Local Anesthetics - Pharm Test 1

Front 1

How do local anesthetics work? Where can they work?

Back 1

they reversibly block the action potentials for nerve conduction

they can act on any part of the nervous system

they can effect any type of nerve fiber

Front 2

What was the first local anesthetic discovered?

Back 2

Cocaine -- made into synthetic substitutes such as procaine and lidocaine

Front 3

What is the structure of the typical local anesthetics?

Back 3

contains hydrophilic and hydrophobic domains

-hydrophilic group is usually a tertiary amine

-hydrophobic group is an aromatic moiety

Front 4

There are two main types of local anesthetics. What are they and what part of the structure dictates this?

Back 4

Ester or Amide

determined by the intermediate chain (linkage) between the benzene ring (the aromatic group) and the "amine" portion

Front 5

What kind of local anesthetics are used most clinically?

Back 5

Amides (they contain nitrogen)

Front 6

How does the lipophilicity of a local anesthetic affect it?

Back 6

-increases potency and DOA d/t crosses membranes easily so it takes less LA

-increases toxicity r/t how much of the drug diffuses and gets into the systemic circulation (the more lipophilic it is, the lower the therapeutic index)

-impacts time for onset: slows onset by limiting amount of drug getting to the neural membrane (because it spreads out and binds to tissue)

Front 7

What determines onset with local anesthetics?

Back 7

the proportion of molecules that are lipid-soluble (in-ionized) rather than water-soluble (ionized) at the nerve fiber

Front 8

What does pH/pKa determine about local anesthetics?

Back 8

determines proportion of molecules in the ionized and in-ionized state

-the pKa for all LA's is greater than 7.4

(if a LA has a pKa of 7.4 and the tissue has a pH of 7.4 then 50% of the molecules will be ionized and 50% will be in-ionized)

Front 9

What is the pH of inflamed/infected tissue?

Back 9

< 7.4

Front 10

How does molecular size affect local anesthetics?

Back 10

-it influences the rate of dissociation of LA from receptor sites

-smaller drug molecules can dissociate from receptor sites more rapidly

Front 11

How are local anesthetics excreted?

Back 11

via the kidneys

Front 12

How are ester-type agents metabolized?

Back 12

they are hydrolyzed very rapidly in the blood by psuedocholinesterase (very short half-lives)

Front 13

How are amide agents metabolized?

Back 13

they are hydrolyzed in the liver by the cytochrome P450 enzyme system

Front 14

What is the MOA of local anesthetics?

Back 14

they prevent the generation and conduction of nerve impulses; primary site of action is the voltage-gated sodium channels on the cell membrane

Front 15

How do local anesthetics affect action potential?

Back 15

they slow the rate of depolarization of the nerve action potential so that threshold potential is not reached

-AP cannot be propagated and conduction blockade occurs

Front 16

What does the degree of block produced by local anesthetics depend on?

Back 16

how the nerve has been stimulated and on its resting membrane potential

-a resting nerve is less sensitive than one that is repetitively firing

-higher freq of stim and more positive membrane potential = greater degree of block

Front 17

What is binding and dissociation at receptor sites within the sodium channels determined by?

Back 17

pKa, lipid solubility, molecular size

Front 18

What kind of agents require a high degree of nerve stimulation and why?

Back 18

rapidly dissociating agents; so that drug binding during the AP exceeds drug dissociation during resting potential

Front 19

What does frequency-dependence of local anesthetic action depend on?

Back 19

the rate of dissociation from receptor sites

Front 20

What kind of fibers are blocked first by LAs?

Back 20

small unmyelinated C fibers (pain) and small myelinated A-delta fibers (pain and temp)

Front 21

What kind of fibers carry postural, touch, pressure and motor information?

Back 21

larger myelinated A-gamma, A-beta and A-alpha fibers

Front 22

What are some amide local anesthetics?

Back 22

Lidocaine, Bupivacaine, Prilocaine, Ropivacaine, Etidocaine (most potent), Mepivacaine

Front 23

What are some Ester local anesthetics?

Back 23

procaine, tetracaine (most potent), chloroprocaine

Front 24

What are some adverse effects of local anesthetics?

Back 24

they can interfere with the function of all organs in which conduction or transmission of impulse occurs

-risk is proportional to the concentration of LA in systemic circulation

Front 25

What are some determinants of LA blood levels?

Back 25

total dose given - site of injection - addition of vasoconstrictors - drug-induced local vasodilation - local tissue binding - tissue perfusion - concomitant drug therapy - renal or hepatic disease

Front 26

Which injection site has lower risk of adverse effects?

Back 26

intercostal > epidural > brachial plexus

(spinals have lower risk, topical has higher)

Front 27

How does the addition of vasoconstrictors affect systemic absorption?

Back 27

they decrease it

Front 28

List some CNS adverse effects.

Back 28

-central stimulation followed by central depression

-restlessness, tremors, convulsions (treat with benzos)

-drowsiness, sedation

Front 29

What are some adverse effects of LAs in the neuromuscular junction and ganglionic synapse?

