Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Gen Exam 3 + Final > Basic Pharmacology of LAs > Flashcards

Basic Pharmacology of LAs Flashcards

1
Q

LAs are ___ molecules

A

amphipathic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

T/F
LAs bind exclusively to Na channels and plasma proteins

A

False
primarily to Na channels
but also K, Ca, & G-protein-coupled receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

🔷
What determines…
onset
potency
duration

A

onset = pka
potency = lipid solubility
duration = protein binding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

⭐️
T/F
LAs suppress action potentials in excitable tissues by blocking ligand-gated Na+ channels.

A

False
voltage gated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

LAs block pain impulse transmission by inhibiting action potentials in ___ fibers

A

nociceptive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Four groups of myelinated A fibers

A

Aa: skeletal muscle
Ab: tactile sensation
Ag: muscle spindles
Ad: nociception & cold

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Unmylinated C

A

dull pain from skin and viscera

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Myelinated B

A

autonomic preganglionic
slower

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Where are voltage-gated Na channels found?

A

nerves
myocardium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Which fibers are affected by Surgical incision or trauma

A

free nerve endings of Ad
(skin, muscle, joints, bone and viscera)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Voltage-gated Na channel
structure

A

pore-forming alpha subunit
-one or two b subunits.

alpha subunit:
four domains (I-IV) each w/ six segments (S1-S6) that wrap round a bell-shaped central channel

channel is formed by:
S5 & S6 segments + short loops of amino acids linking them

inactivation gate:
loop connecting domains III & IV

S4 in each domain:
+ charged arginine or lysine amino acids
voltage-sensitive region of the Na+ channel.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

voltage-sensitive region of the Na+ channel.

A

S4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Resting-state:
MP
generated by…

A

-70 mv
K+ out (along their gradient)
anions stay inside (mostly proteins)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

inactivation gate location

A

between domains III and IV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

S4 segment activity

A

resting state:
S4 in “down” position
makes it nonconductive

depolarization:
outward spiraling opens Na channel
exposes inactivation gate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

🔷
The ionized form binds to ___ voltage-
gated Na+ channels in a reversible and concentration-dependent manner.

A

open

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

binding site for local anesthetics

A

domain IV, loop S6
only accessible when the channel is open

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

use-dependent or phasic block

A

binding of LA to open Na+ channels increases with the frequency of nerve depolarization

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

(MoA)
Dose dependent effects of LAs

A

increased LA [ ]:
↓ peak action potential
↑ firing threshold
↓ impulse conduction
↑ refractory period

↓ all nerve conduction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Why does Bupivicaine cause more cardiac effects than Lidocaine?

A

bupivacaine:
higher affinity & slower dissociation
↓
accumulates in diastole
↓
prolong conduction
↓
re-entry-induced arrhythmias

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

(para/sympathetic) fibers are most easily blocked & require lowest LA [ ].

A

sympathetic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Usually reaches higher dermatome

A

sympathetic block

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

LAs are ___ soluble salts of lipid-soluble ___

A

water
alkaloids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How can LA structure be changed to increase lipid solubility, potency & duration of action

A

increasing the length of carbon chains attached to either the aromatic ring, amide linkage, or the tertiary amine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Replacement of the tertiary amine by a piperidine ring

A

↑ lipid solubility and duration of action

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

butyl group in place of the amine on the benzene ring of procaine gives

A

tetracaine

27
Q

addition of a propyl or butyl group to the amine end of mepivacaine results
in

A

ropivacaine or bupivacaine, respectively

28
Q

Bupivacaine enantiomers

A

dextro-enantiomer: selectively blocks 🩷 Na channels

bad
so we started using 2 different Levo-enantiomers
levobupivacaine & ropivacaine
(less effect on 🩷 conduction & contractility)

29
Q

pKa

A

pH at which the ionized and unionized forms are present in equal amounts

30
Q

LAs are (acids/bases) so a higher pka means (more/less) inonization

A

bases
more

31
Q

high protein binding to ___ have a longer duration of action and lower
bioavailability.

