Amides - list drugs:
- lidocaine
- articaine
- mapivacaine
- etidocaine
- prilocaine
- bupivacaine
- ropivacaine
- levobupivacaine
Esters - list drugs:
- procaine
- cocaine
- chloroprocaine
- tetracaine
- benzocaine
local anesthesia definition:
loss of sensation limited to a local area or region of the body
local anesthetic definition:
drug that blocks generation and propagation of nerve impulse that results in reversible, regional loss of function (analgesia)
local anesthesia advantages and disadvantages:
adv:
-drug is delivered directly to target organ - minimal loss of function=increased safety bc less disruption of organ systems
disadv:
-high concentration in small area may increase potential for systemic toxicity, poor min-min control and may not be adequate for procedure
Clinical uses for local anesthetics:
- topical
- perineural infiltration- need a lot of drug but easy to administer
- nerve block- less drug but needs to be skillful administered in a specific spot
- spinal block-into subarachnoid-large body area blocked but all areas distal to block are also useless - HYPOTENSION or could reach the brain
- epidural block- injection into extradural space- not in spinal canal yet blocks large area
Local anesthetics - MOA:
- *-blockade of voltage gated sodium channels
- decrease in generation and conduction of action potentials
- inh of Na and K conductance
- inh of depolarization and repolarization
Local anesthetics - sites of action:
- biotoxins (saxitoxins, tetrodotoxin) - EXTRACELLULAR PART - no man made drugs hit this site
- lidocaine (receptor theory) (INTRACELLULAR PART)
- benzococaine (uncharged) (IN LIPID BILAYER –> DISTURB GEOMETRY OF ION CHANNEL) (membrane expansion theory)
- combo lido and benzo (most clinically used
Two major Local anesthetic drug classifications?
amides
esters
figuring out which name is amide and which is ester?
- end in “-caine” suffix
- usually amides have 2 i’s in their name while esters have only 1 i.
Local anesthetic properties:
- weak bases - available as salts
- cationic form (LAH+) = msot active form at sodium receptor
- uncharged form (LA) = important for lipid penetration of membraness
- rapid absorption in highly vascular areas
- smaller and more lipophilic LAs are more potent, have faster rate of interaction with sodium channels and have longer duration of action
**Amides properties:
- *-longer halflife and longer duration of action
- half-life altered with liver issues
**Esters properties:
- short plasma half-life = short duration of action
- rapid metabolism by hydrolysis via butyrylcholinesterase (BChE)
- excreted in urine
Factors that influence LA onset and recovery of nerves - factors:
1) FIBER SIZE:
a) LAs block all nerves - not just nociceptors
b) smallest fibers most sensitive
c) myelinated more sensitive
d) blocking effect:
1st—–B (preganglionic, small, myelinated)
—–C (small, non-myelin–>slow pain and temp)
—–A-delta (medium, myelin–>fast pain, temp, crude touch)
—–A-gamma (medium, myelin–>muscle spindle)
—–A-beta (large, myelin - discriminative touch)
last—–A-alpha (motor, proprioception)
2) SITE OF DEPOSITION: anesthesia occurs first at the outer fibers as the drug moves down conc gradient
3) pH: inc pH = dec Cm (inc potency)
4) nerve stimulation rate: higher frequency nerves (Sensory) are more sensitive
5) Ca conc: Inc Ca = inc Cm (dec potency)
6) Addition of vasoconstrictors:
- epinephrine, phenylephrine, levonordefrin
- increase duration of action
- increase in local neuronal abs at site of drug administration
- vasoconstrictor substances reduce local blood flow and reduce systemic abs and toxicity
**minimum anesthetic concentration (Cm) =
=minimum concenration of drug for standard block
=relative standard of potency
Increase fiber size = _____ Cm?
increase Cm
INC POTENCY = relationship to Cm
DEC Cm
DO NOT DO what what with LA and vasoconstrictor?
Do not inject LA with vasoconstrictor into areas with end arterioles ex) digits, toes, ear lobe, nose, penis)
=== potential development of gangrene or sloughing of tissue due to impaired blood flow
factors that affect reversal of LA:
1) dilution by ECF - reduces concentration of LA in ICF
* **2) absorption into circulation: MOST IMPORTANT- depends on local blood supply (vascularity), metabolism dependent
3) redistribution to other areas: function of organ blood flow and plasma protein binding (drugs with little protein binding produce less toxicity)
4) use of vasoconstrictors (epinephrine etc): decrease in blood flow== increase duration of action
Metabolism of amides:
- liver by p450 enzymes into INACTIVE METABOLITE
- longer halflife and longer duration of action
- **ALTERED IN PATIENTS WITH LIVER ISSUES
Metabolism of esters:
- plasma by BChE into inactive metabolite (PABA moiety)
- short plasma halflife == short duration of action
- **PABA is prone to allergic reactions!!! Check patient Hx for PABA allergies
Adverse effects and toxicity - LAs:
1) hypersensitivity - esters due to PABA metabolite but ANY drug has potential for hypersensitivity
2) Systemic tox: all can have systemic tox but less likely with esters due to raid metabolism in blood – AMIDE MORE PRONE TO SYSTEMIC TOX BC MET IN LVIER
more prone to systemic tox?
Amides
more prone to allergic reaction?
esters
