MSK 04 Flashcards
(33 cards)
Goal of Treatment for OA & RA?
Reduce Pain
Improve function
Improve quality of life
Arrest or reverse joint destruction If possible
What are the strategies for management of Arthritis?
Pharmacological
non-pharmacological
Surgery
Complementary and alternative meds
What are the unwanted effects of NSAIDs?
Higher dosage higher risk Heart attack Stroke GI ulceration GI bleeding Acute Renal failure
TXA2 (Thromboxane A2) plays a major role on?
platelet aggregation or clot formation and vasoconstrictor.
PGI2 (prostacyclin) plays a major role on?
also known as prostacyclin plays a major role of inhibition of platelet aggregation,
PGE2 plays a major role on?
A good amount of COX1 plays GI mucosal protection or integrity by mucus production, blood flow. In contrast if we experience tissue damage via induced cox2 than PGE2 levels increase. As a result, high level of PGE2 cause pain and inflammation. By increase blood flow(vasodilation) body become red, warmth(fever).
Cyclooxygenase 1 Vs 2
Cox 1
Small amount of proteinoids production & do homeostatic or housekeeping function
Regulate Renal, gastric blood flow, gastric protection
Cox 2
Large no of proteinoids
Rapidly upregulate by cytokines or(inflammatory mediators)
So when we see a large amount of Cox2 production we experience inflammation
What is prostaglandin?
Prostaglandins are group of lipids made at sites of tissue damage. Involved in dealing with injury and illness. They control processes such as inflammation, blood flow, the formation of blood clots and the induction of labour
Prostaglandin action depends on Number of things
Circumstances
Site
Amount
How NSAIDS work to prevent the inflammation from occurring?
By inhibiting cox enzyme function.
Classical NSAIDs are selective or non-selective?
Nonselective.
Diclofenac and Celecoxib is which Cox inhibitor?
Cox2 selective inhibitor
Why Coxibs (Cox2 selectivity) developed?
To reduce unwanted effect.
Keeping analgesic and anti-inflammatory effects without altering COX 1 functions.
What if NSAIDs advocated for specific indication like for Goat or period pain.
There is not such evidence of superiority when dosed appropriately.
Choice depends on:
patient’s tolerance
Frequency of dosing, long or short acting.
What is ceiling effect of NSAIDs?
The Maximum amount of dose been used and after that we will not receive any further analgesic or anti-inflammatory effect or other benefit instead of we will experience side effect or toxicity.
Analgesic mechanism of NSAIDs?
Analgesic effects of NSAIDS is due to inhibition of CoX-2 as the PGs is the result of COX2 upregulation.
So how they produce their
Analgesia effect: by in 2 ways
i. Reducing “peripheral sensitisation”: peripheral sensitisation occur after tissue damage. through reduction of prostanoid in “inflammatory soup”
i. “CNS component”
NSAIDs also can Reduce pain intensity by reducing prostanoid formation.
Reduce formation of prostanoid formation in the spinal cord
Reduced neurotransmitter release results less excitation, less pain.
What is the Anti-inflammatory effects Mechanism of NSAIDs is?
Decrease Cox2 generated prostaglandins which ultimately reduce vasodilation or oedema in the injured area in the infection.
NSAIDs also reduce inflammation by reducing “superoxide free radical formation” by neutrophils
NSAIDs also give inflammatory effects by “Uncouple G-protein regulated processes” in inflammatory cell membranes as a result the injured cells become much less responsiveness against inflammation.
Antipyretic mechanism of NSAIDs?
Circulating pyrogens (typically produced by a bacterium) Like IL-1 “Enhance PGE2” in hypothalamus.
NSAIDs reduce fever by depress temperature-sensitive neuron responses.
So, Fever reduced by Inhibition of hypothalamic COX-2 but no effect on normal body temp only decrease elevated temperature.
How NSAIDS give anti platelet effect?
Some NSAIDs has Anti-platelet effects so when TXA2 (which is a potent platelet aggregating agent) comes into place to aggregate blood clot. NSAIDs inhibit TXA2 by synthesising Cox-1 by using antithrombotic drugs (NSAIDs). Ex: Aspirin. 200 times more potent than COX-1 COX-2 and need less dose compared to anti-inflammatory drugs.
What does PGI2(prostacyclin) does in our body?
Inhibit platelet aggregation
What does Thromboxane do in our body?
TXA2 derives platelet aggregation
What kind of COX-1 inhibition Aspirin does in our body?
Irreversible inhibition of platelet COX 1
What kind inhibition effects shows Other NSAIDS?
Reversible inhibition of COX enzyme as a result they have weaker effect
Other NSAIDS show Reversible effects Except?
Naproxen