Back 29

they block skeletal muscle response to maximal motor-nerve stimulations and acetylcholine

Front 30

What are some CV adverse effects?

Back 30

decrease electrical excitability, conduction rate and force of contraction of the myocardium

-usually seen with high doses only

-greatest with bupivacaine and etidocaine

Front 31

What are the symptoms of LA hypersensitivity? Which type of LA are usually the culprit?

Back 31

allergic dermatitis or asthmatic attack

-asso with esters d/t PABA metabolite

-asso with the preservative in amides

Front 32

What effect does adding epinephrine to LAs have?

Back 32

-prolongs anesthesia duration

-reduces systemic absorption

-increases intensity of blockade through vasoconstriction and stimulation of alpha-2 receptors (which decreases substance P release and reduces sensory neuron firing)

Front 33

When should epinephrine not be added to LAs?

Back 33

unstable angina - cardiac arrhythmias - uncontrolled hypertension - uteroplacental insufficiency - peripheral nerve block in areas without collateral blood flow (digits) - IV regional anesthesia

Front 34

List the different ways local anesthetics can be used.

Back 34

topical - local infiltration - IV regional - peripheral nerve block - epidural - spinal

Front 35

How does topical anesthesia work on mucous membranes?

Back 35

-tetracaine, lidocaine or cocaine

-topical epinephrine not effective

-peak effect occurs in 2-5 minutes

-lasts 30-60 mins

-anesthesia is superficial

-absorbed rapidly into systemic circulation

Front 36

What is EMLA?

Back 36

a eutectic mixture of lidocaine and prilocaine

-produces deeper penetration (up to 5mm)

-used for skin and subcutaneous structures

-uses an occlusive dressing to facilitate penetration

-do not use on mucous membranes or abraded skin

Front 37

How is infiltration anesthesia used?

Back 37

it is the injection of LA directly into tissue

-can be used for superficial to deep procedures

-duration can be prolonged with added epi

-lidocaine and bupivacaine most commonly used

Front 38

What is a nerve block?

Back 38

injection of LA into or about individual peripheral nerves or nerve plexuses

-produces greater area of anesthesia than infiltration

-also anesthetizes motor nerves to produce skeletal muscle relaxation

Front 39

What are some determinants of the onset of sensory anesthesia following injection near a nerve?

Back 39

proximity to the nerve - concentration an volume of drug - degree of ionization of drug - time

Front 40

Can you give more or less LA when you add epinephrine?

Back 40

More. . . and it lasts longer d/t the vasoconstriction caused by the epi - keeps it where you want it

Front 41

What is a benefit of liposomal bupivacaine?

Back 41

longer duration of analgesia - 72 hours

may reduce need for opioids

Front 42

How long must you wait between administration of LAs and liposomal bupivacaine?

Back 42

bupivacaine liposome should not be given within 20 minutes of non-bupivacaine LA and non-liposomal bupivacaine should not be given within 96 hrs of bupivacaine liposome (may cause immediate release of bupivacaine from the liposomal formulation)

Front 43

What block is liposomal bupivacaine contraindicated in?

Back 43

obstetric paracervicular block anesthesia

Front 44

What is IV regional?

Back 44

relies on the vasculature to carry the LA to the nerve trunks and endings

-use tourniquet for at least 15-30 mins and max of 2 hours

-potential for significant systemic toxicity

-most often used for forearm and hand

-drug of choice is 0.5% lidocaine

-do not give epinephrine

Front 45

What is spinal anesthesia?

Back 45

the injection of local anesthetic into the CSF in the lumbar space

-can produce significant anesthesia with lower doses

-lidocaine, bupivacaine and tetracaine commonly used

-epinephrine often added to prolong duration

Front 46

What is baricity?

Back 46

the density of the drug relative to the density of CSF

-determines direction of migration within the dural sac: hyperbaric (denser) solutions settle in dependent portions, hypobaric migrates in opposite directions

-controlled by adding glucose (adds density)

Front 47

What are some complications of spinal anesthesia?

Back 47

persistent neurologic deficits - foreign substance entering into subarachnoid space - infection, hematoma - direct mechanical trauma - high concentrations can cause irreversible block - postural headache

Front 48

What is epidural anesthesia?

Back 48

injecting LA into the epidural space

-primary site of action is on the spinal nerve roots

-epinephrine added to increase DOA and decrease systemic absorption

Front 49

How does the volume of LA given with epidural affect anesthesia?

Back 49

affects segmental level of anesthesia acheived
-each 1-1.5mL of lidocaine 2% will give an additional segment of anesthesia

Front 50

How does concentration of anesthetic used affect an epidural?

Back 50

determines the type of nerve fibers blocked

high concent: sympathetic, somatic sensory and somatic motor blockade

intermediate: allow somatic sensory anesthesia without muscle relaxation

low: blocks only preganglionic sympathetic fibers

Front 51

What are some complications of epidurals?

Back 51

-can produce high systemic blood concentrations depending on total dose given

-higher risk of inadvertent IV injection

-LAs can cross placenta