13.3 Anesthetic Medications: Pharmacology, Reactions, Contraindications, and Interactions

The anesthetic drug armamentarium is divided by role: premedication (sedation, anxiolysis, analgesia, dose-sparing of induction and maintenance agents), induction (rapid loss of consciousness to allow intubation), and maintenance (sustained surgical anesthesia). Each class has predictable benefits and predictable traps.

Premedications

Acepromazine is a phenothiazine tranquilizer. It provides sedation and anxiolysis but no analgesia, so it is always paired with an opioid. Mechanism is dopamine D2 receptor blockade. Key points and traps:

• Causes vasodilation and hypotension — problematic in dehydration, shock, or cardiac disease
• Boxers are famously sensitive — acepromazine has been linked to cardiovascular collapse and bradyarrhythmias in this breed; many clinicians avoid it entirely in Boxers
• Lowers the seizure threshold (caution in epileptic patients)
• Long duration (6–8 hours), so recovery may be prolonged

Dexmedetomidine is a selective alpha-2 adrenergic agonist. It produces profound sedation and dose-sparing analgesia. Key pharmacology:

• Initial peripheral alpha-2B vasoconstriction causes transient hypertension, followed by reflex bradycardia as baroreceptors respond; cardiac output falls markedly
• Contraindicated in cardiovascular disease, hepatic or renal disease, severe debilitation, and very young or geriatric patients — the drop in cardiac output is dangerous in these groups
• Fully reversible with atipamezole (Antisedan) — this is one of the only true reversals in anesthesia and a frequent VTNE trap. Reversal is given IM at the same volume as the dexmedetomidine dose
• Vomiting is common at onset, especially in cats

Opioids are the analgesic backbone of premedication. Full agonists (morphine, hydromorphone, methadone, fentanyl) provide the strongest analgesia; partial agonists (buprenorphine) have a ceiling effect but less respiratory depression. Key points:

• Cats may show dysphoria (rubbing, rolling, vocalizing) rather than sedation; combining with an alpha-2 or acepromazine reduces this
• Morphine can cause histamine release when given IV rapidly — give slowly or choose hydromorphone for IV use
• Buprenorphine has slow onset (30–45 min) but long duration (6–8 h); useful for postoperative analgesia in cats
• All opioids are controlled substances and require log documentation

Benzodiazepines (diazepam, midazolam) provide muscle relaxation and mild sedation with minimal cardiovascular or respiratory depression — they are the safest premedication class for critically ill patients. They have no analgesia and can cause paradoxical excitement in healthy cats and dogs, so they are usually combined with an opioid or ketamine.

Induction agents

Induction agents produce rapid loss of consciousness so the airway can be secured.

Propofol is the most common induction agent. It is a GABA-A agonist, given IV to effect. Key features:

• Smooth, rapid induction and rapid recovery (redistributes quickly, then hepatic and extrahepatic metabolism)
• Apnea at induction is common, especially in cats — be ready to manually ventilate immediately
• Dose-dependent hypotension and respiratory depression; pre-oxygenation is mandatory
• Repeated doses or CRI in cats causes Heinz body anemia (oxidative damage to hemoglobin) — limit propofol CRI in cats
• Propofol is a controlled substance (Schedule IV) in the United States

Ketamine, combined with diazepam or midazolam, is a popular induction alternative. Ketamine is an NMDA receptor antagonist that produces a dissociative state. Key pharmacology and traps:

• Causes catecholamine release — heart rate and blood pressure rise. Useful in hypovolemic shock, but contraindicated in hypertrophic cardiomyopathy (increases myocardial oxygen demand) and in patients with existing hypertension
• Preserves airway reflexes better than propofol — patients may still swallow and swallow reflex is partially intact
• Increases intraocular and intracranial pressure — contraindicated in glaucoma, penetrating ocular injury, or head trauma with raised ICP
• Cats salivate profusely; premedicate with an anticholinergic or antisialagogue if needed
• Eyes stay open — apply ophthalmic ointment to prevent corneal drying

Etomidate is chosen when cardiovascular stability is critical. It produces minimal change in blood pressure, heart rate, or cardiac output — the agent of choice for severe cardiac disease (mitral regurgitation, DCM, pericardial effusion). Traps:

• Causes adrenal suppression (inhibits 11-beta-hydroxylase); single induction doses are generally acceptable, but CRI or repeated dosing can cause Addisonian crisis
• Pain on injection (propylene glycol carrier) and myoclonus
• More expensive than propofol or ketamine

Alfaxalone is a newer neuroactive steroid induction agent with a similar profile to propofol but less respiratory depression and no Heinz body risk in cats. It is useful for induction in cats and small dogs and can be used as a CRI.

Thiopental is an ultra-short-acting barbiturate, largely replaced by propofol but still tested. Traps:

• Recovery depends on redistribution to fat; sighthounds (lean, low body fat) have prolonged recovery
• Histamine release — avoid in patients with mast cell tumor or atopic disease
• Arrhythmogenic when combined with catecholamines
• Falls into Schedule III controlled substance in the United States

Maintenance: inhalant anesthetics

Inhalants sustain surgical anesthesia after induction. They differ in potency (MAC) and solubility (blood:gas partition coefficient):

Lower blood:gas solubility means the alveolar concentration equilibrates with the blood (and therefore the brain) faster, so depth changes are rapid. Desflurane is the fastest; isoflurane is the slowest. Higher MAC means a less potent agent — desflurane at 7.5% is less potent than isoflurane at 1.3%.

Drug interactions and VTNE trap callouts

Several interaction patterns recur on the VTNE:

• Alpha-2 agonists are reversible with atipamezole — the only true anesthetic reversal (naloxone reverses opioids; flumazenil reverses benzodiazepines)
• Ketamine causes catecholamine release — avoid in HCM and raised ICP
• Acepromazine causes vasodilation — avoid in Boxers, hypovolemia, cardiac disease
• Propofol causes apnea in cats — always pre-oxygenate and be ready to ventilate
• Brachycephalic + mask induction — upper airway obstruction risk; avoid masks, secure airway early
• Opioids + benzodiazepines — synergistic sedation, the safest combination for debilitated patients
• NSAIDs + corticosteroids + ACE inhibitors — renal injury risk; do not stack nephrotoxic drugs

Knowing both the indication and the contraindication is the VTNE standard — most missed questions test the "don't" side, not the "do" side.