Flashcards in NSAIDS Deck (38):
List the main actions of NSAIDs.
What do NSAIDs do?
INHIBIT PROSTAGLANDIN BIOSYNTHESIS BY DIRECT INHIBITION OF CYCLO-OXYGENASE (COX)
What are the two main mechanisms used by NSAIDs to inhibit COX?
Irreversible, time dependant inhibition of COX
A rapid, reversible competitive inhibition of COX
Give an example of a NSAID that inhibits the COX enzyme irreversibly.
Describe the mechanism of action of aspirin.
Acetylates the alpha-amino group of the terminal serine of the enzyme forming a covenant bond, thus inhibiting it
Give an example of a NSAID that inhibits the COX enzyme reversibly.
Describe the mechanism of action of ibuprofen.
Bind reversibly with COX, competing for its active site with the natural substrate, arachidonic acid
What are prostaglandins?
Family of cyclic fatty acids which have hormone-like effects on the body
What is the difference between autocrine and paracrine cell signalling?
Autocrine has an effect on the cell that secreted the chemical signal
Paracrine has an effect on a more distant area, but still in the vicinity of the cell secreting the chemical signal
What two substances combine to produce prostaglandins?
Name three substances that are all products of arachidonic acid metabolism.
What is the function of COX-1?
Constitutive (i.e. is produced continuously in the body regardless of the needs of cells
Important in maintaining GI tract integrity
What is the difference in structure between COX-1 & COX-2 and what does this mean with regard to inhibition?
COX-2 has a 'side pocket' in its structure (additional ring)
This means that inhibitors have to be specific to either COX-1 or COX-2
What is the function of COX-2?
Inducible (i.e. brought about when needed)
Involved in inflammatory response
Implicated in cancer development
What specifically, when considering this topic, is released upon inflammation?
PGD2 from mast cells
What is the function of these specific prostaglandins in an inflammatory response?
Have combined effects with other inflammatory mediators, e.g. histamine & bradykinin
Potentiate histamine & bradykinin actions on post-capillary venue permeability & pain sensory nerves
What is the primary function of NSAIDs?
To reduce many of the local signs and symptoms of inflammation, i.e. redness, heat, swelling, pain
Run through the anti-pyretic (anti-feverish) effect that NSAIDs have.
Bacterial endotoxins cause release of factors such as INTERLEUKIN 1 from macrophages
Interleukin 1 causes generation of prostaglandins in the hypothalamus (PGEs)
PGE prostaglandins increase the set point of temperature ---> fever.
HOWEVER, NSAIDs prevent the formation of these prostaglandins, preventing rise in temperature
Describe the analgesic (pain relieving) effect NSAIDs have.
Inflamed regions painful due to histamine & bradykinin release (activate nociceptors)
Prostaglandins sensitise nociceptive nerves to histamine & bradykinin
NSAIDs prevent prostaglandin production ---> no pain
What are the salicylates?
The aspirin family
What is aspirin a pro-drug to?
What can aspirin also be metabolised to and what metabolises it to this compound?
By plasma & tissue esterases
How long does it take for salicylate to appear in the plasma and after what time do they peak in plasma concentration?
Appear after 30 minutes
Peak within 1-2 hours
List some side effects of salicylate.
Stomach - bleeding, ulcers
Systemic - tinnitus, dizziness, impaired hearing, nausea, vomiting, hypersensitivity
Metabolic changes - acid/base balance affected
Haemostasis - blood coagulation affected through action on platelets
CNS - initial stimulation, ultimately coma & respiratory depression
Renal - insufficiency with chronic use & OD
What category of drugs do ibuprofen and naproxen fall under?
Give an example of a fenamate.
List some advantages paracetamol has.
Good analgesic & antipyretic activity
Well tolerated in GI tract
Given orally (convenient) and well absorbed
Fewer side effects than other NSAIDs
After how long does paracetamol reach its peak plasma concentration?
(Half life 2-4 hours for therapeutic doses)
List some disadvantages paracetamol has.
Weak COX inhibitor (& may be specific to COX-3)
What is a major issue associated with paracetamol overdose?
Hepatotoxicity ---> hepatic necrosis (due to saturation of liver inactivation enzymes)
What is the name given to selective COX-2 inhibitors?
Give an example of a selective COX-2 inhibitor.
What are selective COX-2 inhibitors used to treat?
To treat osteoarthritis & rheumatoid arthritis
When are COX-2 inhibitors generally used?
When the traditional NSAIDs produce too severe GI tract side effects
List some cases in which NSAIDs would be used.
Dysmenorrhea (painful menstruation)
Bony metastases of cancers
Which NSAIDs are used in cases of SHORT term analgesia?
Which NSAIDs are used in cases of LONGER lasting chronic analgesia?