Anaesthesia and Analgesia 2 — Comprehensive Study Notes Summary & Study Notes

🎯 Intended learning outcomes

Understand basic pharmacology applied to analgesics, including mechanisms, targets and clinical effects. Explain how analgesic drugs act and how they affect body systems. Review major analgesic classes and their receptor targets.

⏱️ Pre-emptive analgesia

Pre-emptive analgesia is administration of analgesics before surgical trauma. It reduces central sensitization, often gives better pain control and lowers overall postoperative analgesic requirements.

🧩 Multimodal analgesia

Multimodal analgesia uses drugs from different classes to target multiple receptors or steps in the pain pathway. This approach can produce synergy, reduce dose-related adverse effects, and is often more effective than increasing dose of a single agent.

💊 Drug classes & routes

Major pharmacological options: NSAIDs, paracetamol, opioids, alpha-2 agonists, local anaesthetics, and adjuvants (ketamine, amantadine, gabapentinoids, cannabinoids, anti-NGF antibodies, tricyclic antidepressants). Routes include systemic (PO, IV, IM, SC), topical (transdermal, transmucosal, ocular) and locoregional techniques.

🎯 Targets in the pain pathway

Key molecular/receptor targets: NMDA receptors (glutamate), opioid receptors (mu/MOP, kappa/KOP, delta/DOP, nociceptin/NOP), voltage-gated calcium channels (CaV), noradrenaline/serotonin systems, cannabinoid receptors and prostaglandin pathways (COX enzymes). Local anaesthetics target voltage-gated sodium channels, including subtype $Na_V1.6$.

🔬 Actions at stages of the pain pathway

• Transduction: conversion of noxious stimulus into electrical impulse — targeted by local anaesthetics, NSAIDs, opioids, corticosteroids.
• Transmission: conduction of impulses along nerves — targeted by local anaesthetics and alpha-2 agonists.
• Modulation: spinal and supraspinal processing and descending controls — targeted by local anaesthetics, opioids, alpha-2 agonists, tricyclics, NMDA antagonists, NSAIDs.
• Perception: cortical interpretation of pain — targeted by opioids, alpha-2 agonists, benzodiazepines and general anaesthetics.

🐶 Pain mechanisms in osteoarthritis (OA)

OA pain is complex and chronic with nociceptive, inflammatory and neuropathic components. Both peripheral sensitization and central changes contribute. This complexity often necessitates multimodal treatment (pharmacologic + non-pharmacologic).

🩺 NSAIDs

Mechanism: inhibit cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis and peripheral sensitization. Classified by COX selectivity: COX-2 specific ("-coxibs"), COX-2 selective (e.g., meloxicam), non-selective, and rare COX-1 selective agents. Benefits include analgesia and anti-inflammatory effects; risks include gastrointestinal, renal and hepatic adverse effects. Use caution and follow licensing guidelines.

🔥 Paracetamol (acetaminophen)

Analgesic and antipyretic but weak anti-inflammatory. Thought to act centrally, possibly on a COX-3-like mechanism. Not suitable for cats at standard doses due to deficient glucuronidation and high risk of toxicity.

☠️ Opioids

Opioids are the gold standard for analgesia. They vary by receptor efficacy and intrinsic activity: full agonists (morphine, fentanyl, methadone, hydromorphone), partial agonists (buprenorphine) and agonist–antagonists (butorphanol).

🧠 Opioid receptors and effects

Subtypes: MOP (mu), KOP (kappa), DOP (delta), NOP (nociceptin). Receptors are widespread (brain, spinal cord, GI, synovium, urinary tract). Common dose-dependent effects: analgesia, sedation or dysphoria, respiratory depression, bradycardia, nausea/vomiting. Most opioids undergo hepatic metabolism with renal excretion.

Special notes: buprenorphine is a high-affinity partial mu agonist with lower maximal analgesic efficacy than full agonists. Butorphanol is a kappa agonist and mu antagonist/partial agonist.

🩹 Local anaesthetics

Local anaesthetics block voltage-gated sodium channels to prevent conduction of sensory input from periphery to CNS. They can be given perineural, epidural, interfascial, topical or infiltration. Action is reversible and use-dependent. They are the only drugs that can completely block peripheral sensory conduction when applied appropriately.

🧭 Nerve fibre types & order of blockade

Different fibre types vary by diameter, myelination and function. Typical order of blockade: B > C = A-δ > A-γ > A-β > A-α. Clinically, small, lightly myelinated or unmyelinated fibres (pain, temperature, autonomic) are blocked before large motor fibres.

✅ Benefits of locoregional anaesthesia

Locoregional techniques improve perioperative pain control, reduce systemic analgesic requirements, decrease morbidity and hospital time, and can be used in chronic pain management. They offer potential economic and outcome benefits.

🧴 Lidocaine specifics

Lidocaine is unique among local anaesthetics in that systemic toxicity is low enough for intravenous use (e.g., CRIs). It has prokinetic, antioxidant and antiarrhythmic properties and acts as a class Ib antiarrhythmic by blocking fast sodium channels.

🐂 Alpha-2 agonists

Alpha-2 receptors are centrally and peripherally located. These drugs act on the locus coeruleus to reduce sympathetic outflow and provide profound sedation. They produce significant cardiovascular effects (initial vasoconstriction and reflex bradycardia). Examples in veterinary use include dexmedetomidine, medetomidine, romifidine, detomidine and xylazine, with varying alpha-2:alpha-1 selectivity.

🧪 Adjuvants & other agents

• Ketamine: NMDA receptor antagonist, dissociative anaesthetic, provides analgesia and prevents central sensitization; can cause dysphoria/excitation. Used IV, IM, SC or as CRI.
• Gabapentinoids (gabapentin, pregabalin): bind alpha2-delta subunit of voltage-gated calcium channels; useful for neuropathic pain and chronic pain adjunct therapy.
• Amantadine: NMDA antagonist used as an adjunct in chronic pain.
• Cannabinoids, anti-NGF antibodies, tricyclic antidepressants: additional options for specific chronic pain states.

🔁 Pharmacokinetics vs Pharmacodynamics

Pharmacokinetics = what the body does to the drug (absorption, distribution, metabolism, excretion). Pharmacodynamics = what the drug does to the body (mechanism of action, receptor effects, clinical effects). Both inform dosing, side-effect profiles and drug selection.

🛡️ Non-pharmacologic management

Important adjuncts include good nursing care, mobilization and physiotherapy, hydrotherapy, weight management, environmental control, cooling/warming, nutrition and stress management. These complement pharmacologic strategies in multimodal care.

🧾 Practical considerations

Always consider patient species, comorbidities and licensing when selecting agents. Use multimodal and pre-emptive strategies when possible, tailor locoregional techniques to surgery and patient, and monitor for system-specific adverse effects (CNS, cardiovascular, respiratory, renal, hepatic, hematologic and immune impacts).