NSAIDS and Pain Processing Flashcards
What are eicosanoids?
Small lipid molecules derived from arachidonic acid
What is the rate limiting step in the production of eicosanoids?
Release of AA by phospholipase A
List three examples of eicosanoids
Prostaglandins
Thromboxanes
Leukotrienes
What drives the synthesis of eicosanoids?
Stimuli such as cell death
Eicosanoids have a role in inflammation
Present at tissue damage site
Which two fatty acids metabolise eicosanoids?
COX1 and COX2
Describe co enzymes COX1 and COX2
COX1- constitutive, expressed all the time, in most tissues (platelets)
normal physiological wellbeing
COX2- Induced in activated inflam cells- IL1/TNF gamma produce prostaglandin inflam mediators
List the 4 cyclic endoperoxides
PGI2- vasodilator- IP receptor PDG2- vasodilator DP receptor TXA2- vasoconstrictor TP receptor PGF2- acts on FP receptor PGE2- EP receptor
How does inflammation occur
Inflam due to release of PGE2 and PGI2- gen by local tissue and bv
Mast cells release PGD2
What is the main effect of chronic inflammation?
Increase in macrophages/monocytes
What is the main effect of PGD2, PGI2, PGE2?
Powerful vasodilators
Increase blood flow to inflammation and leakiness of bv
How is itch produced?
Prostanoid synergises with histamine
How is pain produced?
Prostanoid synergises with bradykinin
Why is there redness?
Increased blood flow to the area
Describe bradykinin
Synthesised de novo during tissue damage
Made in vasculature by activated enzymes
PG sensitive nociception
Activate nociceptors by B1 and B2 receptors, increase PG prod, enhance nociceptor response to BK
What are the three main uses of NSAIDs?
Anti inflammatory- decrease vasodilation and oedema
Anti pyretic- decrease body temp. NSAIDs reset thermostat in hyp. Block changes in hyp by PG
Analgesic- for pain assoc with inflam/tissue damage eg arthritis, muscle pain, toothache
What are NSAIDs used in combination with?
Opioids to decrease chronic pain post op/cancer
What are the clinical uses of NSAIDs?
Short term- Ibuprofen, aspirin, paracetamol
Long term- naproxen, piroxicam
Chronic/acute inflam- lupus, gout, rheum arthritis- high dose
Decrease temp in fever
How does aspirin work?
Irreversible inactivation of COX1/2
Oralm rapid absorp, 75% metab in liver
1st order elimination, half like of 48 hours
Antiplatelet drug in MI therapy+ CVA prophylaxis
What are the main side effects of NSAIDs
GI effects- gastric ulcers- bleeding
Dyspepsia, bloating, diarrhoea, nausea, vomiting
Skin rash, dizzy, deaf, tinnitus, viral encephalitis in kids
Toxic dose- uncompensated resp and metabolic acidosis
How does paracetamol work?
Analgesic, antipyretic, anti inflam
Metab in liver- 2-4 hours, few side effects- kidney damage with high dose
Toxic dose- nausea and vom and liver damage
How do selective COX2 inhibitors work
VIOXX, Merck- risk of heart attack, stroke, CV death
Celecoxib- 375 fold selective for COX2
