Pharm2 - Local Anesthetics (Spring 2012)

Front 1

3 structures of local anesthetics

Back 1

- Benzene ring (lipophilic)
- Intermediate carbon group (ester or amide)
- Quaternary Amine (hydrophilic)

Front 2

Esters vs. Amides
(Metabolism, DOA, allergic potential)

Back 2

Ester: (one I)
- Meta --> cholinesterase
- DOA --> short
- Allergy --> Yes

Amide: (two I's)
- Meta --> hepatic, CYP450
- DOA --> long
- Allergy --> No

Front 3

Are there cross allergies between locals?

Back 3

No

Front 4

Which is an ester or amide?
Procaine
Prilocaine
Articaine
Tetracaine
Chloroprocaine
Mepivacaine
Benzocaine
Bupivicaine
Lidocaine

Back 4

Procaine --> Ester
Prilocaine --> Amide
Articaine --> Amide
Tetracaine --> Ester
Chloroprocaine --> Ester
Mepivacaine --> Amide
Benzocaine --> Ester
Bupivacaine --> Amide
Lidocaine --> Amide

Front 5

Which link is this?
NH-C=O

Back 5

Amide

Front 6

Which link is this?
O-C=O

Back 6

Ester

Front 7

Which form is ionized, a quaternary or tertiary amine?

Back 7

quaternary
Ionized & hydrophilic

Front 8

What two factors determine the ionization of a local anesthetic?

Back 8

The body's pH and the pKa of the drug

Front 9

Which form of the LA will penetrate the nerve epineurium (ionized or nonionized)?

Back 9

Nonionized

Front 10

What fraction of local anesthetics (ionized or nonionized) block Na-receptors?

Back 10

The ionized form

Front 11

How do local anesthetics work?

Back 11

They block Na-channels

Front 12

What is the proposed primary site on a neuron (based on N&P) in which LAs exert their action?

Back 12

Nodes of Ranvier

- limited diffusion barriers to penetrate and high concentration of Na-channels

Front 13

Local anesthetics have a greater tendency to bind Na-receptors in what state (open or closed)? How is this clinically relevant?

Back 13

Open/inactive

Prevents the channel from returning to the resting/repolarized state --> blockade

Front 14

What is the relationship between IV local anesthetics and Substance P?

Back 14

LAs prevent the binding of substance P to its spinal cord receptors, thereby blocking nociceptive responses.

Front 15

Absorption of LA marks the (onset/offset) of the drug action?

Back 15

Offset

Front 16

pKa of a LA determines what?

Back 16

Onset of action

Front 17

Low pKa has a (slow or fast) onset? High pKA?

What's the general rule of thumb w/ pKA (except what Rx)?

Back 17

Low pKa = more nonionized = more lipid soluble = faster onset
High pKa = more ionized = more h2o soluble = slower onset

Closer the pKa is to physiological pH (7.4), the faster the onset of action. Chloroprocaine.

Front 18

Local anesthetics are acids or bases?

Back 18

Basic

Front 19

What Rx is the exception to the pKa rule & why?

Back 19

Chloroprocaine; despite high pKa of 8.7, and high ionization, Rx is given in high concentration and thus overcomes the ionization rule.

Front 20

How does PB affect the effect of LA since Rx does not bind proteins?

Back 20

Higher PB%, the longer the DOA 2* greater receptor affinity

Front 21

Amide with the fastest onset? Longest duration?

Back 21

Mepivacaine fastest
Bupivacaine

Front 22

Onset of action for Amides (Fastest to slowest)

Back 22

(Fastest onset --> slowest onset for Amides)
Mepivacaine
Etidocaine
Lidocaine &
Prilocaine
Bupivacaine
Ropivacaine

Front 23

DOA for Amides (shortest to longest)

Back 23

(Shortest to longest DOA - Amides)
Prilocaine
Lidocaine
Mepivacaine
Etidocaine
Ropivacaine
Bupivacaine

Front 24

Onset of action for Esters (fastest to slowest)

Back 24

Chloroprocaine
Tetracaine
Cocaine
Procaine

Front 25

DOA of Esters (shortest to longest)

Back 25

Procaine
Tetracaine
Cocaine

Front 26

Overall, which class of local anesthetics works faster?

Back 26

Amides

Front 27

What two factors influence the sensitivity of nerve fibers to LAs?

Back 27

nerve diameter & myelination

Front 28

What are the three types of nerve fibers? Largest? Fastest? Slowest?

Back 28

A, B, C

A-alpha is largest (15-20microns) and fastest
C is smallest (1-2microns) and slowest

Front 29

Which nerve fibers are unmyelinated?

Back 29

C fibers

Front 30

What nerve fibers are responsible for motor functions?

