NSAIDs Flashcards
Define pain
Unpleasant sensory and emotional experience associated with actual or potential tissue damage
What is allodynia
Pain due a stimulus that does not usually elicit pain
What is hyperalgesia
An increased response to a stimulus is normally painful
How does somatic pain feel
- Aching
- Constant
- May be dull/ sharp
- Well localised, except when deep
What is Hiltons law
Nerve that supplies a joint capsule also supply the muscles that move the joint and the skin over the joint
How much of COX-2 must be inhibited for anti-inflammatory properties to work
80%
What is the main mode of action of NSAIDs
Inhibitions of COX enzymes (1 and 2)
3 properties of NSAIDS
Analgesic, antipyretic and anti-inflammatory
How do ibuprofen, duclofenac, ketoprofen differ from asprin
Additional mechanisms as well as asprisin
Name 4 selective COX-2 inhibitors
Roflecoxib
Celecoxib
Etoricoxib
Meloxicam
Name 4 NSAIDs which are mainly for pain
-Aceclofenax
Etoricoxib
Fenbufen
Tiaprofenic acid
What NSAID is mainly for pain
Paracoxib
Which NSAID comes in eye drop
Ketorolac
By inhibiting COX enzymes what is inhibited
Prostaglandins
Where are prostaglandins derived from
Archidonic acid
What happens to the arachidonic acid during prostaglandin synthesis
- Injected into COX enzymes hydrophobic channel
- Interacts with molecular oxygen to produce either prostacyclins, prostaglandins or thromboxane
What is the action of prostaglandin E2
Vasodilator
What is the action of prostaglandin D2
Vasodilator
Inhibits platelet aggregation
What is the action of prostaglandin F2
Vasoconstrictors
Works on the uterus to make it contract
What is thromboxane
Thrombotic and vasoconstrictor
What enzyme catalyses the formation of prostaglandin from arachidonic acid
Enzyme cyclooxygenase
Describe how the shape of COX1/ COX2 differs
Cox 1 is narrower
Cox 2 is less rigid
What is prostacylin also known as
PGI2
Where do prostaglandins diffuse to
Very locally
What kind of receptors are the prostaglandin receptors
GPCR
How many different prostaglandin receptors are there
9
What is COX 1’s function
‘house keeping’
contributes to homeostasis
Which COX is inducible
COX 2
What induces COX 2
Pro-inflammatory cytokines
How long does COX 2 take to be induced
half an hour- 4 hours
Why can COX 2 be induced and prostaglandins be produced easily
Looser hydrophobic channel allows more things in
Which COX is mainly found in the stomach and where specifically in the stomach is it found
COX 1
Protects against injury and damage
Where is the stomach is COX 2 found
Low level of COX 2 found in the superficial mucosa
What prevents platelet aggregation
PGI2 from endothelial cells
What induces platelet aggregation
Thromboxane A2 COX 1
Does ibuprofen have long term or short term effect on platelets
Short
In which area are both COX 1 and COX 2 found under resting location
CNS and spinal cord
Where in the kidney is COX 2 found
In the macula densa
When does COX 2 increase in the kidney
In salt deprivation
What cell types are activated when COX 2 is induced
Macrophages
Synoviocytes
How much of COX 1 does aspirin inhibit if 80% of COX 2 is inhibited
90
What category of NSAID are ibuprofen/ piroxicam
Cateogory 1: rapid, competitive, reversible binding of COX 1/2
What category of NSAID are diclofenac/ indomethacin
Rapid, lower affinity reversible followed by time dependent, high affinity slowly reversible binding of COX 1/2
What category of NSAID is aspririn
Rapid reversible binding followed by covalent modification of COX 1 and or COX 2 non competitive reversible
What are coxibs
Selective to COX 2 inhibitors
What adverse effects have been reported in use of selective COX 2 inhibitors
Increased CV risk
Is GI risk more significant in selective cox 2 or non selective
Non selective
2 proposed mechanisms for paracetomol
- Modulate endogenous cannaboid system and trpv1 by am404
- activates serotonergic descending pathways
