Overview
This lecture reviews non-opioid analgesics, focusing on acetaminophen, NSAIDs, and capsaicin, covering mechanisms, clinical uses, side effects, and monitoring considerations.
Acetaminophen (Tylenol)
- Available in multiple oral and IV formulations; IV use limited due to cost.
- Acts mainly in the CNS by inhibiting cyclooxygenase-3; no anti-inflammatory properties.
- Ceiling dose is 4,000 mg/day; some recommend lowering this to 3,000–3,500 mg for at-risk patients.
- Overdose risks: hepatotoxicity, nephrotoxicity, and acid-base disturbances.
- Metabolism involves phase 2 (UGT, sulfation); overdose saturates these, shifting more drug to toxic metabolite (NAPQI) via CYP2E1.
- Chronic alcohol use induces CYP2E1, increasing toxicity risk.
- Antidote is N-acetylcysteine (NAC), which replenishes glutathione.
- Treatment: Oral NAC (140 mg/kg loading, then 70 mg/kg q4h × 17 doses over 72 hrs), or IV NAC (150 mg/kg over 1 hr, followed by 50 mg/kg over 4 hrs, then 100 mg/kg over 16 hrs), best within 8–10 hours of overdose.
- Monitor Tylenol levels using the 4-hour post-ingestion nomogram.
NSAIDs (Nonsteroidal Anti-Inflammatory Drugs)
- Weak acids, mostly undergo enterohepatic recirculation (except nabumetone).
- Equally effective at equipotent doses; differ in half-life, COX selectivity, and route.
- Used for osteoarthritis, RA, acute pain, headaches, fever, gout, menstrual pain, kidney stones, pericarditis, post-op pain, and PDA closure.
- Inhibit cyclooxygenase (COX) enzymes; NSAIDs are competitive inhibitors, aspirin irreversibly inhibits COX-1.
- COX-1 is constitutive (protective roles in gut, platelets); COX-2 is inducible (inflammation).
- COX-2 selective NSAIDs have less GI risk but can increase CV events.
- Side effects: GI ulcers/bleeds, hypertension, renal dysfunction, increased CV risk, platelet effects, and allergic reactions.
- Risk factors for GI ulcers: age >65, prior ulcers, use of anticoagulants/antiplatelets/corticosteroids, H. pylori.
- NSAIDs can interact with ACE inhibitors, ARBs, and diuretics by affecting renal blood flow and RAS.
Topical and Ophthalmic NSAIDs
- Topical diclofenac used for localized pain (sprains, osteoarthritis) to reduce systemic side effects.
- Ophthalmic NSAIDs used post-eye surgery or for allergic conjunctivitis; can increase intraocular pressure.
Capsaicin
- Available as OTC cream (≤0.1%) and high-dose patch (8%).
- Activates TRPV1 receptors on nerves, causing initial burning then reduced pain with continuous use.
- Cream: Apply 3–4×/day, requires consistent use for effect; not for PRN use.
- Patch: Clinic-administered, applied for 1 hour, can provide relief for up to 3 months; premedicate due to burning.
Key Terms & Definitions
- COX (Cyclooxygenase) — enzyme involved in prostaglandin synthesis; COX-1 is protective, COX-2 is inducible.
- NAPQI — toxic acetaminophen metabolite responsible for liver damage.
- N-acetylcysteine (NAC) — antidote for acetaminophen poisoning, replenishes glutathione.
- Enterohepatic recirculation — recycling of drug/metabolites between liver and intestines.
- TRPV1 — receptor activated by capsaicin, leading to nerve desensitization.
- RAAS (Renin-Angiotensin-Aldosterone System) — hormone system regulating blood pressure and fluid balance.
Action Items / Next Steps
- Review dosing and toxicity management protocols for acetaminophen and NSAIDs.
- Study risk factors and monitoring parameters for GI and renal toxicity with NSAID use.
- Be familiar with the use and counseling of topical capsaicin products.