SNS & Local Anaesthetics Flashcards
1
Q
Somatic Nervous System
A
- Skeletal muscle voluntary control of body movements Is responsible for muscle contraction
- Only one neurone from spinal cord to the skeletal muscle- Neurotransmitter= acetylcholine
- Somatic NS has lots of reflex arcs e.g. patellar reflex
2
Q
Neuromuscular Junctions
A
- Junction between the terminal of a motor neuron and a muscle fibre
- Motor endplate regions- specialised grooved structures on surface of skeletal muscle–> ↑ contact area
3
Q
NMJ Transmission
A
- AP–> voltage gated calcium channels open–> ca2+ enters pre-synaptic terminus–> Release of Ach quanta which diffuses across cleft & binds on post synaptic receptors (Ach is the rapidly broken down) –>Opening of Na+/K+ channels –>Post-synaptic membrane depolarisation–> muscle AP
4
Q
Specificity of NMJ
A
- Contraction of a muscle fibre= all or nothing
- To ensure synaptic transmission will occur with a high safety factor:
- There’s excess release of NT- One vesicle = contains 1 quantum (~ 10,000 molecules of Ach), each nerve impulse can–> 100 quanta released–> can activate >200,000 receptors simultaneously
- NMJ has a very narrow synaptic cleft, motorend plate regions & has many nicotinic receptors
- Axon of the motor neuron divides into fine branches–> innervate many muscle fibres (one motor unit), ensures generation of AP on every muscle fibre
5
Q
Nicotinic Receptors
A
- Are ligand-gated ionic channels that specifically bind Ach
- Composed of 5 subunit types: α (α1-α10), β (β2-β5), δ, ε, γ.
- At the NMJ, the N1(or Nm) nicotinic cholinergic receptor= most important
- Synaptic Transmission: Ach binds to receptor on sarcolemma–> conformational change which opens pore–> Na+ influx which causes depolarizing potential (70mV) called the end plate potential (EPP)–> opens voltage gated sodium channels–> ↑ Na+ influx–> AP, which propagates along muscle fibre–> release of Ca2+ from sarcoplasmic reticulum–> muscle contraction
6
Q
How to block Cholinergic Transmission
A
1. Non- depolarising Blocking Agents
- Neuromuscular blockers which don’t depolarize the motor end plate.
- Widely used as muscle relaxants, alongside anaesthesia for surgeries
- Side effects: hypotension & tachycardia
- Reversed by acetylcholinesterase inhibitor drugs (competitive antagonists)
- Tubocurarine, Pancuronium
2. Depolarising Blocking Agents
- Work by depolarizing the plasma membrane of muscle fibre (mimic Ach)
- ↑ resistant to acetylcholinesterase degradation–> ↑ persistent depolarisation (unlike Ach, which has transient effects- rapidly degraded)
- Succinylcholine (suxamethonium), in clinical use.
7
Q
Local Anaesthetics
(Pain Awareness)
A
- Is mediated by nerve ending receptors in peripheral tissues & transmitted–> CNS.
- Transmission can be disrupted by drugs acting on NT receptors or by blocking Na+ channels
8
Q
Local Anasthetics
A
- =Drugs which reversibly block generation & propagation of electrical impulses in excitable tissues
- Have local analgesic effects- prevent/ relieve pain in specific regions without loss of consciousness
- Local anaesthetics disrupt voltage-dependent Na+ ion channel function within the neuronal membrane preventing the transmission of the neuronal AP (in sensory, motor and sympathetic nerve fibres).
9
Q
Properties of Local Anaesthetics
A
- Composed of 3 parts: an aromatic ring (lipophilic), an intermediate linkage (an ester or an amide) & a terminal amine (hydrophilic)
- 2 classes clinically used:
-Aminoamide (-NH-CO-) Most commonly used
-Aminoester (-O-CO-)
10
Q
Ester Agents
A
rapidly inactivated in plasma & tissue by esterase enzymes
- Cocaine- derived from Erythroxylon coca leaves- historically important LA but rarely used now
- Procaine- first synthetic agent used. Short half-life & poor penetration- no longer used
- Tetracaine (= amethocaine) and cinchocaine are older agents. Tetracaine is used for spinal anaesthesia
11
Q
Amides
A
more stable & have longer half-life
- Lidocaine (= lignocaine) and mepivacaine. Good penetration, medium half life- lidocaine= commonly used by iv injection as an anti-dysrythmic
- Bupivacaine, ropivacaine & levobupivacaine- longest duration of action (200 min) Widely used.
12
Q
Local Anaesthetics
(Mode of Action)
A
- All LAs are weak bases with pKa between 8 & 9 ∴ at physiological pH, they’re mainly ionised but not completely- allows them to penetrate nerve sheath (completely ionised compounds cannot)
- LAs penetrate the nerve sheath & axonal membrane as unionised species (have to be weak bases)
- LA activity= strongly pH dependent: ↑ activity at alkaline pH as proportion of ionised molecules is low
- Inflamed tissue= acidic ∴ resistant to LAs (as LAs will be ionised ∴ can’t penetrate)
- Once inside the axon it is the ionised form which physically plugs the pore of the Na+ channel
13
Q
Local Anaesthetics
(2 pathways)
A
1. Hydrophobic pathway (non-use dependent)
When Na+ channel is in the closed state, the blocking site on the inner surface can be reached via the membrane by the unionised version of the LA.
2. Hydrophilic pathway (use-dependent)
↑ opened Na+ channels–> ↑ block, as LAs can enter the channel more readily & access the blocking site- interact with blocking site in ionised form
- This is typical of antidysrhythmic & antiepileptic drugs.
- These 2 pathways= simplified- as there’s factors which may affect LA action: pH & membrane properties (fluidity, microviscosity & permeability)
14
Q
Local Anaesthetic Use
A
- Acute pain (trauma, surgery, infection)
- Chronic pain
- Surgery and dentistry
- To enable painless venipuncture
- Surface anaesthesia for endoscoping
- Often minor procedures:
- Epidurals, c-sections & orthopaedics
- LA of the eye for examination
15
Q
Application of Local Anaesthetics
A
- Topical surface anaesthesia- Applied by spray, ointment. Usually applied to the nose, mouth, bronchial tree, cornea and urinary tract. Risks: systemic toxicity at high concentration
- Infiltration- Applied subcutaneously directly in to tissue or around nerves. Used in minor surgery Risks: only suitable for small areas or risk of systemic toxicity
- Intravenous regional anaesthesia- Injected intravenously distal to pressure cuff to arrest blood flow. Used for limb surgery Risks: systemic toxicity when cuff is removed
- Nerve block Injection close to nerve trunk to cause loss of sensations Used for dental surgery Risks: accurate placement of needle is essential
- Spinal anaesthesia- applied into subarachnoid space to act on spinal roots. Used when general anaesthesia can’t be used. Risks: Bradycardia and hypotension due to sympathetic block
- Epidural anaesthesia: applied into epidural spaces blocking spinal roots. Used when general anaesthesia cannot be used (child birth) Risks: similar to spinal but less probable
