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Flashcards in NSAIDs Deck (15)
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1
Q

Talk about COX-1?

A

Expressed in wide range of tissues
Ensures optimised local perfusion
Narrow mouthed

2
Q

Talk about COX-2?

A

Expression induced by inflammatory mediators (bradykinin)
Always expressed in parts of brain and kidney
Wide mouthed

3
Q

What prostaglandins are released in injury?

A

PGE2 and PGD2

4
Q

What is the action of prostaglandins?

A

Released from local tissues and blood vessels to act as potent vasodilators
(Don’t increase capillary permeability directly -> synergise bradykinin and histamine)

5
Q

What is sensitising afferent nociception?

A

Painful stimuli carried by afferent C fibres
Following trauma, neurones synthesise PGE2
PGE2 binds with c fibre neuronal EPI GPCR receptor

6
Q

What is sensitising peripheral nociception?

A

GPCR activation results in: increased neuronal sensitivity to bradykinin, inhibition of K+ channels (can’t hyperpolarise -> closer to AP), increase Na+ channel sensitivity (increase AP chance)
Increased C fibre activity
Increased intracellular Ca2+ -> increased neurotransmitter release

7
Q

What is sensitising central nociception?

A

Increased sustained nociception signalling peripherally leads to increased cytokines levels in the dorsal horn -> increased COX-2 and PGE synthesis -> PGE2 acts via local GPCR EP2 receptor -> increase sensitivity of secondary interneurones -> removal of glycinergic inhibition

8
Q

What is the mechanism of pyrexia?

A

Bacterial endotoxins stimulate macrophage release of IL-1 -> PGE synthesis -> EP3 receptor -> Increased heat production and decrease heat loss

9
Q

MoA of NSAIDs?

A

Competitive inhibition of COX-2

10
Q

ADRs of NSAIDs?

A

Long term use in elderly -> increased morbidity and mortality
GI - pain, nausea, heart burn, gastric bleeding, ulceration (offset with PPIs)
Renal - long term decreased GFR, hypertension (due to reduced renal function)
Vascular - increase bleeding time
Skin rashes
Bronchial asthma
Reye’s syndrome - rare brain/liver injury usually in viral infections treated with aspirin

11
Q

Name some specific COX-2 inhibitors?

A

Rofecoxib

Celecoxib

12
Q

Drug interactions of NSAIDs?

A
Opiates
Heavily plasma bound:
Sulphonlurea -> hypoglycaemia
Warfarin -> increased bleeding
Methotrexate
13
Q

MoA of aspirin?

A

Irreversibly inhibits COX enzymes by acetylation

14
Q

ADRs of paracetamol?

A

Caution if decreased hepatic function/alcoholics

OD leads to increase in NAPQI (toxic)

15
Q

Treatment of paracetamol overdose?

A

Activated charcoal orally if 0-4hrs

N-acetylcysteine IV if 0-36hrs