Anesthetics

Question 1

List the inhaled anesthetics

Answer 1

o Isoflurane
o Sevoflurane
o Desflurane
o N2O

Question 2

List the IV anesthetics

Answer 2

o Thiopental
o Propofol (both induction and maintenance)
o Etomidate
o Ketamine (also for analgesia)

Question 3

List the local anesthetics

Answer 3

Benzocaine
Bupivacaine 
Cocaine
Eutectic Mixture of Local Anesthetics (EMLA)
Lidocaine
Mepivacaine
Prilocaine
Procaine
Ropivacaine
Tetracaine

Question 4

Goals of general anesthesia

Answer 4

o	Hypnosis: loss of consciousness
o	Amnesia: loss of recall
o	Analgesia: loss of pain sensation 
o	Muscle relaxation: loss of movement
o	Physiologic homeostasis: maintenance of ventilation, oxygenation, perfusion

Question 5

Describe the effects of inhaled anesthetics drugs

Answer 5

o Onset/offset depends on uptake and solubility
o Little metabolism
o Pulmonary elimination

Adverse effects:
• Cardiovascular depression
• Respiratory depression (rapid shallow breaths)
• Can increase intracranial pressure (decrease CMRO2 but increase CBF)
• Bronchodilators → impaired mucociliary clearance
• Airway irritation: (Desflurane > Isoflurane > Sevoflurane)

Question 6

Describe the characteristics and mechanisms of action of inhaled general anesthetic drugs

Answer 6

o Includes: Isoflurane, nitrous oxide, Sevoflurane, Desflurane
o Have a halogen
o Lipophilic
o Liquids at room temperature, but easily vaporized (volatile)

MOA:
• Volatile Anesthetics:
• Enhance GABAA receptor function → hypnosis, amnesia
• Na+, Ca2+, K+ channels → Analgesia, skeletal muscle relaxation
• Nitrous Oxide: blocks NMDA receptors → analgesia

Question 7

Describe the characteristics and mechanisms of action of IV general anesthetic drugs

Answer 7

o Includes: Thiopental, Etomidate, Propofol, Ketamine
o Have an aromatic ring
o Lipophilic
o Fast onset

MOA:
• Thiopental, Propofol, Etomidate: enhance GABAA receptor function → hypnosis, amnesia
• Ketamine: blocks NMDA receptors → analgesia; other CNS targets → dissociative state, catalepsy

Question 8

Describe the relationship between lipid solubility and pharmacokinetics for inhaled agents.

Answer 8

• Faster a drug equilibrates with blood → more quickly drug passes into brain → anesthetic effects
• More soluble a drug = slower induction of anesthesia
• Less soluble = faster

Question 9

Describe the pathophysiology and treatment of malignant hyperthermia, and distinguish it from serotonin syndrome and neuroleptic malignant syndrome.

Answer 9

• Fatal reaction to volatile anesthetics
• Mutations in proteins involved in EC coupling in skeletal muscle → Ca2+ leaks out of SR → increased myoplasmic Ca2+

Hypermetabolism 
o	Rigidity 
o	Heat (due to ATP consumption)
o	CO2 production and acidosis
o	Rhabodmyolysis 
o	Hyperkalemia 

Treatment:
o DC volatile anesthetic
o IV Dantrolene (prevents Ca2+ channels form opening)

Question 10

Identify the two main classes of local anesthetics and describe their similarities and differences.

Answer 10

Types:
1) Amides
• Metabolized in liver
2) Esters
• Hydrolyzed by plasma esterases
• Metabolite: p-amino-benzoic acid (PABA)
• Can cause allergic reactions (anaphylaxis)

Question 11

Describe how the solution pH and the pKa of a local anesthetic influence the onset of nerve block.

Answer 11

Local anesthetics = contain lipophilic aromatic group AND hydrophilic tertiary amine
• Amine = has acid-base reactions:

Protonated/charged form:
• Commercial form (HCl salts = more stable)
• Active form

Unprotonated/neutral form
• Weak base (pKa’s 8-9)
• Diffusible form = can cross cell membrane to block inner Na+ channel
• Once in cell = acid environment → protonated to active form

Question 12

Describe factors influencing absorption of local anesthetics and explain how epinephrine can alter their duration of action.

Answer 12

• Acid-base environment
• Absorption = related to blood flow
o Fastest: intercostal > epidural > brachial plexus > sciatic/femoral > field block
• Administer with a vasoconstrictor (ex: epinephrine) = decrease absorption

Question 13

Describe the molecular and electrophysiologic mechanisms of action of local anesthetics.

Answer 13

Main use = analgesia

Local administration near peripheral nerves
o Sensory block
o Motor block
o Sympathetic block

Blocks voltage gated Na+ channels → prevents AP generation

Question 14

How to avoid systemic toxicity with a local anesthetic

Answer 14

Administer safe doses:
• Lidocaine: ≤ 5 mg/kg
• Bupivacaine: ≤ 2.5 mg/kg
• Ropivacaine: ≤ 3 mg/kg

Administer with a vasoconstrictor (ex: epinephrine) = decrease absorption

Avoid intravascular injection
• Aspirate before injection
• Give slowly in incremental doses

Question 15

Effect/symptoms of systemic toxicity with local anesthetics

Answer 15

Suppression of ventricular ectopy
Lightheaded, circomoral paresthesias
Tinnitus, N/V, tremors, confusion
Seizures, cardiorespiratory depression
Coma
Respiratory arrest
Cardiac arrest

Question 16

How to treat systemic toxicity with a local anesthetic

Answer 16

Supportive:
• Airway
• Benzodiazepines for seizures
• ACLS for arrhythmias, CV collapse

Lipid emulsion (20%) = acts as sink for lipophilic drugs
• 1.5 mL/kg IV bolus (~100 ml)
• 0.25-0.50 mL/kg/min (~18-35 mL/min)

Question 17

Methemoglobinemia

Answer 17

Systemic absorption of Prilocaine and Benzocaine

High levels oxidize iron atom in hemoglobin
• Fe2+ → Fe3+
• Fe3+ can’t carry oxygen

Normally both agents used topically (considered safe, so insidious onset)