Paracetamol for pain

Obviously, the question - does Paracetamol help with pain - may arise in cases where the tablet of this analgesic-antipyretic did not give the expected analgesic effect. However, this is the most commonly used medicine for pain and fever, and WHO has included it in the list of essential medicines - the most effective and safest.[1]

Other trade names for Paracetamol: Acetaminophen, Amphenol, Panadol, Tylenol, Taynol, Tayolfen Hot, Dafalgan, Paralin, Piremol, Perfalgan,  Kalpol , Rapidol, Mexalen, Milistan, Anapiron, Tempramol, Streamol, Flutabs and Efferapegan (Sheffel) ( candles).

In addition, Paracetamol is part of drugs such as Askofen, Citramon, Excedrine and Farmadol (paracetamol + acetylsalicylic acid + caffeine), Daleron C (with vitamin C), Fanigan and Panoxen (with diclofenac), Papaverine (in combination with drotaverine), Fervex (with ascorbic acid and the antihistamine pheniramine), Tamipul (with ibuprofen and caffeine), Pentalgin (with analgin, caffeine, phenobarbital and codeine), Pharmacitron (with pheniramine, phenylephrine and ascorbic acid).

Indications Paracetamol

Paracetamol is taken as an antipyretic for colds and SARS (when body temperature rises to + 38.5 ° C and above), as well as in cases of low-grade febrile states of various etiologies.

Does Paracetamol relieve pain? It removes, but not all, due to its pharmacological properties. With mild to moderate manifestation of pain, as a symptomatic agent, Paracetamol is used:

• from a headache, including with migraine, with psychogenic headache (tension cephalgia), headache of toxic etiology - from a hangover; The combination of caffeine and paracetamol in the treatment of a hangover can cause a risk of liver damage.
• from toothache;
• with minor arthralgia and myalgia, that is, from pain in the joints and muscles. Paracetamol can relieve pain in mild arthritis, but does not affect underlying inflammation, redness, and swelling of the joint;[2]
• from back and lower back pain associated with myositis. [3]

Paracetamol will help women with menstrual (menstrual) pain or algodismenorrhea (although Spazmalgon or Baralgin can better cope with severe pain). However, some studies have compared NSAIDs with acetaminophen (paracetamol). They suggest that NSAIDs are slightly more effective than acetaminophen in relieving menstrual cramps.[4]

Paracetamol is ineffective for pain in the kidneys, since renal pain is associated with spasms of the smooth muscles of the ureters, and antispasmodics are used to remove them, in particular, No-spa (Drotaverin), Papaverine hydrochloride, Platifillin, Metacin, Spazmolitin (Difacil). Acetaminophen alone or in combination with low-activity opioids has mild anti-inflammatory properties and has been shown to be effective in both acute and chronic inflammatory conditions of the kidneys [5]. Although acetaminophen is considered the safest non-narcotic analgesic in patients with kidney disease, it should be remembered that it can be nephrotoxic with prolonged use of high doses.[6]

Not applicable Paracetamol for abdominal pain of a spastic nature.

It should be borne in mind that with psychogenic cephalalgia, doctors often recommend to patients not Paracetamol, but drugs that block H-cholinergic receptors (muscle relaxants) and / or sedative antidepressants. And in the case of joint pain, preference is given to non-steroidal anti-inflammatory drugs (NSAIDs), including Diclofenac, Ibuprofen, Indomethacin and others. Paracetamol is used for acute treatment of episodic tension headache in adults.[7], [8]

Otolaryngologists do not prescribe Paracetamol for sore throat or ear, as it does not help reduce inflammation.

Release form

Paracetamol is available in the form of tablets (200, 325 and 500 mg each), capsules (325 mg each), syrup, liquid suspension, injectable solutions, rectal suppositories (0.08 g, 0.17 g and 0.33 g each) each).

Pharmacodynamics

Paracetamol - N-acetyl-p-aminophenol - is an acetyl derivative of the phenolic organic compound aniline (paraaminophenol or 4-aminophenol), i.e. Refers to anilides.

Unlike NSAIDs, Paracetamol practically does not show anti-inflammatory properties, since its pharmacodynamics is primarily due to the effect on the neurons of the thermoregulatory centers of the hypothalamus and spinal cord - with the restoration of their functions that normalize temperature homeostasis.

Paracetamol from pain acts by inhibiting the activity of the membrane enzyme of the brain cortex cells - cyclooxygenase of the third type (COX-3), which provides the synthesis of mediators (prostaglandins) PGE2 and PGF2α.

In addition, the active metabolite of the drug N-arachidonoylaminophenol (AM404), on the one hand, inhibits the production of cyclooxygenase COX-1 and COX-2, and on the other hand, stimulates TRPV1 receptors of nociceptive peripheral nervous system neurons that are involved in the transmission, modulation and integration of pain signals. [9]

Pharmacokinetics

Paracetamol is highly bioavailable (88%) when taken orally, it is well absorbed in the digestive tract and reaches peak blood concentrations 90 minutes after a single dose of the standard dose. Anesthesia lasts for two to four hours.

Paracetamol passes through the BBB and passes into the breast milk of lactating women. With plasma proteins, the relationship of the drug is insignificant (no more than 22-25%), and the half-life is 1.5-2.5 hours.

In the metabolism of Paracetamol, the main load falls on the liver. By sulfotransferase enzymes, it is broken down into pharmacologically inactive conjugates of glucuronic acid and sulfates. And cytochrome P450 enzymes catalyze its oxidation to the reactive metabolite NAPQI (N-acetyl-p-benzoquinone imine), which binds to the sulfhydryl group of liver glutathione and is then excreted in the urine in the form of cysteine and mercapturic acid compounds.[10]

Dosing and administration

The maximum therapeutic dose of Paracetamol is 4 g / day for adults and 50–75 mg kg / day for children. More detailed information on the dosage of various forms of this drug is presented in the publication -  Paracetamol .

