NSAIDs Flashcards
Somatic / nociceptive pain is well localised except for when pain is occuring from which areas? [1]
When deep: in a joint:
* Muscle
* tendon
* ligament
* bone
* fascia
* joints
State Hilton’s law [1]
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
Hip pain is referred to which location? [1]
Knee
State two drugs which are classified as strong [2] and weak [2] opiods
Strong opoids: morphine, oxycodone, fentanyl and buprenorphine
“Weak” opioid analgesics. Codeine, dihydrocodeine and tramadol: no less risky than morphine.
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
B. Hydrocodone
What type of NSAID is indomethacin
Acetic acid derivative
Propoinic acid derivative
Selective COX-2 inhibitros
Salicylates
What type of NSAID is indomethacin
Acetic acid derivative
Propoinic acid derivative
Selctive COX-2 inhibitros
Salicylates
do more
What type of NSAID is diclofenac
Acetic acid derivative
Propoinic acid derivative
Selective COX-2 inhibitor
Salicylates
What type of NSAID is diclofenac
Acetic acid derivative
Propoinic acid derivative
Selctive COX-2 inhibitros
Salicylates
What type of NSAID is aspirin
Acetic acid derivative
Propoinic acid derivative
Selective COX-2 inhibitor
Salicylates
What type of NSAID is aspirin
Acetic acid derivative
Propoinic acid derivative
Selctive COX-2 inhibitros
Salicylates
What type of NSAID is ibuprofen
Acetic acid derivative
Propoinic acid derivative
Selective COX-2 inhibitor
Salicylates
Propoinic acid derivative
What type of NSAID is celecoxib
Acetic acid derivative
Propoinic acid derivative
Selective COX-2 inhibitor
Salicylates
Selective COX-2 inhibitor
What type of NSAID is naproxen
Acetic acid derivative
Propoinic acid derivative
Selctive COX-2 inhibitor
Salicylates
Propoinic acid derivative
State the role of COX-1 & COX-2 enzymes [4]
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
What therapeutic effects does aspirin have? [3]
analgesic, antipyretic, anti-inflammatory
Ibuprofen, diclofenac and ketoprofen have what therapeutic effects? [2]
analgesic and anti-inflammatory effects (not anti-pyretic)
Name two selective COX-2 inhibitors
Celecoxib
Etoricoxib
Meloxicam
Which is the most common NSAID prescribed in the UK?
celecoxib
diclofenac
ibuprofen
indomethacin
naproxen
naproxen
Which pathway do NSAIDs specifically inhibit? [1]
Stop AA to Prostaglandin G2
Describe the difference in shape of COX 1 and COX 2
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)
What are the classes of prostaglandins? [3]
D, E and F
Prostacyclin (PGI2)
Thomboxane A
State when COX-1 & COX-2 are released [2]
COX-1 produced during normal homeostatic processes and produces constant supply of prostaglandins
COX-2 produced when tissue injury occurs
State two functions of homeostatic COX-1 [2]
. Protect the lining of the stomach & increase bloodflow of the kidney
State when each of the following are produced
PGD
PGE
PGF
PGI2
TXA2
Which prostaglandin causes the most bronchoconstriction in asthma patients?
PGE2
PGD2
PGI2
PGF2α
TXA2
PGD2
Which prostaglandin causes has mixed vascular effects (constriction and dilation)?
PGE2
PGD2
PGI2
PGF2α
TXA2
PGF2α
Which prostaglandins cause uterine contraction? [2]
PGE2
PGD2
PGI2
PGF2α
TXA2
PGF2α;
TXA2
Which prostaglandin causes uterine relaxation?
PGE2
PGD2
PGI2
PGF2α
TXA2
Which prostaglandin causes uterine relaxation?
PGE2
PGD2
PGI2
PGF2α
TXA2
Which prostaglandin causes inhibits platelet aggregation?
PGE2
PGD2
PGI2
PGF2α
TXA2
PGI2
Which prostaglandin causes induces platelet aggregation?
PGE2
PGD2
PGI2
PGF2α
TXA2
TXA2
Which prostaglandin suppresses lymphocytes?
PGE2
PGD2
PGI2
PGF2α
TXA2
PGE2
Describe the differences of action of COX-1 and COX-2
Describe the mechanism of action of COX enzymes in joint pathology [2]
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
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]
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
In the stomach, NSAIDs for long periods blocks which prostaglandin generation?
PGE2
PGD2
PGI2
PGF2α
TXA2
PGE2
Describe the affects of COX enzymes in CV system [2]
PGI2 (prostacyclin) from COX2 in endothelial cells prevents platelet aggregation and vasodilation
Thromboxane A2 from COX1 in platelets promotes aggregation and vasoconstriction
Describe the DDI of aspirin and ibupofren in CV system
Aspirin binds to COX-1 and binds to serine; produces irreversible 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
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]
Find both COX1 & COX2 in resting conditions
COX2 is important in spinal nociceptive transmission
Role of COX-1 [2] and COX-2 [1] in the kidney?
Via which prostaglandins? [2]
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
How much inhibition of COX-2 is needed for a therapeutic affect? [2]
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%
