Butadione

Butadion, also known by its international nonproprietary name phenylbutazone, is a nonsteroidal anti-inflammatory drug (NSAID) that is commonly used to treat pain and inflammation associated with rheumatic diseases such as rheumatoid arthritis and gout. Phenylbutazone works by inhibiting cyclooxygenase enzymes (COX-1 and COX-2), which are involved in the synthesis of prostaglandins, important mediators of inflammation and pain.

Phenylbutazone was widely used in the mid-20th century to treat rheumatism and other inflammatory conditions, but its use declined over time due to serious side effects and the emergence of safer alternatives.

Indications Butadione

1. Rheumatoid arthritis: This is a chronic inflammatory disease that affects the joints and can cause pain, inflammation, and joint deformity. Butadion can help reduce inflammation and pain symptoms in rheumatoid arthritis.
2. Osteoarthritis: This is a joint disease in which cartilage tissue is destroyed, leading to pain, stiffness and decreased mobility of the joints. Butadion can help reduce pain and inflammation in the joints associated with osteoarthritis.
3. Gout: This is a form of arthritis caused by a disorder of uric acid metabolism in the body, leading to the formation of uric acid crystals in the joints. Butadion can be used to relieve inflammation and pain associated with gout.
4. Other inflammatory conditions: Butadion may also be used to treat other inflammatory conditions such as ankylosing spondylitis and vasculitis.

Release form

Phenylbutazone, commercially known as Butadion, is usually available as tablets for oral administration. Phenylbutazone tablets may have different strengths depending on the country and manufacturer, usually 100 mg or 200 mg.

Pharmacodynamics

1. Anti-inflammatory action: Phenylbutazone has the ability to reduce inflammation by inhibiting the activity of cyclooxygenase (COX), an enzyme involved in the synthesis of prostaglandins from arachidonic acid. This leads to a decrease in the formation of prostaglandins, which play a key role in the mediation of inflammatory processes.
2. Antirheumatic action: Phenylbutazone also has the ability to reduce pain and inflammation associated with rheumatic diseases such as rheumatoid arthritis and osteoarthritis. It can help reduce swelling and inflammation in the joints, leading to improved symptoms and function.
3. Anti-inflammatory action in the bladder: Phenylbutazone can be used to treat urinary stone pain and other inflammatory conditions of the bladder.
4. Analgesic action: In addition to its anti-inflammatory effect, phenylbutazone may also have an analgesic effect, reducing pain associated with inflammation and various rheumatic conditions.
5. Long-term effect: Unlike some other NSAIDs, the effects of phenylbutazone may persist for a long time after you stop taking it.
6. Possible side effects: It is important to note that, like other NSAIDs, phenylbutazone can cause unwanted side effects, including dyspepsia, stomach and intestinal ulcers, as well as an increased risk of cardiovascular complications and kidney damage.

Pharmacokinetics

1. Absorption: Phenylbutazone is usually rapidly and completely absorbed from the gastrointestinal tract after oral administration.
2. Distribution: It is well distributed throughout the tissues and organs of the body, including the joints, where it is found to exert its anti-inflammatory and analgesic effects.
3. Metabolism: Phenylbutazone is metabolized in the liver to form active metabolites. The main metabolic pathway is hydroxylation, which leads to the formation of 4-hydroxyphenylbutazone and 4-hydroxyethylbutazone.
4. Excretion: Phenylbutazone and its metabolites are excreted from the body primarily through the kidneys.
5. Half-life: The half-life of phenylbutazone is approximately 5-8 hours.

Dosing and administration

1. Oral administration (tablets):

   • Adults: The initial dose is usually 200-400 mg daily, given in divided doses (e.g., 100 mg 2-4 times daily). The maintenance dose may be reduced to 100 mg daily depending on the clinical response and patient tolerance.
   • Children: The use of phenylbutazone in children is not recommended due to the high risk of serious side effects.

2. Intravenous and intramuscular administration:

   • Injections are intended for short-term use in acute conditions and are usually performed in a hospital setting. The dosage and method of administration should be strictly controlled by medical personnel.

Use Butadione during pregnancy

Risks of using phenylbutazone during pregnancy:

1. Effect on the fetus:

   • NSAIDs, including phenylbutazone, may cause cardiopulmonary complications in the fetus, including premature closure of the ductus arteriosus, which may cause serious cardiovascular complications in the fetus.
   • There is a risk of low amniotic fluid (oligohydramnios), which can affect the development of the lungs and other vital organs in the fetus.

2. Impact on pregnancy:

   • Phenylbutazone may increase the risk of bleeding during pregnancy and childbirth, which poses a health risk to both mother and baby.
   • NSAIDs may delay labor or increase the risk of preeclampsia.