A

a1-acid glycoprotein

32
Q

decreases protein binding & thus and increases the risk of toxicity (3)

A

Hypoxia, hypercarbia, and acidaemia

33
Q

vasoactivity of local anaesthetics influences (2)

A

potency
duration

34
Q

Levobupivacaine and ropivacaine
bimodal vasoactivity

A

vasodilate at clinical doses
vasoconstrict at subclinical doses

35
Q

Routes of administration

A

topical (skin and airway)
subcutaneous
intravenous
perineural
epidural
intrathecal

36
Q

peak plasma concentration after a
single dose

A

intrapleural > intercostal > lumbar epidural >brachial plexus > subcutaneous > sciatic > femoral.

M&M:
intravenous (or intraarterial) > tracheal > intercostal > paracervical > epidural > brachial plexus > sciatic > subcutaneous

37
Q

Which are less protein bound?
esters or amides

A

esters
(lower protein binding = shorter duration)

38
Q

Tissue distribution tends to be proportional to (3)

A

LA’s tissue/blood partition coefficient
tissue mass
tissue perfusion

39
Q

We’re concerned about PABA with (ester/amide) LAs

A

ester

40
Q

(ester/amide) LAs are more prone to accumulation with hepatic dysfunction or reduced hepatic blood flow

A

Amide
they are metabolized by the liver
and
have slower metab than esters

(esters = rapid hydrolysis by plasma esterases!)

41
Q

undergoes metabolism in the lungs

A

Prilocaine

42
Q

An allergy to an amide LA is most likely due to…

A

an additive such as the stabilizing
agent methylparaben
or
response to vasopressors mistakenly seen as allergy

43
Q

has a high hepatic extraction ratio: clearance depends on hepatic blood flow & ~unaltered by changes in hepatic enzyme activity

A

Lidocaine

44
Q

LA Adjuvants

A

adrenaline
clonidine
opioids
ketamine
dexamethasone
dexmedetomidine
midazolam

45
Q

eutectic

A

mixing 2 compounds to produce a substance that has 1 set of physical characteristics

46
Q

eutectic mixture of local anaesthetic (EMLA)

A

crystalline bases of 2.5% lidocaine and 2.5% prilocaine in an oil/water emulsion

↓ melting point than separately

can use higher [ ]

47
Q

rate and degree of diffusion across the
placenta depends on

A

protein binding
pKa
maternal & fetal pH

48
Q

Considerations for LAs in prolonged labour

A

acidosis in the fetus
↓
ion trapping
↓
accumulation in the fetus

49
Q

(Amide/ester) LAs do not cross the placenta in significant amounts

A

Ester
d/t rapid hydrolysis

50
Q

T/F
Local anesthetics cause both systemic AND local toxicity.

A

True

51
Q

lower systemic toxicity among the amides

A

Ropivacaine and levobupivacaine
lower affinity for 🩷 channels

52
Q

T/F
majority of perioperative nerve injuries are unrelated to regional anaesthesia

A

True

53
Q

methaemoglobinaemia shifts the OxyHgb curve

A

left
↓ ability of Hgb to release oxygen to tissues

54
Q

LAs that can cause methemoglobinemia

A

prilocaine
Benzocaine
lidocaine

55
Q

Intra-articular local anaesthetics
risks

A

chondrotoxicity (esp w/ osteoarthritis)

56
Q

LAs anti-inflammatory effects
MoA

A

↓ polymorphonuclear leukocyte adherence, migration & accumulation at site

alters macrophage and monocyte function

57
Q

LAs anti-inflammatory effects
cons

A

~↑risk bacterial infxn

58
Q

Possible antimetastatic properties

A

Surgery
↓ antitumour cell activity
↑ protumor activity

LA may ↓ cancer recurrence:
-attenuation this stress response
-direct anti-tumor effect

not proven

59
Q

lidocaine for neuropathic pain
MoA

A

unexplained by only blockade of voltage gated Na channels

reduction of spontaneous pain, allodynia, & hyperalgesia

60
Q

Catheter for continuous or repeated administration of local anesthetic

risks

A

leakage, migration, infection

61
Q

Phentolamine mesylate

A

non-selective alpha-adrenergic antagonist

vasodilates

halve the reversal time of LA

62
Q

T/F
All local anesthetics target the voltage-gated Na channel

A

True

63
Q

T/F
Only certain LAs carry risk of toxicity.

A

False
All have toxicity risk

Gen Exam 3 + Final (13 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions