Analgesia

Question 1

How do NSAIDs like ibuprofen, naproxen, aspirin work?

Answer 1

Analgesia = decreased PGE2 synthesis in dorsal horn –> decreased neurotransmitter release –> decreased excitability of neurons in pain relay

Anti-inflammatory = COX inhibition results in reduction of prostaglandins released during injury

Antipyretic = inhibition of hypothalmic COX2 where cytokine induced prostaglandins synthesis is elevated

Question 2

Are aspirin, ibuprofen, naproxen more COX1 selective or COX2?

Answer 2

more COX1 selective

Question 3

What are some ADRs for NSAIDs?

Answer 3

GI:
dyspepsia, nausea, peptic ulcer, bleeding, perforation
(decreased mucosal blood flow, decreased mucus/HCO3- secretion, NSAIDs are also mildly acidic)

Renal:
increased salt/water retention, hyperkalaemia due to decreased renin secretion

CVS:
increased salt/water retention exacerbates HF and BP, vasoconstriction= reduces efficacy of antihypertensives

Question 4

Why are COX2 inhibitors sometimes preferred?

Answer 4

less GI ADRs

Question 5

Indications and contraindications for NSAIDs?

Answer 5

Inflammatory conditions eg. joints
OA
Post-op pain
low dose aspirin for platelet aggregation inhibition 
menorrhagia
etc

Contraindications:
CVS disease, old age (renal function), GI disease, level of pain
DDIs eg. ACEi, ARBs, warfarin, etc.

Question 6

How does paracetamol work?

Answer 6

COX2 selective inhibition in CNS (spinal cord)

this results in decreased pain signals to higher centres

Question 7

What is the mechanism for paracetamol overdose?

Answer 7

NAPQI (N-acetyl-p-benzoquinone imine) is a higihly reactive oxidation product of paracetamol

Usually hepatic glutathione makes it harmless.

But when hepatic glutathione runs out, NAPQI builds up

Question 8

How do patients present in paracetamol overdose and what is the management?

Answer 8

nausea, vomiting, abdo pain in 24 hours

then liver damage, upper quadrant pain

Management:
- bloods and prothrombin time to assess damage
- activated charcoal 
- glutathione thiol replacement
(IV acetylcysteine)

Question 9

How does the WHO analgesic ladder work?

Answer 9

Step 1:
Nonopioid analgesics, NSAIDs, paracetamol

2:
Weak opioids eg. Codeine

3:
Strong opioids eg. Morphine, Fentanyl, Methadone, oral/transdermal patch

4:
Nerve block epidurals, PCA pump, neurolytic block therapy, spinal stimulation

Question 10

How does morphine work?

Answer 10

It is a strong opioid receptor agonist
(strong affinity to μ receptors, minimal for k and δ)

Metabolism:
Morphine + glucuronic acid –> M6G (analgesic) + M3G

Question 11

SE and contraindications for morphine?

Answer 11

CKD or AKI as it is renal elimination.

SE:

• resp depression as medullary resp centres become less responsive to CO2
• Emesis as CTZ is triggered = nausea
• decreases motility and increases sphincter tone in GI = constipation

Question 12

How does codeine work?

Answer 12

Moderate opioid receptor agonist

1/10 potency of morphine

Metabolism:
Codeine -CYP2D6-> Morphine

Question 13

Contraindications and SE of codeine?

Answer 13

Renal insufficiency as it is renally excreted

If high levels of CYP2D6, codeine is broken down rapidly to morphine.
Lots of circulating morphine = toxicity.

Low levels of CYP2D6 means you will not break codeine down, you will just excrete it.
Therefore you will not feel the effects as there is less circulating morphine.

Question 14

Compare Lidocaine with Bupivacaine as local anaesthetics

Answer 14

Bupivacaine is more potent, and has a longer duration of action.

Both are amides so both are stable and long lasting. (as opposed to esters)
Both have slow onset (L =pKa7.8, B=pKa8.2)

Question 15

What is the mechanism of local anaesthetics?

Answer 15

Reversibly bind to and inactivate fast voltage gated Na+ channels in neuronal cell membranes