Local Anesthetics - Duan

Question 1

What are the characteristics of local anesthetics?

Answer 1

1. applied locally
2. produce loss of sensation to pain in a specific area of the body
3. no loss of consciousness
4. mechanism - block axonal conduction in nerves when applied in appropriate concentrations
5. mechanism is reversible

Question 2

Which local anesthetics are esters?

Answer 2

1. cocaine
2. procaine
3. tetracaine
4. benzocaine

Question 3

Which local anesthetics are amides?

Answer 3

1. lidocaine
2. etidocaine
3. bupivacaine
4. levobupivacaine
5. mepivacaine
6. prilocaine

Question 4

What group is common to all of the ester anesthetics?

Answer 4

They all have a lipophilic group.

Question 5

How do the ester anesthetics differ in duration of action?

Answer 5

1. cocaine - medium duration
2. procaine (novocain) - short duration of action
3. Tetracaine - long duration
4. benzocaine - topical use only

Question 6

Describe cocaine.

Answer 6

1. an ester
2. hydrolyzed very rapidly in blood
3. a potent sympathomimetic and vasoconstrictor
4. a potent CNS stimulant
5. very addictive
6. behavioral toxicity similar to paranoid schizophrenia
7. fatalities from arrhythmias (V-fib), myocardial infarction or seizures

Question 7

What enzyme is responsible for hydrolyzing cocaine in the blood?

Answer 7

Pseudocholinesterase.

Question 8

What properties of cocaine make it addictive?

Answer 8

1. causes euphoria
2. causes CNS stimulation
3. reduces fatigue
4. perceived increase in mental ability

Question 9

Describe Procaine.

Answer 9

1. brand name = novocaine
2. the first synthetic local anesthetic - a derivative of cocaine
3. slow onset
4. short duration
5. less potent than cocaine
6. higher potential to cause allergic reactions
7. sympathomimetic - causes release of adrenaline
8. increases heart rate and feelings of nervousness

Question 10

Describe chloroprocaine.

Answer 10

1. also called nesacaine
2. slightly more potent than procaine
3. shorter duration of action than procaine

Question 11

Describe Tetracaine.

Answer 11

1. also called Pontocaine
2. 10X more potent than procaine
3. slower onset and longer duration of action than procaine

Question 12

Describe Benzocaine.

Answer 12

1. also called americaine, ora-jel and solarcaine
2. does not contain the terminal hydrophilic amine group so only slightly soluble in water
3. slowly absorbed with prolonged duration
4. only used topically

Question 13

What structural groups are common to the amide anesthetics?

Answer 13

They all have a lipophilic group and an amine substituent group.

Question 14

What are the duration of action of the amide anesthetics?

Answer 14

1. lidocaine - medium duration
2. mepivacaine - medium duration
3. bipuvacaine - long duration
4. etidocaine - long duration
5. prilocaine - medium duration
6. rapivacaine - long duration

Question 15

Describe Lidocaine.

Answer 15

1. brand name = Xylocaine
2. an amine
3. inactive drug is activated in liver by amidase
4. little allergic reaction
5. 2-3 X more potent than procaine
6. rapid onset of action
7. longer duration of action when combined with epinephrine - increases half life
8. clinically versatile

Question 16

Describe how Lidocaine is activated and inactivated in the liver.

Answer 16

The inactive form undergoes N-dealkylation via amidase to become monoethylglicexylidide or MEGX. MEGX undergoes hydrolysis to the inactive glycine xylidide by a liver cytochrome P450 when inactivated.

Question 17

Name some clinical applications of Lidocaine.

Answer 17

1. can be used topically
2. used as a peripheral nerve block
3. used in infiltration anesthesia
4. used as spinal anesthesia
5. used in epidural anesthesia
6. used as an anti- arrhythmia agent

Question 18

Describe Mepivacaine.

Answer 18

1. also called carbocaine
2. pharmacologically similar to lidocaine
3. coadminister with epinephrine to prolong duration of action
4. effective without a vasoconstrictor
5. can be used in elderly patients and those with cardiovascular disease
6. not useful in obstetrics because of prolonged metabolism in fetus and neonate - increases risk of toxicity

Question 19

Describe Bupivacaine.

Answer 19

1. also called Marcaine
2. 10X more potent than procaine
3. long duration of action - about 24 hours

Question 20

Describe Ropivacaine.

Answer 20

1. long duration of action like Bupivacaine

2. slightly less potent than Bupivacaine

Question 21

What is the MOA of pain?

Answer 21

1. free nerve endings are stimulated
2. upon stimulation, sodium enters the neuron and causes depolarization of the nerve and initiation of an AP
3. the AP is propagated down the nerve to the CNS where it is interpreted as pain

Question 22

Describe the MOA of local anesthetics.

Answer 22

Local anesthetics block the inward sodium current by blocking he voltage gated sodium channels in neuronal membranes that are responsible of signal propagation, the membrane of the postsynaptic neuron will not depolarize and will thus fail to transmit an AP.

Question 23

What is the concept of differential block?

Answer 23

1. preferentially block small-diameter, unmyelinated nerve fibers first. These are c-fibers for pain and temp stimuli.
2. large diameter myelinated nerve fibers appear to be less susceptible and require greater doses to achieve neural blockade.
3. size is more important than myelination as a factor for anesthesia

Question 24

Describe the order of pain blockage in reference to nerve fibers.

Answer 24

Local anesthetics work on certain nerve fibers more preferentially than others.

