Regulating neuronal excitability Flashcards
Describe the difference between local and general anaesthetics?
Local anaesthetics produce regionalised inhibition of pain/sensory pathways, with no loss of consciousness
General anaesthetics depress cortical processing of pain/sensory signals, and result in loss of consciousness
What is the site of action for analgesics?
Peripheral nerves, spinal cord and brain cortex
What is the site of action for local anaesthetics?
Peripheral nerves and spinal cord
What is the site of action for general anaesthetics?
Brain cortex
What the first local anaesthetic?
Cocaine
Describe the broad action of local anaesthetics?
Drugs that reversibly block conduction of nerve impulses at the axonal membrane Interfere with influx of Na
Are local anaesthetics acidic or basic? Are they strong or weak?
Weak bases
How do the various local anaesthetic agents differ?
Differ in onset, duration and toxicity
List three classes of local anaesthetics?
Aminoesters Aminoamides Benzocaine
What is the difference in duration and metabolism between aminoesters and aminoamides?
Aminoesters are shorter acting and are hydrolysed by esterases Aminoamides are longer acting and undergo hepatic metabolism
What sorts of tissue can local anaesthetics affect?
Will affect all nerves and excitable tissue
What do local anaesthetics selectively bind to?
Na channels
How can systemic distribution of local anaesthetics be limited? Why is this important?
Local application Limits toxicity and makes them safer
Describe the difference in sensitivity to local anaesthetics between motor and sensory nerves?
Sensory nerves more sensitive (require less drug for same effect)
How can the level of nerve blockade achieved with local anaesthetics be altered?
Alter dose of drug
Which part of the Na channel do local anaesthetics interact with?
Transmembrane domain
Which part of the Na channel do toxins interact with?
Bind extracellular domain
What are the two mechanisms of action of local anaesthetics?
Hydrophobic Hydrophilic
What is the difference between the hydrophobic and hydrophilic mechanisms of local anaesthetics, in terms of speed and use dependence?
Hydrophobic: fast, non use dependent Hydrophilic: slow, use dependent
What limits the rate of onset/offset of local anaesthetics?
Diffusion across membranes (hydrophobic fast vs hydrophilic slow)
How does the size of nerves affect the rate of onset/offset?
Small nerves > smaller membranes > quicker access
Are sensory nerves or motor nerves larger?
Motor nerves are larger
What is the extracellular gate of the Na channel called?
m-gate
What is the intracellular gate of the Na channel called?
h-gate
Describe the hydrophobic mechanism for local anaesthetics?
Describe the hydrophilic mechanism for local anaesthetics?
Why are local anaesthetics that use the hydrophobic mechanism not use-dependent?
Hydrophobic > can cross membrane > doesn’t matter whether gates are open or closed
Why are local anaesthetics that use the hydrophilic mechanism use dependent?
Hydrophilic> cannot cross membrane > requires gates to be open
What is the effect of local anaesthetics on axon membrane potential?
Stabilises axon membrane
No change in resting membrane potential
When is the effect of local anaesthetics more pronounced?
In a basic medium
Describe the effect of a basic medium on local anaesthetics?
Have a more pronounced effect
What determines the toxicity of local anaesthetics?
Proprtional to blood level
Dose determines effect
Describe some of the toxic cardiovascular effects of local anaesthetics?
Direct myocardial depression
Depression of vasomotor centre
Hypotension
Describe of the toxic CNS effects of local anaestheitcs?
Excitation
Tremor
Convulsion
Respiratory arrest
How can we tell if a local anaesthetic is acting in the wrong location?
Begin to see toxic side effects
Which side effects of local anaesthetics are not proportional to blood level?
Hypersensitivity reactions
Which side effect is particularly common with local anaesthetics?
Hypersensitivity reactions
Which forms of local anaesthetics are available over the counter?
Lozenge
Gels
Which forms of local anaesthetics are for professional use only?
Eye drops
Injection
Describe the four stages of general anaesthesia?
Stage 1: amnesia, euphoria
Stage 2: excitement, delirium, resistance to handling
Stage 3: unconsciousness, regular respiration, decreasing eye movement
Stage 4: respiratory arrest, cardiac depression and arrest
At which stage of general anaesthesia is surgery commenced?
Stage 3
How long does it take to progress from Stage 1 to Stage 3 once general anaesthetics are administered?
Seconds
What are the main methods of administration for general anaesthetics?
Inhalation
Intravenous injection
What are some of the respiratory side effects of general anaesthetics?
Impaired ventilation
Depression of respiratory centre
Obstruction of airways
How can retention of secretions due to obstruction of airways be combatted under general anaesthesia?
Administer ant-MuscR
List the cardiovascular side effects of general anaesthetics?
Decreased vasomotor centre function
Depress contracility
Peripheral vasodilation
Cardiac arrythmias
Inadequate response to fall in BP or CO
When can the side effect of inadequate response to fall in BP under general anaesthesia become a problem?
If the patient must be moved upright for surgery
What are the theories of mechanism of action of general anaesthetics?
Lipid theory
Receptor interaction theory
Describe the the lipid theory of general anaesthetics?
Act by dissolving in the fatty fraction of brain cells and removing fatty constituents from them, thus changing activity of brain cells and inducing anaesthesia.
Describe the receptor interaction theory of general anaesthetics?
Inhibit excitatory receptors (glutamate, NMDA)
Enhance effects on inhibitory receptors (GABA, glycine)
