NSAIDs: Non-Steroidal Anti-inflammatory Drugs Flashcards
What is the traditional NSAID?
Aspirin (ASA)
(aspirin, motrin, aleve)
Salicylates vs. non-salicylates?
Salicylates – aspirin
Non-salicylates – ibuprofen (Advil)
When was aspirin first produced?
Purified acetyl salicylic acid (ASA) helps with pain
Modified structure gave us aspirin (1897), the first synthetic drug to help diminish side effects
Who and which company is aspirin associated with?
1894 Bayer pharmaceuticals with Felix Hoffman
Wanted to find something to deal with chronic pain and made a big breakthrough
History of NSAIDS, what plants was ASA/salicin first discovered?
1428: white willow extracted
1839: meadowsweet
Extract was salicin
When and how was aspirin’s mechanism of action found?
1971 found out the mechanism of action because of John Robert Vane’s research on prostaglandins
Pharmacodynamics of NSAIDs?
The cell membrane has a lot of arachidonic acid (fatty acid) which are used to make prostaglandins (EICOSANOIDS, 20 carbon structure)
Phospholipase A removes them from the membrane
Cox 1 and cox 2 are used to make prostaglandins which help with gastrointestinal protection and inflammation and pain
What are prostaglandins?
- Made by almost all cells
- Autocrine and paracrine functions (act on the same cell and neighboring cells)
- Rapidly inactivated
Prostaglandins have multiple roles in normal physiology and pain reaction and inflammation, initiate fever
What is a cyclooxygenase?
Cyclooxygenase is a dimer in the ER that forms a ring by adding 2 oxygens
- AA enters one of the two active sites
- It is converted to prostaglandin
- Further modifications to make different subtypes
What are the 2 major cyclooxygenases?
- Cox-1: active all the time, protects the stomach by making gastric mucous
- Cox-2: inducible after injury, involved un chronic inflammation
NSAIDS block both types of cyclooxygenases
What do prostaglandins act on?
- Act on GPCRs
- Subgroups, PGD, PGE, PGF, PGI, PGT (receptors DP1, DP2, …, EP1, EP2…TP1)
- Different receptors do different things, they are differentially expressed in different parts of the body
Role of prostaglandins, pathologic and physiologic?
Pathologic:
Fever, asthma, ulcers, diarrhea, dysmenorrhea, inflammation, bone erosion, pain
Physiologic:
Temperature control, bronchial tone, cytoprotecting, intestinal mobility, myometrial tone, semen viability
Concerned with pathological role when giving drugs
We are Concerned with pathological role when giving drugs
NSAIDS block prostaglandin synthesis to treat 3 main effects?
Inflammation – anti inflammatory
Pain – analgesic
Fever – antipyretic
How do prostaglandins create a pain response in the periphery
(nerve endings are more sensitized to other mediators because of prostaglandins)
Nociceptors: prostaglandins sensitize to other mediators
How do NSAIDs reduce pain?
Pain is initiated in the periphery, travels to spinal cord, then brain
NSAIDS in the periphery start action
Injured cells release PGE2 and other Prostaglandins as well as other mediators, NSAIDs inhibit their production, to prevent them from sensitizing nerve endings to pain.
What type of pain are NSAIDS useful for treating?
-Temporary pain, not severe pain
- If more serious or persisting pain use miso
- If cancer pain use opioids but can also use NSAIDS as a mix
- Relief of mild/moderate pain (headache, toothache, myalgia)
- Relief of inflammatory disorders (arthritis, osteoarthritis, gout)
- Reduce fever
What other effect does aspirin have?
Prophylaxis of myocardial infraction (heart attack) and stroke (aspirin only)
prevents these by reducing blood clots
Tissue injury causes?
COX activated, prostaglandins synthesized at injury site, sensitize nerve endings to activity of other mediators
acute vs chronic inflammation?
Acute inflammation: small cut, goes away quickly
Chronic inflammation: arthritis, cardiovascular disease, chronic inflammatory disease, bone muscular and skeletal disease (osteoporosis), cancer
What NSAIDs are toxic to cats?
ASA and acetaminophen
How is fever produced in the body?
Fever: produced by activity in hypothalamus (temperature control)
PGE2 raises temperature, (COX-2, PGE2)
How is inflammation produced in the body?
Take in liquid mediators, monocytes, basophils, neutrophils that release Brady Kinin and PGE2
NSAIDs upper GI tract and renal side effects?
Stomach creates mucus that sits on top of cells to protect them from the HCl acid in the stomach
Chronic NSAIDS interfere with prostaglandins that make mucus, making the cells exposed to HCl acid
Frequent and serious side effects with chronic use, even make Ulcers
(can antacids be used to prevent this)
Therapeutic effects of ASA? (4)
Analgesic, anti-inflammatory, and antipyretic effects (usual effects of NSAIDS)
Antithrombotic effects – blocks blood clots
