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Chapter: Modern Medical Toxicology: Miscellaneous Drugs and Poisons: Analgesics and Antihistamines

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Propionic Acids - Non-Steroidal Anti-Inflammatory Drug(NSAID)

All propionic acids inhibit PG synthesis as well as platelet aggregation (thereby increasing bleeding time).

Propionic Acids

The first member of this group to be introduced into pharmaco-therapeutics was ibuprofen in 1969. All propionic acids inhibit PG synthesis as well as platelet aggregation (thereby increasing bleeding time). They are widely used today in the relief of musculoskeletal disorders, fractures, sprains, and dysmenor-rhoea. Examples include benoxaprofen, carprofen, fenbufen, fenoprofen, flurbiprofen, ibuprofen, indoprofen, ketoprofen, ketorolac, loxoprofen, oxaprozin, pirprofen, suprofen, and tiaprofenic acid.

Angioedema, hives, itching, rash, and swelling have been reported with therapeutic use. GI distress, nausea, and epigas-tric pain are the most common adverse effects with therapeutic doses; upper GI bleeding may occur after acute or chronic ingestion. Oesophageal stricture may occur with minimal liquid intake. Enteropathy may occur with chronic ingestion. Effective October 1999, the FDA requires an alcohol warning on all over-the-counter pain relievers, which includes aspirin, other salicylates, paracetamol, ibuprofen, ketoprofen, and naproxen sodium. The statement is as follows: If you drink 3 or more alcoholic drinks every day, ask your doctor whether you should take ibuprofen or other pain relievers/fever reducers. Ibuprofen may cause stomach bleeding.

Isolated cases of thrombocytopenia, agranulocytosis, haemolysis, lymphopenia, and pancytopenia have been reported after therapeutic use of propionic acids.

Ibuprofen overdoses have been commonly reported in the literature, while the other members of this group are less commonly mentioned. Children ingesting less than 200 mg/kg generally are asymptomatic or have mild effects. Ingestions of 400 mg/kg in children have been associated with severe toxicity. Therapeutic plasma levels should be between 20 to 30 mcg/ml.

Main symptoms include vomiting, abdominal pain, diar-rhoea, seizures, apnoea, hypotension, bradycardia, metabolic acidosis, and renal and hepatic dysfunction. Lethargy, drowsi-ness, headache, nystagmus, diplopia, tinnitus, ataxia, apnoea (particularly in infants), adult respiratory distress syndrome, and hypothermia may develop. Miosis has been reported in acute overdose. Hypokalaemia, hypophosphataemia, hyponatraemia, and hyperkalaemia (associated with renal failure) can occur.

Overdose of ketoprofen produces only mild symptoms, based upon reports from Great Britain. Symptoms include vomiting and drowsiness; ingestion of 5 grams in an elderly male produced no symptoms.

Treatment involves gastric lavage, activated charcoal, and supportive measures. Monitor for signs and symptoms of gastro-intestinal ulceration and/or haemorrhage, i.e. stool guaiac test. Antacids may be of some value in patients with GI symptoms. Patients with severe epigastric pain, dysphagia or drooling should be evaluated for possible oesophageal stricture. Management of hypotension, acidosis, and gastrointestinal bleeding may be necessary. Enhanced elimination using urine alkalinisation or haemodialysis has not been shown to be of benefit.

Possible complications of use during pregnancy include delayed labour, complications during delivery, postpartum bleeding, and respiratory depression in the newborn.


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