LA Supp

Question 1

What are local Anesthetics?

Answer 1

Drugs that reversibly block the conduction of electrical impulses along nerve fibers.

Question 2

The ability of the local anesthetic to produce a reversible conduction blockade of impulses along central and peripheral nerve pathways is dependent on?

Answer 2

Physiochemical properties of the local anesthetic.

Anatomy of the nerve being blocked.

Question 3

Nueron electrophysiology

Answer 3

Resting membrane potential of a peripheral nerve is
-70mV

Rapid depo somewhere around -53

NA+ leaks in during impulse and depolarizes cell to +35

Resting membrane potential is restored by active removal of intracellular Na+ by the sodium/potassium pump. (3:2)

Question 4

Nerve fibers are classified into three groups: A,B,C and based on?

Answer 4

diameter and myelination of nerve fibers

Question 5

Charcteristics of A Fibers Slide 17

Answer 5

Slide 17

Question 6

Characteristics of B fibers

Answer 6

Diameter (4µm)
Slower conduction velocity and less myelination than A fibers.
Preganglionic autonomic nerves

Question 7

Characteristics of C fibers

Answer 7

Diameter (1-2µm)
Slowest speed of conduction
Conduct pain and temperature impulses
The only fibers that are unmyelinated

Question 8

What is LA MOA?

Answer 8

Reversibly block sodium channels

These receptors, located on the intracellular side of the cell membrane, have a greater affinity for the charged form of the local anesthetics.

Local anesthetics must first penetrate the cell membrane before they produce their effects. Penetration of the local anesthetic is greatly facilitated if the drug is in the uncharged or non-ionized state.

Question 9

All local anesthetic molecules have three characteristic segments. What are they?

Answer 9

An unsaturated aromatic ring system

An intermediate carbon group

A tertiary amine

Question 10

What are the major difference in the core structure of local anesthetics?

Answer 10

Ester vs. amide linkage binding the aromatic ring to the tertiary amine.

(The type of linkage is clinically important because it has implications for metabolism and allergic potential.)

Question 11

Ester VS Amide

Answer 11

Ester: 
Procaine
Chloroprocaine
Tetracaine
Cocaine

Amides all have “I”s in them. Example Li docaine
Mepi vacaine

Question 12

Onset of action determinants 1

Lipid solubility

Answer 12

major determinant is amount of LA that is in the non-ionized form.
(If its more in the non-ionized form, it will be more lipid soluble.)

Question 13

Onset of action determinants 2

What is the PKA?

Answer 13

Is the pH of the LA at which the amount of ionized and non-ionized drug is equal.

(LA with a pKa closet to physiologic pH will have a higher concentration of non-ionized form that can readily pass thru the nerve cell membrane)

Question 14

What is ion trapping and how does it relate to fetal circulation. What factors contribute more to it?

Answer 14

results from changes in pH in relationship to the agent’s pKa.

Acidosis resulting from hypoxia may increase the ionized fraction of local anesthetic Accumulation in fetal circulation

Hypoxia & injection into infected tissue

Question 15

What does DOA correlate with

Answer 15

lipid solubility

(Highly lipid soluble LA have a longer duration of action, because they are less likely to be cleared by blood flow (sequestered in lipid depot).

(LA that are highly lipid soluble are also (typically) highly protein bound.)

Question 16

Kinetics

The higher the __________ of drug injected that remain in the area of the nerve/nerves to be blocked, the ____________the onset of action.

Answer 16

concentration (number of molecules)/faster

Systemic absorption away from the tissue injection site results in the offset and termination of drug effect.

Question 17

Systemic absorption of injected LA depends on?

Answer 17

blood flow

The more vascularized the area the greater the systemic absorption

Question 18

Adding a vasoconstrictor helps?

Answer 18

Addition of epinephrine
Decreases vascular absorption
Increases nerve cell uptake
Enhances the quality of analgesia
Prolongs the duration of action
Limits toxic side effects

Question 19

All local anesthetics (except cocaine) produce?

Answer 19

relaxation of vascular smooth muscle.

Resultant vasodilation increases blood flow to the surrounding tissue where the drug is deposited.
This results in increased LA absorption, limits its duration of action and increases the probability of toxic effects.

Question 20

What are esters predominantly metabolized by?

