Inflammation Flashcards
Which class do acetlysalicylic acid and Diflunisal belong to?
salicylates
What is the mechanism of action of Diflunisal?
reversibly inhibits COX1 and 2
longer half life than aspirin, less GI side effects, less Platelet effects.
Has Analgesic effects and wheal antipyretic activity.
COX 1 vs COX 2
Cox 1 : Constitutively produced
Gastric protection, platelet aggregation, renal blood flow autoreg, initiation of parturition (PGF2)
Cox 2 : Induced during Inflammation –> produces prostaglandins at the site of inflammation/ tissue injury
Both are inhibited by NSAIDS
What is the mechanism of action of acetylsalicylic acid and its metabolite salicylic acid?
Irreversibly acetylates COX-1 and -2;
metabolite, salicylic acid reversibly inhibits COX-1 and -2
What is acetylsalicylic acid used to treat?
Antiplatelet, analgesic and antipyretic, and anti-inflammatory (in ascending order of amount taken)
What is Diflunisal used to treat?
Osteoarthritis, cancer pain from Bone mets, musculoskeletal strains/sprains, pain after dental extraction, and postepisiotomy pain
What is acetaminophen used to treat?
analgesic and antipyretic (minimal anti-inflammatory b/c of its poor ability to inhibit COX in the presence of a high conc. of peroxides, which are usually found at the site of inflammation. Also, COX inhibition may be disproportionately pronounced in the brain –> hence the antipyretic efficacy)
usually used in patient intolerant to aspirin
What can happen when acetaminophen is chronically abused or overdosed?
@ an ordinary dose: virtually no side effects
chronic abuse- renal tubular necrosis
overdose-hepatic necrosis from depletion of glutathione
Which has more GI side effects; acetlysalicylic acid or Diflunisal?
acetylsalicylic acid
Name the 2 Indoles that reversibly inhibit COX1 and 2 (with a preference for COX1)
Indomethacin and Sulindac (half as potent as indomethacin)
Name the para-amino phenol that reversibly inhibits COX1 and 2.
Acetaminophen
Name the 4 proprionic acid drugs that reversibly inhibit COX 1 and 2 (with a preference for COX1).
Ibuprofen,
Naproxen (Aleve: 13 hr half life),
Flurbiprofen (obtains high synovial conc, available for topical opthalmic formulation)
Oxaprozin (Daypro: 50 hr half life)
What medication can be used to treat acetaminophen overdose?
acetylcysteine (MUCOMYST) to protect the liver
What are the indoles Indomethacin and Sulindac used to treat and what are their side effects?
Rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, acute gout
side effects- thrombocytopenia, aplastic anemia, and severe frontal headaches and nephrotoxicity in elderly/hypovolemic
What are the proprionic acid drugs used to treat? (Ibuprofen, Naproxen Flurbiprofen, and Oxaprozin)
Rheumatic disorders, osteoarthritis, ankylosing spondylitis, postpartum pain, dysmenorrheal pain, and many types of surgeries
What are the side effects of the proprionic acid drugs?
Ibuprofen, Naproxen Flurbiprofen, and Oxaprozin
GI irritation and hepatotoxicity (less frequent than aspirin)
List the proprionic acid derivatives in order of increasing half life length.
Ibuprofen and Flubiprofen, Naproxen and Oxaprozin
What class of drugs is Ketorolac from and what is its mechanism of action?
Good alternative to opiods: 4-6 hr half life
heteroaryl acetic acids; reversibly inhibits COX 1 and 2 (with a preference for COX1)
What class of drugs is Piroxicam from and what is its mechanism of action?
Enolic acid; reversibly inhibits COX1 and 2. favors COX 1
Name the 2 selective COX2 inhibitors.
“COXIBS”
Larger molecules than NSAIDS and fit the larger hydrophobic channel of COX2 better.
Celecoxib (x10-20 more COX2 selective) and etoricoxib (x100 more selective for COX2)
Have no effects on platelets therefore aren’t cardio protective like the traditional NSAIDS.
What is piroxicam used to treat and how often is it taken?
Long-term treatment of rheumatoid arthritis or osteoarthritis, also ankylosing spondylitis, acute musculoskeletal disorders, acute gout; taken once per day because long half life (45hrs)
What is ketorolac used to treat and how is it administered?
Post-operative pain; IM injection
inflammatory eye conditions; topically
Fairly, nonirritating to tissues
What are the selective COX2 inhibitors used to treat?
Same anti-inflammatory, antipyretic, and analgesic effects as NSAIDs with less GI toxicity
What limits the use of Indomethacin?
SHLDNT BE GIVEN TO KIDS!! EXCEPT- FOR CLOSURE OF THE DUCTUS ARTERIOSUS FOR WHICH IT IS FDA APPROVED!!
TOXICITY! Nephrotoxicity in the elderly and the hypovolemic
Otherwise, it is 10x more potent than aspirin
In which patients are COX2 inhibitors contraindicated?
patients with heart problems/pregnancy
What are some of the side effects of the salicylates?
GI Irritation, nephrotoxicity (more so in elderly or hypovolemic), bleeding and anemia, hepatotoxicity, hypersensitivity reaction and toxicity