Back 30

A-alpha fibers

Front 31

What nerve fibers are responsible for proprioception?

Back 31

A-alpha fibers

Front 32

What nerve fibers are responsible for reflexes/muscle tone?

Back 32

A-gamma fibers

Front 33

What nerve fibers are responsible for touch & pressure sensation?

Back 33

A-beta fibers

Front 34

What nerve fibers are responsible for pain and temperature sensation?

Back 34

A-delta fibers and C-fibers

Front 35

What nerve fibers constitute the preganglionic autonomic nerves?

Back 35

B fibers

Front 36

What is order of nerve blockade? (first to last)

Back 36

C-fibers, B-fibers, A-delta, A-gamma, A-beta and then A-alpha

Front 37

Which nerve fibers are least resistant to blockade?

Back 37

C-fibers

Front 38

The potency of an LA is strongly related to what Rx characteristic?

Back 38

Lipid solubility

Front 39

What is the order of sensation loss with nerve blockade? (first to last)

Back 39

- Loss of autonomic function
- loss of superficial pain perception
- loss of touch
- loss of temperature
- loss of motor function
- loss of proprioception

Front 40

All LAs, except these two, produce relaxation of vascular smooth muscle/vasodilation?

Back 40

Cocaine & Ropivacaine

Front 41

What nerve fibers are associated with vasomotor function?

Back 41

B-fibers

Front 42

All LAs need the additional of this vasoconstrictor to prolong DOA, except for Cocaine & Ropivicaine? Why?

Back 42

Epinephrine, because Cocaine & Ropivicaine have innate vasoconstrictive properties

Front 43

Vascularity of injection sites (most --> least)

"BIICEPSS"

Back 43

**higher vascularity, quicker absorption**

Blood
Intraracheal
Intercostal
Caudal
Epidural
Brachial Plexus
Sciatic
Subcutaneous

Front 44

What are the four reasons to add epinephrine to local anesthetics?

Back 44

1.) IV marker
2.) homeostasis
3.) Increases DOA
4.) reduces systemic toxicity (by slowing absorption & decreasing drug levels)

Front 45

What is the concentration of Epinephrine used with local anesthetics?

Back 45

1:200,000 (5mcg/mL)

Front 46

Why does ion trapping occur?

Back 46

Changes in pH in relationship to the Rx's pKa --> changes the ionization of the drug

Front 47

What are five ways in which ion trapping may occur?

Back 47

- LAST 2* hypoxemia
- Fetal accumulation (fetal pH < maternal pH)
- Acidotic tissue (decr lipid solubility)
- Carbonation (makes inside of nerve more acidotic)
- Alkalization (makes outside of nerve more basic, nonionized)

Front 48

The addition of Bicarb to local anesthetics provides what patient-centered care effect?

Back 48

Decreases the sting of infiltration of the Rx

Front 49

Epi will extend the DOA of which agents (shorter or longer acting agents)?

Back 49

Shorter acting agents will be most benefited by the additional of Epi

Front 50

Adding Epi to spinal anesthesia will (speed/prolong) onset of action?

Back 50

prolongs

Front 51

Adding Epi to LAs will (incr/decr) peak plasma concentration of the drug?

Back 51

Decrease

Front 52

Chloroprocaine
Trade name
Max safe dose
pKa - onset
PB% - DOA

Back 52

Chloroprocaine (Nesacaine)
w/ 3% --> 14mg/kg
pKa 8.7
PB% n/a

Front 53

Procaine
Trade name
Max safe dose
pKa - onset
PB% - DOA

Back 53

Procaine (Novocaine)
w/ 1% --> 14mg/kg
pKa 8.9
6% PB

Front 54

Priolocaine

Trade name
Max safe dose
pKa - onset
PB% - DOA

Back 54

Prilocaine (Citanest)
w/ 3% --> 8.5mg/kg
pKa 7.9
55% PB

Front 55

Lidocaine

Trade name
Max safe dose
pKa - onset
PB% - DOA

Back 55

Lidocaine (Xylocaine)
w/ 1-2% --> 7mg/kg
pKa 7.9
64% PB

Front 56

Mepivacaine

Trade name
Max safe dose
pKa - onset
PB% - DOA

Back 56

Mepivacaine (Carbocaine)
w/ 2% --> 7mg/kg
pKa 7.6
77% PB

Front 57

Ropivacaine

Trade name
Max safe dose
pKa - onset
PB% - DOA

Back 57

Ropivacaine (Naropin)
w/ 0.75% --> 3.5mg/kg
pKa 8.1
94% PB

Front 58

Bupivacaine

Trade name
Max safe dose
pKa - onset
PB% - DOA

Back 58

Bupivacaine (Marcaine, Sensorcaine)
w/ 0.75% --> 3.2mg/kg
pKa 8.1
95% PB

Front 59

Tetracaine

Trade name
Max safe dose
pKa - onset
PB% - DOA

Back 59

Tetracaine (Pontocaine)
w/ 1% --> 1mg/kg
pKa 8.5
95% PB

Front 60

Etidocaine

Trade name
Max safe dose
pKa - onset
PB% - DOA

Back 60

Etidocaine
pKa 7.7
95% PB

Front 61

Cocaine

Trade name
Max safe dose
pKa - onset
PB% - DOA

Back 61

Cocaine
w/ 4% max 200mg (3mg/kg)
pKa 8.5
98% PB

Front 62

What is LAST?

