NSAIDs Flashcards
what are the main actions of NSAIDs?
+ anti-inflammatory
+ analgesic
+ anti-pyretic
what is the primary action of NSAIDs?
inhibit prostaglandin biosynthesis by direct action on cyclo-oxygenase enzymes
what are the 2 mechanisms by which NSAIDs inhibit cyclo-oxygenase?
- an irreversible, time-dependent inhibition of enzyme
2. a rapid, reversible competitive inhibition of enzyme
name a drug that follows this mechanism of action: irreversible, time-dependent inhibition of enzyme
aspirin
name a drug that follows this mechanism of action: rapid, reversible competitive inhibition of enzyme
ibuprofen
what are prostaglandins?
+ PGE2, PGI2
+ PGD2 from mast cells
+ generated in tissues from a precursor (arachidonic acid) by cyclo-oxygenase enzymes
what are the two main cyclo-oxygenase enzymes?
+ COX-1
+ COX-2
what is the role of prostaglandins?
+ prostaglandin release accompanies inflammation
what are features of prostaglandins (PGE2, PGI2, PGD2)?
+ act as potent vasodilators
+ synergise with other inflammatory mediators (histamine and bradykinin)
+ potentiate histamine and bradykinin actions on postcapillary venule permeability and pain sensory nerves
what type of inflammation are prostaglandins important mediators of?
vasodilation and resultant oedema
what is the relationship between NSAIDs and prostaglandins in regards to inflammation?
NSAIDs only effect aspects of inflammation in which prostaglandins play a significant part
which local signs and symptoms of inflammation can NSAIDs reduce?
+ redness
+ heat
+ swelling
+ pain
body temperature is regulated by the hypothalamus - how are prostaglandins involved?
+ fever occurs when hypothalamic thermostat “set point” is raised
+ bacterial endotoxins cause release of factors (interleukin 1) from macrophages
+ interleukin 1 causes generation of prostaglandins in hypothalamus (PGEs)
+ prostaglandins increase thermostat “set point”
what is the relationship between NSAIDs and prostaglandins in regards to anti-pyretic effects?
NSAIDs act by preventing formation of prostaglandins and prevent the rise in temp
- no effect on normal body temp
what is the relationship between NSAIDs and prostaglandins in regards to analgesic effects?
+ prostaglandins sensitise nocioceptive nerves to histamine and bradykinins
+ by preventing prostaglandin production NSAIDs prevent sensitisation to pain-producing compounds
what are features of aspirin?
+ pro-drug (acetylsalicylic acid)
- can directly acetylate COX enzyme
+ also metabolised to active compound (salicylic acid) by plasma and tissue esterases
+ salicylates found in plasma within 30 mins
+ peak plasma concentrations within 1-2 hr
what kind of unwanted effects of salicylates can occur?
+ stomach
- bleeding, ulcers
+ systemic
- tinnitus, dizziness, impaired hearing, nausea, vomiting, hypersensitivity
+ metabolic changes
- blood coagulation affected, action on platelets
+ CNS effects
- stimulation initially, ultimately coma and respiratory depression
+ renal
- insufficiency in susceptible patients with chronic use and overdose
what examples of drugs are propionic acids, and what are their features?
+ ibuprofen and naproxen
- not prodrugs
- well absorbed
- last for 4-6 hours
what is an example of a fenemate?
mefenamic acid
what is an alternate name for paracetamol?
acetaminophen
what are features of paracetamol?
+ good analgesic
+ good antipyretic activity
+ well tolerated in GIT
+ weak COX inhibitor
-may be selective inhibitor of CNS-specific, COX-3
+ given orally, well absorbed
why might paracetamol have fewer side effects than other NSAIDs?
due to its selectivity for COX enyzmes
what is the major issue due to overdose of paracetamol?
hepatotoxicity
what are examples of COX-2 inhibitors?
coxibs
e.g. celecoxib
what are features of coxibs?
+ used for osteoarthritis and rheumatoid arthritis
+ restricted for when traditional NSAIDs produce too severe GIT side effects
+ cardiovascular risk needs to be assessed
what are examples that NSAIDs might be used to treat, as analgesics?
\+ headache \+ dysmennorhea \+ backache \+ bony metastases of cancer \+ postoperative pain
what drugs are short-term analgesics?
+ aspirin
+ paracetamol
+ ibuprofen
what are longer-lasting analgesic drugs for chronic pain?
+ naproxen
+ diclofenac
for anti-inflammatory action, what is the preferred drug?
ibuprofen
for anti-pyretics, what is the preferred drug?
paracetamol
name products generated from arachidonic acid by COX enzymes
- thromboxanes
- prostaglandins
- leukotrines
COX-1
- constitutive
- important in maintaining GIT integrity
- flurbiprofen (inhibitor)
COX-2
- inducible
- involved in inflammatory response
- implicated in cancer development
- celecoxib (inhibitor)
what causes inflamed regions to be painful?
due to histamine and bradykinin release:
- activate nocioceptive afferent nerve terminals
- register a painful stimulus
