Pain-COX inhibitors Flashcards
What are Prostanoids?
- Prostoglandins (PGs) and thromboxanes (TXs)
- PGE2, PGI2, and PGD2 are powerful vasodialtors
1. Synergise with histamine and bradykinin (other potent vasodilators) —-> Redness and inc blood flow in areas of acute inflammation
2. Potentiate the post-capilliary venules permeability effect of histamine and bradykinin - PGE2 mediates the increase in temperature generated by endogenous cytokines
What is Cyclo-Oxygenase (COX)?
- Enzyme responsible for the formation of prostanoids from arachidonic acid
- Expressed as a homodimer in the membrane of the ER
What are cyclo-oxygenase (COX) inhibitors inhibitors?
- Traditional NSAIDs (non-steroidal-anti-inf-drugs)–Inhibit COX-1 & COX-2
- COXIBs–More selective for COX-2
- NSAIDs–Inhibit prostoglandin biosynth by direct action on the cox
- Other COX inhibitors prev arachidonic acid from accessing the catalytic site of COX
Describe the Pharmacological actions of COX inhibitors.
- The therapeutic actions stem from the suppression of prostanoids synthesis in inf cells
- Mainly through the inhibition of COX-2 isoform
What are the anti-inflammatory effects of COX inhibitors?
- Prostoglandins (mainly derived from COX-2) play an important part in inf reactions
- By inhibiting the formation of these PGs, NSAIDs reduce inflammatory reactions
1. Red synthesis of vasodilator PGs (vasodilation facilitates and potentiated the action of mediators that increase the permeability of capilliary venules)
2. NSAIDs suppress the signs and symptoms of inflammation, they do not treat the underlying cause of such imflammatory processes
What are the analgesic effects of COX-inhibitors?
- NSAIDs are effective against mild/moderate pain
- Peripherally–> Decreases in PGs that sensitise nociceptors to inf mediators
- Centrally–> Decrease of PG release in spinal cord
What are the antipyretic effects? (dec in body temoerature)
- Fever occurs when there is a disturbance of the hypothalamic ‘thermostat’–A centre in the hypothalamus that regulates body temp
- NSAIDs ‘reset’ this thermostat (mainly by Red PG production in hypothalamus)
- Once there has been return to normal ‘set point’ –> Reduction of temp by reg mechanisms (e.g. sweating)
What are clinical uses of COX inhibitors?
- Antithrombotic
- Analgesic
- Anti-inflammatory
- Antipyretic
Give an example of an Antithrombotic COX inhibitor?
Aspirin for patients with high risk of arterial thrombosis
Give an example of an Analgesic COX inhibitor?
- (analgesia is things like: Headache, backache etc)
- Short term: Aspirin, paracetamol, ibruprofen
- Chronic pain: More potent, longer lasting drugs, e.g. Naproxen
Give an example of an Anti-inflammatory COX inhibitor?
Ibruprofen for symptomatic relief in rumatoid arthritus etc
Give an example of an Antipyretic COX inhibitor?
Paracetamol
What are unwanted effects of COX inhibitors?
- NSAIDs have a high burden of unwanted side effects
- When used for joint diseases (high doses), high incidence of side effects (GI, liver, kidney, spleen, blood and bone marrow)
- Most side effects derive from inhibition of the role of PGs in normal physiology.
What are the adverse GI effects caused by COX inhibitors?
- Casued by inhibition of COX-1 (Normally synth PGs that inhibit secretion of gastric acid)
- Symptoms: Gastic discomfort, constipation, nausea and vomiting, gastric bleeding and ulceration.
- (can also carry risk of haemorrhage and/or perforation)
- Oral admin of ‘replacement’ PG analogues help reduce damage
What are adverse skin reactions casued by COX inhibitors?
- Cause/mechanism unclear
- Common with mefenamic acid (10-15%) and Suldinac (5-10%)
- Symptoms: Mild erythematous, urticarial and photosensitivity reactions to serious, potentially fatal stevens-johnson syndrome and toxic epidermal necrolysis