Back 62

Local Anesthetic Systemic Toxicity

Front 63

What are the s/s of therapeutic doses of LA? Therapeutic dose range?

Back 63

lightheadedness, tinnitus, circumoral & tongue numbness

<5mcg/mL

Front 64

What is the progression of s/s of LAST?

Back 64

lightheadedness, dizziness, tinnitus, circumoral & tongue numbness --> visual disturbances (diplopia), muscular twitching (fasciculations), convulsions/seizures, unconsciousness/coma, resp arrest & CV depression

Front 65

Why do patients experience CNS excitation during LAST?

Back 65

Disinhibition

Front 66

LAST spontaneously subsides 2* to what pharmokinetic phenomenon?

Back 66

Redistribution of drug from brain to periphery

Front 67

How are esters metabolized?

Back 67

Hydrolysis via plasma cholinesterase in plasma, RBC & liver

Front 68

How are amides metabolized?

Back 68

CYP450 enzyme in the liver

Front 69

Which local anesthetic class is more toxic, esters or amides?

Back 69

Amides

Front 70

Which ester is most toxic?

Back 70

Tetracaine

Front 71

What patient population would you be cautious in administering ESTER local anesthetics to?

Back 71

Patients who have liver disease or reduced plasma cholinesterase levels

Front 72

What amide has the slowest rate of hepatic metabolism?

Back 72

Bupivacaine

Front 73

The rate of elimination of local anesthetics is based on what two hepatic centered functions?

Back 73

Enzyme activity
Hepatic blood flow

Front 74

What patient populations should receive reduced AMIDE anesthetic doses?

Back 74

Hepatic or circulatory dysfunction

Front 75

Greater spread & depth of local anesthetics in pregnant women is attributed to this...?

Back 75

Increased progesterone levels in CSF

Front 76

What is unique about Bupivacaine toxicity?

Back 76

Preferential binding w/ myocardial protein --> cardiac arrest, no CNS symptoms

Front 77

LA potency is determined by...

Back 77

lipid solubility

Front 78

LA onset is determined by...

Back 78

pKa

Front 79

DOA of LA is determined by...

Back 79

% Protein binding

Front 80

When will LAST occur? when will it resolve?

Back 80

During injection (within 1min); resolves w/ redistribution ~ 5-10min

Front 81

How can you treat LAST, aside from ABCs?

Back 81

IV lipid rescue

Front 82

Primary CNS s/s of LAST?

Back 82

Seizure

Front 83

Primary CV s/s of LAST?

Back 83

Bradycardia/Asystole

Front 84

With LAST, 45% of the time you will only see _____ s/s, but the other 44% of the time you'll see _______. It is rare that you would only see this effect_____.

Back 84

45% of time you will only see CNS s/s
44% of time you'll see CNS w/ CV progression
11% of time you'll only see CV arrest

Front 85

How to prevent LAST:

AbCDEFG

Back 85

- Aspirate before each injection (A)
- Injections should be incremental & encompass 1 circulation time (C)
- Use lowest effective dose (D)
- Use IV marker (Epi) (E)
- Fixed needle approach (F)
- US guidance (G)

Front 86

What dose of Epi should you use in Adults? Children?

Back 86

Adults 10-15mcg/mL
Children 0.5mcg/mL

Front 87

Convulsions following injection of a local anesthetic, is this indicative of...? Headache or tachycardia following injection of a LA are indicative of ... ?

Back 87

Convulsions --> LAST
HA, tachycardia --> reaction to injection

Front 88

What meds would you use to treat a seizure following injection w/ LA?

Back 88

Benzos - ideal
Sux - will stop seizure, but not cross BBB
Propofol - avoided in CV compromise

Front 89

What drugs should you NOT administer in LAST?

Back 89

Avoid Vasopressin, CCB, B-blockers, Lidocaine

Front 90

When should you start lipid emulsion therapy?

