Regulating Neuronal Excitability Flashcards Preview

MD1 Neuroscience > Regulating Neuronal Excitability > Flashcards

Flashcards in Regulating Neuronal Excitability Deck (49):
1

What is an example of a neurotransmitter not stored in a vesicle?

NO

2

What kind of inputs do motor nerves receive?

Excitatory
Inhibitory

3

What happens in epilepsy?

Excessive discharge
Too little inhibition - get spasms
Too much excitation - excessive motor stimulatio

4

What are the two neurotransmitters relevant to epilepsy?

GABA
Glutamate

5

What is the best target for modulating inhibitory activity in epilepsy?

Enhance GABA receptor activity

6

How do benzodiazepines work?

Used to treat epilepsy
Enhance GABA receptor activity
Allosteric modulators
Increase GABA binding

7

How do you reduce excitatory input in epilepsy?

Limit excitatory nerve activation
Inhibit T-type Ca channels
- Specific to some neurons
- More readily expressed on excitatory nerves
Inhibit NMDA receptor

8

Describe phenytoin

Used in treating epilepsy
Stops nerve action by inhibiting Na channels

9

Describe ethosuximide

Inhibits T-type Ca channels
Stops vesicle release

10

Describe felbemate

Inhibits NMDA receptor
Enhances GABA receptor

11

What else do many epileptic drugs cause?

Sedation; eg:
- Benzodiazepines
- Some others
Analgesia

12

What are some examples of analgesics?

NSAIDs
Anti-pyuretics
Opioids

13

What is an analgesic?

Targets pain/sensory pathways
Sets threshold to determine what degree of excitation is sent to brain
Increases pain threshold

14

What is a local anaesthetic?

Targets pain/sensory nerves as well as others in the region
No loss of consciousness

15

What is a general anaesthetic?

Depresses cortical processing of pain/sensory signal
Causes loss of consciousness
Not regionalised

16

Which drug category has the highest degree of selectivity?
a) Analgesics
b) Local anaesthetics
c) General anaesthetics

b) Local anaesthetics

17

What was the first local anaesthetic?

Cocaine

18

Describe local anaesthetic agents

Drugs that reversibly block conduction of nerve impulses at axonal membrane - influence action potential

19

What are the weak base local anaesthetics?

Aminoesters
- Eg: procaine
- Shorter acting
- Hydrolysis by choliesterases
Aminoamides
- Eg: lignocaine, bupivicaine, ropivicaine
- Longer acting = 1-1.5 hrs
- Hepatic metabolism
Benzocaine

20

What are examples of lethal toxins that share a target with local anaesthetics?

Tetrodotoxin in puffer fish
Saxitoxin in dinoflagellates

21

Describe the clinical use of local anaesthetics

Safe
- Very specific binding to Na channel
- Reversible binding with no nerve damage
- Will affect all nerves/excitable tissues because Na channel fundamental to all excitable tissues
Local application to limit systemic distribution - makes them safe

22

What are the effects if local anaesthetics act on non-sensory nerves?

Peripheral motor nerves
- Paralysis
Autonomic nerves
- Hypotension
- CNS convulsions
- Coma
Heart
- Anti-dysrhythmic
- Cardiac arrest

23

What happens to the nerves with increasing concentrations of local anaesthetic?

More sensory block
More motor block because drug reaches these fibres
More autonomic block

24

What is the relative sensitivity of nerve types to local anaesthetics?

Sensory > autonomic > motor

25

What is the site of interaction of local anaesthetics?

Intracellular transmembrane domain on Na channel

26

What is the difference in binding between local anaesthetics and toxins that share the same receptor target?

Local anaesthetics bind intracellularly and toxins bind extracellularly

27

What are the two mechanisms of action of local anaesthetics?

Hydrophobic
- Faster
- Non-use dependent
- Eg: benzocaine
Hydrophilic
- Slower
- Use dependent
Eg: aminoesters, aminoamides
- Mainly ionised at physiological pH

28

What determines the rate of onset/offset of local anaesthetics?

