Non Steroidal Antiinflammatory Drugs

Question 1

What are NSAIDs

Answer 1

They are analgesics and anti inflammatory.

Question 2

What is the therapeutic action of NSAIDs

Answer 2

It inhibits Cox

Cox one is always active and Cox 2 is inducable

Question 3

How does aspirin cause irreversible reaction to Cox?

Answer 3

Yes

Question 4

Antipyretic effect of NSAIDs

Answer 4

Bacterial endoroxibs stimulate macrophage to release interleukin 1 , IT1beta acts on the hypothalamus to release PGE2 via Cox 2, this molecule depress temperature sensitive neuro a and elevates the set point of temperature result in fever.

NSAIDs block PgE2 production to so the temperature set point is lowered to normal value.

NSAIDs have no effect on normal body temperature

Question 5

Analgesic action of NSAIDS

Answer 5

PGs sensitise and stimulate nociceptors, oedema produced by inflammation also activates nociceptive nerve fibres.

PGs also work with other substances such as kinins, 5-HT and histamine to produce hyperalgesia.

Inhibition of PG production break this cycle and lead to pain relief

Question 6

Anti inflammatory actions of NSAIDs

Answer 6

PGE2 and PGI2 have powerful acute inflammatory effects such as arteriolar dilation, increase permeability in post capillary venules, both of which cause influx of inflammatory mediators into interstitial space

NSAIDs only provide systematic relief but does nothing to the underlying causes

Question 7

Cardiovascular pharmacology of NSAIDs

Answer 7

TXA2 causes platelet aggregation and vasoconstriction, NSAIDs decrease TXA2 and increase bleeding time.
Aspirin is beneficial because is decrease TXA2 production from COX 2 in endothelial cells and platelets, however COX2 will recover in endothelial cells so you still get PG production but a decrease in TXA2 so less coagulation.

Question 8

Skeletal effect of NSAIDs

Answer 8

NSAIDs decrease PGs and decrease their acute inflammatory response in swelling and pin in arthritis. This is due to arteriolar dilation which increase microvascular permeability and hyperalgesia.

Question 9

NSAIDs effect on the GI tract

Answer 9

PGE and PGI protect the gastric mucosa. They stimulate mucus secretion and inhibit gastric acid secretion. NSAIDs decrease these cytoprotective mechanism which can result in bleeding and ulceration. Gastric side effects are the most common adverse reactions to older NSAIDs. Cox 2 selective inhibitors may be gastric friendly as it is suggested Cox 1 is expressed in the gut

Question 10

Cox 2 selective agents are?

Answer 10

Celecoxib
Valdecoxib
Etoricoxib
Rofecoxib

Question 11

NSAIDs and CNS?

Answer 11

NSAIDs inhibit pyrexia, however when over dosed it produce hyper pyrexia, stupor and coma. This is because t increase metabolism and increase metabolic acid secretion. Reye’s syndrome (brain and liver damage) is a risk when used in children with influenza or chicken pox.

Question 12

Genital tract and NSAIDs

Answer 12

PGs cause pain and smooth muscle spasm during menstruation so NSAIDs can be used as treatment.

However PGs are important in uterine contraction in childbirth such NSAIDs delay contractions. Many NSAIDS increase postpartum blood loss because TXA2 prevents it.

Question 13

Kidney and NSAIDs

Answer 13

Vasodilator PHs regulate renal blood flow. PGI2 mediates renin release and PGE2 decrease sodium absorption. Thus NSAIDs reduce renal blood flow.

Inhibition of Cox 2 decrease sodium excretion and increase intravascular volume. It cause average blood pressure to rise about 3/2 mmhg. Low dose aspirin doesn’t seem to interfere with anti hypertensive therapy but regular use should be avoided.

Question 14

Respiratory system and NSAIDs

Answer 14

PGD2 and PGF2alpha are constrictors and dilator effects on airway smooth muscle but NSAIDs have no effects on normal airway tone, 20%of asthma patients wheeze when given aspirin or other NSAIDs because they are hypersensitive to these drugs.

At toxic dose aspirin stimulate respiration and alkalosis due to hyperventilation

Question 15

What can be given to treat ductus arteriosclerosis in neonates?

Answer 15

Ibuprofen and indomethacine

Question 16

Ulcerative colitis is inflammation of the bowel how can we treat it?

Answer 16

First you can give them aminosalicylates which are -salazine. Another treatment option is to decrease inflammation for mild or moderate ulcerative colitis. It can be used to short term flare ups. Ulcerative colitis is caused by increase in PGs.

Question 17

What is the mechanism of suldasalazine

Answer 17

It reduce the synthesis of eicosanoids by blocking cyclooxygenase and lipooxygenase

Side effect include indigestion, feeling or being sick, abdominal pain and diarrhoea. Dizziness, headache and difficulty sleeping and tinnitus. Coughing, itchy rash and may even affect you taste and cause sore mouth.

Question 18

Anti inflammatory agents for gout and what is it?

Answer 18

Gout is a type of arthritis that involve the accumulation of iris acid crystals in joints. These Utica acids build up in the joints and cause painful inflammations. auric acids can be found in blood and it is harmless in low levels. Iris acid prevents damage to blood vessel linings. It is suppose to pass out with the urine and faeces. The crystals in joints induce inflammation and pain.

Drugs are naproxen, diclofenac, and indomethacin

Question 19

Mechanism of action of naproxen

Answer 19

It inhibits COx1 and 2 which lower PG levels. In reduce pin and inflammation and decrease fever. It also inhibit platelet aggregation due to TXa2 not being produced.

Side effect include dizziness, nausea, indigestion, blurred vision, diarrhoea, abdominal liver function test, water retention.