Back 90

at first signs of LAST after airway management

- 1.5mL/kg 20% lipid emulsion
- infuse 0.25mL/kg/min for 10min, repeat once or twice @ 0.5ml/kg
- Max 10mL/kg over 30 min

Front 91

Factors that increase the likelihood of LAST

Back 91

- advanced age
- heart failure
- ischemic heart disease
- conduction abnormalities
- metabolic disease
- liver disease
- low plasma protein concentration
- metabolic/respiratory acidosis
- medications that inhibit Na-channels

Front 92

Toxicity can be delayed for up to ____ min?

Back 92

30min, seizures may reoccur

Front 93

Epidural anesthesia (does/does not) adversly affect uterine tone.

Back 93

does not

Front 94

True/False: Repeated epidural injection of lidocaine may result in greater accumulation of drug in preeclampsia than healthy pregnant women.

Back 94

True

Front 95

Are local anesthetics teratogenic?

Back 95

No

Front 96

Who has a longer amide elimination half-life, adults or babies? Why?

Back 96

Newborns, greater blood volume

Front 97

Which LA additive posses the greatest increased risk of hypotension w/ epidural anesthesia?

Back 97

Bicarb
Alkalinization

Front 98

The bioavailability of hydro-______ drugs is greater than that of hydro-_____ drugs.

Back 98

hydrophilic bioavailability is greater

Front 99

The most common side affects of neuraxial opioid administration...

Back 99

N/V, pruritus

Front 100

The most serious compllication of neuraxial opioid administration is...

Back 100

fetal bradycardia & maternal respiratory depression

Front 101

Can you get additive toxicity when you combine local anesthetics?

Back 101

Yes

Front 102

Do pregnant women need more or less local anesthesic?

Back 102

less

Front 103

What does EMLA cream consist of?

Back 103

Lidocaine & Priolocaine

Front 104

What does LET consist of?

Back 104

Lidocaine, epinephrine, tetracaine

Front 105

What does TAC consist of?

Back 105

Tetracaine, epinephrine, cocaine

Front 106

Cetocaine spray can cause what adverse effect?

Back 106

Methemoglobinemia

Front 107

What is the recommended safe dose of TAC?

Back 107

3-4mL for adults
0.05mL/kg for children

Front 108

What is Oraverse? How does it work?

Back 108

Phentolamine mesylate (alpha-antagonist), reverses dental anesthesia via vasodilation

Front 109

Local reactions to LAs include...?

Back 109

pain
hematoma
abscess
Ecchymosis
tissue necrosis
neurotoxicity

Front 110

Per Nagelhout's text, circumoral numbness (is/is not) a result of CNS toxicity.

Back 110

IS NOT; result of extracellular extravasation of the drug in the tongue & mouth

Front 111

True/False: The potential for a LA to produce CNS toxicity relates to its potency.

Back 111

True

Front 112

What physical state (acidosis/alkalosis) increases the propensity for toxicity?

Back 112

Acidosis, resulting in...Vasodilation, dcr intracellular pH & reduction of plasma protein binding

Front 113

What EKG changes will be seen with LA administration?

Back 113

Incr in PR and wide QRS

Front 114

What effect do LA have on the pacing threshold?

Back 114

Increase the pacing threshold

Front 115

What makes esters more allergy-sensitive?

Back 115

Derivatives of para-aminobenzoic acid (PABA) and metabolized to PABA

Front 116

What is the preservative of amide LAs (which may produce RARE allergic reactions)?

Back 116

methylparaben

**PABA may be found in preservative-free/multidose AMIDE LA vials, so beware of allergic potential in these cases**

Front 117

How do you treat methemoglobinemia?

Back 117

Methylene blue

Front 118

FYI -->
LA are CNS depressants, however if plasma levels increase significantly, both inhibitory and facilitory pathways are depressed and CNS depression will occur.

Back 118

FYI -->
LA are CNS depressants, however if plasma levels increase significantly, both inhibitory and facilitory pathways are depressed and CNS depression will occur.

Front 119

Priolocaine is contraindicated in which patient populations?

Back 119

Anemia, OB (2* fetal hemoglobin)

Front 120

Is cocaine a sympatholytic or sympathomimetic?

Back 120

Sympathomimetic

Front 121

What is so awesome about Ropivacaine?

Back 121

It is an analogue of Bupivacaine, but less cardiotoxic

Less potent then Bup and shorter DOA, with reduced CV/CNS toxicity

Less motor blockade

Front 122

LA with the fastest onset?

Back 122

Chloroprocaine

Front 123

LA with the slowest onset?

Back 123

Procaine

Front 124

LA with the shortest DOA?

Back 124

Chloroprocaine

Front 125

What is the FIRST indication that a block is taking effect?

Back 125

Drop in BP 2* autonomic block

Front 126

FYI -->
The first nerve fibers to be blocked are the smallest, and these are also the last to recover.

Back 126

FYI -->
The first nerve fibers to be blocked are the smallest, and these are also the last to recover.