LA Pharmacology 1 Flashcards
explain the structure of LA
lipophilic ring end so can diffuse through membrane
hydrophilic end to bind to Na channel
middle intermediate chain with either ester or amide. We use amide LA
how does LA work?
by reversibly blocking Na+ channels which blocks the action potential
what are the two theories as to how LA works?
membrane expansion theory
specific receptor theory
what is the membrane expansion theory?
anaesthetic caught up in the membrane, filling space in the membrane and squashes the channels shut
what is the specific receptor theory?
anaesthetic outside the cell must diffuse inside the nerve (hence lipophilic), it will then bind to the inactivation gate in the sodium channel to keep it shut
LA drugs are poorly soluble in aqueous environment. When it is dissolved it exists in 2 states in equilibrium.
what are the two states?
uncharged LA
charged LA
explain the path charged and uncharged LA take to bind to Na channels
Uncharged LA will go through the membrane into the nerve, it re-equilibrates into a proportion of charged and uncharged in the nerve. Its the charged part that then binds to the channel protein.
how does low pH affect LA using this equation
lots of H+ so pushes reaction towards charged LA, less uncharged LA, so less diffuses across membrane, less gets recharged so less binds to sodium channels
name three properties of LA
protein binding
vasodilators
lipid solubility
explain the LA property protein binding
Binds to large plasma proteins that provide a pool of anaesthetic that is slowly released so increased duration (Bupivicaine and Articaine)
explain the LA property of vasodiltion
muscle contraction controlled by electrical signals so Na+ channel blockers relax muscle. Increased blood flow increases uptake so LA wears off faster (least vasodilatory - prilocaine and mepivacaine)
explain the LA property of lipid solubility
High lipid solubility will easily pass through nerve membrane so faster onset (articaine has high lipid solubility)
what happens when LA enters the blood stream?
its affect is lost
it may enter an organ
which organs are highly perfused and thus likely for LA to enter?
brain
liver
kidneys
placenta
how does LA affect the CNS?
depresses it
how does LA affect peripheral vessels?
vasodilation -> hypotension
how does LA affect the respiratory system?
bronchodilation
how does LA affect the myocardium?
calms the heart by reducing excitability and conductivity
what are the 3 that LA can metabolise in?
plasma
lungs
liver
where is most LA metabolised?
liver
where is articaine metabolised? what does this mean?
plasma and liver therefore seen safer as has short half life
name 3 things vasoconstrictors do
extend duration of LA
reduce circulating LA conc.
reduce haemorrhage (bleeding)
name 2 vasoconstrictors and their manufacturing name
adrenaline - epinephrine
fellypressin - octapressin
how does adrenaline (epinephrine) work?
Binds to a1 receptors in arterial blood vessels causing vasoconstriction reducing blood flow to and from a tissue
its not possible to be allergic to adrenaline, if a patient says they are allergic what is the likely cause?
they are allergic to the preservative as adrenaline requires it.
how does fellypressin (octapressin) work?
Vasoconstriction on venous blood so doesn’t reduce blood flow in only out of tissue so not as good as adrenaline
when should fellypressin be avoided? why?
Pregnancy: avoid due to mild oxytocic effect (oxytocin given to induce labour)
name 4 LA and their manufacture name in order of most used
lidocain (lignospan special)
prilocaine (citanest)
mepivacaine (scandonest)
articaine (septanest)
what is the anaesthetic in lidocaine?
lidocaine hydrochloride
what is the vasoconstrictor in lidocaine?
adrenaline
is there preservative in lidocaine?
yes
what is the maximum dose per kg and absolute max dose of lidocaine?
4.4mg/kg
300mg
when is lidocaine used?
most of the time
when should lidocaine not be used?
cardiac conditions
allergy to preservative
tricyclic antidepressants
mono-amine oxdiase inhibitors (antidepressants)
what is the anaesthetic in prilocaine?
prilocaine hydrochloride
what is the vasoconstrictor in prilocaine?
fellypressin
is there preservative in prilocaine?
no
what is the maximum dose per kg and absolute max dose of prilocaine?
6mg/kg
400mg
when should prilocaine be used?
Use as alternative to lidocaine to avoid adrenaline or if preservative allergy
when should prilocaine not be used?
pregnancy
which LA is the least vasodilatory?
mepivacaine
what is the anaesthetic in mepivacaine?
mepivacaine hydrochloride
what is the vasoconstrictor in mepivacaine?
none
what is the preservative in mepivacaine?
none
what is the maximum dose per kg and absolute max dose of mepivacaine
4.4mg per kg
300mg
when should mepivacaine be used?
as alternative to prilocaine
what is the vasoconstrictor in articaine?
adrenaline
is there preservative in articaine?
yes
when should articaine be used?
potentially as alternative to inferior alveolar blocks
what cautions do we have to reduce the dose for?
liver disease
beta blockers
calcium chain blockers
drug abuse
