Diclofenac, Paracetamol

Pharmacological properties

Diclofenac sodium - NSAIDs. exhibits anti-inflammatory, analgesic and antipyretic activity. mechanism of action - inhibition of prostaglandin synthesis due to inhibition of the prostaglandin synthetase enzyme. blocking the synthesis of prostaglandins, diclofenac eliminates or significantly reduces the severity of the symptoms of inflammation. reduces the increased sensitivity of nerve endings to mechanical stimuli and biologically active substances caused by prostaglandins; also reduces elevated body temperature due to the impossibility of the effect of prostaglandins on the structures of the hypothalamus, which are involved in the process of thermoregulation; diclofenac reduces the concentration of prostaglandins in menstrual blood and the intensity of pain in primary dysmenorrhea.

Paracetamol has analgesic, antipyretic and mild anti-inflammatory properties. The mechanism of action is associated with inhibition of prostaglandin synthesis and the predominant effect on the thermoregulation center in the hypothalamus.

After oral administration, the active ingredients of the drug are rapidly and almost completely absorbed in the digestive tract.

After absorption, about 99.7% of diclofenac binds to serum proteins. The volume of distribution is 0.12–0.17 l / kg. Diclofenac is able to penetrate into the synovial fluid, where its maximum concentration is reached 2–4 hours later than in blood plasma. Paracetamol is well distributed in tissues, with the exception of adipose tissue and cerebrospinal fluid. The binding of paracetamol to blood plasma proteins is approximately 10% and slightly increases with an overdose.

Diclofenac sodium is metabolized in part by glucuronidation of an unchanged molecule, but mainly due to methoxylation, which leads to the formation of several phenolic metabolites, most of which are conjugated with glucuronic acid. Paracetamol is metabolized primarily in the liver by conjugation with glucuronide, conjugation with sulfate and oxidation with the participation of mixed liver oxidases and cytochrome P450.

The half-life of diclofenac from blood plasma is 1-2 hours, the half-life of metabolites is 1-3 hours. About 60% of the diclofenac used is excreted in the urine in the form of glucuronic conjugates and metabolites, most of which also turn into glucuronic conjugates. In an unchanged state, less than 1% of diclofenac is excreted. Part of the administered dose is excreted in the form of metabolites with bile and feces. Significant changes in the pharmacokinetics of diclofenac in elderly people, patients with kidney disease, chronic hepatitis or compensated liver cirrhosis are not noted.

The half-life of paracetamol is 1-3 hours. In patients with cirrhosis, the half-life is increased. The renal clearance of paracetamol is 5%. It is excreted in the urine mainly in the form of glucuronide and sulfate conjugates. Less than 5% is excreted as unchanged paracetamol.

Indications

Rheumatism, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, gout, juvenile chronic arthritis, lumbago, neuralgia, myalgia, primary dysmenorrhea, mild to moderate pain, including headache, migraine, toothache, algomenorrhea; pain with injuries, burns; fever for infectious and inflammatory diseases.

Application

Adults and children over 14 years of pain are used orally 1 tablet 2-3 times a day. for maintenance therapy, the daily dose is 1 tablet 2 times a day.

The duration of the course of treatment is set individually.

The maximum daily dose in terms of diclofenac sodium is 100 mg or 4 tablets.

For the treatment of dysmenorrhea, the drug is used 2-3 times a day.

The drug is recommended to be used without chewing during or immediately after a meal, drinking ¹/₂ glasses of water.

Contraindications

Hypersensitivity to the components of the drug; erosive and ulcerative lesions of the gastrointestinal tract in the acute phase; history of attacks of bronchospasm, urticaria, acute rhinitis, which are associated with the use of acetylsalicylic acid or other NSAIDs; pregnancy and lactation, childrens age.

Side effects

From the side of the central nervous system: irritability, convulsions, impaired sensitivity or vision (diplopia), tinnitus, fatigue, dizziness, headache, rarely drowsiness, loss of consciousness.

From the gastrointestinal tract and liver: epigastric pain, heartburn, nausea, vomiting, flatulence; rarely - erosive and ulcerative lesions of the gastrointestinal tract, sometimes complicated by bleeding, increased activity of hepatic transaminases, exacerbation of ulcerative colitis, intestinal perforation.

Allergic reactions: asthma attacks, urticaria.

Dermatological reactions: skin rash, itching; rarely - photosensitivity.

On the part of the blood system: in some cases, anemia, leukopenia, thrombocytopenia, agranulocytosis, methemoglobinemia.

From the urinary system: interstitial nephritis, nephrotic syndrome, very rarely - acute renal failure. Nephropathy occurs in case of prolonged use of the drug.

Other: peripheral edema, hypertensive crisis.

special instructions

During pregnancy and breastfeeding. during pregnancy, the use of the drug is possible only if there are absolute indications, if the likely benefit to the mother outweighs the potential risk to the fetus. if it is necessary to use the drug during breastfeeding, it is necessary to decide on the termination of feeding.

Caution should be exercised when using the drug in patients with severe impaired renal function, liver, including alcoholic liver disease, biliary tract diseases, chronic heart failure.

Throughout the course of treatment, it is necessary to monitor kidney and liver function. With prolonged use of Bol-Run, you need to refrain from driving vehicles and performing potentially hazardous work that require increased attention and speed of reactions.

Interactions

Gcx potentiate the toxic effects of diclofenac. For patients receiving methotrexate, diclofenac is prescribed 24 hours before or after administration of methotrexate, since the concentration and toxic effect of the latter may increase.

With the simultaneous use of diclofenac with saluretics, the diuretic effect of “loop” diuretics may decrease. Diclofenac reduces the effectiveness of antihypertensive drugs.

With the simultaneous use of diclofenac with acetylsalicylic acid and other NSAIDs, the risk of side effects increases and the effectiveness of one of the drugs decreases.

With the simultaneous use of diclofenac with lithium preparations and digoxin, the concentration of the latter in blood plasma increases.

When using diclofenac in combination with potassium-sparing diuretics, an increase in the concentration of potassium in the blood is possible.

When used in conjunction with anticoagulants, the risk of developing hemorrhagic complications significantly increases.

With the simultaneous use of the drug with barbiturates, anticonvulsants, rifampicin, alcohol, the risk of hepatotoxic effects of paracetamol is significantly increased.

Overdose

Symptoms: a sharp headache, motor excitement, dizziness, convulsions.

Perhaps the hepatotoxic effect of paracetamol, which is manifested by pale skin, anorexia, nausea, vomiting, with a significant overdose - hepatonecrosis. The toxic effect of paracetamol develops when taking the drug in a dose of more than 10-15 g.The clinical picture of liver damage manifests itself after 1-6 days, in some patients, renal failure (tubular necrosis) may develop against the background of impaired liver function.

Symptomatic treatment; with the development of hepatotoxicity, donors of SH groups, precursors of glutathione synthesis (methionine), acetylcysteine ​​are administered. In acute poisoning with Bol-Ran, the stomach is washed through a tube and activated charcoal is prescribed.

Storage conditions

In a dry place at a temperature not exceeding 25 ° C.