Local Anaesthetics

Question 1

______(communication) cells and ___________ (mechanical activity) cells have electrical excitability and can generate action potentials.

Answer 1

1. Nerve

2. Cardiac/striated muscle

Question 2

The resting potential of cells is _______ and the flow of Na+ is always from the ______-cellular to ______-cellular (favoured by both concentration and electrical gradient)

Answer 2

1. negative
2. extra
3. intra

Question 3

Voltage-gated Sodium Channels opens transiently when membrane is _________ (less negative charge in cell), allowing propagation of signal. Both the channel itself and the gating mechanism can open/close.

Answer 3

depolarized

Question 4

Ion channels can have 4 states: Activated, Closed, Inactivated and deactivated. Both the channel itself and the gating mechanism can open/close.
_________ refers to ion flow blocked by a gating mechanism only.
_________ refers to ion flow blocked by closing of channel only.
_________ refers to ion flow blocked by closing of both channel and gating mechanism.

Answer 4

1. Inactivation
2. Closed
3. Deactivation

Question 5

LAs prevent membrane ____________ by blocking Na+ channels itself (mediating pain signals) in the axonal membrane. LAs can pass through ____________ and many LAs bind most strongly to the ________ and ________ states.

Answer 5

1. depolarization
2. the gating mechanism
3. inactivated
4. activated

Question 6

If a channel is _________ or _______, LAs will be unable to enter the channel to block it.

Answer 6

1. deactivated

2. closed

Question 7

LAs are weak bases (pKa 8-9). Only the ______, ________ form can pass through the neural membrane to be converted to the ______, ________ form intracellularly to exert its action.

Answer 7

1. inactive, un-protonated

2. active, protonated

Question 8

If the tissue is inflamed (______ pH), LAs will exist mainly in the ______, ______ form extra-cellularly and be unable to pass through the membrane to exert its action, resulting in lowered LA action.

Answer 8

1. acidic

2. active, protonated

Question 9

Passage of train of action potentials (i.e. in pain) causes the sodium channel to ______________________. This ________ depth of LA nerve block. (the more pain there is, the more effective LAs work)

Answer 9

1. cycle through open and inactivated states.

2. increases

Question 10

Depth of LA nerve block increases with action potential frequency because LA molecules gain access to the channel more readily when channel is _____ and have _________ for the inactivated than for the resting (closed) channels.

Answer 10

1. open

2. higher affinity

Question 11

LAs are ________ for Na+ channels but are ‘non-selective’ in the sense that all neurons have Na+ channels. Selectivity can be achieved by _____________________.

Answer 11

1. selective

2. delivering LA to a limited area

Question 12

More hydrophobic LAs such as T__________, E___________, B_________ are ______ potent and have a _____ duration of action.

Answer 12

1. tetracaine
2. etidocaine
3. bupivacaine
4. more
5. longer

Question 13

Less hydrophobic LAs such as L__________, P___________, M_________ are ______ potent and have a _____ duration of action.

Answer 13

1. Lidocaine
2. Procaine
3. Mepivacaine
4. less
5. shorter

Question 14

LAs act on all nerves but have a preference for:

1. ______ neurones
2. _____ frequency firing neurones (i.e. sensory)
3. C_____________ position neurones (closer to surface)
4. ________ neurones

Answer 14

1. Smaller
2. Higher
3. Circumferential
4. Myelinated

Question 15

List the following in order of speed of nerve block by LAs:

1. large myelinated axons
2. Small myelinated axons (i.e. Nociceptive and Sympathetic axons)
3. small non-myelinated axons

Answer 15

2, 3, 1

Question 16

Among these 4 (size/frequency/position/myelination), the most important factor is _____ as ________ neurones provide easier access for LAs. The next most important factor is _________ neurones.

Answer 16

1. size
2. smaller
3. Myelinated

Question 17

Examples of Ester LAs include: P______ and T________. They are metabolized via _______________ esterases and have a risk to induce _______.

Answer 17

1. Procaine
2. Tetracaine
3. plasma/tissue non-specific
4. PABA allergies

Question 18

Examples of Amide LAs include: B__________, M_________ and L________. They are metabolized by _______ enzymes and have a ______ risk of allergy compared to Ester LAs.

Answer 18

1. Bupivacaine
2. Mepivacaine
3. Lidocaine
4. hepatic
5. lower

Question 19

LAs mainly have local action (topically applied) but can be absorbed into the blood. A ______ rate of perfusion results in more systemic absorption and side effects. LAs can be combined with E________ (reduces vessel diameter) to prevent systemic distribution from site of application. It is not an antidote for LA toxicity.

Answer 19

1. higher

2. Epinephrine

Question 20

LAs that penetrate the axon most rapidly have the fastest onset. The 3 most important factors here are _______ , _______ and _______.

Answer 20

1. size
2. % ionization
3. lipid solubility

Question 21

Unintended IV administration of LAs result in _______ toxicity while an overly large dose of LA local injection results in _______ onset of toxicity.

Answer 21

1. immediate

2. delayed

Question 22

B__________ is more cardiotoxic than most LAs while C_______ blocks NA reuptake, resulting in vasoconstriction and hypertension.

Answer 22

1. Bupivacaine

2. Cocaine

Question 23

O-toluidine (metabolite of P________) causes _____________ (that can be treated using iv methyleneblue/ascorbic acid) while Ester LAs are hydrolyzed to ____ which can cause _________.

Answer 23

1. prilocaine
2. methaemoglobin
3. PABA
4. allergic reactions

Question 24

Some CNS side effects of LAs (from low dose to highest) include: 
D\_\_\_\_\_\_\_\_\_
Visual and auditory 
Restlessness
N\_\_\_\_\_\_\_
S\_\_\_\_\_\_\_
Convulsion
Stoppage of vital functions
Death

Answer 24

1. Drowsiness
2. Nystagmus
3. Shivering

Question 25

Some CNS side effects of LAs (from low dose to highest) include:
_______ Cardiac Contraction (cardiac muscle)
Arteriolar dilatation and H________ (vascular smooth muscle)
CVS collapse

Answer 25

1. Lowered

2. Hypotension

Question 26

There are many clinical applications for topical administrations of LAs. _____ (minor wounds), ____ (removal of foreign objects), _____ (to allow gum injection), ______ insertion and __________ in gynaecology (lidocaine).

Answer 26

1. Skin
2. Eye
3. Dental
4. endoscope
5. episiotomy cuts

Question 27

L_________ and B_________ can be used in epidural anaesthetics for analgesia. They may be combined with F________ to reduce LA dose.

Answer 27

1. Lidocaine
2. Bupivacaine
3. fetanyl

Question 28

L_________ and B_________ can be used in Dental anaesthesia. They may be combined with E__________ to control bleeding and systemic side effects.

Answer 28

1. Lidocaine
2. Bupivacaine
3. epinephrine

Question 29

LAs have the fastest onset at _________ pH.

Answer 29

physiological

Question 30

LAs should be chosen based on desired ________. For example, Surface anaesthesia requires rapid penetration of the skin (mucosa) and limited tendency to diffuse away.

Answer 30

duration of action

Question 31

C______ gives good penetration and vasoconstriction, thus most often used for ear, nose and throat procedures

Answer 31

Cocaine