phenylbutazone

Action and Spectrum

Actions and Spectrum: 

phenylbutazone, is a non-steroidal anti-inflammatory drug that was commonly used in the past to relieve pain and inflammation in humans and animals.  

Action: phenylbutazone works primarily by inhibiting the activity of cyclooxygenase. COX is responsible for the synthesis of PG (prostaglandins), which are chemical messengers involved in promoting inflammation, pain, and fever. By inhibiting COX, phenylbutazone reduces the production of prostaglandins, leading to decreased pain, inflammation, and fever. 

Spectrum: phenylbutazone was used to treat a range of conditions associated with inflammation and pain, including: 

• Arthritis: phenylbutazone was often prescribed to relieve pain and inflammation together with various forms of arthritis, including rheumatoid arthritis and osteoarthritis. 
• Musculoskeletal Disorders: The drug alleviated pain and inflammation in conditions affecting muscles, joints, and soft tissues. 
• Fever: phenylbutazone was sometimes used to reduce fever, as its anti-inflammatory properties could help lower body temperature. 
• Equine Medicine: Phenylbutazone gained popularity in veterinary medicine and was commonly used in horses to manage pain and inflammation associated with musculoskeletal injuries. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Stomach pain 

Nausea 

Vomiting 

Diarrhea 

Constipation 

Itching 

Dizziness 

Skin rash 

Headache 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Hypersensitivity: Individuals with a known hypersensitivity or allergic reaction to phenylbutazone or other NSAIDs should avoid its use, as it can lead to severe allergic reactions. 
• Peptic Ulcers and Gastrointestinal Bleeding: Phenylbutazone can increase the risk of gastrointestinal ulcers, and perforation. Individuals with a history of peptic ulcers, gastrointestinal bleeding, or inflammatory bowel disease are generally advised against phenylbutazone due to the increased risk of exacerbating these conditions. 
• Severe Kidney or Liver Impairment: phenylbutazone can affect kidney and liver function. Individuals with severe kidney or liver impairment may experience worsened function or an increased risk of adverse effects, making phenylbutazone inadvisable. 
• Heart Conditions: Phenylbutazone can have cardiovascular effects, including fluid retention and increased blood pressure. People with pre-existing heart conditions or hypertension should use caution when considering phenylbutazone. 
• Blood Disorders: Individuals with blood disorders, like anemia or clotting disorders, should avoid phenylbutazone, as it can further affect blood cell counts and clotting mechanisms. 
• Pregnancy and Breastfeeding: phenylbutazone is generally contraindicated during pregnancy, especially in the late stages, due to its potential to cause the harm to the developing fetus. It’s also not recommended during breastfeeding, as it can be excreted in breast milk. 
• Children and Elderly: phenylbutazone in children and elderly individuals may require careful consideration, as these populations can be more vulnerable to the drug’s adverse effects. 
• Combination with Other NSAIDs: Combining phenylbutazone with other NSAIDs can enhance the risk of gastrointestinal bleeding and other adverse effects. 
• Combination with Anticoagulants: phenylbutazone can interact with anticoagulant medications (blood thinners), potentially increasing the risk of bleeding. 
• Alcohol Consumption: Alcohol consumption while taking phenylbutazone can enhance the risk of gastrointestinal bleeding and other adverse effects. 
• Systemic Lupus Erythematosus (SLE): phenylbutazone use is generally avoided in individuals with SLE, as it can exacerbate the condition. 

