regulating neuronal excitability Flashcards Preview

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Flashcards in regulating neuronal excitability Deck (27):
1

motor neurons receive excitatory and inhibitor output. In the case of epilepsy, there is an excess of [...] input, with inordinate amounts of NT [...] released on the post synaptic motor neuron.

excitatory
glutamate.

2

one tx option for epilepsy would be to enhance GABA receptor activity on the motor nerve, accomplished through [....] type drugs

benzodiazepines

3

epilepsy may be tx by specifically limiting the excessively firing nerves releasing glutamate, with drugs such as [...].

OR inhibiting T-type calcium channels in these excessively firing nerves, with drugs such as [...]

OR by inhibiting the NMDA receptor for glutamate on the post synaptic motor nerve., with drugs such as [...]

phenytoin

Ethosuximide

Felbemate

4

analgesics target the [...] and [...] pathways

pain and sensory (regulate the pain rather than stopping sensation all together like local anaesthetics

5

[....] induce regional inhibition of pain/sensory pathways. They DO NOT cause loss of consciousness.

local anaesthetics

6

[....] depress cortical processing of pain/sensory signal. Causes loss of consciousness, with widespread, not regionalized effect.

general anaesthetics

7

cocaine was an early local anaesthetic, works by inhibiting [...] reuptake. it is a cns [....]

NA

stimulator

8

local anaesthetics agents are drugs that [....] block conduction of nerve impulses at the [....].

the clinically used agents tend to be [...] bases with differing onset, duration and toxicity.

reversibly
axonal membrane

weak bases.

9

aminoesters are [....] acting local anaesthetics, and undergo hydrolysis by [....].

A common drug is [...]

short
esterases

procaine.

10

aminoamides are [....] acting local anaesthetics, and undergo metabolism by [....].

common drugs are [....]

long
hepatic metabolism

lignocaine
bupivicaine
ropivicaine

11

local anaesthetics are safe/effective when they remain in the periphery due to selectine [...] channel binding, reversible binding without nerve damage, blanket effect on all nerves and [....].

Na+
excitable tissues.

12

Depending on dose/systemic absorption In the CNS, local anaesthetics can cause [....] in the heart, [....] on autonomic nerves. and [....] peripheral nerves.

anti-dysrhythmic function, but cardiac arrest in excess.
causes hypotension, but CNS convulsion/coma in excess.
causes sensory loss, but paralysis in excess.

NB: how they're used and who uses them makes them safe!

13

In epidural injection of local anaesthetic, for the same dose of anaesthetic sensory fibres are blocked [...] % while motor fibres will be blocked [....] %.

This is because local anaesthetics only bind [......]
----> favouring [....] fibres more.

Conversely, toxins bind [....] causing blanket effects.

100
25

intracellular portion of transmembrane domain receptor (S6 in domain IV).
sensory fibres more.

extracellular portion of channel, causing blanket sensory and motor suppression.

14

how do local anaesthetics interact with the Na+ channel membrane?
(two mechanisms)

1) fast, and non-use dependant path .....
Which drugs use this path?

2) slow, use dependant.....
Which drugs use this path?

With this in mind, what limits the rate of onset of these drugs?

1) hydrophobic but lipophilic drug, so can diffuse through membrane to reach intracellular channel binding site.
This is fast, and non-use dependant (independent of nerve firing).

Benzocaine.

2) Slow path, use dependant. Depends on use of Na+ channels to slip through and reach intracellular membrane binding site (ie lignocaine is 65% protonated at normal pH 7.4, more than half wont be able to cross membrane).

All the aminoesterases and aminoamides can use this path.


Rate of onset limited by diffusion accross membrane and use-dependance of the Na channels.

15

which pathway of local anaesthetic channel inhibition is most potent? (hydrophobic vs hydrophilic)

hydrophobic/lipophilic pathway crosses membrane independant of use, however binds weakly to Na channel, only physically obstructing the channel.

Hydrophilic/lipophobic pathway is most potent! Although limited by slow-onset.
Half the drug is not protonated at normal pH, and crosses the membrane. The other half crosses when the Na channel opens. They combine on the intracellular side, revert to charged form, and exert a much stronger effect on blocking influx of Na+ through its channel.

16

The extraneuronal side of the Na+ channel is termed the [....] gate. Open during nerve [....]

The intranenuronal side of the Na channel is termed the [...] gate. Open during nerve [....], closed during nerve [....]

M gate.
throughout depolarization and repolarization-->open

H gate.
depolarization -->open
repolarization -->closed

17

in response to local anaesthetics, [...] fibres are most sensitive.

small fibres most sensitive, more fibres are least sensitive. (sensory>ANS>motor)

18

all local anaesthetics act to prevent [.....]

propagation of nerve action potential.

19

T/F local anaesthetics cause no change in the resting membrane potential.

TRUE. They only make it less excitable by obstructing the membrane channel.

20

Why is the effect of local anaesthetics more pronounced in more basic pH conditions?

how is this relevant to states of infection?

hard to cross the membrane in ionized form. In basic conditions there are more circulating uncharged species.
NB: charged and uncharged forms are both essential (recall they combine and become ionized intracellularly, more potent that way)

in states of infection, there will be a more acidic environment, thus weaker activity of local anaesthetics.

21

local anaesthetic toxicity side effects that are proportional to dosing/blood level? (CNS and CV)

CNS
-excitation
-tremor
-convulsion
-resp arrest

CV
-direct myocardial depression
-depression of vasomotor centre
-hypotension (except cocaine, --->would increase NA, increasing HR, increasing, BP)

22

local anaesthetic toxicity effects that are irrespective of dosing/blood level?

hypersensitivity (allergic) reactions

23

Stages of general anaesthesia?

Stage I (awake)
-amnesia
-euphoria

Stage II "excitement"
-excitement
-delirium
-resistance to handling

Stage III "surgical anaesthesia" (surgery commencement)
-unconsciousness
-regular respiration
-decreasing eye movement

Stage IV "Medullary depression" (avoid this stage!!!!!)
-resp arrest
-cardiac depression and arrest

24

2 methods of adminstering general anaesthetics {...}.

Which drugs fit into each category?

inhaled
-desflurane
-isoflurane
-sevoflurane

intravenous
-propofol
-fluoropentane

NB: GE is a balance of both administration methods typically.

25

What are the potential respiratory side effects of general anaesthetics?

impaired ventilation
depression of resp centre
obstruction of airways (retention of secretions b/c mucociliary elevator inhibition)-->should administer atropine pre-operatively to reduce secretion

26

What are the potential cardiovascular side effects of general anaesthetics?

-decreased vasomotor centre function
-depress contractility
-peripheral vasodilation
-cardiac arrhythmias
-inadequate response to fall in BP or CO

27

describe two theories related to general anaesthetic mechanism of action:

1. lipid theory
-correlation b/w anaesthetic potency and lipid solubility
-anaesthesia caused by volume expansion of membrane lipids

2. receptor interaction
-anaesthetic agents inhibit excitatory receptors--> glutamate, NMDA
-enhance effects on inhibitory receptos (GABA, glycine)