Pharmacology of Local Anesthetics

Question 1

Local anesthetics act on

Answer 1

Every type of nerve ifber

Also on cardiac, skeletal muscle and brian

No damage ot nerve cell

Question 2

Ideal local

Answer 2

Short onset wiht long duration but not too long

Question 3

Chemical structures of local

Answer 3

Weakly basic with lipophilic aromatic raing

Intermediate ester or amide

Hydrophilic carbon chain bearing amino group

Either R or S

Question 4

Channel vs ion carrier

Answer 4

Channel is defined pathway for ion transport when open

Carrier shuttles bac kand forth carrying ions across the membrane

Question 5

Na channel structure

Answer 5

Larger alpha and 1 or 2 smaller beta

ALpha is site of ion conduction and binding

10 genes on 4 chromosomes

Question 6

Local anesthetics MOA

Answer 6

Block permeability ot NA

Bind to internal membrane of sodium channel

Potential and gradeint unchanged

Only bind in open and inactive state

Question 7

How does anesthetic get in

Answer 7

Uncharged passes through membrane…then binds hydrogen ion inside the cell to become charged

Question 8

Why not use local on abscess

Answer 8

Acidic enviroment charges it and it can’t cross the mmebrane

Question 9

Local anesthetics and AP

Answer 9

Decrease amplitude

Slow rate of depolarization

Increase threshold

Slow condcuiton

Inrease refractoyr period

Question 10

Pharmacokinetics of locals

Answer 10

Enterb y direct injection or absorption (often with epinephrine to constrict BV)

Considerable first pass uptake in lung

Bind to alpha 1 glycoprotein and labumin

Question 11

Distrivbution of local`

Answer 11

Alpha - rapidly into well perfused (brian. lung ,kidney, heart)
Beta - slower into less perfused (muscle and fat)
gGamma - clearance representing metab and excretion

Question 12

Esters and amides metab

Answer 12

Esters - hydrolyzed in plasma by pseudocholinesterase into PABA

Amides metabolized in ER of hepatocytes…tertiary into secondary which hydrolyzed by amidases

Question 13

Lipid solubility determines

Answer 13

POtency
Higher value is more potent
Amides>esters

Lipid:water partition coefficient

Also determines duration

Not related ot protein

Question 14

Rapidity of onset realted to

Answer 14

pKa
Esters closer to 7.4 so faster
Ph=pKa+log(unionized/ionized)

Question 15

Allergic reactions

Answer 15

More common in esters because of PABA

Question 16

Most OTC anesthetics are

Answer 16

Esters because have quicker onset of action, less potent, and removed quikcer

Question 17

CNS toxicity

Answer 17

More potent means more likelyto cause

Seizrues

Question 18

Toxic effects wiht inreasing concentration

Answer 18

First - convulsion, nnumbness of tongue, etc.

Coma

Resp arrest

CVS depresison

Question 19

How to correct seizrues

Answer 19

Benzodiazepine or propofol

Question 20

CV toxocity

Answer 20

NEgative inotropic effect b/c calcium signaling

Automaticity - negative chronotropic

Ventriclar arrythmias

Question 21

Bupivacaine exception

Answer 21

Dysrythmias seen more often

D isomer worse

Question 22

Tx of cardiac toocity

Answer 22

Lipid emulsions

Question 23

Effects on smooth muscle

Answer 23

Low concentrations - vasoconstriction

High concentrations - vasodilation (except cocaine)

Question 24

Ropivacaine

Answer 24

Solely as S isomer so less cardiotoxic

Question 25

Levobupivacaine

Answer 25

Much less cardiotoxic than bupivacaine

Question 26

EMLA

Answer 26

lidocaine, prilocaine, emulsifier, thickener, distilled H2O

Question 27

Local anesthetics and apoptosis

Answer 27

Has been used to tx mammary epithelial cells

Question 28

HIgher lipid partition coefficient means

Answer 28

More potent and longer duration

Question 29

Metallic tastei n mouth could mean

Answer 29

CNS toxicity