4- pharm LA Flashcards
regional anes vs analgesia
regional anes - patient is still conscious, particular part of the body insensitive to pain
Analgesia- loss of pain
T/F LA drugs are weak bases
True
why is HCl mixed with LA drugs
LA drugs are weak bases and they are ineffective as base so they are mixed with HCl to form salts. these salts are water-soluble and will readily dissolve into saline solution – usuable form
T/F LA drugs should be hydrophobic and lipophilic
False!
hydrophilic - to diffuse effectively
lipophilic - to penetrate the nerve membrane (lipid bilayer)
T/F LA drugs act on the axon
False! they act on the membrane itself not on the axon
impulse transmission is due to ??
a change in polarity
INSIDE: more +
Properties of ideal LA solution
- reversible
- no irritation to tissues
- rapid and sufficient duration
- low degree of systemic toxicity
- should not produce allergic reaction
- rapidly undergoes biotransformation
- sterile
theories of LA
- ACh theory
- Ca displacement theory
- surface charge (repulsion) theory
- membrane expansion
- specific receptor
explain membrane expansion
molecules bind to the receptors of membrane –> expand –> Na channel constricted –> no ingress –> polarity does not reverse
Acetylcholine theory states that –
Acetylcholine is involved in nerve conduction, not just as a neurotransmitter in synapses
but no evidence
Calcium Displacement Theory
LA displaces calcium –> blockade of Na
Calcium ions bathing nerve does not change the LA potency
Surface charge (repulsion) theory
LA binds to surface membrane –> change EP to more + at the membrane surface –> inc threshold potential –> dec excitability
buuuuut???
- RP is unaltered by LA
- LA acts within membrane channel, not on surface
- Cannot explain activity of uncharged LA e.g. Benzocaine
theory that can explain benzocaine’s activity
membrane expansion
T/F benzocaine has no cationic form
true
Specific Receptor
LA binds to specific receptors on Na channel (external or internal axoplasmic)
T/F amide and esters are structurally different
FALSE! structurally same.. both have an aromatic lipophlic group and hydrophilic end
difference: intermediate chain
common properties of LA groups
- synthetic compound
- contain amino and aromatic groups
- weak base w/ poor water solubility
- combined with usually HCl to form water soluble salts
- alkali inc concentration of unionized free base
- compatible w/ epinephrine
- hydrolyzed by plasma cholinesterase or undergo biotransformation in the liver
determines the relative proportion between cation (RNH+) and free base (RN)
pH of solution
pKa of specific compound
when can RNH+ and RN exist in equal proportion?
pH = pKa
free bases are for ____ and cations are for ____
free base (RN): penetration cations (RNH+): nerve blockade
T/F anes are acidic in nature
true
our tissues will buffer them –> cation is released
pKa affects
onset
low pKa = rapid onset
lipid solubility affects
potency
more lipid soluble = more potent, more toxic
protein binding affects
duration
high protein binding = longer duration
