

This combination can not be used often, because the use of aspirin leads to irreversible changes in the blood composition.

A “triad” may also be used, which, in addition to paracetamol, includes aspirin with analgin. Paracetamol can also be supplemented with suprastinum with no-spaa, analginum with no-spaa, or suprastinum with analginum.

But shpa (papaverine can also be used instead) helps open spasmodic capillaries, and antihistamines (such as tavegil or suprastin) potentiate the effects of antipyretic drugs.

If you take the drug is required to provide antipyretic effect, it can be used for a maximum of 3 days in a row.

If the drug is used to eliminate pain, the treatment cycle should last a maximum of 5 days. The possibility of its subsequent use is determined by the treating doctor.

It is required to remember that the drug helps to eliminate the symptoms of the disease (such as dental or headaches), but the very cause of their appearance does not cure.

[26], [27], [28], [29], [30], [31]

Use Paracetamol during pregnancy

The drug may pass through the placenta, but no negative impact on the development of the fetus has yet been identified.

During the tests, it was determined that the use of Paracetamol during pregnancy (especially in the second half of it) increases the likelihood of asthma, respiratory disorders, wheezing and allergy symptoms in a child.

It should be borne in mind that in the 3rd trimester, the toxic effects of infectious diseases can be just as dangerous as the effects of individual drugs. With hyperthermia, the mother is likely to have hypoxia in the fetus.

When using drugs on the 2nd trimester (more specifically, starting from the 3rd month and approximately until the 18th week), the child may experience abnormalities in the development of internal organs, often manifested after birth. Because of this, the drug in this period is used only sporadically and solely as a last resort.

But at the same time, this particular medicine is considered the safest painkiller for pregnant women.

Taking large portions of the drug during pregnancy can have a negative impact on the kidneys and liver. If a pregnant woman has a fever in connection with SARS or influenza, Paracetamol is required to take 0.5 tablets per use. This therapy should last for a maximum of 7 days.

Only a minimal amount of the drug passes into the mother's milk during lactation. This allows you to not interrupt breastfeeding in cases where the drug is used for a maximum of 3 days in a row.

During lactation, it is allowed to take a maximum of 3-4 tablets of 0.5 g per day (tablets are taken after the feeding procedure). It is recommended to feed the next time at least 3 hours after drinking the drug.

Contraindications

Main contraindications:

• the presence of intolerance regarding the drug;
• congenital hyperbilirubinemia;
• lack of G6FD enzyme;
• severe hepatic or renal diseases;
• blood diseases;
• alcohol addiction;
• severe anemia or leukopenia.

[22], [23], [24]

Side effects Paracetamol

Negative manifestations after taking the drug usually have the form of signs of severe sensitivity (allergies) - pruritus, angioedema, urticaria and rash.

Sometimes the use of the drug leads to the development of disorders of hematopoiesis (thrombocyto-, neutro-, leuco- or pancytopenia, as well as agranulocytosis) and dyspeptic symptoms.

Prolonged use in large portions can provoke a hepatotoxic effect.

[25],

Overdose

Manifestations of intoxication that occur on the first day: pallor of the skin, pain in the abdominal zone, nausea, metabolic acidosis, vomiting, anorexia, and the breakdown of glucose metabolism.

After 12–48 o'clock, symptoms of hepatic dysfunction may develop.

In severe overdose, pancreatitis is noted, liver failure (there is progressive encephalopathy on its background), insufficiency of the renal activity in the acute form (accompanied by necrosis of the tubular nature), arrhythmia and comatose state.

In some cases, when poisoning with Paracetamol, death may occur (with very severe intoxication).

For the treatment of disorders, the victim requires the introduction of methionine with acetylcysteine (in the period of 8-9 hours), which are precursors of glutathione binding processes, and with it donators of SH categories.

Subsequent therapy depends on the prescription of the drug and its level inside the blood.

[32], [33], [34], [35], [36], [37], [38],

Interactions with other drugs

The drug weakens the effectiveness of uricosuric drugs. Using together with large portions of the drug enhances the effects of anticoagulants (by reducing the production of procoagulants inside the liver).

Drugs that promote the induction of microsome oxidation processes inside the liver, as well as hepatotoxic drugs and ethyl alcohol increase the production of hydroxylated metabolic products with drug activity, which can cause severe poisoning even with minimal overdose.

Drug efficacy decreases with continued use of barbiturates. Ethyl alcohol causes the appearance of pancreatitis in acute form. Drugs that inhibit the oxidation of microsomes inside the liver, reduce the likelihood of hepatotoxic effects.

Prolonged combination with other NSAIDs can provoke necrotic papillitis, analgesic nephropathy, as well as the development of the terminal (dystrophic) stage of kidney failure.

The combination of Paracetamol (in large portions) with salicylates over an extended period of time increases the risk of developing kidney or urinary carcinoma. Diflunisal 50% increases the plasma values of paracetamol, which increases the likelihood of hepatotoxicity.

Myelotoxic substances potentiate the hematotoxic properties of drugs; antispasmodics lead to a delay in its absorption; cholesterol with enterosorbents reduce its bioavailability.

[39], [40], [41], [42], [43]

Storage conditions

Paracetamol is required to be kept in a dark and dry place, closed to children. Temperature indicators for syrup - maximum 18 ° C (it can not be frozen); for suppositories, a maximum of 20 ° C.

[44], [45], [46]

Shelf life

Paracetamol in suppositories and syrup can be used within 24 months from the moment of release of the medicine. Shelf life of tablets is 36 months.

[47]

Analogs

Paracetamol-containing substances such as Strimol, Paracetamol 325, Perfalgan with Paracetamol MC, Cefecon D, Ifimol, Flutabs and Paracetamol Extratab with Panado Daleron, as well as Paracetamol UBF and Efferalgan.

Drugs that have a similar mechanism of action, but a different active ingredient: Antiflu, Coldrex, Antigrippin, Novalgin and Solpadein with Caffetine and Vervex, and in addition, Maxicold, TheraFlu, Panadol Extra and Femizol.

[48], [49], [50], [51], [52], [53], [54], [55],

Reviews

Paracetamol is most often mentioned in the context of treating children, since they are more likely to become infected with SARS, and the medicine is most effective in such diseases.

Parents generally leave positive reviews of the drug - it quickly lowers the temperature and reduces the severity of the negative symptoms of fever. At the same time, it is well tolerated by people of different ages - it rarely provokes the development of negative signs typical of NSAIDs.

Doctors are calling to not forget that the medicine removes only the manifestations of the disease, not eliminating it itself, and also remind you that in order to obtain a positive effect it is very important to choose the form of drug release and calculate the required dosage.