Paracetamol for pain

Obviously, the question of whether Paracetamol helps with pain may arise in cases where a tablet of this analgesic-antipyretic does not provide the expected pain-relieving effect. At the same time, it is the most commonly used medicine for pain and fever, and the WHO has included it in the list of essential medicines - the most effective and safe. [ 1 ]

Other trade names of Paracetamol: Acetaminophen, Amphenol, Panadol, Tylenol, Tylol, Tylolfen Hot, Dafalgan, Paralen, Piremol, Perfalgan, Calpol, Rapidol, Mexalen, Milistan, Anapiron, Tempramol, Strimol, Flutabs and Efferalgan (effervescent tablets), Cefekon (suppositories).

In addition, Paracetamol is a component of such drugs as Askofen, Citramon, Excedrin 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), Farmacitron (with pheniramine, phenylephrine and ascorbic acid).

Indications Paracetamol

Paracetamol is taken as an antipyretic for colds and acute respiratory viral infections (when the body temperature rises to +38.5°C and above), as well as in cases of subfebrile febrile conditions of various etiologies.

Does Paracetamol relieve pain? It does, but not all pain, which is due to its pharmacological properties. In mild to moderate pain syndromes, Paracetamol is used as a symptomatic remedy:

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

For women, Paracetamol may help with period pain or algomenorrhea (although Spazmalgon or Baralgin may be better for severe pain). However, some studies have compared NSAIDs with acetaminophen (paracetamol). They suggest that NSAIDs are slightly more effective than acetaminophen in relieving period pain. [ 4 ]

Paracetamol is of little use for kidney pain, since renal pain syndrome is associated with spasms of the smooth muscles of the ureters, and antispasmodics are used to relieve them, in particular, No-shpa (Drotaverine), Papaverine hydrochloride, Platyphylline, 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 ]

Paracetamol is not used for abdominal pain of a spastic nature.

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

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

Release form

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

Pharmacodynamics

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

Unlike NSAIDs, Paracetamol has virtually no anti-inflammatory properties, since its pharmacodynamics are determined primarily by the effect on the neurons of the thermoregulatory centers of the hypothalamus and spinal cord - with the restoration of their functions, normalizing temperature homeostasis.

Paracetamol works against pain by inhibiting the activity of the membrane enzyme of cerebral cortex cells – cyclooxygenase type 3 (COX-3), which ensures 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 neurons of the peripheral nervous system, which are involved in the transmission, modulation and integration of pain signals. [ 9 ]

Pharmacokinetics

Paracetamol has high bioavailability (88%) when taken orally, it is well absorbed in the gastrointestinal tract and reaches peak concentrations in the blood 90 minutes after a single standard dose. Pain relief lasts for two to four hours.

Paracetamol penetrates the blood-brain barrier and enters the breast milk of lactating women. The drug has a low plasma protein binding (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. Sulfotransferase enzymes break it down into pharmacologically inactive glucuronic acid conjugates 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? It is not advisable to use the drug 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 permitted from 1 month at a daily dose of 50 mg per kilogram of body weight. Pediatricians recommend children's suspension Calpol, syrup and rectal suppositories Efferalgan, suspension and rectal suppositories Panadol baby.

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

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

The American Academy of Pediatrics (AAP) continues to recommend acetaminophen for pain and fever in children, but experts advise against its use if the child has asthma or is at risk for developing it. Use of acetaminophen in therapeutic doses is generally safe, although liver toxicity may occur at recommended doses in children. [ 15 ]

Use Paracetamol during pregnancy

Paracetamol is the first choice for antipyretic or analgesic treatment throughout pregnancy. Consequences such as increased risk of asthma [ 11 ] or attention deficit hyperactivity disorder have been discussed. [ 12 ] Paracetamol consumption, especially in the third trimester, results in a decrease in the relative number of hematopoietic stem cells in cord blood, independent of maternal age, first trimester BMI, parity, gestational age and birth weight. [ 13 ]

During pregnancy, the use of Paracetamol requires caution, in particular, it is prohibited to take it during the first three months.

Detailed information in the material - Paracetamol during pregnancy

Paracetamol during breastfeeding

All the details and recommendations of doctors are given in the article - Can a nursing mother take Paracetamol?

Contraindications

Contraindications to taking Paracetamol for pain and fever 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;
• decreased level of leukocytes in the blood;
• children under 4 weeks of age.

Side effects Paracetamol

Possible side effects of Paracetamol include:

• the appearance of skin itching and rashes, including urticaria, as well as exudative erythema and toxic epidermal necrolysis of the Stevens-Johnson syndrome type;
• development of an acute allergic reaction with angioedema;
• nausea and abdominal pain;
• disturbance of the blood composition, in particular, anemia, decreased levels of platelets and leukocytes, increased 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. [ 14 ]

Overdose

Single dose consumption of more than 7 g for an adult and 150 mg/kg for a child is considered potentially liver toxic, for more details see – Hepatotoxicity of Paracetamol.

Signs of an overdose usually begin to appear within a few hours of taking the drug – in the form of nausea, vomiting, increased sweating and pain in the hypochondrium. [ 16 ]

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

The antidote is N-acetylcysteine, which, by acting as a glutathione precursor and neutralizing the reactive metabolite of Paracetamol NAPQI, helps reduce liver damage.[ 17 ]

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 together with sedatives of 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 long-term 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 tablets is three years, the shelf life of syrup and suspension is two years.

Analogues

Paracetamol for pain has many analogues - drugs of the group of non-narcotic analgesics, that is, tablets for headaches without Paracetamol, including Analgin (Metamizole sodium), Baralgin, Tempalgin, Sedalgin, Flupirtine (Katadolon, Nolodatak), Diflunisal (Dolobid), etc.

Reviews

Reviews from surgeons support the use of Paracetamol in combination with non-steroidal anti-inflammatory drugs (NSAIDs) to reduce post-operative pain.

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

But for toothache or pain resulting from dental procedures, NSAIDs (Ibuprofen, Naproxen, etc.) are considered more effective.