Caution 

• Dosage and Duration: phenylbutazone should be used at the low effective dose for the shortest possible duration to minimize the risk of adverse effects. Prolonged use or high doses can increase the likelihood of side effects. 
• Gastrointestinal Effects: phenylbutazone can cause gastrointestinal irritation, ulcers, and bleeding. Individuals with a history of gastrointestinal disorders or those taking other medications that can affect the gastrointestinal tract (such as corticosteroids or anticoagulants) should use phenylbutazone cautiously. 
• Kidney and Liver Function: phenylbutazone can affect kidney and liver function. Regular kidney and liver function monitoring through blood tests is essential, especially for individuals with pre-existing kidney or liver conditions. 
• Cardiovascular Risk: Phenylbutazone can increase the risk of cardiovascular events like heart attack or stroke, particularly with prolonged use or in individuals with pre-existing cardiovascular disease. 
• Fluid Retention and Blood Pressure: phenylbutazone can cause fluid retention and increase blood pressure. Individuals with hypertension or heart failure should use phenylbutazone cautiously and under medical supervision. 
• Asthma and Respiratory Disorders: NSAIDs, including phenylbutazone, can exacerbate asthma symptoms or cause allergic respiratory reactions in some individuals. People with a history of asthma or other respiratory disorders should be cautious when using phenylbutazone. 
• Elderly Population: Elderly individuals are generally more susceptible to the side effects of phenylbutazone, such as gastrointestinal bleeding, kidney dysfunction, and fluid retention. Lower doses and careful monitoring are advised for this population. 
• Interaction with Other Medications: phenylbutazone can interact with various medications, including other NSAIDs, anticoagulants, diuretics, and certain antihypertensive drugs. These interactions can affect the efficacy and also safety of phenylbutazone and other medications. 
• Allergic Reactions: Individuals with a history of hypersensitivity reactions to NSAIDs, including aspirin, should exercise caution when using phenylbutazone, as they may be at increased risk of allergic reactions. 
• Skin Reactions: Phenylbutazone can cause skin reactions such as rashes or photosensitivity. Individuals who experience skin reactions while taking the medication should discontinue its use and seek medical attention. 
• Pregnancy and Breastfeeding: phenylbutazone is generally not recommended during pregnancy, especially in the third trimester, because of potential risks to the developing fetus. It’s also not recommended during breastfeeding. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: Not assigned 

Lactation:   

Excreted into human milk: Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence, these categories of drugs need to be avoided by pregnant women.    
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

Phenylbutazone is a non-steroidal anti-inflammatory drug that exerts its pharmacological effects primarily by inhibiting the activity of cyclooxygenase enzymes (COX-1, COX-2), which are involved in the synthesis of prostaglandins, mediators of the inflammation, pain, and fever. By blocking prostaglandin production, phenylbutazone reduces inflammation and provides analgesic (pain-relieving) and antipyretic (fever-reducing) effects.

It also has anti-inflammatory and immune-modulating actions. However, phenylbutazone is associated with a range of adverse effects, including gastrointestinal irritation, ulceration, bleeding, kidney dysfunction, and cardiovascular risks, which limit its use and have led to the adoption of safer alternatives in clinical practice. 

Pharmacodynamics: 

Mechanism of action: phenylbutazone, a non-steroidal anti-inflammatory drug (NSAID), exerts its therapeutic effects primarily through the inhibition of the COX (cyclooxygenase enzymes, which are generally involved in the synthesis of prostaglandins.  

• COX Enzymes and Prostaglandins: Inflammation, pain, and fever are often mediated by the production of prostaglandins, which are lipid compounds synthesized from arachidonic acid. Cyclooxygenase enzymes are the key enzymes responsible for converting arachidonic acid to prostaglandins, commonly called COX-1 and COX-2. 
• Inhibition of COX Enzymes: phenylbutazone inhibits both COX-1 and COX-2 enzymes. COX-1 is constitutively expressed in the tissues and also plays a role in maintaining physiological functions, while COX-2 is induced during inflammation. By inhibiting these enzymes, phenylbutazone reduces the production of prostaglandins. 
• Reduction of Prostaglandins: Prostaglandins have multiple functions, including promoting inflammation, vasodilation, pain sensitization, and fever generation. By reducing the production of prostaglandins, phenylbutazone helps mitigate these effects. This leads to decreased pain, inflammation, and fever. 
• Therapeutic Effects: Phenylbutazone’s inhibition of prostaglandin synthesis results in its anti-inflammatory, analgesic (pain-relieving), and antipyretic (fever-reducing) effects. These properties make it helpful in treating conditions characterized by pain, inflammation, and fever, such as arthritis and musculoskeletal disorders. 
• Other Effects: Beyond its effects on prostaglandins, phenylbutazone can also modulate other immune responses, although the exact mechanisms are not fully understood. 

