NSAIDS Flashcards
What are the clinical features of inflammation?
Swelling, redness, pain & heat
What is the enzyme that breaks down phospholipids?
Phospholipase
What is Phospholipids broken down to?
Arachidonic acid
- -> Leukotriene
- -> Prostaglandins
- -> Thromboxane
- -> Prostacyclin
What are Prostaglandins (PGE2) responsible for?
Uterine contraction
Vasodilation- contraction of GI smooth muscles
Inhibition of gastric acid secretion
What are Thromboxane responsible for?
Platelet aggregation
What are Prostacyclins (PGI2) responsible for?
Inhibits platelet aggregation
Vasodilation
Gastric xytoprotection
What are Leukotrienes responsible for?
Chemotaxis
Hyperalgesia (hyper sensitivity to pain)
Broncho-constricion
Edema
What condition would your body produce a lot of Leukotrienes for? Specifically LTC4, LTD 4, LTE4
Asthma
How to corticosteroids work?
Work on Cyclo-oxygenase, shutting off the Cox 1 & Cox 2 pathways
Is Acetominophen (tylenol) an NSAID?
NO!
Is Aspirin an NSAID?
YES!
What is also known as the Constitutive pathway?
COX 1
Because it will always be there
What is know as the inducible pathway?
COX 2
Because this is not always available, you have to turn this on when needed.
Why would you not want COX 2 to always be on?
Because It makes you more sensitive to pain, so only turn on when needed
What do NSAIDs inhibit?
COX 1 & COX 2 pathways
Where is Prostacycline (PGI2) located?
Vascular endothelium
Where is the Cyclooxygenase (COX) pathway located?
Endoplastmatic reticulum
What are the 3 Isoforms of COX?
COX 1 (constitutive) -->Pysiological conditions COX 2 (Inducible) ---> inflammation, pain COX 3 --> Brain
Are NSAIDs selective or nonselective COX inhibitors?
NON selective
What is Acetylsalicylic acid?
Aspirin
What are some examples of Nonselective COX 1/COX 2 inhibitors?
Acetylsalicylic acid Diclofenac Indomethacin Sulindac Piroxicam Piroxicam beta-cyclodextrin (prodrug) Lornoxicam Tenoxicam Flurbiprofen Ibuprofen Ketoprofen Naproxen
What are the benefits of NSAIDs?
- Analgesia–> Prevents pain
- Antipyresis–> reduces body temp
- Reduces inflammation
- Anti-thrombotic action–> in low doses prevents clotting/platelet aggregation
- Closes the Patent Ductus Arteriosus (Indomethacin)
What are some side effects of NSAIDs?
Gastric mucosal damage Bleeding Decreased renal flow Delay/prolonged labor/contractions Asthma/anaphylaxis
What is a direct result of NSAID use that can cause ulcers
Direct toxicity “Ion trapping”
What are the 2 compounds that Aspirin splits into when metabolized?
Acetic Acid
Salicylate
What happens to the Aspirin metabolites if oxidized?
Can become Gentisic Acid
What happens to the Aspirin metabolites if conjugated with glycine?
Become Salicyluric acid
What are some risks of Aspirin in children with rheumatoid arthritis?
Hepatic encephalopathy (Reyes Syndrome)
What is the lower age limit for Aspirin?
Under 15, unless specifically indicated for Juvenile arthritis
What is an effect of being on chronic Aspirin?
Thinning of blood, increased risked of hemorrhagic stroke
What happens in an Aspirin OD?
Fever N/V Decreased urination Diplopia Restlessness/irritability Dizzy/confused LOC, impaired cognition Drowsy Hallucinations
What is the interaction of ACE inhibitors with NSAIDs?
Decreases the affect of ACE (decrease antiHTN effect)
What is the interaction of Cyclosporine with NSAIDs?
Increased Nephrotoxicty
What is another name for Ibuprofen?
Advil
What is Ibuprofen a derivative of?
Phenylpropionic acid
How is oral Ibuprofen usually prescribed?
In a low dose b/c is has anlagesic but not anti-inflammatory effects
What would a liquid gel preparation of Ibuprofen be used for?
Postsurgical dental pain
What are some difference between Ibuprofen and Indomethocin?
Ibuprofen decreases urine output and causes less fluid retention
Are NSAIDs useful in closing the ductus arteriosus in preterm infants?
YES
What is Ketoprofen used for?
RA
Osteoarthritis
Gout
Dysmenorrhea
What is Indomthacin used for?
Juvenile rheumatoid arthritis Gout Ankylosing spondylitis Postepisiotomy pain Treats patent ductus arteriosus reduces conjunctival inflammation Reduces pain after traumatic corneal abrasion Gingival inflammation
What are the side effects of Indomethacin?
GI and CNS side effects --> At high doses GI bleeding Diarrhea Frontal headache Mental confusion
What is Diclofenac used for>?
Prophylaxis for postoperative ophthalmic inflammation Intra-ocular lens implantation Strabismus surgery Solar Keratoses Analgesia Postoperative Nausea
What are the AEs of Diclofenac?
GI distress
Occult bleeding
Gastric ulceration
What happens when you combine Diclofenac and Misoprostol?
Decreases upper GI ulceration or Diarrhea
What are the indications for Piroxicam?
Rheumatic indications
What happens when Prioxicam is given at high doses?
Increases risk of peptic ulcer & bleeding (10x higher risk)
What is the MOA of Piroxicam?
A non-selective COX-1/COX-2 inhibitor inhibits polymorphonuclear leukocyte migration
It decreases oxygen radical
production, and inhibits lymphocyte function
What is the MOA of Indomethacin?
Non-selective COX inhibitor
It can inhibit phospholipase A and C, reduce
neutrophil migration, and decrease T cell and B cell
proliferation
What are some examples of COX 2 inhibitors?
Celecoxib
Meloxicam
Nabumetone
Which of the 3 COX 2 inhibitors is preferentially selective instead of highly selective?
Meloxicam
What is the main risk with COX 2 inhibitors?
Infertility
Prothrombotic cardiovascular risk
What is the DOC for Acute rheumatic fever?
Aspirin
Which med is as effective as other NSAIDs in the
treatment of rheumatoid arthritis and osteoarthritis,
and in trials it has caused fewer endoscopic ulcers
than most other NSAIDs, probably because it is a sulfonamide?
Celecoxib
What makes Acetominophen different Aspirin?
It is not an anti-inflammatory
What is the preferred drug for patients who are allergic to Aspirins or Salicylates?
Acetomoniphen
What is Acetominophen used for?
Mild to moderate pain –> HA, myalgia, postpartum pain
Would you give Aspirin or Acetominophen to a child with a viral infection?
Acetominophen
What are the AEs of Acetominophen?
Acute acetaminophen poisoning
Hepatic toxicity
Nephrotoxicity
What would you used to an alcoholic with side effects from Acetominophen?
Activated charcoal
What meds would you give for an acute Gout attack?
Colchicine PLUS pain reliever --> Diclofenac Indomethacin Naproxen Piroxiam
What meds would you give for chronic Gout?
Uricostatics (Xantine Oxidase inhibitors)
Allopurinol (DOC)
Febuxostat
Uricosurics
Probenecid, benzbromarone
Sulfinpyrazone
Uricolytics: Uricase, Rasburicase
What is a combo drug that could be used for Gout?
Harpagin (allopurinol & benzbromarone)
