Pharmacology: Local Anesthetics

Front 1

Where are local anesthetics placed?

Back 1

In close proximity to nerve cell membranes

Front 2

Local anesthetics produce ____, ____ blockade of ____ ____ (____ ____) conduction

Back 2

-Transient, reversible
-Nerve impulse (action potential)

Front 3

Order of sensitivity of nerve blockade:

Back 3

autonomic > sensory > motor

Front 4

Recovery from local anesthesia is ____, without ____ to nerve fibers

Back 4

Spontaneous, damage

Front 5

Local anesthetics contain a ____ group and a ____ group connected by a ____ ______ ____

Back 5

-Aromatic, amine
-Short intermediate chain

Front 6

The aromatic group is usually:

Back 6

A substituted benzene ring

Front 7

The amine group is usually

Back 7

A tertiary amine

Front 8

The intermediate chain contains either an ____ or an ____ bond:

Back 8

Ester, amide

Front 9

How are local anesthetics classified?

Back 9

-Esters
-Amides

Front 10

Why are local anesthetic classifications important?

Back 10

Important with respect to how the drugs are metabolized and the potential for allergic reactions

Front 11

What are the esters?

Back 11

-Tetracaine
-Procaine
-Chloroprocaine
-Cocaine

Front 12

What are the amides?

Back 12

-Lidocaine
-Ropivacaine
-Mepivacaine
-Bupivacaine
-l-bupivacaine
-Etidocaine
-Prilocaine

Front 13

What group of local anesthetics have two "i's" in their name?

Back 13

Amides

Front 14

Why are modifications of chemical structures important?

Back 14

They have significant effects on lipid solubility, potency, and duration of action

Front 15

Compare tetracaine and procaine:

Back 15

-Tetracaine has a butyl substituion on the amino group of the benzene ring
-Procaine does not have this substitution
-Tetracaine is more lipid soluble, more potent, and has a longer duration of action (due to slower metabolism)

Front 16

How do local anesthetics prevent conduction of nerve impulses (action potentials)?

Back 16

-Block sodium channels in nerve axon membranes
-Stabilize in inactivated-closed position (preventing return to rested-closed state)

Front 17

Where do local anesthetics bind?

Back 17

To receptor sites within the sodium channels

Front 18

How do inactivated-closed sodium channels prevent depolarization/action potential?

Back 18

They are impermeable to Na+

Front 19

Local anesthetics do NOT affect the ____ ____ ____ or the ____ ____

Back 19

-Resting membrane potential
-Threshold potential

Front 20

Why are peripheral nerves "compound" nerves?

Back 20

They contain numerous axon bundles (i.e. fascicles)

Front 21

Each axon in a fascicle is surrounded by:

Back 21

Connective tissue coat: endoneurium

Front 22

Each fascicle is surrounded by:

Back 22

A layer of cells: perineurium

Front 23

Each peripheral nerve is surrounded by:

Back 23

Collagen sheath: epineurium

Front 24

How do local anesthetics reach individual axons?

Back 24

By diffusing through several layers of tissue

Front 25

Differential sensitivity of nerve axons to local anesthetic blockade:

Back 25

Type B > Type A-delta = Type C > Type A-beta > Type A-alpha

Front 26

What kind of fibers are Type A-delta and Type C?

Back 26

Pain-conducting fibers

Front 27

What type of fibers are blocked by similar concentrations of local anesthetic?

Back 27

Type A-delta and Type C

Front 28

What kind of fibers are Type B?

Back 28

Preganglionic autonomic nerve fibers

Front 29

What kind of fibers are the most sensitive to local anesthetics?

Back 29

Type B

Front 30

Axons in the nerve ____ are anesthetized before axons in the ____:

Back 30

Mantle, core

Front 31

Mantle fibers innervate more ____ structures:

Back 31

Proximal

Front 32

What kind of anesthesia occurs first? Proximal or distal?

Back 32

Proximal, followed by distal spread

Front 33

Which occurs first? Proximal skeletal muscle paralysis or distal sensory blockade?

Back 33

Proximal skeletal muscle paralysis (mantle/proximal first.... core/distal second)

Front 34

Local anesthetics are ____ and are readily ____ at physiological __.

Back 34

Bases, protonated, pH

Front 35

Which form is lipophilic?

Back 35

Nonionized

Front 36

Which form is hydrophilic?

Back 36

Ionized (can donate H+ and undergo ionization)

Front 37

What form of the drug crosses the nerve sheath to reach sodium channels in the nerve axon membrane?

