Anesthetics

• Analgesics
  • Bolus at induction and before surgical incision
  • Opioid Withdrawal
    • 6-12 hours: Morphine, oxycodone
    • 24-48 hours: Methadone
  • Fentanyl
    • Metabolized by CYP3A4, High protein binding
    • Safest long-acting in kidney and liver failure
    • Increased bioavailability in liver failure, low dose patch
    • Airway reflexes are blunted, may cause respiratory arrest
  • Hydrocodone
    • Metabolized by CYP2D6, low protein binding
    • Increased time to analgesic onset in liver failure
  • Hydromorphone
    • Metabolized by liver glucuronidation, low protein binding
      • Better use in kidney disease
    • Reduced dose and frequency in liver failure/cirrhosis
  • Loperamide
    • SE: QRS prolongation, QT prolongation, Ventricular Tachycardia
  • Meperidine
    • Only opioid that does not cause miosis
    • SE: Seizures, Serotonin syndrome
  • Methadone
    • SE: QT prolongation, Torsade de pointes, miosis, rash, pruritis, hypotension
    • CI: naloxone concurrently
  • Morphine sulfate
    • Metabolized by liver glucuronidation
      • Metabolites cleared by the kidney
      • Avoid in liver failure and kidney failure
        • Increased bioavailability vs toxic metabolites
    • SE: May cause histamine release and mild hypotension
  • Oxycodone
    • Metabolized by CYP2D6/CYP3A4 (Unlike hydromorphone/morphine)
  • Remifentanil (Ultiva)
    • SE: Respiratory depression, bradycardia, hypotension, constipation, chest wall rigidity, pruritus, visual disturbances
  • Tramadol Hydrochloride (Ultram)
    • 50mg-100mg IR QID PO/IV/IM
    • 50mg up to 300mg ER
    • MOA: mu-opioid receptor agonist, inhibits 5-HT and NE reuptake
      • Metabolized by CYP2D6/CYP3A4 (Unlike hydromorphone/morphine)
    • Variable time to onset and efficacy in liver failure
    • SE: Serotonin Syndrome, Seizures
• Sedative-Hypnotics
  • CNS depression
    • Sedation
    • Hypnosis
    • Anesthesia
    • Coma
  • Benzodiazepines
    • Anxiolysis, hypnosis, amnesia, no analgesic properties
    • Midazolam commonly used
    • Metabolized by the liver
    • Flumazenil to treat OD
  • Barbiturates
    • Phenobarbital
      • Can be used in Crigler-Najjar II to induce UDP-glucuronyl transferase
  • Ketamine
    • PCP analog
    • Intense analgesia, amnesia, dissociative anesthesia
    • Increases HR and BP, maintains spontaneous ventilation
      • Excellent bronchodilator
    • Pre-medicate with benzodiazepines to limit illusions and dysphoria
    • Not respiratory depressant
  • Thiopental (Pentothal)
    • Barbiturate, unconsciousness in 30s
    • No analgesic effects
    • Decreases cerebral O2 demand, excellent anticonvulsant
    • Requires repeated dosing
    • Hypotension, HF, Beta-blockade
  • Morphine
    • 5mg IV
  • Hydromorphone (Dilaudid)
    • 75mg IV
  • Fentanyl
    • 50mcg IV (50-150mcg/hr)
  • Propofol (Diprivan)
    • CYP2B6 Substrate
    • Antipyretic and antiemetic properties
      • Mild analgesic effect
      • Metabolized by the liver and plasma esterase
    • SE: Severe hypotension due to myocardial depression (inhibits sympathetic drive)
      • Avoid in patients with ventricular systolic dysfunction
      • Prolonged sedation even after discontinuation
  • Dexmedetomidine (Precedex)
    • Alpha-2 Agonism
  • Etomidate (Amidate)
    • Inhibition of 11B-hydroxylase
    • Adrenal insufficiency in elderly and critically ill
    • May cause respiratory arrest
    • No analgesic effects
    • No change in BP
    • Metabolized by the liver and plasma esterase
  • Halothane (Fluothane)
    • Acute Hepatic toxicity in Adult women
  • Nitrous Oxide (N2O)
    • Inhibition of methionine synthase, inactivates B12
    • Neurotoxicity in pts with B12 deficiency
    • SE: mild ICP, CBF, CMRO2, PONV, decreased hepatic/renal blood flow
• Long time to induction
  • Opioid Abuse
• Long time coming out anesthesia
  • Absence of pseudocholinesterase
  • Lambert-Eaton Myasthenia
    • Increased sensitivity to both depolarizing muscle relaxants (succinylcholine): takes more time to reaccumulate acetylcholine
• Depolarizing NM blocking
  • Used for endotracheal intubation usually
  • Succinylcholine
    • Depolarizing agent, Increases Serum potassium
    • Fastest onset, shortest Duration
    • Metabolized by pseudocholinesterase
• Nondepolarizing NM blocking
  • Rocuronium
    • Fastest non-depolarizing agent
    • Metabolized by the liver
  • Cisatracurium
    • Nonenzymatic breakdown
    • Action not prolonged in renal or liver disease
  • Pancuronium
    • Non-Depolarizing
    • Longest Acting
• Upregulation of Acetylcholine Receptors (toup-regulation)
  • Muscle trauma (burn/stroke), Guillain-Barre, polyneuropathy in critical illness
    • Succinylcholine is a depolarizing neuromuscular blocker by binding to postsynaptic Acetylcholine receptors
      • influx of Na, efflux of K+
      • 45-60s for onset, 6-10minutes of action
    • May cause cardiac arrhythmia 2ndary to hyperkalemia
      • Check [K+]
    • Use Non-depolarizing agents instead in pts with upregulated post-synaptic Ach receptors
      • Vecuronium, rocuronium are competitive Acetylcholine receptor antagonists, do not affect postsynaptic ligand-gated ion channels
        • Anticholinesterases are used to reverse
• Cyclobenzaprine (Flexeril)
  • Centrally acting antispasmodic
  • Poorly understood, inhibition of muscle stretch reflex
  • Hepatic metabolism, 4-6hr duration
  • Use: acute spasm due to muscle injury/inflamamtion
  • SE: Antimuscarinic effects
• Methocarbamol (Robaxin)
• Baclofen
  • GABAb agonist, facilitates spinal inhibition of motor neurons
  • Centrally acting spasmolytic
  • Oral
  • SE: Weakness, sedation, rebound spasticity on abrupt withdrawal
• Tizanidine (Zanaflex)
  • Alpha2 agonist in the spinal cord
  • Oral, renal and hepatic elimination
  • Lasts 3-6 hours
  • Use: Spasm 2/2 MS, stroke, ALS
  • SE: Weakness, sedation, hypotension, hepatotoxicity (rare), rebound hypertension on abrupt withdrawal
• Dantrolene
  • Blocks RyR1 Ca2+ release in the SR of skeletal muscle
  • Direct acting muscle relaxant