Rate of diffusion across membrane

29

Describe how hydrophobic local anaesthetics block the Na channel

Enter cell by diffusing across lipid membrane
Block gate like plug

30

Describe how hydrophilic local anaesthetics block the Na channel

Non-ionised form diffuses across membrane into cell
Re-ionises
Blocks channel in ionised form

31

What are the general properties of local anaesthetics?

Prevemt propagation of nerve action potential
Small fibres more sensitive
Stabilise axon membrane
- No change in resting membrane potential
Effect more pronounced in basic medium
- Allows more drug to cross membrane
Greater effect at high frequency

32

What happens when local anaesthetics are used during an infection?

Infection creates more acidic environment
Decreases effect of drug, therefore need higher concentration to get same effect as normal

33

What is the toxicity of local anaesthetics?

Generally safe
Toxicity proportional to blood level - if they enter bloodstream
Cardiovascular effects
- Direct myocardial depression
- Depression of vasomotor centre
- Hypotension - except cocaine > causes hypertension instead
Can cross BBB > CNS effects
- Inhibitory fibres more sensitive > excitation
- Tremor
- Convulsion
- Respiratory arrest

34

Are hypersensitivity reactions proportional to blood level?

No

35

Who can get hypersensitivity reactions to local anaesthetics?

Both patient and practitioner, as even handling drugs can cause development

36

Describe the topical application of local anaesthetics

Over the counter
- Lozenge: throat drops containing benzocaine
- Gels: generally poorly absorbed across skin and over inflamed areas because even though fibres exposed, at low pH
- Contain very low concentrations of lignocaine
- Menthol doing most of the work
Professional use only
- Eye drops: ocular procedures, often including a dye
- Injection: specific procedural use; eg: IV lignocaine for dysrhythmia

37

What are the types of ways local anaesthetics are used when injected?

Infiltration: combination with vasoconstrictor prolongs action
Nerve block: injection close to major nerves
Epidural and intrathecal

38

What are the stages of anaesthesia?

Stage 1
- Amnesia
- Euphoria
Stage 2
- Excitement
- Delirium
- Resistance to handling
Stage 3
- Unconsciousness
- Regular respiration
- Decreasing eye movement
Stage 4
- Medullary depression
- Respiratory arrest
- Cardiac depression and arrest

39

How can general anesthetics be formulated?

Inhalation
IV

40

What does formulation of general anaesthetics influence?

Slight differences in pharmacokinetics

41

What are some inhaled general anaesthetics?

Desflurane
Sevoflurane
Isoflurane

42

What are some IV general anaesthetics?

Propofol
Thiopentone

43

What are the relevant pharmacokinetics for general anaesthetics?

Dose and duration of action
Absorption - when inhaled
Distribution
- Vd
- t1/2
- Get into compartments other than brain
Metabolism
Elimination
- Kidneys
- Liver
- Lungs
Drug interactions

44

What are the side effects of general anaesthetics?

Happen at final endpoint depression = stage 4
Respiratory
- Impaired ventilation
- Depression of respiratory centre
- Obstruction of airways
- Retention of secretions
Cardiovascular
- Decreased vasomotor centre function
- Depress contractility
- Peripheral vasodilation
- Cardia arrythmias
- Inadequate response to fall in BP or CO

45

What is given to counteract the retention of secretions that happens when a patient is given general anaesthetics?

Anti-muscarinics administered

46

What are the two theories on mechanism of action of general anaesthetics?

Lipid theory
Receptor interaction

47

What is the lipid theory in relation to mechanism of action of general anaesthetics?

Close correlation between anaesthetic potency and lipid solubility
Anaesthesia caused by volume expansion of membrane lipids
Effect can be reversed by pressure - pushed out of membranes

48

What is the receptor interaction in relation to mechanism of action of general anaesthetics?

Many anaesthetic agents inhibit excitatory receptors
- Glutamate
- NMDA
Many anaesthetic agents enhance effects on inhibitory receptors
- GABA
- Glycine

49

What is an NMDA receptor agonist?

Ketamine

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