Local Anesthetics

Question 1

Esters

Answer 1

Rapidly hydrolyzed by plasma pseudocholinesterase

Significant metabolite, PABA, known allergen

Question 2

Amides

Answer 2

Metabolized by hepatic p450

- rare allergic reactions

Question 3

Local anesthetics structure

Answer 3

Lipophilic benzene ring linked to amine group by hydrocarbon chain of ester or amide

Question 4

Pharmacodynamics

Answer 4

Ionization best correlates with onset of action

-exist in both ionized and non-ionized forms

Question 5

Ionized form

Answer 5

Binds receptor and exerts drugs action but is very hydrophilic and cannot penetrate nerve membrane

Question 6

Non-ionized form

Answer 6

Lipid-soluble and allows drug to penetrate nerve membrane

Question 7

Potency of LA

Answer 7

Correlates with lipid solubility

Higher solubility = higher potency

Question 8

Duration of action

Answer 8

Correlates with protein binding

Question 9

pKa

Answer 9

Relative portion of drug ionized vs non-ionized

*low pKa = greater fraction of non-ionized at given pH -> faster onset

Question 10

Speed of onset

Answer 10

Low pKa = fast onset
Bicarbonate addition = more non-ionized -> quicker onset
High lipid solubility = slower onset

Question 11

Duration of LA

Answer 11

Protein binding = longer duration
More vascular sites = shorter duration
Vasodilation = all LA are vasodilators
Pseudocholinesterase activity = increases duration of esters
Liver disease = increases duration of amides

Question 12

Chloroprocaine

Answer 12

Most rapid hydrolysis of esters
Increasing popularity for short acting spinal
Useful in OBdue to rapid onset

Question 13

Lidocaine

Answer 13

Versatile - topical, regional, IV, peripheral, epidural, spinal
Transient Neuro symptoms after spinal
- pain/sensory change in low back/buttocks
- complete resolution of symptoms in 10 days

Question 14

Bupivacaine

Answer 14

Useful due to long duration in peripheral and epidural blocks
High quality sensory anesthesia relative to motor blockade
Severe, refractory CV collapse with toxic IV doses

Question 15

Ropivacaine

Answer 15

Greatest margin of safety among locals

More vasoconstriction, less lipid solubility

Question 16

Tetracaine

Answer 16

Useful in spinals due to rapid onset and long duration

Question 17

Cocaine

Answer 17

Vasoconstrictor property unique among LA
CNS stimulant
Used in topical solution for laceration repair

Question 18

Emla cream

Answer 18

Topical anesthesia for minor procedures (peds IV)
Onset in 45-60 min
Lidocaine and prilocaine

Question 19

Ester LA

Answer 19

Chloroprocaine
Cocaine
Procaine
Tetracaine

Question 20

Amide LA

Answer 20

Bupivacaine
Lidocaine 
Mepivacaine
Prilocaine
Ropivacaine

Question 21

Additives to LA

Answer 21

Vasoconstrictors (epi) decrease vascular uptake -> decrease systemic absorption -> increased duration and intensity

Question 22

Systemic toxicity

Answer 22

Results from excessive plasma [ ]

• dose related
• rate of injection/infusion
• vasodilation
• lipid solubility
• site of injection

Question 23

Toxicity effects

Answer 23

CV: transient increase in HR, BP due to CNS stimulation
-dose dependent myocardial depression
- increased PR interval, QRS, QT
CNS: affected first
- lightheadedness, facial/oral numbness/tingling, tinnitus, seizure, unconsciousness, arrest

Test dose: if in intravascular space -> bump in HR and BP

Question 24

LA toxicity treatment

Answer 24

Stop injection/infusion -> GET HELP
maintain airway and give 100% O2, consider hyperventilating
- benzos and proposal
Treat cardiac arrest by standard protocols

Question 25

Methemoglobinemia

Answer 25

Caused by LA, antibiotics, nitrates
Signs and symptoms: sob, chest pain, cyanosis, AMS, loss of consciousness
Blood is chocolate brown, ABG reveals normal pO2 with metabolic acidosis -> measure met-Hb
Tx: O2, methylene blue 1-2 mg/kg, hyperbaric O2

Question 26

MOA

Answer 26

Weak bases, hydrophilic, tertiary amines
- act by binding Na+ channels, blocking depolarization induced influx and blocking propagation of nerve impulse
-block depends on myelination and diameter
Autonomic > sensory > motor