NSAIDs

Question 1

Swelling changes include what?

Answer 1

Increased capillary permeability

Dilation of blood vessels
- redness and warmth caused

Increased tissue pressure and action of inflammatory mediators
- pain caused

Question 2

Eicosanoid receptor types

Answer 2

PGD2: mast cells and neurons

• active in Alzheimer’s disease
• controls sleep functions

PGE2: all kinds of tissues

• responds to pain stimuli
• causes fever, vasodilation, mucus production

PGF2a: smooth muscles
- promotes vascular tone

ALL 3 types are G-coupled protein receptors that promote bronchoconstriction

Question 3

Chemical mediators in causing fever

Answer 3

Prostaglandins

Question 4

Chemical mediators causing Increased vascular permeability

Answer 4

Histamine

Bradykinin

Substance P

CGRP

Question 5

Chemical mediators causing pain

Answer 5

Prostaglandins

Bradykinin

Substance P

CGRP

Question 6

Chemical mediators causing vasodilation

Answer 6

Histamine

Prostaglandins

Bradykinin

Question 7

Prostaglandins general mode of action

Answer 7

Increase sensitivity of nociceptive neurons to pain by turning on peripherally active PGE2 and PGI2 receptors

Also increase hypothalamus stimulation (Fever) via COX-2 ligands (PGE2) crossing the BBB and acting on EP 1 and 3 receptors on the hypothalamus
- causes hypothalamus to increase body temp

Question 8

NSAIDs general MOA

Answer 8

• inhibts COX-1 and/or COX-2 action that transforms arachidonic acid to prostaglandins.
• centrally activated PGE2, PGI2 and PGF2 receptors in nociceptive neurons which decreases prostaglandin sensitivity.
• inhibts fever via inhibiting COX-2 action

Question 9

Indications of NSAIDs

Answer 9

Reduce pain, inflammation and fever

Question 10

OA general charcterisitcs

Answer 10

Caused by loss of articular cartilage

• presents asymmetrically
• deep aching pain and stiffness
• duration of pain is <30mins
• weather directly affects pain levels
• Herberden and Bouchard nodes present

Question 11

Non-pharmacological management of OA

Answer 11

Recommend non weight bearing exercise, weight loss and educate patient in OA

Can use heat, sole insoles and walking assistive devices if needed

Question 12

1st line analgesic for OA management

Answer 12

Acetaminophen

• does have significant risk for hepatotoxicity

Question 13

COX-1

Answer 13

Gene that encodes COX-1 enzyme

• Considered the housekeeping enzyme and constitutional enzyme
• involved primarily in homeostasis
• direct link to gut integrity, vascular tone, platelet aggregation (clot formation), nerve and brain integrity, kidney integrity
• found pretty much everywhere but ESPECIALLY in the GI mucosa

Question 14

COX-2

Answer 14

Gene that produces COX-2 enzymes

• also caused the inducible enzymes
• Does some homeostasis management, but also produces pro-inflammatory prostaglandins, regulates temperature and inhibits clot formation
• Induced by cytokines via trauma/ inflammation
• direct link to inflammation, pain, fever, cancer and allergies
• usually found in cardiovascular system (vessels, heart and lungs)

Question 15

Predominantly pro-inflammatory prostaglandins

Answer 15

PGE2 and PGI2

Question 16

What prostaglandin mediates clotting?

Answer 16

Thromboxane (TxA2)

- promotes clots

Question 17

What prostaglandin balances the effects of thromboxane?

Answer 17

Prostacyclin (PGI2)

- reduces likelihood of clotting

Question 18

What prostaglandin is produced only by Mast cells?

Answer 18

PGD2

Question 19

What NSAID is a thrombolytic?

Answer 19

Aspirin (decreases TxA2 levels)

Question 20

What synthetic prostaglandin analogue prevents NSAID induced ulcers?

Answer 20

Misoprostol

Question 21

What NSAIDs can be taken intravenously?

Answer 21

Ketorolac and ibuprofen

Question 22

What is the only NSAID that irreversibly inhibits COX activation?

Answer 22

Aspirin

Acetylates the COX enzyme which makes this irreversible

Question 23

Reye’s syndrome

Answer 23

Caused by giving aspirin to children when they are fighting an infection.

Question 24

NSAIDs and elderly

Answer 24

• Recommended against chronic pain use but okay with acute pain.
• must use proton pump inhibitors in conjunction with NSAIDs due to renal issues that arise with old age

Question 25

Celecoxib

Answer 25

Inhibts COX-2 enzyme only Must be avoided in patients with heart failure or patients on diuretics Decreases PGI2 which results in unchecked TXA2 levels and increased platelet aggregation Used to combat GI-bleeding

Question 26

What is the primary derivative of all prostaglandins?

Answer 26

Arachodonic acid

Question 27

What is the ADE that is caused by all NSAIDs with chronic use?

Answer 27

Heart issues (especially celecoxib)

Question 28

Common ADE in all non-selective COX inhibitors

Answer 28

GI ulcers and bleeding - disrupts gastric mucosa which weakens GI integrity - patients should take non-selective NSAIDs with food for this reason

Question 29

What two NSAIDs should not be taken together?

Answer 29

Aspirin and profens/ naproxen Both compete for the same binding site so its more potential risk for no benefit

Question 30

What propanoic acid derivative is used the most and why?

Answer 30

Naproxen because it has a super high half-life (18hrs) and is the least likely to have cardio issues compared to all the other propanoic acid derivatives - contraindicated in breastfeeding women though and not the greatest choice in pregnant women altogether

Question 31

Which acetic acid derivative is the best used for opioid alternatives

Answer 31

Ketorolac | - however cannot be on this drug for more than 5-7 days since it can quickly cause renal and GI issues

Question 32

What is bound to the reactive intermediate of acetaminophen that prevents liver damage?

Answer 32

Glutathione: binds the reactive subunit and allows excretion through renal system without harm - in OD cases, the body is depleted of this because it is all used up already, and the reactive metabolite will cause liver damage - codeine is prescribed with high doses of acetaminophen to prevent this