NSAIDs

Question 1

Somatic / nociceptive pain is well localised except for when pain is occuring from which areas? [1]

Answer 1

When deep: in a joint:
* Muscle
* tendon
* ligament
* bone
* fascia
* joints

Question 2

State Hilton’s law [1]

Answer 2

The nerve supplying a joint (capsule) also supplies the muscles that move the joint and the skin over the joint and the insertion of the muscles

Question 3

Hip pain is referred to which location? [1]

Answer 3

Knee

Question 4

State two drugs which are classified as strong [2] and weak [2] opiods

Answer 4

Strong opoids: morphine, oxycodone, fentanyl and buprenorphine

“Weak” opioid analgesics. Codeine, dihydrocodeine and tramadol: no less risky than morphine.

Question 5

A 65-year-old man with metastatic prostate cancer to bone presents with bone pain. He has had no pain relief with aspirin. The clinician decides to choose a drug from the next level of the analgesic ladder. What is the most appropriate next drug on the WHO ladder for cancer pain relief in adults?

A. Methadone
B. Hydrocodone
C. Fentanyl
D. Morphine

Answer 5

B. Hydrocodone

Question 6

What type of NSAID is indomethacin

Acetic acid derivative
Propoinic acid derivative
Selective COX-2 inhibitros
Salicylates

Answer 6

What type of NSAID is indomethacin

Acetic acid derivative
Propoinic acid derivative
Selctive COX-2 inhibitros
Salicylates

do more

Question 7

What type of NSAID is diclofenac

Acetic acid derivative
Propoinic acid derivative
Selective COX-2 inhibitor
Salicylates

Answer 7

What type of NSAID is diclofenac

Acetic acid derivative
Propoinic acid derivative
Selctive COX-2 inhibitros
Salicylates

Question 8

What type of NSAID is aspirin

Acetic acid derivative
Propoinic acid derivative
Selective COX-2 inhibitor
Salicylates

Answer 8

What type of NSAID is aspirin

Acetic acid derivative
Propoinic acid derivative
Selctive COX-2 inhibitros
Salicylates

Question 9

What type of NSAID is ibuprofen

Acetic acid derivative
Propoinic acid derivative
Selective COX-2 inhibitor
Salicylates

Answer 9

Propoinic acid derivative

Question 10

What type of NSAID is celecoxib

Acetic acid derivative
Propoinic acid derivative
Selective COX-2 inhibitor
Salicylates

Answer 10

Selective COX-2 inhibitor

Question 11

What type of NSAID is naproxen

Acetic acid derivative
Propoinic acid derivative
Selctive COX-2 inhibitor
Salicylates

Answer 11

Propoinic acid derivative

Question 12

State the role of COX-1 & COX-2 enzymes [4]

Answer 12

Take arachidonic acid and convert to prostaglandin G2

Prostaglandin G2 converts to Prostaglandin H2

PH2 then converted to tissue specific prostaglandins

Different prostaglandins are found in different tissues and have different effects.

Prostaglandins are local tissue hormones; made in the tissue where you need it

Question 13

What therapeutic effects does aspirin have? [3]

Answer 13

analgesic, antipyretic, anti-inflammatory

Question 14

Ibuprofen, diclofenac and ketoprofen have what therapeutic effects? [2]

Answer 14

analgesic and anti-inflammatory effects (not anti-pyretic)

Question 15

Name two selective COX-2 inhibitors

Answer 15

Celecoxib
Etoricoxib
Meloxicam

Question 16

Which is the most common NSAID prescribed in the UK?

celecoxib
diclofenac
ibuprofen
indomethacin
naproxen

Answer 16

naproxen

Question 17

Which pathway do NSAIDs specifically inhibit? [1]

Answer 17

Stop AA to Prostaglandin G2

Question 18

Describe the difference in shape of COX 1 and COX 2

Answer 18

COX1: narrower
COX2: wider entrance, less rigid more flexible and has side pocket active site: wider binding site in COX-2

Difference is around mouth of hydrophobic channel making it less rigid than COX1 and position 523 (COX1=isoleucine, COX2=valine)

Question 19

What are the classes of prostaglandins? [3]

Answer 19

D, E and F
Prostacyclin (PGI2)
Thomboxane A

Question 20

State when COX-1 & COX-2 are released [2]

Answer 20

COX-1 produced during normal homeostatic processes and produces constant supply of prostaglandins

COX-2 produced when tissue injury occurs

Question 21

State two functions of homeostatic COX-1 [2]

Answer 21

. Protect the lining of the stomach & increase bloodflow of the kidney

Question 22

State when each of the following are produced

PGD
PGE
PGF
PGI2
TXA2

Answer 22

Question 23

Which prostaglandin causes the most bronchoconstriction in asthma patients?

