Term
| What is the relationship between pH and LA structure/function? |
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Definition
BASIC- Neutral form in membrane and acidic form in cytoplasm are effective, by acidic form outside are NOT- so keep the pH higher!
1) LA are derivatives of Aniline or Benzoic acid linked to amine by ester (Procaine-short lasting) or amide (Lidocaine-long lasting) linkage.
2) The un-charged basic form of these drugs is hydrophobic and readily diffuses into nerves across axonal membranes.
3) In the cytoplasm, they are protonated, become water-soluble (both neutral form in membrane and acidic form in cytoplasm are effective, BUT acidic form extracellularly is NOT)
4) Lowering pH lowers concentration of neutral form and decreases effectiveness (when infections are constricted, or when repeated injections of LA in acidic vehicle in poorly perfused areas like SC) |
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Term
| When might you co-administer an LA with epinephrine? |
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Definition
The vasoconstrictor will lengthen the time of action of ester LA's such as Procaine.
** Amide LAs such as Lidocaine are already long** |
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Term
| What are the molecular targets of LAs and how does this interaction occur? |
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Definition
1) LAs bind voltage-gated sodium channels in a dose-dependent manner (repeated use increases effect)
- Stabilize inactivated state of channel
- DO NOT block channel pore (they reduce the frequency of channel opening, but NOT single channel conductance or lifetime of single channel openings) |
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Term
| How do LAs exert a "differential blockage" of nerve fibers? |
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Definition
1) LAs preferentially block small diameter axons, because of their shorter length constants (signal will travel shorter distance).
2) Pain and Temperature fibers are small diameter axons, are preferentially blocks at low doses of LA (motor control and pressure, touch and position senses are left in tact)
3) Axons in mantle >> than Axons in core (REMEMBER YOUR ANATOMY for LA) |
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Term
| What are some undesirable actions of LAs? |
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Definition
Act on all tissues that express VG-sodium channels (CNS neurons and heart).
1) If administered systemically, patient can develop drowsines, restlessness, tremor and convulsions (many cells are inhibited by synaptic input, so you might be "removing a brake" on transmission).
2) Can cause cardiac arrest if given with Epinephrine
3) Hypersensitivity to ester LAs (procaine) or vasoconstrictors (Epi) given with them |
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Term
| What is the order of sensory function block in terms of amount of LA given? |
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Definition
1) Pain
2) Cold
3) Warmth
4) Touch
5) Deep pressure
6) Motor |
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Term
| What is the difference between LA effectiveness at Mantle bundles vs. Core bundles in Nerve trunks? |
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Definition
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