Pharmacology (Locals)

Question 1

Locals are drugs that produce a ___ interruption of neural impulses along __ and ___ pathways.

Answer 1

1. Reversible
2. sensory
3. Motor

Question 2

A nerve membrane is composed mostly of

Answer 2

biphospholipids with NA+ channels

Question 3

nerve membranes are found where in unmyelinated nerves?

Answer 3

all throughout

Question 4

nerve membranes are found where in myelinated nerves?

Answer 4

nodes of Ranvier

Question 5

How many nodes are Ranvier need to be blocked to inhibit nerve transmission

Answer 5

2 successive nodes

Question 6

What nerve fibers are commonly effected first?

Answer 6

B fibers

Question 7

Type B Fibers

1. Function
2. Diameter
3. Myelinated?
4. Conduction velocity

Answer 7

1. Pregangloinic autonomic

2.

Question 8

A fiber Alpha function

Answer 8

proprioception & motor

Question 9

A fiber Beta function

Answer 9

Touch & pressure

Question 10

A fiber Gamma function

Answer 10

muscle spindles

Question 11

Will local anesthetics have any impact on closed ion channels?

Answer 11

No, they do not work when channels are closed

Question 12

Where do locals prevent neural action?

Answer 12

Prevent the opening of NA+ channels, thereby preventing the membrane potential from reaching threshold potential.

Question 13

H gate?

Answer 13

Where locals are inactivated

Question 14

Most commonly administered Ester Local?

Answer 14

Procaine (Novocaine)

Question 15

What do ester locals yeild?

Answer 15

PABA

Question 16

What is PABA? Why can it be a problem?

Answer 16

Para-amnio benzoic acid - is excreted UNCHANGED in the urine.

Is responsible for most producing most allergic reactions with Esters

Question 17

Are there Esters in the CSF?

Answer 17

No

Question 18

What specifically causes ester elimination?

Answer 18

plasma cholinesterase deficiency (genetic OR acquired)

Question 19

What sets cocaine apart from other Ester locals?

Answer 19

partially metabolized by N-methylation and ester hydrolysis in the liver, also partially unchanged in the urine.

Question 20

Cocaine - why is it a problem?

Answer 20

Causes reuptake of norepineprhine by adrenergic nerve terminal, causing and increase in SNS tone.Board Q

Question 21

What are the amide locals? How can you tell easily?

Answer 21

Lidocaine (Xylocaine)
Bupivicaine (Marcaine)
Prilocaine (Citanest)
Ropivicaine (Naropin)

Question 22

Most commonly administered local?

Answer 22

Bupivicaine (Marcaine)

Question 23

How are Amides metabolized? What is significance?

Answer 23

microsomal enzymes in Liver, liver failure = increased DOA as well as cumulative effects.

Question 24

Prilocaine - Whats the deal?

Answer 24

metabolized to Ortho-tulidine (O-tulidine! O-tulidine!)

- an oxidizing compound which converts hemoglobin to methemoglobin.

Question 25

What is methemoglobinemia and why is it a problem? What will clinical presentation be? What do you treat it with?

Answer 25

Does not carry O2 well, leads to hypoxia, cyanosis. (blue) Tx with 02 and methelyne blue 1-2mg/kg, 7 mg/kg max

Question 26

pKa

Answer 26

determines ONSET since locals are WEAK BASES, prepared in acid solutions with slightly elevated pKa values above physiologic pH

Question 27

Lipid solubility

Answer 27

POTENCY - and to a lesser degree DOA

Question 28

protein binding

Answer 28

Duration, connected to lipid solubility (increased DOA due to the difficulty it has dissocating from NA+ channel) *chloroprocaine possessed virtally NO protein binding, therefore short DOA*

Question 29

Onset is delayed if?? Why??

Answer 29

Onset is delayed if: drugs's pKa is further from 7.4 pH of environment injected into is

Question 30

pKa of Common Locals.... 1. Bupiv 2. Lido 3. Prilo 4. Ropiv 5. Tetra 6. Cocaine 7. Chloroprocaine

Answer 30

1. 8.1 2. 7.9 3. 7.9 4. 8.1 5. 8.5 6. 8.7 7. 8.7

Question 31

Protein Binding of Locals short acting locals: intermediate acting: long acting:

Answer 31

short: procaine, chloroprocaine intermediate: (LMP) lidocaine, mepivacaine, prilocaine long: BET (you can BET on them!) bupivacaine (and rop) etidocaine tetracaine

Question 32

Progression of blockade

Answer 32

ATP, TP, MVP (Energy, Toilet paper, MVP) | Autonomic, temperature, pain, touch, pressure, motor, proprioception

Question 33

LAST

Answer 33

board loves this Bupivicaine = cardiotoxicity - goes from good to code very quickly lidocaine = more progression, more of a clue

Question 34

LAST: Plasma [ ] of LA:

Answer 34

r/t volume of dose, vascularity of injection site (airway, intercostal, interplueral, caudal, BP, peripheral, spinal) use of EPI: less systemic absorption, probably quicker onset

Question 35

Epi What does it do? Where to avoid?

Answer 35

produces vasoconstriction Finger, nose, toes, hoze,

Question 36

LA Toxicity Early symptoms

Answer 36

``` Circumoral numbness Tinitus vertigo, blurred vision drowsiness restlessness, muscle twitching metalic taste in mouth ```

Question 37

LA Toxicity Late symptoms What is TX??

Answer 37

LOC -> Coma seizures (dangerous - CMRO2 is not lowered by LA) apnea CV depression TX is supportive in nature.

Question 38

LAST Cardiac: What are s/s? Why? Which local most implicated?

Answer 38

Interaction with cardiac NA+ channels ``` first manifested as hypotension depression of conduction and automaticity depression of contractility dysrhythmias high grade A-V block ``` BUPIVICAINE is selectively cardiotoxic, magnified in parturient

Question 39

Intralipid How does it work? What is %? What is dose?

Answer 39

Lipids accelerate the removal of local from circulation 1.5ml/KG (weight based) inrused over first minute repeat every 3-5 minutes to maximum of 3 ml/kg continuous = 0.25 ml/kg/min - until HEMODYNAMIC Recovery-

Question 40

What is ion trapping? what block is it most common? What locals are most common for this to occur with?

Answer 40

local crosses placenta and becomes more ionized in relatively acidic fetus "becomes trapped" - may cayse systemic toxicity in fetus *noted with paracervical blocks* less likely to happen with esters due to rapid metabolism, also drugs HIGHLY protein bound more slowly cross barrier. Most common Locals: Mepivicaine & prilocaine (not highly protein bound)

Question 41

Why specifically what does adding NaHCO3 do to LAs?

Answer 41

``` Adding NaHCO3 (Bicarb) will raise the pH of the solution. This speeds onset of block because more of the LA exists in the unionized form (AKA buffering) lidocaine -> 1mEq/10 ml of local bupivicaine -> 0.1 mEq/20 ml of local (will PPT with higher volume of bicarb) ```

Question 42

Active metabolites of Lidocaine?

Answer 42

MEGX - monothylglycinexylidide | GX - glycinexylidide

Question 43

EMLA cream is what?

Answer 43

eutectic mixture of lidocaine and prilocaine 5% EMLA cream topically applied for 45 minutes or more greatly reduces the pain associated with venipuncture in the pediatric population methemoglobinemia possible but rare (topical sprays like cetacaine can be a problem in GI suites)