Pharmacology (Locals) Flashcards
Locals are drugs that produce a ___ interruption of neural impulses along __ and ___ pathways.
- Reversible
- sensory
- Motor
A nerve membrane is composed mostly of
biphospholipids with NA+ channels
nerve membranes are found where in unmyelinated nerves?
all throughout
nerve membranes are found where in myelinated nerves?
nodes of Ranvier
How many nodes are Ranvier need to be blocked to inhibit nerve transmission
2 successive nodes
What nerve fibers are commonly effected first?
B fibers
Type B Fibers
- Function
- Diameter
- Myelinated?
- Conduction velocity
- Pregangloinic autonomic
2.
A fiber Alpha function
proprioception & motor
A fiber Beta function
Touch & pressure
A fiber Gamma function
muscle spindles
Will local anesthetics have any impact on closed ion channels?
No, they do not work when channels are closed
Where do locals prevent neural action?
Prevent the opening of NA+ channels, thereby preventing the membrane potential from reaching threshold potential.
H gate?
Where locals are inactivated
Most commonly administered Ester Local?
Procaine (Novocaine)
What do ester locals yeild?
PABA
What is PABA? Why can it be a problem?
Para-amnio benzoic acid - is excreted UNCHANGED in the urine.
Is responsible for most producing most allergic reactions with Esters
Are there Esters in the CSF?
No
What specifically causes ester elimination?
plasma cholinesterase deficiency (genetic OR acquired)
What sets cocaine apart from other Ester locals?
partially metabolized by N-methylation and ester hydrolysis in the liver, also partially unchanged in the urine.
Cocaine - why is it a problem?
Causes reuptake of norepineprhine by adrenergic nerve terminal, causing and increase in SNS tone.Board Q
What are the amide locals? How can you tell easily?
Lidocaine (Xylocaine)
Bupivicaine (Marcaine)
Prilocaine (Citanest)
Ropivicaine (Naropin)
Most commonly administered local?
Bupivicaine (Marcaine)
How are Amides metabolized? What is significance?
microsomal enzymes in Liver, liver failure = increased DOA as well as cumulative effects.
Prilocaine - Whats the deal?
metabolized to Ortho-tulidine (O-tulidine! O-tulidine!)
- an oxidizing compound which converts hemoglobin to methemoglobin.
What is methemoglobinemia and why is it a problem? What will clinical presentation be?
What do you treat it with?
Does not carry O2 well, leads to hypoxia, cyanosis. (blue)
Tx with 02 and methelyne blue 1-2mg/kg, 7 mg/kg max
pKa
determines ONSET
since locals are WEAK BASES, prepared in acid solutions with slightly elevated pKa values above physiologic pH
Lipid solubility
POTENCY - and to a lesser degree DOA
protein binding
Duration, connected to lipid solubility
(increased DOA due to the difficulty it has dissocating from NA+ channel)
chloroprocaine possessed virtally NO protein binding, therefore short DOA
Onset is delayed if??
Why??
Onset is delayed if:
drugs’s pKa is further from 7.4
pH of environment injected into is
pKa of Common Locals….
- Bupiv
- Lido
- Prilo
- Ropiv
- Tetra
- Cocaine
- Chloroprocaine
- 8.1
- 7.9
- 7.9
- 8.1
- 8.5
- 8.7
- 8.7
Protein Binding of Locals
short acting locals:
intermediate acting:
long acting:
short:
procaine, chloroprocaine
intermediate: (LMP)
lidocaine, mepivacaine, prilocaine
long: BET (you can BET on them!)
bupivacaine (and rop)
etidocaine
tetracaine
Progression of blockade
ATP, TP, MVP (Energy, Toilet paper, MVP)
Autonomic, temperature, pain, touch, pressure, motor, proprioception
LAST
board loves this
Bupivicaine = cardiotoxicity - goes from good to code very quickly
lidocaine = more progression, more of a clue
LAST:
Plasma [ ] of LA:
r/t volume of dose, vascularity of injection site
(airway, intercostal, interplueral, caudal, BP, peripheral, spinal)
use of EPI: less systemic absorption, probably quicker onset
Epi
What does it do? Where to avoid?
produces vasoconstriction
Finger, nose, toes, hoze,
LA Toxicity
Early symptoms
Circumoral numbness Tinitus vertigo, blurred vision drowsiness restlessness, muscle twitching metalic taste in mouth
LA Toxicity
Late symptoms
What is TX??
LOC -> Coma
seizures (dangerous - CMRO2 is not lowered by LA)
apnea
CV depression
TX is supportive in nature.
LAST
Cardiac: What are s/s? Why?
Which local most implicated?
Interaction with cardiac NA+ channels
first manifested as hypotension depression of conduction and automaticity depression of contractility dysrhythmias high grade A-V block
BUPIVICAINE is selectively cardiotoxic, magnified in parturient
Intralipid
How does it work? What is %? What is dose?
Lipids accelerate the removal of local from circulation
1.5ml/KG (weight based) inrused over first minute
repeat every 3-5 minutes to maximum of 3 ml/kg
continuous = 0.25 ml/kg/min - until HEMODYNAMIC Recovery-
What is ion trapping?
what block is it most common?
What locals are most common for this to occur with?
local crosses placenta and becomes more ionized in relatively acidic fetus
“becomes trapped” - may cayse systemic toxicity in fetus
noted with paracervical blocks
less likely to happen with esters due to rapid metabolism, also drugs HIGHLY protein bound more slowly cross barrier.
Most common Locals: Mepivicaine & prilocaine (not highly protein bound)
Why specifically what does adding NaHCO3 do to LAs?
Adding NaHCO3 (Bicarb) will raise the pH of the solution. This speeds onset of block because more of the LA exists in the unionized form (AKA buffering) lidocaine -> 1mEq/10 ml of local bupivicaine -> 0.1 mEq/20 ml of local (will PPT with higher volume of bicarb)
Active metabolites of Lidocaine?
MEGX - monothylglycinexylidide
GX - glycinexylidide
EMLA cream is what?
eutectic mixture of lidocaine and prilocaine
5% EMLA cream topically applied for 45 minutes or more greatly reduces the pain associated with venipuncture in the pediatric population
methemoglobinemia possible but rare (topical sprays like cetacaine can be a problem in GI suites)
