NSAIDs

Question 1

What does NSAID stand for?

Answer 1

Non-steroidal anti inflammatory

Question 2

Chemical property of NSAIDs

Answer 2

non-lipid soluble

Question 3

Non-lipid soluble NSAIDs work by

Answer 3

sticking to the outside of the cell

Question 4

Where / how to NSAIDs work

Answer 4

peripherally, so at the sight of inflammation but also at the spinal cord

Question 5

Three indications to take NSAIDs

Answer 5

Inflammation, Pain, Fever

Question 6

Examples of conditions for which NSAIDs are used:

Answer 6

acute: headaches, menstrual cramps, fractures, sprains
chronic: arthritis
post operatively: dental surgery

Question 7

How are pain and inflammation related?

Answer 7

when the inflammatory process is triggered, hundreds of pro inflammatory chemicals are released, most importantly: prostaglandins which induce a painful stimulus

Question 8

What do prostaglandins do?

Answer 8

1. Prostaglandins drop the threshold of a nociceptor from normally -55Mv to unlock the sodium channel and trigger a painful stimulus to -77Mv meaning it takes less to trigger a painful stimulus
2. Prostaglandins have vascular effects
3. Prostaglandins trigger the release of interleukins

Question 9

What do Interleukins do?

Answer 9

They are released from macrophages after prostaglandin triggers it, they then travel to the hypothalamus and cause an increase in body temperature (fever)

Question 10

HOW do NSAIDs stop inflammation, pain and fever

Answer 10

by stopping the production of prostaglandins

Question 11

How are prostaglandins produced?

Answer 11

by two enzymes: Cox-1 and Cox-2 from arachidonic acid of broken down membranes at the injury site, there are 5 subsets of prostaglandins and COX-1 and COX-2 produce slightly different prostaglandins with slightly different effects

Question 12

What is arachidonic acid?

Answer 12

A breakdown product of cell membranes - phospholipid membranes

Question 13

What is Thromboxane?

Answer 13

a pro-thrombotic, produced in an activated platelet to cause further platelet aggregation

Question 14

COX-1 enzyme

Answer 14

makes prostaglandins which play a role in maintaining gut health and stomach lining by supporting the two protective barriers and mediates thromboxane

Question 15

Mechanisms with which the stomach protects itself from acid

Answer 15

1. creation of a mucus membrane which creates a barrier
2. bicarbonate neutralises the hydrogen ions

Question 16

COX-1 enzyme effects

Answer 16

mucus membrane protection + clot / platelet aggregation

Question 17

COX-2 enzyme

Answer 17

produces prostaglandins involved in STOPPing clotting (ANTI clot, platelet inhibition)

Question 18

COX-1 v COX-2 effects

Answer 18

1. maintain mucus membrane, clotting
2. PRO clot, platelet inhibitor

Question 19

Prostaglandins promote

Answer 19

inflammation, fever, pain

Question 20

Prostaglandins and kidneys

Answer 20

prostaglandins help renal perfusion by maintaining glomerular filtration rate (keep it from going too high or low)

Question 21

Example of a pure COX-1 inhibitor

Answer 21

Aspirin

Question 22

Example of a COX-1 > COX-2 inhibitor

Answer 22

Naproxen

Question 23

Example of a COX-1=COX-2 inhibitor

Answer 23

Ibuprofen

Question 24

Example of a COX-2 > COX-1 inhibitor

Answer 24

Diclofenac

Question 25

Example of a COX 2 inhibitor

Answer 25

Celecoxib

Question 26

Aspirin

Answer 26

Willow Bark - Salicylic acid, most commonly used drug in the world
only true COX-1 selective/specific inhibitor, esp. in low dose
given to patients at high risk for MI / stroke (as reduced clotting)
can be given for pain
take with food as significant effect on mucus production, usually prescribed with PPI (proton pump inhibitor)

Question 27

Aspirin side effects

Answer 27

GI bleeding, Ulceration, Gastritis, may induce asthma

Question 28

Aspirin vs Ibuprofen

Answer 28

to achieve the same anti-inflammatory response as with ibuprofen, you would need 4g of Aspirin (toxic dose)
aspirin: cardio protective

Question 29

Naproxen

Answer 29

COX-1 > COX-2
made of propionic acid
smallest risk of CV of all NSAIDs
stops fever, pain, inflammation
since mostly COX-1: GI side effects, often prescribed w PPI

Question 30

Ibuprofen

Answer 30

COX-1=COX-2
low dose necessary to be equally as effective as paracetamol and aspirin
good option for gout, OA
brand names: Advil, Neurofen
do NOT take with aspirin

Question 31

Ibuprofen side effects

Answer 31

Gut issues
Kidney disease / Insufficiency
- inhibition of prostaglandins -> no regulation of GFR

Question 32

Effect of Ibuprofen / lack of prostaglandin on kidneys

Answer 32

PG dilate afferent arteriole of the blood flow into the nephron, diameter of the blood vessels effect how much blood will be filtered, NSAIDs like ibuprofen constrict those afferent arterioles which causes a reduction in the blood getting perfused and results in acute kidney injury

Question 33

Diclofenac

Answer 33

Voltarol (brand name)
COX-2 > COX-1
pro clotting, possibly increases CV risk (investigated)
appears to be absorbed better -> a lot of topical use w gels or patches
best mostly COX-2 anti inflammatory

Question 34

Celecoxib

Answer 34

COX-2
used for chronic joint pain in RA, OA and GA
not used much now, diclofenac seen as more effective

Question 35

Paracetamol

Answer 35

exact mechanism unknown, very safe in therapeutic dose
acts mildly on COX-1, reduces fever and pain
does not need to be taken with food, can be combined w ibuprofen
used in: toothache, headaches, joint and muscle pain

Question 36

Paracetamol toxicity

Answer 36

high amounts -> extremely hepatotoxic
absorbed via stomach, then travels to liver where it accumulates
CAUTION in pediatric patients, toxic dose is a lot lower
ingestion of >4g of paracetamol -> kills hepatocytes -> acute liver failure

Question 37

Paracetamol overdose

Answer 37

8 hours to give the antidote (NAC drug), if this window is missed, the patient will go into multi organ failure
blocks the metabolite building up
irreversible damage
BIGGEST CAUSE of acute liver failure in western world