3Rd Pharmacology Exam - Local Anesthetic Drugs

Front 1

what do local anesthetic drugs do?

Back 1

produce a reversible blockade of nerve conduction (sensory and motor)

Front 2

what are the groups of local anesthetics?

Back 2

esters and amides

Front 3

what do all esteres and amides have?

Back 3

lipophilic portion, intermediate alkyl chain, hydrophilic portion

Front 4

what determines the pharmacolocial properties of local anesthetic drugs?

Back 4

the balance between lipophilic and hydrophilic properties

Front 5

what does increased lipid solubility of a local anesthetic drugs result in?

Back 5

increased potency, duration, and systemic toxicity

Front 6

how are local anesthetics used clinically?

Back 6

topical anesthesia, infiltration anesthesia, field block anesthesia, nerve block anesthesia, intravenous regional anesthesia, spinal anesthesia, epidural anesthesia

Front 7

name early local anesthetics?

Back 7

cocaine, procaine, lidocaine

Front 8

name the local anesthetics most frequently used in vet med?

Back 8

bupivacaine, lidocaine, proparacaine, tetracaine, mepivacaine

Front 9

how are esteres metabolized?

Back 9

by tissue and plasma esterases; usually shorter half-life than amides (tetracaine is exception)

Front 10

how are amides metabolized?

Back 10

by liver microsomal enzymes; poor choice for an animal with severe liver disease (lidocaine, bupivicaine, mepivicaine)

Front 11

what drugs have been used to treat post-op ileus in horses?

Back 11

Cisapride (difficult to obtain), Domperidone, Metoclopramide (bizarre behavioral effects), Ranitidine (H2-receptor antagonist), Lidocaine (anesthetic action)

Front 12

how does lidocaine produce a pro-motility effect?

Back 12

administered IV (same dose as to treat cardiac arrhythmias). Does NOT stimulate intestinal motility; relieves pain from ileus (which stimulates sympathetic output from CNS to reduce motility) decreasing sympathetic output, enabling normal intestinal motility

Front 13

why are opiod analgesics not suitable for the treatment of post-op ileus?

Back 13

inhibits intestinal motility

Front 14

how do local anesthetics produce conduction blockade?

Back 14

block initiation and ropagation of the action potential by preventing the voltage-dependent increase in Na+ permeability that accompanies a small increase in membrane depolarization

Front 15

what factors influence the sensitivity of nerves to conduction blockade?

Back 15

(1) use-dependent block of Na+ channels (greater the frequency of channel openings, the more easily the nerve is blocked) (2) locan anesthetic activity is strongly pH dependent (3) anatomical structure of the nerve

Front 16

how does use-dependent block of Na+ channels affect the sensitivity of nerves to conduction blockade?

Back 16

rapidly-firing nerves more likely to be blocked because more channels in open-inactivated state: (a) local anesthetics must access channel from INSIDE cell, not outside (b) resting channels = low affinity for local anesthetics, open channels = high affinity for local anesthetics, inactivated/refractory channels = very high affinity for local anesthetics

Front 17

how does pH dependency affect the sensitivity of nerves to conduction blockade?

Back 17

local anesthetics are weak bases with a pKa of 7.9, so if extracellular pH decreases (inflammed tissues has a pH of 6.0) more drug is required to produce conduction blockade because less drug is un-ionized (24x more drug is required to produce a conduction blockade at pH 6.0)

Front 18

how does diameter of nerve affect the sensitivity of nerves to conduction blockade?

Back 18

for conduction blockade to occur, a critical length of nerve must be blocked and since smaller diameter nerves have Na+ channels closer together, they are more easily blocked; the nociception-conducting C- and A-delta fibers (smallest) are most easily blocked (can only compare myelinated to myelinated and unmyelinated to unmyelinated, small diameter enteric neurons are more easily blocked than PNS neurons, and pain is easier to block than other modalities like proprioception)

Front 19

describe the pharmacokinetics of local anesthetics?

Back 19

designed to work at site of administration; therefore absorption from the site of administration terminates the effects of the local anesthetic and can lead to systemic effects

Front 20

what affects absorption of local anesthetics from the site of administration ?

Back 20

dosage (increase = increased absorption), site of injection (more vascular = increased absorption), extent of tissue binding (lipid solubility = decreased absorption), concurrent administration of vasoconstricting substances (= decrease absorption) and all local anesthetics are vasodilators (= enhance own absorption)

Front 21

what are the systemic effects of local anesthetics?

Back 21

eventually all local anesthetics are absorbed into the bloodstream; with sufficiently high plasma levels the effects are seen in the CNS, cardiovascular system, and neuromuscular junction and can result in toxicity

Front 22

what are the systemic and toxic effects of local anesthetics?

Back 22

produce hypotension (decrease cardiac contractility causing a decrease in stroke volume and cardiac output and causes arteriolar dilation by blocking postganglionic sympathetic neurons) but cocaine's toxic effects are different (vasoconstriction and hypertension)

Front 23

what class of drug is cocaine?

Back 23

local anestic ester

Front 24

what is the action of cocaine?

Back 24

reversibly block nerve conduction

Front 25

what are the side effects of cocaine?

Back 25

blocks reuptake of NE into neuroeffector junction

Front 26

what class of drug is lidocaine, mepivicaine, bupivicaine, proparacaine?

Back 26

local anesthetic Na+ channel blocker (prevents voltage-dependent increase in Na+ permeability)

Front 27

what is the action of lidocaine, mepivicaine, bupivicaine, proparacaine?

Back 27

reversibly block nerve conduction

Front 28

what are the clinical uses of lidocaine, mepivicaine, bupivicaine, proparacaine?

Back 28

post-op ileus in horses, cardiac arrhythmias, topical anesthesia, infiltration anesthesia, nerve block anesthesia, IV regional anesthesia, spinal anesthesia, epidural anesthesia

Front 29

what are the side effects of lidocaine, mepivicaine, bupivicaine, proparacaine?

Back 29

CNS effects (tremors, convulsions) & cardiovascular hypotension (arteriodilation by blocking postganglionic SNS nerves), and decreases myocardial contractility/CO