Test 3: 34 local

Question 1

what is a local anesthetic

Answer 1

drug that causes reversible loss of sensory perception and motor function, in a localized area of the body

Question 2

lidocaine is used because

Answer 2

antiarrhythmic
prokinetic
MAC reduction
analgesia

systemic administration

Question 3

local anesthetics work on what type of channels

Answer 3

periphery: Na channels

dorsal horn spinal cord: LAs inhibit K+ or Ca2+ channels, inhibit substance P binding and reduce glutamatergic transmission by reducing N-methyl-D-aspartate (NMDA) postsynaptic depolarization. Work on serotoninergic and AcH receptors

Question 4

how does lidocaine effect Na channels

Answer 4

lidocaine either ionized or uncharged

uncharged version will cross lipid membrane, become ionized and bind to inside of Na Channel from the intracellular side

this will prevent Na channel from opening and prevents Na from entering the cell → can can not depolarize and send signal

Question 5

if the local has an ester group it will be broken down by

Answer 5

hydrolyzed by plasma esterases

Question 6

if local has an amide group it will be broken down in

Answer 6

metabolized in the liver

Question 7

All clinically useful local anesthetics are —, and as such they exist in equilibrium between the neutral, non‐ionized, lipid soluble form (B) and the ionized (charged), water‐soluble form (BH+).

Answer 7

weak bases

Question 8

The neutral/uncharged form is — and easily crosses the cell membrane. The — form is more water soluble and can cross only through the open channel.

Answer 8

lipid soluble

ionized

Question 9

what three physiochemical properties control the effect of Local

Answer 9

The pKa of a LA determines the onset of the pharmacological effect

The lipid solubility of a LA determines its potency

The protein binding (of a LA with serum proteins) determines the duration of the pharmacological action

Question 10

what is the pKa for most LA

Answer 10

ph>7.4

Question 11

The — the pKa, the greater the degree of ionization or proportion of local anesthetic in the ionized, charged, hydrophilic form at physiologic pH (7.4), and the — the onset of action.

Answer 11

higher

slower

(if LA is in ionized form it can not cross through membrane, takes longer for effect to happen)

Question 12

a local anesthetic with a — pKa will have a greater proportion of the non-ionized lipid-soluble form at physiologic pH and a more — onset of action.

Answer 12

low

rapid

(at a pka< 7.4, the LA will be in the nonionized, neutral form, it can easily move across membranes and attach to NA channels on the intercellular side → rapid onset)

Question 13

Increasing lipid solubility facilitates the penetration through lipid membranes, potentially — onset of action.

Answer 13

hastening

the more lipid soluble the greater the potency of a drug

Question 14

the lower the lipid solubility, the — the potency

Answer 14

lower

Question 15

Higher protein binding is associated with — duration of action

Answer 15

increased

only free, unbound drug is active, if most of the drug is bound to protein, it will take a long time to use up the drug

Question 16

lidocaine, procaine, and tetracaine have what chirality?

Answer 16

achiral

Question 17

what are some S-enantiomer LA

Answer 17

Left: leviosomers
levobupivacaine and ropivacaine

they are less toxic then their Right versions (bupivicane)

Question 18

what is differential blockade

Answer 18

Some LA can produce vasodilation →loss of sensory → motor loss based on dose of med given

Ropivacaine > Bupivacaine > Lidocaine = Mepivacaine

Local anesthetics with an amide group, high pKa, and lower lipid solubility show greater differential blockade

Question 19

if you give low dose ropivacaine what will happen

Answer 19

differential blockade

at low does will have vasodilation and some sensory loss, but motor still intact

if you increase dose will lose all three

Question 20

what length exposed to drug is important for differential pattern

Answer 20

three or more nodes of Ranvier

Therefore, larger fibers with greater internodal distances are less susceptible to local anesthetic blockade

Question 21

decremental conduction

Answer 21

usually need 3 nodes of ranvier for effect

DC: describes the diminished ability of successive nodes of Ranvier to propagate the impulse in the presence of a local anesthetic. This principle explains why the propagation of an impulse can be stopped even if none of the nodes has been rendered completely unexcitable, as occurs for example with low concentrations of local anesthetics.

