anaesthesia 7 - analgesics Flashcards
what is the general sturcture of local anaesthetics? what does this mean? 2 types or sturcture?
have a lipid soluble aromatic ring. plus a carbon linkage!!!!…..this linkage could be either an ester link or an amide link!!!.
local anaesthetics - what do they do and how do they work?
interfere with action potentials generation and concudtion of noxious stimuli. block the propagation of an action potential near the area. block the pathway to the cns and so no pain felt from that area.
give an example of an ester?
give an example of an amide?
ester- procaine, cocaine 9procaine is the only local that is licensed in cattle!
amide - lidocaine and bupivicaine.
what are differences between the esters and amides? what are the metbolites of esters? problem?
esterss - link easily broken by tissue esterases and so are more difficult to store and are more heat sensitive and less stable in solution. metabolism of these produces para-aminobenzoates. (PABA) which can cause allergic reactions. (procaine in cattle)
amides - stored for longer and are more heat stable.
what is stereoisomerism?
multiple forms of a drug. (mirror images) drugs must fit into receptors to be able to work. isomers may have exactly the same chemical sturcture but still may not fit in the same receptor. they may also have different action properties.
give an example of stereoisomerism? what are 2 enantomers of bupivicaine? which is active? what is a racemic mixture?
bupivicaine - amide. has 2 enantomers.
-levobupivicaine (left one and is active)
-dextrobupivicaine
most commercial drugs contain a mix of 50:50 (racemic mixture)
some may just contain levobupivicaine as it is less cardiotoxic and neurotoxic.
explain the absorption and distribution of these locals?
they are available in spray, inj, cream and gels. can be administered around a nerve requiring a block. eg. lower limb/teeth.
they are weak bases and may be ionised or nonionised. - more ionised in general and so does not really distribute.
explain how the ph can affect LA’s? what is pka? wht is tissue ph? if tissue is infected then what happens?
pka = ph at which concentration of ionised and non-ionised drug are equal. and la are weak bases. they are more ionised in tissue. the closer the pka to the tissue ph = faster onset of action.
eg. lidocaine pka = 8.1 (rapid onset compared to procaine which has a pka of 9.1.)
if tissue is infected then it has a lower ph therefore the absorption of locals is impaired. (pka further away)
explain the pharmacodynamics of local anaesthetics? how do they work? how do nerves differ in sensitivity? why are they more effective in alkaline? what are the proerties that make nerve fibres more sensitive?
block the transmission of an ap by binding na+ channels. and prevent depolarisation. (more effective in alkaline as must be uncharged to penetrate the sheath. )
nerve fibres differ in sensitivity - small more than large, myelinated before unmyelinated, pain is blocked before touch is.
what does use dependant mean?
these drugs are more effective when fibres are firing.
how are locals administered?
local infiltration, splash blocks, specific nerve blocks, IVRA (iv regional anaesthesia), extradural, topical.
what is EMLA?
EUTECTIC MIXTURE OF LOCAL ANAESTHETICS. mixed drugs in an oil based cream. (used for skin)
why would you add adrrenaline to locals? exception? what influences duration and distribution? absorption depends on?
locals are vasodilators - add adrenaline to cause vasoconstriction and reduce systemic absorption. (less cardiac effects). except cocaine which causes vasoconstriction.
dist and duration are influenced by protein binding and free drug acan cross the placenta.
absorption depends on where you injected it. - low = subcutaneous, brachial plexus, epidural, intercostal = high. here there is more chance of cardiac effects.
what is the metabolism and excretion of 1. esters? 2. amides?
ester - broken down by plasma esterases and excreted by kidneys. (short duration as broken down at the site)
amide - metabolised by hepatic amidases. excreted by kidney. (must go systemic).
what are some unwanted effects of locals? which drug has most heart effects?
cns -effects nerve firing and leads to tremors, resp depression, convulsions.
cvs - reduce heart. vasodilate (except cocaine)…..especially bupivicaine.
others - reduced epithelial repair, dont give i/v , allergic reactions (ester metabolites. )
