Week 2 Reg. Anesthesia and analgesia 2 of 4

Question 1

list 3 clinical examples related to the “inactivated state” concept of the action potential:

involving:
1 cardioplegic solutions
2 succinylcholine
3 local anesthetics

Answer 1

1 High K+ concentration in cardioplegic solution causes membrane depolarization, locks the Na+ channels in the inactive state causing heart arrest. heart muscle is in a permanent absolute refractory period.

2 Succinylcholine causes continuous depolarization of skeletal muscle motor end plate inactivating gated Na+ channels causing electrical arrest of skeletal muscle (flaccid paralysis)

3 LA interrupt nerve conduction by blocking Na+ channels (locking Na+ channels in inactivated state)

Question 2

in the action potential what is MOST responsible for resting membrane potential

Answer 2

Potassium efflux (through “leaky” channels)

Question 3

what is responsible for depolarization of the axon in the action potential

Answer 3

diffusion of Na+ ions INTO the cell

Question 4

what is responsible for re-polarization of the axon in the action potential

Answer 4

diffusion of K+ ions OUT of the cell

Question 5

what causes the absolute refractory period in the action potential

Answer 5

When the Na+ channel is in the inactivated state, another action potential cannot be fired- the neuron is in the absolute refractory period

Question 6

How would K+ disorders affect the action potential?

Hypokalemia vs Hyperkalemia

Answer 6

Hypokalemia: increases the diffusion gradient causing hyperpolarization which causes muscle weakness

Hyperkalemia decreases the diffusion gradient causing depolarization. AP does not occur because Na+ channels are inactivated and closed by depolarization. Without AP , there is no contraction causing muscle weakness.

Question 7

describe local anesthetics (molecular level)

Answer 7

Lipophilic group (benzene ring) separated from a hydrophilic group (tertiary amine) by an intermediate chain that includes an ester or amide linkage

Question 8

examples of amide LAs

Answer 8

Bupivacaine, etidocaine, lidocaine, mepivacaine, prilocaine, ropivacaine

Question 9

examples of ester LAs

Answer 9

Chloroprocaine, cocaine, procaine, tetracaine

one i’d ester

Question 10

mechanism of action of LAs

Answer 10

Blocks voltage sensitive Na+ channels from inside of neuron
Inhibit conduction of impulses from periphery to CNS
Produces transit loss of sensory, motor and autonomic function

Question 11

what form of a LA enters the nerve (crosses the membrane)

Answer 11

the unionized form which is lipid soluble

The lipid soluble form readily diffuses across neural sheath (epineurium) and passes through the nerve membrane

Question 12

what happens once the LA crosses the nerve membrane (MOA of LA)

Answer 12

Once the LA gains access to the cytoplasmic side of the NA channel (inside the axoplasm), the drug re-equilibrates and the charged cation (ionized form (LA+), binds to the receptors inside the sodium channel

Question 13

where are voltage-gated Na+ channels found

Answer 13

voltage-gated Na+ channels are found ONLY in the nerve’s axon

Question 14

which form of the LA is required for a conduction block

Answer 14

both the nonionized and the ionized forms

“Unionized form enters and ionized form attaches”

Question 15

Conduction of a LA block is _______ dependent?

Answer 15

frequency

Greater the frequency of action potential, the faster the nerve is blocked by LA (conduction of the block is frequency dependent)

Question 16

what does the LA attach to when it is in the inactivated state

Answer 16

the Na channel

the faster/more often the nerve is firing, the more likely it is to “catch” the sodium channel in the inactive state

Question 17

For myelinated axons how many nodes of Ranvier must be blocked to stop nerve conduction

Answer 17

2-3

myelinated are harder to block

Question 18

explain the specific receptor theory for LAs

“where do LA work?)

Answer 18

• LA act by binding to specific receptors on the Na channel
• the action of the drug is direct and is NOT mediated by some change in the general properties of the cell membrane
• a specific receptor site for LA exists in the Na channel which eliminates permeability to the Na ions therefore no impulse conduction occurs

Question 19

what happens to weak bases as pH increases

Answer 19

Weak bases become more nonionized as pH increases (H+ decreases)
Base + base = nonionized

Question 20

what is pKa

Answer 20

The pKa is the pH at which 50% of the LA is in ionized form and 50% is in unionized form

Question 21

4 examples of weak bases

Answer 21

most LA, Ketamine, opioids, benzos

Question 22

The Nonionized form of a weak base is the _____ and the ionized form is the _______

which part is the acid and which part is the base

Answer 22

Nonionized form of a weak base is the base, and the ionized form is the conjugate acid

Question 23

what is the pKa range of LAs

Answer 23

7.6 - 9.1

Question 24

which LA will be most nonionized at a pH of 7.4:

a LA with a pKa of 7.6 or a LA with a pKa of 9.1

Answer 24

the LA with a pKa of 7.6

it will undergo less ionization vs the LA that has a higher pKa