Analgesics Drugs 2: NSAID's

Question 1

What types of pain do NSAID’s deal with?

Answer 1

Inflammatory pain

Question 2

What is the mechanism of action of NSAID’s

Answer 2

Inhibits the cyclo-oxygenase enxyme (COX1 and COX2) leading to suppression of prostanoid production
Typically reversible and incomplete (not aspirin)

Traditional inhibit both, newer COX2

Question 3

Effects of NSAID’s

Answer 3

Decrease inflammation; relieve mild pain; anti-pyretic; anticoagulation (TXA2)

Decrease in prostaglandins

Question 4

Prostaglandins

precursor

Answer 4

Lipid compunds released by most cell with a wide array of biological actions. Very short half life

Arachidonic acid, converted by COX

in the context of inflammation cause things like vasoconstriction, erythema, pain, fever

Question 5

Prostanoids

Answer 5

Part of the eicosanoids, encompasses prostaglandins, prostacyclin and thromboxane

Question 6

COX1 pathway

Answer 6

COX1 is constitutive and is in the cell. Will form several prostaglandins necessary for homeostatic function. Inhibition is not desirable.

Explains side effects

Question 7

COX2 Pathway

Answer 7

COX2 is induced, needs to be stimualated, for example during inflammation. COX2 makes prostaglandins that contribute to inflammation, so inhibition is desirable (NSAID’s and glucocorticoids)

Question 8

COX2 inhibitors side effects

Answer 8

Gastro and heart problems, heart attacks and strokes

Question 9

Pharmacokinetics of NSAID’s

Answer 9

• Very lipophilic, so absorbed rapidly
• Very high bioavailability
• High degree of protein binding, so low volume distribution
• Slow onset of action
• different clearances

Question 10

What is the negative affect of the high protein binding ability of NSAID’s?
Renal tubular secretion?

Answer 10

When taken with other drugs, will bind to the proteins, dissociating that drug, losing the action.
Bad with anticoagulants, anti-cancer drugs

Compete with uric acid for secretion, careful of gout

Question 11

NSAID side effects

Answer 11

Bleeding (may increase post operative blood loss, or epidural haematoma’s); GI tract; Renal; liver; pregnancy/lactation; Reye’s syndrome

Question 12

Aspirin:

• excretion and gout?
• COX1 intreaction

Answer 12

• Conjuated in liver with gylcine, exarcebates gout

- stops formation of TXA2, thus decreasing platelet adhesion. Note spares the prostacyclin vasodilator)

Question 13

Aspirin induced asthma

Answer 13

Exactly what is says it is, after ingesting NSAID’s. Onset usually 30 years

Decrease in PGE2, a bronchodilator, which will activate some inflammatory mediators, bronchospasms

Question 14

Asprins triad

Answer 14

1) Aspirin intolerance in the form of rhinitis and facial flushing
2) A few days later asthma
3) Nasal Polyps

Question 15

Reye’s syndrome

Answer 15

Occurs in children who take aspirin after a viral illness,
Causes brain encephalopathy, and a fatty liver. Quite fatal.

Avoid aspirin use in children with viral illness

Question 16

NSAID’s and kidney damaged

Answer 16

Usually only occurs in compromised patients, but can lead to ATN and nephritis.

Question 17

Prostaglandins and pregnancy

Answer 17

Instigate uterine SM contractions (labor) and maintain DA patency in foetus.

Thus NSAID’s can stop premature labor, and to close DA in premature babies

Question 18

Paracetamol

Answer 18

Not an NSAID as does not have much anti-inflammatory properties.
Cyt P450 ofc