PGE2
PGD2
PGI2
PGF2α
TXA2

Answer 23

PGD2

Question 24

Which prostaglandin causes has mixed vascular effects (constriction and dilation)?

PGE2
PGD2
PGI2
PGF2α
TXA2

Answer 24

PGF2α

Question 25

Which prostaglandins cause uterine contraction? [2] PGE2 PGD2 PGI2 PGF2α TXA2

Answer 25

**PGF2α**; **TXA2**

Question 26

Which prostaglandin causes uterine relaxation? PGE2 PGD2 PGI2 PGF2α TXA2

Answer 26

Which prostaglandin causes uterine relaxation? **PGE2** PGD2 PGI2 PGF2α TXA2

Question 27

Which prostaglandin causes inhibits platelet aggregation? PGE2 PGD2 PGI2 PGF2α TXA2

Answer 27

**PGI2**

Question 28

Which prostaglandin causes induces platelet aggregation? PGE2 PGD2 PGI2 PGF2α TXA2

Answer 28

TXA2

Question 29

Which prostaglandin suppresses lymphocytes? PGE2 PGD2 PGI2 PGF2α TXA2

Answer 29

**PGE2**

Question 30

Describe the differences of action of COX-1 and COX-2

Answer 30

Question 31

Describe the mechanism of action of COX enzymes in joint pathology [2]

Answer 31

COX2 mRNA and protein is increased in joints with osteo or rheumatoid arthritis: * **IL1, TNF and IL17**: stimulates **iNOS**, which induces **COX2** * **Mechanical stress** may directly **activate production of PGE2**

Question 32

Which COX enzyme is mainly present in the stomach? [1] Which prostaglandin does this make? [1] Explain the affect of NSAIDs on the stomach [1]

Answer 32

Mainly **COX1 isoform**: normal **PGE2** helps gastric mucosa But NSAIDS inhibit COX-1 and and induce COX-2: **reduce the protection of the stomach** and can lead to the development of **gastric ulcers,** **gastritis** Increases chance of gastric ulcer

Question 33

In the stomach, NSAIDs for long periods blocks which prostaglandin generation? PGE2 PGD2 PGI2 PGF2α TXA2

Answer 33

**PGE2**

Question 34

Describe the affects of COX enzymes in CV system [2]

Answer 34

**PGI2 (prostacyclin)** from **COX2** in endothelial cells **prevents platelet aggregation and vasodilation** **Thromboxane A2** from **COX1** in platelets **promotes aggregation and vasoconstriction**

Question 35

Describe the DDI of aspirin and ibupofren in CV system

Answer 35

Aspirin binds to COX-1 and binds to **serine**; produces i**rreversible covalent chain**. Stops the platelet from producing **thromboxane A2**; which is an **anti-coagulant effect.** **Ibuprofen**; binds to same **serine chain**; but is **reversible**; which is why is not an **anti-coagulant.** When **ibuprofen is given**, **aspirin** **cant** bind to **COX-1** and **produce anti-coagulant affect**

Question 36

# Spinal Cord & CNS What is the role of COX2 in this location? [1] Under what conditions is COX-2 found in the spinal cord and CNS? [1]

Answer 36

Find both COX1 & COX2 in **resting conditions** COX2 is important in spinal **nociceptive transmission**

Question 38

Role of COX-1 [2] and COX-2 [1] in the kidney? Via which prostaglandins? [2]

Answer 38

COX1: produces **PGE2** and **PGI2** * PGE2: regulates sodium reabsoprtion * PGI2 regulates potassium excretion COX2: * present in small amounts in **macula densa** but increases in salt deprivation

Question 40

How much inhibition of COX-2 is needed for a therapeutic affect? [2]

Answer 40

All NSAIDs depend on COX2 inhibition for therapeutic effects. Most also inhibit COX1 to some extent at normal clinical doses, this gives the unwanted effects Substantial evidence that NSAIDs and COX2 inhibitors have their maximum anti-inflammatory effect when **COX2 is inhibited by about 80%**