Question 22

which type of nerve fiber is blocked first with LA

Answer 22

B > C = A-δ > A𝛄 > Aβ > A⍺

Question 23

Systemic absorption depends on several factors including

Answer 23

site vascularity: ↑ vessels= ↑ absorption

intrinsic vasocativity: vasodilators ↑ absorption, constrictors (ropivacaine and levobupivacaine) ↓ absorption

lipid solubility, protin binding, dose

the lower the systemic absorption the safer the med, increased systemic absorption can be toxic

Question 24

which LA injection site has increased vascularity

Answer 24

intercostal > epidural > brachial plexus > sciatic/femoral

Question 25

which LA are vasoconstrictive

Answer 25

ropivacaine and levobupivacaine constriction will lead to slower systemic absorption →less toxicity

Question 26

if you add epi to lidocaine will it dilate or constrict vessels

Answer 26

lidocaine- dilate epi- constrict constriction wins= less systemic absorption of LA

Question 27

what type of LA is widely distributed throughout body

Answer 27

**amino-amides** amino-ester LA are rapidly hydrolyzed = ↓ distribution

Question 28

explain 1st pass pulmonary uptake

Answer 28

amino-amides LA are widely distributed throughout the body amino-amides will go through 1st pass pulmonary uptake = **lung will absorb a lot of the lipid-soluable, ↓pKa drugs** (bupivacaine> lidocaine) increased risk of toxicity if **R-L cardiac shunt** (drug doesn't get to lungs to be cleaned out) increased risk if **↓ blood pH**, cause that will ↑ ionized form of meds and lungs abdorb the unionized version

Question 29

what happens when LA amino-amides get into placenta

Answer 29

ion trapping maternal pH is higher then the baby, the lower pH makes more ionized form of LA, that can not cross back out of baby

Question 30

use --- LA in pregnant pts to prevent ion trapping

Answer 30

lidocaine > bupivacaine

Question 31

breakdown of benzocaine and procaine can produce ---

Answer 31

PABA → rare allergic reaction amino-ester LA that are hydrolyzed by plasma pseudocholinesterases

Question 32

Prilocaine is broken down by --- and forms ---

Answer 32

prilocaine is an amino-amide metabolized in liver by **CYP450** makes toxic metabolite **methemoglobin**

Question 33

lidocaine is broken down by --- and makes ---

Answer 33

Lidocaine= amino-amide LA broken down in liver by **CYP450** produce **MGEX** toxic

Question 34

The dose of a local anesthetic causing systemic toxicity will depend on the ---

Answer 34

route and speed of administration (rapid intravenous administration will be more likely to cause high plasma levels), the species involved patient factors (such as acid–base balance, serum potassium levels) more lipid soluble drugs will be more potent R-enantiomers more toxic

Question 35

what are signs of LA toxicity

Answer 35

**CNS**: excitation, seizure, depression and coma **cardiac**: ↓Na into a cell= prolonged PR and QRS intervals = bradycardia, ↓BP, ↓ contractility, asystole ↑potassium = toxic

Question 36

how does increased PaCO2 lead to ↑ risk of seizures with LA

Answer 36

↑PaCO2= vasodilation in the brain= more LA into the brain = ↑ toxicity → seizures

Question 37

how does increased PaO2 protect from seizures from LA

Answer 37

**hypoxemia** increases the CNS and cardiovascular toxicity of local anesthetics high O2 vasoconstrictive?

Question 38

how to treat LA overdose

Answer 38

**supportive care**: oxygen, ventilation may need to do CPR, epi and difibrillate DO NOT USE LIDOCAINE to treat arrhythmias: **use amiodarone or IV lipid emulsion**

Question 39

local LA can be neurotoxic to --- cells and is --- dependent

Answer 39

schwann cells time and concentration mepivacaine < lidocaine < ropivacaine < bupivacaine.