How much to drink? The drug is undesirable for more than three to five days in a row.

Application for children

According to the official instructions, the use of Paracetamol for children is allowed from 1 month from the calculation of the daily dose - 50 mg per kilogram of body weight. Pediatricians recommend the suspension of children Kalpol, syrup and rectal suppositories Efferalgan, suspension and rectal suppositories Panadol baby.

In the same way, the maximum allowable daily dosage of the drug is determined, which at an elevated temperature is allowed to be taken up to four times during the day, observing the 4-hour interval between doses.

• From 3 months to 6 months: 2.5 ml of infant paracetamol suspension administered up to four times a day.
• From 6 months to 24 months: 5 ml of infant paracetamol suspension administered up to four times a day.
• From 2 to 4 years: 7.5 ml of infant paracetamol suspension, administered up to four times a day.
• From 4 to 6 years: 10 ml of children's paracetamol suspension, administered up to four times a day.
• From 6 to 8 years: 5 ml of a suspension of paracetamol six plus, prescribed up to four times a day.
• From 8 to 10 years: 7.5 ml of a suspension of paracetamol six plus, is prescribed up to four times a day.
• From 10 to 12 years: 10 ml of a suspension of paracetamol six plus, prescribed up to four times a day.

The American Academy of Pediatrics (AAP) continues to recommend Paracetamol for pain and fever in children, but experts do not recommend it if the child has asthma or the risk of developing it. The use of paracetamol in therapeutic doses is generally safe, although hepatotoxicity may develop at recommended dosages in children.[16]

Use Paracetamol during pregnancy

Paracetamol is the first choice for an antipyretic or analgesic treatment throughout pregnancy. Consequences such as increased risk of asthma [11]or attention deficit hyperactivity disorder were discussed. [12]The consumption of paracetamol, especially in the third trimester, leads to a decrease in the relative amount of hematopoietic stem cells in cord blood, regardless of the mother’s age, BMI in the first trimester, ratio, gestational age and body weight at birth.[13]

During the period of gestation, the use of Paracetamol requires caution, in particular, it is forbidden to take it in the first three months. [14]

Detailed information in the material -  Paracetamol during pregnancy

Breastfeeding paracetamol

All details and recommendations of doctors are given in the article -  Is Paracetamol possible for a nursing mother

Contraindications

Contraindications to taking Paracetamol from pain and temperature include:

• individual hypersensitivity to the drug;
• functional failure of the liver and / or kidneys;
• elevated levels of bilirubin in the blood (congenital or functional);
• hemolytic anemia with a deficiency of the enzyme glucose-6-phosphate dehydrogenase;
• low white blood cell count;
• children under 4 weeks old.

Side effects Paracetamol

Among the possible side effects of Paracetamol are:

• the appearance of skin itching and rashes, including urticaria, as well as exudative erythema and toxic epidermal necrolysis of the type of Stevens-Johnson syndrome;
• the development of an  acute allergic reaction  with angioedema;
• nausea and abdominal pain;
• violation of the uniform composition of the blood, in particular, anemia, a decrease in the level of platelets and leukocytes, an increase in oxidized hemoglobin (methemoglobin);
• kidney damage with the development of interstitial nephritis;

Long-term use of the drug in maximum doses can lead to liver damage. [15]

Overdose

Consumption of a single dose of more than 7 g for an adult and 150 mg / kg for a child is considered potentially toxic to the liver, for details, see -  Hepatotoxicity of Paracetamol .

Signs of an overdose usually begin to appear a few hours after ingestion - in the form of nausea, vomiting, excessive sweating and pain in the hypochondrium. [17]

Without treatment, an overdose can lead to liver failure and death within a few days. Activated carbon can be used to reduce the absorption of the drug.

The antidote is N-acetylcysteine, which, acting as a precursor to glutathione and neutralizing the reactive metabolite of Paracetamol NAPQI, helps to reduce liver damage. [18]

Interactions with other drugs

It should be borne in mind that the simultaneous use of coumarin anticoagulants (Warfarin) and antispasmodics with Paracetamol enhances the effect of these drugs.

With the simultaneous use of antiemetics (metoclopramide or domperidone), the absorption of Paracetamol increases.

Taking Paracetamol along with sedatives from the barbiturate group, anticonvulsants, the anti-tuberculosis antibiotic Rifampicin and ethyl alcohol increases the risk of liver damage.

In addition, the combination of Paracetamol with barbiturates (especially with prolonged use of the latter) leads to a decrease in its antipyretic effect.

Storage conditions

At room temperature (up to + 25 ° C).

Shelf life

The shelf life of the tablets is three years, the shelf life of the syrup and suspension is two years.

Analogs

Paracetamol for pain has many analogues - drugs of the non-narcotic analgesic group, i.e. Headache pills without Paracetamol, including Analgin (Metamizole sodium), Baralgin, Tempalgin,  Sedalgin , Flupirtine (Katadolon, Nolodatak), Diflunisal (Dolobid), etc.

Reviews

Surgeon reviews suggest the use of Paracetamol in combination with non-steroidal anti-inflammatory drugs (NSAIDs) to reduce postoperative pain.

European neurologists recommend using a combination of Paracetamol with caffeine as one of several first-line drugs for the treatment of headaches with migraines and psychogenic headaches.

But with toothache or pain resulting from dental procedures, NSAIDs are recognized as more effective (Ibuprofen, Naproxen, etc.).