Oxicame

from Wikipedia, the free encyclopedia
Piroxicam, first representative
Meloxicam, the first oxicam with a selective COX-2 effect
Lornoxicam (chloro-tenoxicam)

Oxicams are a group of substances that are used in medicine as non-opioid analgesics . Like many other nonsteroidal anti-inflammatory drugs, they act as unselective, reversible inhibitors of cyclooxygenase . Depending on the active ingredient, however, they show a slight preference for cyclooxygenase-2 , as in the case of meloxicam . In contrast to other NSAIDs, most oxicams have a relatively long duration of action. Through targeted chlorine substitution and the resulting faster hydroxylation in para position, a shorter half-life could be achieved with lornoxicam . Oxicams are thought to have analgesic , antipyretic , anti- exudative and anti-inflammatory effects.

use

The following oxicams are or were listed under M01AC in the anatomical-therapeutic-chemical classification system :

  1. Piroxicam
  2. Tenoxicam
  3. Isoxicam - introduced in 1983, withdrawn from the market in 1985.
  4. Droxicam
  5. Lornoxicam
  6. Meloxicam

Cinnoxicam is another name for piroxicam cinnamate. Sudoxicam was not followed up medically due to its hepatoxic effects. Ampiroxicam , Droxicam, and Pivoxicam are prodrugs from Piroxicam. Enolicam is structurally related to the oxicams.

history

The project behind the development of this group of substances began in 1962 with Joseph G. Lombardino and John A. Lowe at Pfizer and led to the first market approvals in 1980. The aim was a new anti-rheumatic agent with a longer duration of action, which is why the search was carried out away from the common carboxylic acids. It should have anti-inflammatory properties and it should be able to be given safely in the long term in chronic illnesses. In 1977, the results of clinical studies were published on the first oxicam, which was later named piroxicam . From 1980 it was approved by the FDA as "Felden". The most important patents for its manufacture expired in 1993. In 1993, lornoxicam was the first oxicam to follow, with a plasma half-life of around 4 hours; in 1996, the more selective COX-2 meloxicam .

Tenoxicam and Lornoxicam were registered by Hoffmann-La Roche , Droxicam by Provesan SA, Meloxicam by Boehringer Ingelheim .

Isoxicam was marketed as " Pacyl " or " Vectren " from 1983 , but was withdrawn from the market in October 1985 after deaths in France. Droxicam's approval was suspended in 1994.

properties

Keto-enol tautomers from piroxicam

Oxicams are also known as "enolic acids" because of their acidic structural element, their physicochemical properties can vary depending on the microenvironment.

They are present as pale yellow to orange solids under standard conditions . The keto-enol tautomerism is shown here using the example of piroxicam.

pharmacology

Mechanism of action

As with other NSAIDs, the mechanism of action consists in the inhibition of cyclooxygenases and a reduction in platelet aggregation . The individual oxicams differ in the strength of their preference for cyclooxygenase-2 .

Pharmacokinetics

The metabolism of this drug class is mainly in the liver by cytochrome P450 2C9 . The bioavailability is over 89% (meloxicam) and can be absolute as with piroxicam and tenoxicam. Oral administration usually takes effect within the first two hours. With the exception of lornoxicam and meloxicam, the plasma half-lives are over 48 hours, which is why a steady state is only reached in the course of the first days or weeks when the effect increases.

Oxicams can cross the placental barrier and appear in breast milk.

literature

Web links

Commons : Oxicame  - collection of images, videos and audio files

Individual evidence

  1. ↑ Mutschler, Ernst: Mutschler drug effects. Pharmacology, clinical pharmacology, toxicology. 10th edition. Stuttgart. 2013.
  2. ↑ M01AC in the ATC / DDD , accessed in February 2016.
  3. ↑ a b Consolidated List of products whose consumption and / or sale have been banned, withdrawn, severely restricted or not approved by Governments , United Nations, 2003, p. 123 (2005 edition ), accessed on February 16, 2016.
  4. ↑ Zhi-Yi Zhang: Sudoxicam Part 2. Compound Articles . In: Handbook of Metabolic Pathways of Xenobiotics . 2014. doi : 10.1002 / 9781118541203.xen294 .
  5. ↑ Discovery of Piroxycam at nature , accessed on February 17, 2016.
  6. ↑ NYCOMED FILES FOR LORNOXICAM , accessed February 2016.
  7. ^ Search for ATC code " M01AC * " in the medicinal specialties register , accessed on February 19, 2016.
  8. ↑ Patent application FR2528433 : Derivatives of oxazinobenzothiazine-6,6-dioxide. Applied on June 15, 1982 , published on December 16, 1983 , applicant: Provesan SA, inventor: José Esteve Soler. ‌
  9. ^ B Auvinet, R. Ziller, T. Appelboom: Comparison of the onset and intensity of action of intramuscular meloxicam and oral meloxicam in patients with acute sciatica. . In: Clinical Therapeutics . 17, No. 6, November-December 1995, pp. 1078-1098. doi : 10.1016 / 0149-2918 (95) 80086-7 . PMID 8750399 .
  10. ^ Fung, A. Thornton, K. Mybeck, JH-h. Wu, K. Hornbuckle, E. Muniz: Evaluation of the Characteristics of Safety Withdrawal of Prescription Drugs from Worldwide Pharmaceutical Markets-1960 to 1999 . In: Therapeutic Innovation & Regulatory Science . 35, No. 1, January 1, 2001, pp. 293-317. doi : 10.1177 / 009286150103500134 .
  11. ↑ Consolidated List of products whose consumption and / or sale have been banned, withdrawn, severely restricted or not approved by Governments , United Nations, 2003, p. 116 (Edition 2005) (English), accessed on February 23, 2016.
  12. ↑ Banerjee R, Chakraborty H, Sarkar M: Photophysical studies of oxicam group of NSAIDs: piroxicam, meloxicam and tenoxicam . In: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy . 59, No. 6, 2003, pp. 1213-1222. doi : 10.1016 / S1386-1425 (02) 00300-1 . PMID 12659890 . (English)
  13. ↑ Ivanova D, Deneva V, Nedeltcheva D, Kamounah FS, Gergov G, Hansen PE, Kawauchi S, Antonov L: Tautomeric transformations of piroxicam in solution: a combined experimental and theoretical study . In: RSC Advances . 5, 2015, pp. 31852-31860.
  14. ↑ DE. Furst: Meloxicam: Selective COX-2 inhibition in clinical practice. . In: Semin Arthritis Rheum . 6, No. 1, June 26, 1997. PMID 9219316 . (English).
  15. ↑ Amy M. Karch: 2014 Lippincott's Nursing Drug Guide, 1st edition (2013), published by Lippincott Williams & Wilkins, ISBN 978-1-4511-8655-0 . (English).