MSK 04

Question 1

Goal of Treatment for OA & RA?

Answer 1

Reduce Pain
Improve function
Improve quality of life
Arrest or reverse joint destruction If possible

Question 2

What are the strategies for management of Arthritis?

Answer 2

Pharmacological
non-pharmacological
Surgery
Complementary and alternative meds

Question 3

What are the unwanted effects of NSAIDs?

Answer 3

Higher dosage higher risk
Heart attack
Stroke
GI ulceration 
GI bleeding
Acute Renal failure

Question 4

TXA2 (Thromboxane A2) plays a major role on?

Answer 4

platelet aggregation or clot formation and vasoconstrictor.

Question 5

PGI2 (prostacyclin) plays a major role on?

Answer 5

also known as prostacyclin plays a major role of inhibition of platelet aggregation,

Question 6

PGE2 plays a major role on?

Answer 6

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).

Question 7

Cyclooxygenase 1 Vs 2

Answer 7

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

Question 8

What is prostaglandin?

Answer 8

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

Question 9

Prostaglandin action depends on Number of things

Answer 9

Circumstances
Site
Amount

Question 10

How NSAIDS work to prevent the inflammation from occurring?

Answer 10

By inhibiting cox enzyme function.

Question 11

Classical NSAIDs are selective or non-selective?

Answer 11

Nonselective.

Question 12

Diclofenac and Celecoxib is which Cox inhibitor?

Answer 12

Cox2 selective inhibitor

Question 13

Why Coxibs (Cox2 selectivity) developed?

Answer 13

To reduce unwanted effect.

Keeping analgesic and anti-inflammatory effects without altering COX 1 functions.

Question 14

What if NSAIDs advocated for specific indication like for Goat or period pain.

Answer 14

There is not such evidence of superiority when dosed appropriately.
Choice depends on:
patient’s tolerance
Frequency of dosing, long or short acting.

Question 15

What is ceiling effect of NSAIDs?

Answer 15

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.

Question 16

Analgesic mechanism of NSAIDs?

Answer 16

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.

Question 17

What is the Anti-inflammatory effects Mechanism of NSAIDs is?

Answer 17

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.

Question 18

Antipyretic mechanism of NSAIDs?

Answer 18

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.

Question 19

How NSAIDS give anti platelet effect?

Answer 19

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.

Question 20

What does PGI2(prostacyclin) does in our body?

Answer 20

Inhibit platelet aggregation

Question 21

What does Thromboxane do in our body?

Answer 21

TXA2 derives platelet aggregation

Question 22

What kind of COX-1 inhibition Aspirin does in our body?

Answer 22

Irreversible inhibition of platelet COX 1

Question 23

What kind inhibition effects shows Other NSAIDS?

Answer 23

Reversible inhibition of COX enzyme as a result they have weaker effect

Question 24

Other NSAIDS show Reversible effects Except?

Answer 24

Naproxen

Question 25

Does Cox2 selective do have platelet inhibition effect in body?

Answer 25

Cox 2 selective do not inhibit platelet aggregation why?

Because Anti platelet effect system driven only by COX-1 system.

Question 26

Why Aspirin must not be given with other NSAIDS?

Answer 26

It fully blocks Aspirin anti-platelet effects so co-administration of Ibuprofen or indomethacin or naproxen is totally NO NO.

Question 27

What is the risk or unwanted effects of using NSAIDS?

Answer 27

Risk of using ANSAIDs related problems are quite low however as this drug are frequently uses so there is a risk of increase potential for adverse events.
They are GI, type 2 diabetes patients are at risk of Renal function, Hypersensitivity, for Older patients it is Increased risk of CV

Question 28

What are the NSAIDs related GI unwanted effects?

Answer 28

Nausea, Ulceration, dyspepsia

Question 29

How NSAIDs cause GI unwanted effects?

Answer 29

By using NSAIDs they are inhibiting the production of helpful PG (prostaglandins) by inhibiting COX1 or COX-2
As NSAIDs are acidic in nature so they decrease mucosal barrier
Increase mucosal permeability

Question 30

How NSAIDs has unwanted effects on renal function?

Answer 30

The main role of PGI2 (works as a vasodilator) is to maintain renal blood flow so Inhibition of PGI2 will decrease GFR as a result impaired renal function.

Question 31

How can NSAIDS case salt and water retention as unwanted effect?

Answer 31

Inhibition of PG in the loop of Henle can interrupt the function of Na+ /K+ /2Cl cotransporter complex which leads to fluid and salt retention due to ADH(Antidiuretic) hormone action which leads to heart failure and Hypertension.

Question 32

NSAIDs may stop other medications effects in our body and they are?

Answer 32

Diuretics
ACE inhibitors
Beta blockers

Question 33

The triple whammy can’t be given together otherwise unwanted side effects?

Answer 33

NSAIDs: inhibit PG which works as vasodilator so no PG result constriction blood vessels and blood flow into the glomerulus in afferent arteriole (jeta diya ashe) and reduce GFR cause renal failure
Diuretics: reduce plasma volume and reduce GFR result cause renal failure
ACE inhibitor: dilates the afferent (means jower pothey) arteriole and reduce GFR result cause renal failure.