Question 40

local LA can be myotoxic to ---- and is --- dependent

Answer 40

skeletal muscle: mess up intracellular Ca and mitochondria **concentration dependent** bupivacaine is worse

Question 41

LA can be chondrotoxic if --- and are --- dependent

Answer 41

intra-articular injection time and concentration dependent mepivacaine < ropivacaine < bupivacaine= lidocaine

Question 42

which LA can produce methemoglobin when broken down

Answer 42

ester type: **benzocaine** and amide type **prilocaine** **chocolate brown colored blood**- not responsive to O2 therapy- need to treat with **methylene blue** or blood transfusions in severe cases

Question 43

it is recommended that animals known to be allergic to ester‐type local anesthetics be treated with a ---

Answer 43

preservative‐free amide‐type agent procaine: **ester**: forms PABA when metabolized, can be allergic

Question 44

procaine

Answer 44

amino ester LA fast onset 30-60 min duration CNS stimulant in horse if given IV metabolism → PABA→allergic reactions

Question 45

benzocaine

Answer 45

fast acting topical only amino ester LA → PABA → allergic reaction Can also cause **Methemoglobinemia** in small animal **used for fish**

Question 46

Tetracaine

Answer 46

amino ester LA **rarely used** due to **very slow onse**t when administered in the periphery and potential for **systemic toxicity** excelent topical anesthetic

Question 47

lidocaine

Answer 47

amino-amide LA * fast onset, 1 hrs duration * inflitration, nerve blocks, epidural and intrathecal blocks, and intravenous regional anesthesia * EMLA cream, patches analgesia from action at Na+, Ca2+, and K+ channels and the NMDA receptors. Class Ib antiarrhythmic drug some anti‐inflammatory effects prokinetic in horses: prevent post op ileus by improving GI motility

Question 48

mepivacaine

Answer 48

amino-amide LA * fast onset, 1-2 hrs * infiltration, nerve block * poor topical * low neurotoxicity- use for **horses** * very slow metabilism in fetus and newborns

Question 49

bupivacaine

Answer 49

amino-amides LA * highly lipophilic= 4 x more potent then lidocaine * slow onset (20-30 mins), long duration 3-10 hrs * infiltrative, peripheral nerve, epidural, and intrathecal blocks * poor topical * **NO IV → cardiotoxic** **Levobupivacaine**: levoisomer or S‐enantiomer of bupivacaine →less cardiotoxic

Question 50

Ropivacaine

Answer 50

amino-amide LA * S- enatiomer = ↓ CV toxic * similar onset to bupivacaine (20-30 mins), duration (6 hrs) * infiltrative, peripheral nerve, epidural, and intrathecal blocks * Biphasic effect of vasculature * > 1% vaso**dilation** * < 0.5% vaso**constriction**

Question 51

why add epinephrine to local

Answer 51

it causes **vasoconstriction** → **Decreased systemic absorption** and **longer duration** * decreases local blood flow to nerves and spinal cord → can cause ischemia * systemic absoprtion will cause CV effects ## Footnote 1: 200,000 (5 mcg/ml)

Question 52

what will bicarb do to LA

Answer 52

↑pH= ↑ unionized form = **shorter onset** * efficacy depends on LA and location * decreases pain of injection ## Footnote 1 mEq/10ml

Question 53

what will adding an ⍺2 agonist do to LA

Answer 53

enhances sensory and motor blockade * receptors not involved- hyperpolarized C fibers shorter onset, longer duration of sensory and motor block, enhanced block quality, lower pain scores, and decreased systemic opioid requirements

Question 54

nocita

Answer 54

72 hr analgesia multivesicular liposomes, that encapsulate aqueous bupivacaine