Final Diagnosis -- Phenylbutazone Toxicity

FINAL DIAGNOSIS

PHENYLBUTAZONE TOXICITY

DISCUSSION:

1. PHENYLBUTAZONE: is a NSAID which was discontinued for human use because of its harmful side effects. It is currently used in veterinary medicine as a pain killer. The girl had access to the drug and had used it in working with livestock. She had recently expressed a desire to kill herself and there was a history of suicidal overdose in the family. When the patient became conscious she admitted that she ingested about 7 grams of PHENYLBUTAZONE as a suicide attempt.

   PHARMACOKINETICS
   Phenylbutazone is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 2 hours after ingestion. It is also readily absorbed when administered rectally. Phenylbutazone is widely distributed throughout body fluids and tissues; it diffuses into the synovial fluid, crosses the placenta, and small amounts enter the CNS and breast milk. It is 98% bound to plasma proteins. It is extensively metabolised in the liver by oxidation and by conjugation with glucuronic acid. Oxyphenbutazone, gamma-hydroxyphenbutazone, and p,gamma-dihydroxyphenylbutazone are formed by oxidation but only small amounts appear in urine, the remainder being further metabolised. It is mainly excreted in the urine as metabolites although about a quarter of a dose may be excreted in the faeces. The plasma elimination half-life is about 70 hours but it is subject to large interindividual variations.

   ADVERSE EFFECTS
   

   • Nausea, vomiting, epigastric distress, diarrhoea, edema due to salt retention, skin rashes, dizziness, drowsiness, headache, and blurred vision. More serious reactions include gastric irritation with ulceration and gastrointestinal bleeding, ulcerative stomatitis, hepatitis, jaundice, haematuria, nephritis, renal failure, pancreatitis, ocular toxicity, and goitre. Phenylbutazone may precipitate heart failure and may also cause an acute pulmonary syndrome with dyspnoea and fever. Salivary gland enlargement (parotitis), hypersensitivity reactions including asthma, and severe generalised reactions including lymphadenopathy, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and exfoliative dermatitis have been reported.

   • The most serious adverse effects of phenylbutazone are related to bone-marrow depression and include agranulocytosis and aplastic anemia. Leucopenia, pancytopenia, hemolytic anemia, and thrombocytopenia may also occur. These adverse hematological reactions have resulted in the indications for use of phenylbutazone being restricted. Blood disorders may develop soon after starting treatment or may occur suddenly after prolonged treatment, and regular hematological monitoring should be carried out as discussed under Precautions.

2. KEBUZONE:
   • A derivative of Phenylebutazone present in the same tablets.
3. Diphenhydramine:
   • Over the counter Antihistamine medication the patient used to take for her cold symptoms.
4. Nicotine Metabolite
   • From Smoking (either the girl smokes or sits with smokers).

5. CHLOROXYLENOL:
   • Is an Antimicrobial used in ointments, creams and shampoos as a topical preparations to prevent bacterial and fungal infections. When the names of CHLOROXYLENOL containing preparations were shown to the mother she recognizd one of them (Blistex) cream and said the her daughter is currently using it for treatment of the mouth angle cracks.

This patient developed the following sings and symptoms of PHENYLBUTAZONE toxicity:

1. Thrombocytopenia.
2. CNS effects: Convulsions and coma.
3. Hepatotoxicity: High Liver Enzymes.
4. Renal Toxicity:
   • Renal Failure. (high BUN and Creat.)
   • Interstitial nephritis. (Hematuria)
5. The patient stayed in coma for 6 days and gradually improved after an exchange Transfusion.
6. Liver and renal function tests improved gradually with plasmapheresis.
7. She was started on Antidepressants and discharged after about 10 days.

1. Prescott LF. Clinical features and management of analgesic poisoning. [Journal Article] Human Toxicology. 3 Suppl:75S-84S, 1984 Aug.
2. Okonek S. Reinecke HJ. Acute toxicity of pyrazolones. [Review] [26 refs] [Journal Article. Review] American Journal of Medicine. 75:94-8, 1983 Nov 14.

Contributed by Hazim Najjar, M.D.