Drugs to Treat Inflammation Flashcards
How is aspirin protective against cardiovascular disease?
Because it tips the balance towards prostacyclin production because prostacyclin producing endothelians can make more COX while thromboxane producing platelets can’t
How do NSAIDs cause bronchoconstriction in 10% of asthmatics?
Inhibition of the production of prostanoids means more arachonic acid is shuttled into leukotriene production which leads to bronchoconstriction
Which of the typical effects of NSAIDs does paracetamol lack?
Anti-inflammatory
In what physiological state are prostaglandins produced at the greatest level?
During inflammation
How do NSAIDs increase bleeding time?
They downregulate thromboxane A2 production which has pro-coagulative effects
How do NSAIDs adversely effect the kidney?
Blocking the tonic vasodilation provided by prostacyclin
What is the mechanism of the analgesic effect of NSAIDs?
Prostaglandins sensitise nociceptors therefore inhibiting their production reduces pain
COX enzymes catalyse the production of what?
Prostaglandins
Prostacyclin
Thromboxane
How does aspirin inhibit COX?
Acetylates it
What is the effect of lipoxins?
Resolution of inflammation
What is unique of the effect of aspirin on COX?
The inhibition of COX is irreversible
When does hepatotoxicity occur with paracetamol use?
When the liver capacity to detoxify the paracetamol is exceeded - usually at dose 20x normal
How are lipoxins made due to aspirin?
Aspirin Acetylated COX2 produces them
What are the general effects of NSAIDs?
Anti-inflammatory
Anti-pyretic
Analgesia
Anti-aggregative
What effect does stimulating canabinoid receptors have on tissue?
Anti-inflammatory as well as
Appetite stimulation
Analgesia
Sedation
Psychoactivity
What are the 3 mechanisms of action of glucocorticoids at a cellular level?
Direct Transactivation
Direct Transrepression
Tethered transrepression
What is mechanism for GIT damage caused by NSAIDs?
Reduce PGE2 > withdraws its protective effects
- increase mucus production
- Increase blood flow
- Decrease H+ secretion
- Promotes angiogenesis
Which COX enzyme is more widely expressed?
COX-1
How do NSAIDs cause an increase in blood pressure?
Decreases the natriuresis effect of PGE2
Why can’t aspirin be used for gout?
Because it shares a renal transporter with uric acid therefore they compete for secretion
What are the limitations to using prostaglandins as treatment?
Generally they are unstable and expensive
What types of drugs are given the name NSAID?
Non-selective inhibitors of COX-1 and COX-2
Why is aspirin contradicted in children?
It is hepatotoxic in a number of children
Which NSAID is preferred for fever?
Paracetamol
How is tumour necrosis factor alpha being targeted in therapies?
Block it to block its inflammatory effects
eg in rheumatoid arthritis
