- What is the difference in the effect of aspirin and non-steroidal anti-inflammatory drugs such as indomethacin on cyclooxygenase activity?
- Some asthmatics exacerbate symptoms when using nonsteroidal anti-inflammatory drugs. How can this be explained from a biochemical point of view?
- Which of the pairs has the opposite effect?
- A – Cholic and lithocholic acid
- B – 5-HPETE and leukotriene D4
- C – Laktosylceramide and galactocerebroside
- D – Thromboxane A2 and prostacyklin (PGI2)
- E – Acetone and 3-hydroxybutyrate
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Question 1.
- Aspirin blocks cyclooxygenase activity irreversibly by acetylating the enzyme molecule. This effect disappears only with the death of platelets, ie in 7-10 days. Indomethacin only temporarily blocks prostaglandin receptors (PGE, PGD and PGI series)
Question 2.
- Non-steroidal anti-inflammatory drugs inhibit cyclooxygenase but not lipoxygenase. Arachidonic acid metabolism cannot continue in the presence of nonsteroidal antiphlogistics via the cyclooxygenase pathway. Therefore, there is more substrate for the lipoxygenase pathway. This produces more leukotrienes, which induce bronchoconstriction. The bronchoconstrictive effect outweighs the bronchodilator effect of prostaglandins and thromboxane.
Question 3.
- A – wrong
- B – wrong
- C – wrong
- D – correct - thromboxane formed in platelets causes arterial contraction and induces platelet aggregation; Prostacyclin has exactly the opposite effect
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A 46-year-old woman was treated on an outpatient basis for astmoid bronchitis by inhaling triamcinolone acetonide. Prior to admission to the hospital, she had an upper respiratory tract infection and her breathing difficulties worsened significantly until she turned into an acute asthma attack with marked bronchospasm. Glukcocorticoids were used i.v.
Questions:
- What is the mechanism of glucocorticoids in the treatment of asthma?
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- Glucocorticoids suppress some manifestations of the inflammatory reaction that induces bronchospasm and thus lead to an acute asthma attack. They inhibit the entry of leukocytes and monocytes / macrophages into inflammatory areas, thus reducing the production of some chemotactic and other substances, especially eicosanoids, which mediate the adverse reaction. Glucocorticoids support the synthesis of e.g. lipocortins and macrocortins, which inhibit phospholipase A 2 activity. As a result, the production of pro-inflammatory prostaglandins and leukotrienes is suppressed.
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Patients with cardiovascular disease[edit | edit source]
Man with coronary heart disease is taking small doses of aspirin as s precaution.
Questions:
- What is the pathobiochemical mechanism of the beneficial effect of aspirin on the incidence of acute myocardial infarction?
- What adverse effects may acetylsalicylic acid have on some patients?
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- Aspirin (acetylsalicylic acid) irreversibly inactivates cyclooxygenase by acetylating it. This blocks the formation of thromboxane A 2 from arachidonic acid. Thromboxane is a potent vasoconstrictor and stimulant of platelet aggregation (ie mechanisms that can significantly narrow to blockage of a coronary artery → acute myocardial infarction). Cyclooxygenase inactivation is irreversible and because mature platelets cannot form new proteins, inactivation takes 7-10 days to generate new platelets.
- Prolonged administration of aspirin may lead to acute gastric ulcers in some patients. By reducing the production of prostaglandins, the dampening effect on gastric acid-induced gastric juice is removed.
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Other chapters from the book MASOPUST, J., PRŮŠA, R .: Pathobiochemistry of metabolic pathways
- MASOPUST, Jaroslav and Richard PRŮŠA. Pathobiochemistry of metabolic pathways. 1st edition. Prague: Charles University, 1999. 182 pp. 98-99. ISBN 80-238-4589-6 .