Answer 20

pseudocholinesterase

Ester hydrolysis is a rapid process

Water soluble metabolites excreted in urine

Pts with genetically abnormal pseudocholinesterase are at risk for toxic side effects

Question 21

Procaine and benzocaine are metabolized to

Answer 21

p-aminobenzoic acid (PABA) ~ associated with allergic reactions

Question 22

Amides Metabolized by?

Answer 22

microsomal P-450 enzymes in liver (N-dealkylation and hydroxylation)

Overall metabolism much slower than ester hydrolysis
Decrease in liver function will reduce metabolism and increase toxicity

Metabolites depend on renal clearance

Question 23

Metabolites of prilocaine (o-toluidine derivatives) ______ after large doses (>10ma/kg) and convert hgb to _________.

Answer 23

accumulate/methemoglobin

Metabolites of benzocaine spray – methgb

Treat significant methgb with IV methylene blue

Question 24

Methemoglobinemia S/S with high concentrations?

Answer 24

Brownish gray cyanosis
Tachypnea
Metabolic acidosis

Severe signs and symptoms ensue with:
Tissue hypoxia
Headache
Irritability
Loss of consciousness

Question 25

Methemoglobinemia: Treatment

Answer 25

Spontaneous recovery in 2-3 hours Immediate reversal with methylene blue IV (Formation of methemoglobinemia not clinically significant in healthy patient. Becomes an issue in patient’s with severe anemia or heart failure that cannot tolerate the reduction in oxygen-carrying capacity.)

Question 26

What influences toxicity?

Answer 26

Absorption and metabolism

Question 27

What are some additives to local anesthetics and what do they do?

Answer 27

Opioids Sodium bicarbonate Epinephrine These are added to increase the safety, quality, intensity, duration and rate of onset of anesthesia.

Question 28

Some causes of toxicity?

Answer 28

Inadvertent intravascular injection Administration of excessive dose

Question 29

CNS toxicity treatment?

Answer 29

Convulsions - increased oxygen consumption in the presence of compromised ventilation. Assure patent airway and adequate ventilation Administration of anticonvulsant Progression to cardiac arrest

Question 30

CV s/s of toxicity

Answer 30

All LA depress myocardial automaticity Reduce the duration of the refractory period High blood levels of LA will depress contractility and conduction All LA produce smooth muscle relaxation and arteriolar vasodilation… (not cocaine) Ensuing combination of bradycardia, heart block, and hypotension may cause cardiac arrest

Question 31

What happens with Bupivacaine if it is accidently injected IV?

Answer 31

severe cardiotoxic reaction. Resuscitation from bupivacaine often requires high doses of vasopressor and prolonged resuscitation effort.

Question 32

CNS s/s of toxicity?

Answer 32

Not acting right to Confusion dizziness metallic taste to seizure

Question 33

What is a lipid rescue used for?

Answer 33

Toxicity. Cardiotoxicity

Question 34

What are the Transient Neurologic Symptoms that can be associated with spinal anesthesia?

Answer 34

Dysesthesia, burning pain, and aching in lower extremities and buttocks. Associated with use of lidocaine for anesthesia

Question 35

Topical Cocaine is a Unique local anesthetic in that it causes?

Answer 35

vasoconstriction Cocaine produces vasoconstriction by blocking norepinephrine and epinephrine uptake into adrenergic nerve endings. Good for nasal surgery

Question 36

Why does the Potential for significant drug interaction exists with topical cocaine an Epi injection into nasal mucosa?

Answer 36

Cocaine blocks the uptake of epinephrine Toxic effect from injection of epinephrine may occur Life threatening ventricular arrhythmias

Question 37

What is EMLA?

Answer 37

Eutectic mixture of Local Anesthetic Mixture of lidocaine and prilocaine Accumulates at the site of dermal pain receptors and nerve endings Satisfactory analgesia occurs about 1 hour after application with an occlusive dressing.

Question 38

What are the special considerations when applying topical anesthetics to mucous membranes?

Answer 38

Absorption of local anesthetics from the mucous membrane is significant and systemic toxicity can occur. ``` Nose – direct Vena Cava Mouth – direct Vena Cava Tracheobronchial tree Esophagus Genitourinary tract ```