Back 37

Nonionized form

Front 38

Local anesthetic potency correlates with:

Back 38

Lipid solubility

Front 39

What does the % of the drug in the nonionized form depend on?

Back 39

-pKa
-local pH

Front 40

What is pKa?

Back 40

The protonated/ionized form of the drug

Front 41

What is the formula for pH?

Back 41

pH = pKa + log(nonionized/ionized)

Front 42

What is the re-arranged formula for pH/pKa?

Back 42

log(nonionized/ionized) = pH - pKa

Front 43

What is the ratio if pH = pKa?

Back 43

Ratio = 1

Front 44

If the pKa = tissue pH, what % is in the ionized/nonionized form?

Back 44

If pKa = tissue pH (7.40):
-50% nonionized
-50% ionized

Front 45

The ___ of local anesthetics is some what ____ than _____ __.

Back 45

-pKa
-Higher
-Physiological pH

Front 46

Less than __% of the drug exists in the ____ form at _____ __.

Back 46

-50
-Nonionized
-Physiological pH

Front 47

Local tissue acidosis (i.e. ____) may further ____ the % of drug in the ____ form and compromise the quality of the block.

Back 47

-Infection
-Decrease
-Nonionized

Front 48

What is the duration of local anesthetic action limited by?

Back 48

Absorption into systemic circulation

Front 49

What is a way to increase the duration of a local anesthetic block?

Back 49

Add a vasoconstrictor to slow systemic absorption

Front 50

What are examples of vasoconstrictors used with local anesthetic?

Back 50

-Epinephrine (1:200,000)
-Phenylephrine (1:20,000)

Front 51

What is local anesthetic action terminated by?

Back 51

Absorption into circulation

Front 52

What is clearance of local anesthetics from the circulation via?

Back 52

Metabolism

Front 53

How do esters undergo clearance?

Back 53

Hydrolysis by plasma pseudocholinesterase

Front 54

How do amides undergo clearance?

Back 54

Hepatic breakdown (in liver)

Front 55

How do metabolism and toxicity affect each other?

Back 55

The rate of metabolism affects plasma levels and therefore the potential for systemic toxicity

Front 56

Is there a high possibility of toxicity with esters? Why or why not?

Back 56

No, they undergo rapid metabolism (greater chance of toxicity with amides)

Front 57

What parts of the body is topical anesthetic applied?

Back 57

Epithelium of the nose, mouth or larynx

Front 58

What agents are used for topical anesthesia?

Back 58

-Lidocaine
-Tetracaine
-Cocaine

Front 59

Why is cocaine unique?

Back 59

It causes vasoconstriction (prevent bleeding)

Front 60

How can topical anesthetics be used?

Back 60

To facilitate intubation/extubation (block sensory nerves of larynx and prevent coughing/reflex increase in BP)

Front 61

When is local infiltration used?

Back 61

Subcutaneous injection is done before placing an IV catheter

Front 62

What agents are used for local infiltration?

Back 62

-Lidocaine
-Mepivacaine
-Bupivacaine
-Ropivacaine

Front 63

What is another name for spinal block?

Back 63

Subarachnoid or intrathecal anesthesia

Front 64

What is done during a spinal block?

Back 64

Injection of local anesthetic into the lumbar subarachnoid space

Front 65

How do spinal anesthetics work (anatomically)?

Back 65

Local anesthetics act on the spinal nerve roots

Front 66

What agents are used for spinal anesthesia?

Back 66

-Tetracaine
-Lidocaine
-Bupivacaine
-Ropivacaine
-Chloroprocaine

Front 67

Why would chloroprocaine be a good agent for spinal anesthesia?

Back 67

-Short duration
-Preservative-free

Front 68

Spinal block produces ____ anesthesia and at least ____ _____.

Back 68

-Sensory
-Motor impairment

Front 69

What else is blocked during spinal anesthesia and why?

Back 69

-Sympathetic preganglionic fibers
-High sensitivity to local anesthetics
-Lie near the surface of the spinal nerve bundles

Front 70

What are complications of spinal blocks?

Back 70

-Hypotension
-"Spinal headache"

Front 71

Why does hypotension occur with spinal blocks?

Back 71

Blockade of sympathetic outflow causes ventilation, pooling of venous blood, decreased venous return, and a fall in cardiac output/blood pressure

Front 72

What else is a possible side effect of spinal blocks if a certain level is reached?

Back 72

Bradycardia at levels T1-4

Front 73

Why do "spinal headaches" occur?

Back 73

Loss of CSF from needle hole in the dura

Front 74

What is done during an epidural block?

