Analgesics

Question 1

NSAIDs: Mechanism of Action

Answer 1

Competitive COX 1 and COX-2 inhibitor

Question 2

NSAIDs: Effects

Answer 2

Mild pain relief and anti-inflammatory

Question 3

NSAIDs: Side Effects

Answer 3

Long term use in elderly particularly associated with iatrogenic morbidity and mortality

Major ADRs seen in stomach /GI tract - stomach pain, nausea, heartburn, gastric bleeding, ulceration

Renal ADRs occur in compromised individuals with HRH or hypovolaemia Heart failure Renal disease Hepatic cirrhosis, PGE2 and PGI2 maintain renal blood flow, If reduced by NSAIDs then GFR ↓ - further risk of renal compromise

Vascular
• Risk ↑ bleeding time ↑ bruising haemorrhage
Stevens Johnson Syndrome - Severe examples
• Immune-complex-mediated hypersensitivity disorder
• Compromised hepatic function
• Rash - skin mucous membranes

Question 4

NSAIDs: Cautions

Answer 4

NSAIDs given in combination increase risk of ADRs. NSAIDs together can affect each others PK/PDs due to competition for plasma protein binding sites - many NSAIDs heavily bound - up to 90-99%
e.g. NSAIDs + low dose Aspirin – Compete for COX-1 binding sites - may interfere with cardioprotective action of Aspirin
↑Sulphonylurea - Hypoglycaemia
↑Warfarin – Increased Bleeding
↑Methotrexate – Wide ranging serious ADRs

Question 5

NSAIDs: Drug Dose

Answer 5

Naproxen: 0.5–1 g daily in 1–2 divided doses.
Note: with food

Ibuprofen apply gel 3 times daily

Question 6

Opioids (Codeine): Mechanism of Action

Answer 6

Bind to GPCRs
μ -outward flux of potassium decreses excitability
δ, k – Influx of calcium via channels decresed CAMP synthesis
inhibit the release of Substance P from nerve terminals.
Inhibitory descending pathways from higher centres in the brain.

Question 7

Opioids (Codeine): Effects

Answer 7

Relief of moderate to severe pain

Question 8

Opioids (Codeine): Side Effects

Answer 8

μ - nausea, vomiting constipation
drowsiness miosis
δ – respiratory depression (monitoring required) hypotension
k- dysphoria - pentazocine

Question 9

Opioids (Codeine): Cautions

Answer 9

Overdose (treat with naloxone – opioid receptor antagonist)

Question 10

Opioids (Codeine): Drug Dose

Answer 10

30–60 mg every 4 hours if required.

Question 11

Paracetamol: Mechanism of Action

Answer 11

Weak COX-1 / COX-2 inhibitor weak inhibitor of synthesis of prostaglandins. analgesic effect of paracetamol is central and is due to activation of descending serotonergic pathways

Question 12

Paracetamol: Effects

Answer 12

pain reflex and decrease pyrexia

Question 13

Paracetamol: Side Effects

Answer 13

N&V

Question 14

Paracetamol: Cautions

Answer 14

Single doses > 10 g (20 tablets) potentially fatal Start N-Acetylcysteine iv Methionine by mouth if NAC cannot be given promptly

Question 15

Paracetamol: Drug Dose

Answer 15

max 4g per day - 1g QDS