Pharmacokinetics: 

Absorption 

Phenylbutazone is well-absorbed following oral administration. It is absorbed from the gastrointestinal tract, particularly in the stomach and small intestine. The absorption process can be influenced by factors like food intake and the presence of other medications. 

Distribution 

Once absorbed into the bloodstream, phenylbutazone is distributed throughout tissues. It has a relatively high volume of distribution, which means it can accumulate in various tissues beyond the bloodstream. This distribution contributes to its therapeutic effects in reducing inflammation and pain. 

Metabolism 

phenylbutazone undergoes hepatic (liver) metabolism through various enzymatic processes. The major metabolic pathway involves hydroxylation and oxidation of the phenylbutazone’s aromatic ring, resulting in metabolite formation. Cytochrome P450 enzymes, particularly CYP2C9, play a role in its metabolism. Some of the metabolites are pharmacologically active, contributing to the drug’s overall effects. 

Elimination and Excretion 

Metabolized phenylbutazone and its metabolites are primarily excreted in the urine. A small portion of the drug and its metabolites may also be excreted in the feces.

Adminstartion

Administration: 

phenylbutazone, is a non-steroidal anti-inflammatory drug (NSAID) commonly used to relieve pain and also inflammation in humans and animals. It’s important to note that its use has become limited due to potential side effects and the availability of safer alternatives.  

Dosage: The dosage of phenylbutazone can vary based on the individual’s weight, the severity of the condition being treated, and the species (human or animal). Phenylbutazone was typically available in tablet or powder form for oral administration.  

Administration: Phenylbutazone was often administered orally, but injectable forms were also available for more rapid relief in cases of severe pain or inflammation. Here’s how phenylbutazone was commonly administered: 

Oral Tablets: If using oral tablets, phenylbutazone could be given with or without food. Giving the tablet with a small amount of food is often recommended to help reduce the risk of gastrointestinal irritation. 

Powder: In some cases, phenylbutazone powder could be mixed with a small amount of soft food or treated to aid administration. Make sure the entire dose is consumed to ensure the correct dosage. 

Injectable Form: Injectable phenylbutazone was administered by a healthcare professional or veterinarian through intravenous (IV) or intramuscular (IM) injection. Injectable forms are usually used when immediate relief is required. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: phenylbutazone 

Why do we use phenylbutazone? 

Phenylbutazone, is a non-steroidal anti-inflammatory drug that was historically used to relieve pain and inflammation in humans and animals.  

Arthritis: phenylbutazone was frequently used to manage pain, inflammation, and stiffness associated with various forms of arthritis, including rheumatoid arthritis and osteoarthritis. 

Musculoskeletal Disorders: The medication alleviated pain and inflammation in conditions affecting muscles, joints, and soft tissues. This included conditions like back pain, muscle strains, and ligament injuries. 

Pain Relief: phenylbutazone was used to relieve various types of pain, such as headaches, menstrual pain, and postoperative pain. 

Fever: Due to its anti-inflammatory properties, phenylbutazone was sometimes used to reduce fever in individuals with febrile illnesses. 

Veterinary Medicine: phenylbutazone was widely used in veterinary medicine, particularly for horses. It was used to manage pain and inflammation associated with musculoskeletal injuries, lameness, and joint problems in horses and other animals. 

Other Inflammatory Conditions: phenylbutazone was used to manage pain and inflammation associated with conditions beyond arthritis, such as tendinitis, bursitis, and gout. 

Palliative Care: phenylbutazone was sometimes used in palliative care settings to provide comfort and pain relief in patients with terminal illnesses or those experiencing severe pain.