Analgesics Flashcards
NSAIDs: Mechanism of Action
Competitive COX 1 and COX-2 inhibitor
NSAIDs: Effects
Mild pain relief and anti-inflammatory
NSAIDs: Side Effects
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
NSAIDs: Cautions
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
NSAIDs: Drug Dose
Naproxen: 0.5–1 g daily in 1–2 divided doses.
Note: with food
Ibuprofen apply gel 3 times daily
Opioids (Codeine): Mechanism of Action
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.
Opioids (Codeine): Effects
Relief of moderate to severe pain
Opioids (Codeine): Side Effects
μ - nausea, vomiting constipation
drowsiness miosis
δ – respiratory depression (monitoring required) hypotension
k- dysphoria - pentazocine
Opioids (Codeine): Cautions
Overdose (treat with naloxone – opioid receptor antagonist)
Opioids (Codeine): Drug Dose
30–60 mg every 4 hours if required.
Paracetamol: Mechanism of Action
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
Paracetamol: Effects
pain reflex and decrease pyrexia
Paracetamol: Side Effects
N&V
Paracetamol: Cautions
Single doses > 10 g (20 tablets) potentially fatal Start N-Acetylcysteine iv Methionine by mouth if NAC cannot be given promptly
Paracetamol: Drug Dose
max 4g per day - 1g QDS