Small, unmyelinated nerve fibers > small, myelinated autonomic fibers > large, myelinated autonomic fibers.

Question 25

What is the order of sensory loss with reference to anesthetics?

Answer 25

Pain is lost first, temperature second, touch third and pressure sensation is lost last.

Question 26

Describe the routes of administration of local anesthetics.

Answer 26

1. regional - inject into area of nerved fibers to be blocked 2. topical - put onto surface - extensively used on mucous membranes such as nasal mucosa, mouth, urethra and wound margins 3. infiltration - injection under the skin. Often used with epinephrine which causes vascular constriction. For use when there is a need to localize drug action. Minimally effective concentration should be used to avoid toxicity.

Question 27

Where are anesthetics injected when used for spinal block?

Answer 27

Into the subarachnoid space.

Question 28

Where are anesthetics injected when used for an epidural?

Answer 28

Administered outside of subarachnoid space but diffuses into it.

Question 29

Where are anesthetics injected when used for a caudal block?

Answer 29

Epidural space.

Question 30

What is a paravertebral nerve block?

Answer 30

?

Question 31

Describe a spinal nerve block.

Answer 31

1. injection into subarachnoid space 2. spread of anesthetics can be controlled by increasing density of anesthetic solution with 10% solution of glucose and by tilting the patient 3. used for upper abdominal surgeries 4. problems - if autonomics are blocked then there is a loss of sympathetic tone and hypotension can result

Question 32

Describe a Caudal block.

Answer 32

1. injected into the epidural space of sacral canal | 2. used for perinea and rectal procedures

Question 33

Describe a Caudal block.

Answer 33

1. injected into the epidural space of sacral canal | 2. used for perinea and rectal procedures

Question 34

Describe an Epidural block.

Answer 34

1. administered outside but diffuses into subarachnoid space | 2. used in labor and delivery and cesarean section

Question 35

What are some factors that affect the reaction of local anesthetics?

Answer 35

1. lipid solubility of the anesthetic 2. pH 3. blood flow

Question 36

Describe how lipid solubility affects reaction of local anesthetics.

Answer 36

The higher the lipid solubility of the anesthetic, the faster the nerve penetration, blockage of sodium channels and onset of action will be.

Question 37

Describe how pH influences reaction of local anesthetics.

Answer 37

1. The uncharged or unionized form of a drug can cross nerve membranes and gain access to their site of action to block sodium channels 2. log(cationic form/uncharged form)=pKa-pH 3. all local anesthetics are weak bases with pKa of 8-9 4. decreases in pH shifts equilibrium toward ionized form, delaying the penetration of the drug and thus its onset of action. Decreases in tissue pH can occur in infected tissues

Question 38

Describe how blood flow can affect the reaction of local anesthetics.

Answer 38

Vasoconstriction can be used to limit vasodilation activity of a local anesthetic. This causes delay of systemic absorption and keeps the anesthetic in place for a longer period and prolongs the action of the drug locally. Epinephrine can be sued to causes vasoconstriction.

Question 39

Name a factor that affects the metabolic degradation of a local anesthetic.

Answer 39

Degradation will vary depending on whether a compound has an ester or amide linkage.

Question 40

Describe the metabolic degradation of esters.

Answer 40

Esters are extensively and rapidly hydrolyzed in blood by plasma pseudocholinesterase and also by liver esterase's. The product is paraaminobenzoic acid or PABA.

Question 41

Describe the metabolic degradation of amides.

Answer 41

Amides undergo N-dealkylation followed by hydrolysis in the liver via cytochrome P450.

Question 42

Describe the order of degradation of some amide anesthetics.

Answer 42

Some anesthetics are degrades more quickly than others. Prilocaine>etidocaine>lidocaine>mepivacaine>ropivacaine>bupivacaine>levobupivacaine.

Question 43

What factors should be taken into account when using amide anesthetics?

Answer 43

Amide anesthetics are metabolized in the liver by cytochrome P450's. This enzyme system is affected by liver disease, reduced hepatic blood flow and are also used to metabolize other drugs also. All of these factors can affect the biotransformation of amides.

Question 44

What are the systemic pharmacological effects of local anesthetics on the CNS?

Answer 44

1. moderate doses lead to CNS stimulation | 2. very high doses lead to CNS depression

Question 45

What are the systemic pharmacological effects of local anesthetics on the cardiovascular system?

Answer 45

1. direct depressant effect on myocardium 2. reduces excitability 3. lowers contractility 4. prolongs the refractory period 5. slows conduction 6. vasodilation 7. vasocontriction - cocaine only

Question 46

Do hypersensitivity reactions occur with local anesthetics?

Answer 46

Yes. they are most common with esters since they form PABA when metabolized. PABA is a known allergen

Question 47

How is toxicity caused when using local anesthetics?

Answer 47

Toxicity is usually caused by systemic absorption and high concentration of local anesthetics due to unintentional IV injection.

Question 48

What factors are taken into account when deciding on dose or concentration of local anesthetic used?

Answer 48

1. age 2. weight 3. health of individual 4. type of solution used 5. presence of vasoconstrictor 6. maximum dose for an individual is usually between 70mg and 500 mg

Question 49

What are the affects of cardiovascular toxicity?

Answer 49

1. reduced excitability 2. reduced contractility 3. reduced conduction 4. blood vessel relaxation (leads to hypotension) or constriction (constriction with cocaine only)

Question 50

What are the affects of neurotoxicity?

Answer 50

1. light headedness 2. irritation and agitation - shivering or twitching 3. seizures 4. numbness