Back 74

Local anesthetic is injected into the epidural space at the lumbar level

Front 75

How does the onset of spinals and epidurals compare?

Back 75

Epidurals have to diffuse across the dura to act on spinal here roots, so the onset of sympathetic blockade is slower

Front 76

Is abrupt hypotension seen with epidurals?

Back 76

Less likely than with spinals, but hypotension is still a potential complication

Front 77

Are smaller or larger doses of local anesthetic needed for epidurals?

Back 77

Larger doses

Front 78

Which has a greater potential for systemic toxicity, epidurals or spinals, and why?

Back 78

-Epidurals
-Requires larger doses of local anesthetics with a greater chance for systemic absorption

Front 79

What agents are used for epidurals?

Back 79

-Lidocaine
-Chloroprocaine
-Mepivacaine
-Bupivacaine
-Ropivacaine

Front 80

How can systemic absorption be decreased with epidurals?

Back 80

Concomitant administration of epinephrine (1:200,000)

Front 81

How is intrathecal/intravascular injection detected with epidurals?

Back 81

-3mL test dose of local anesthetic with 1:200,000 epinephrine injected
-IV injection manifested by HR increase >20%

Front 82

What is done during a peripheral nerve block?

Back 82

Local anesthetic is injected in proximity to individual peripheral nerves or a nerve plexus

Front 83

During peripheral nerve blocks, which nerves are affected first? Last?

Back 83

-First, mantle
-Last, core

Front 84

What agents are used for peripheral nerve blocks?

Back 84

-Procaine
-Chloroprocaine
-Lidocaine
-Mepivacaine
-Bupivacaine
-Ropivacaine

Front 85

How can the duration of action of a peripheral nerve block be prolonged?

Back 85

Concomitant administration of epinephrine

Front 86

What is done during an intravenous block (Bier Block)?

Back 86

Injection of intravenous local anesthetic while blood flow to the extremity is occluded by a tourniquet

Front 87

What is the onset and duration of intravenous block (Bier Block)?

Back 87

-Rapid onset of sensory anesthesia and skeletal muscle relaxation
-Duration of action determined by time tourniquet is applied

Front 88

What agent is frequently used for intravenous block (Bier Block?)

Back 88

Lidocaine

Front 89

With intravenous (Bier) block, what agent has a low incidence of thrombophlebitis?

Back 89

Prilocaine

Front 90

With intravenous (Bier) block, what agent has a rapid metabolism, making it a favorable agent?

Back 90

Prilocaine

Front 91

The dose of prilocaine (___mg) does not cause significant ______ secondary to prilocaine metabolism.

Back 91

-200 mg
-Methemoglobinemia

Front 92

What agent is typically not used for intravenous (Bier) block due to high incidence of thrombophlebitis?

Back 92

Chloroprocaine

Front 93

Bupivacaine is avoided for intravenous (Bier) blocks, why?

Back 93

Potential cardiotoxic effects when circulation to the limb is restored

Front 94

What are other uses for local anesthetics (i.e. lidocaine)?

Back 94

-Prevention/treatment of arrhythmias
-Anticonvulsant

Front 95

What causes systemic toxicity?

Back 95

-Excess plasma levels of the drug
-Result of inadvertent intravascular injection (epidural or peripheral nerve block) or excessive absorption

Front 96

What is the first symptom of systemic toxicity?

Back 96

Numbness of tongue/mouth

Front 97

What kind of nerve block has a high potential for systemic toxicity? Why?

Back 97

-Intercostal
-Highly vascular area

Front 98

What are CNS adverse effects of local anesthetics?

Back 98

-Restless, vertigo, tinnitus, visual blurring, slurred speech
-Skeletal muscle twitching, seizure
-Coma, respiratory/cardiac arrest

Front 99

Which side effects of toxicity are greater, CNS or cardiovascular?

Back 99

-CNS, the cardiovascular system is more resistant to local anesthetic toxicity

Front 100

What is a major CV side effect of toxicity?

Back 100

-Hypotension
-Due to arteriolar vasodilation (decreased peripheral resistance) and myocardial depression (decreased cardiac output)

Front 101

How do CV side effects form toxicity occur?

Back 101

Local anesthetics can block myocardial sodium channels

Front 102

What agent has the highest likelihood of cardiotoxicity?

Back 102

Bupivacaine

Front 103

What agent has LESS cardiotoxicity?

Back 103

l-bupivacaine or ropivacaine

Front 104

What is LipidResuce?

Back 104

IV administration of a lipid emulsion for treatment of severe systemic local anesthetic toxicity (i.e. cardiac arrest unresponsive to conventional therapy)