3. Recommendations:

   • The use of phenylbutazone during pregnancy, especially in the third trimester, is strictly contraindicated due to high risks to the health of the mother and child.
   • If a woman taking phenylbutazone plans to become pregnant or learns that she is pregnant, she should consult her doctor immediately to discuss safe treatment alternatives and possible precautions.

Treatment alternatives:

It is important for women during pregnancy to consider other, safer alternatives for managing pain and inflammation. A healthcare professional can help choose the right medication or treatment that is safe during pregnancy.

Contraindications

1. Individual intolerance: People with known individual intolerance to phenylbutazone or any other component of the drug should avoid using it.
2. History of allergic reactions: In patients with a history of allergic reactions to phenylbutazone or other drugs, including aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs), the use of phenylbutazone may be contraindicated.
3. Blood disorders: Phenylbutazone may cause agranulocytosis (a sharp decrease in the number of white blood cells) and other disorders of blood formation. Therefore, the drug is contraindicated in patients with disorders of blood formation, including agranulocytosis, leukopenia and aplastic anemia.
4. Liver and kidney disease: The use of phenylbutazone may be contraindicated in patients with severe liver or kidney disease due to the risk of developing toxic damage to these organs.
5. Peptic ulcer disease: The use of phenylbutazone may increase the risk of developing gastric ulcer disease and bleeding from them, so the drug is contraindicated in patients with these conditions.
6. Pregnancy and breastfeeding: Phenylbutazone is contraindicated during pregnancy and breastfeeding due to the risk to the fetus or child.
7. Paediatric population: The use of phenylbutazone in children and adolescents may be contraindicated due to the lack of data on efficacy and safety in this age group.

Side effects Butadione

1. Dyspeptic symptoms: These include nausea, vomiting, diarrhea, heartburn, and stomach discomfort. Patients may also experience loss of appetite.
2. Ulcer disease: Butadion may increase the risk of developing gastric and intestinal ulcers, especially in patients with a predisposition to this condition or when taking other NSAIDs concomitantly.
3. High blood pressure: Some patients may experience high blood pressure while taking butadion.
4. Allergic reactions: May include skin rash, itching, angioedema, or allergic dermatitis.
5. Increased uric acid levels: In some patients, butadione may contribute to increased levels of uric acid in the blood, which may be undesirable in gout.
6. Impaired renal function: In some patients, especially with prolonged use and high doses, impaired renal function may occur.
7. Bleeding: Butadion may increase the risk of gastrointestinal bleeding, especially in patients with hypertension or a predisposition to bleeding.

Overdose

1. Ulcers and bleeding: Phenylbutazone can cause ulcers in the stomach and intestines, which can lead to bleeding and perforation. Overdose may increase the risk of these complications.
2. Renal damage and impairment: Acute renal failure may occur in case of overdose of phenylbutazone due to hypotension and hypovolemia caused by bleeding and dehydration.
3. Cardiac complications: Overdose of phenylbutazone may cause cardiac arrhythmias and heart failure due to the drug's potential effects on the cardiovascular system.
4. Neurological symptoms: Headache, dizziness, drowsiness, visual disturbances and other neurological symptoms may occur.
5. Respiratory failure: Respiratory failure may develop due to paralysis of the respiratory muscles.
6. Metabolic disturbances: Electrolyte imbalance and metabolic acidosis may occur.
7. Seizures and convulsions: In rare cases, seizures may occur.

Interactions with other drugs

1. Individual intolerance: People with known individual intolerance to phenylbutazone or any other component of the drug should avoid using it.
2. History of allergic reactions: In patients with a history of allergic reactions to phenylbutazone or other drugs, including aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs), the use of phenylbutazone may be contraindicated.
3. Blood disorders: Phenylbutazone may cause agranulocytosis (a sharp decrease in the number of white blood cells) and other disorders of blood formation. Therefore, the drug is contraindicated in patients with disorders of blood formation, including agranulocytosis, leukopenia and aplastic anemia.
4. Liver and kidney disease: The use of phenylbutazone may be contraindicated in patients with severe liver or kidney disease due to the risk of developing toxic damage to these organs.
5. Peptic ulcer disease: The use of phenylbutazone may increase the risk of developing gastric ulcer disease and bleeding from them, so the drug is contraindicated in patients with these conditions.
6. Pregnancy and breastfeeding: Phenylbutazone is contraindicated during pregnancy and breastfeeding due to the risk to the fetus or child.
7. Paediatric population: The use of phenylbutazone in children and adolescents may be contraindicated due to the lack of data on efficacy and safety in this age group.