Test 3: 34 local Flashcards
what is a local anesthetic
drug that causes reversible loss of sensory perception and motor function, in a localized area of the body
lidocaine is used because
antiarrhythmic
prokinetic
MAC reduction
analgesia
systemic administration
local anesthetics work on what type of channels
periphery: Na channels
dorsal horn spinal cord: LAs inhibit K+ or Ca2+ channels, inhibit substance P binding and reduce glutamatergic transmission by reducing N-methyl-D-aspartate (NMDA) postsynaptic depolarization. Work on serotoninergic and AcH receptors
how does lidocaine effect Na channels
lidocaine either ionized or uncharged
uncharged version will cross lipid membrane, become ionized and bind to inside of Na Channel from the intracellular side
this will prevent Na channel from opening and prevents Na from entering the cell → can can not depolarize and send signal
if the local has an ester group it will be broken down by
hydrolyzed by plasma esterases
if local has an amide group it will be broken down in
metabolized in the liver
All clinically useful local anesthetics are —, and as such they exist in equilibrium between the neutral, non‐ionized, lipid soluble form (B) and the ionized (charged), water‐soluble form (BH+).
weak bases
The neutral/uncharged form is — and easily crosses the cell membrane. The — form is more water soluble and can cross only through the open channel.
lipid soluble
ionized
what three physiochemical properties control the effect of Local
The pKa of a LA determines the onset of the pharmacological effect
The lipid solubility of a LA determines its potency
The protein binding (of a LA with serum proteins) determines the duration of the pharmacological action
what is the pKa for most LA
ph>7.4
The — the pKa, the greater the degree of ionization or proportion of local anesthetic in the ionized, charged, hydrophilic form at physiologic pH (7.4), and the — the onset of action.
higher
slower
(if LA is in ionized form it can not cross through membrane, takes longer for effect to happen)
a local anesthetic with a — pKa will have a greater proportion of the non-ionized lipid-soluble form at physiologic pH and a more — onset of action.
low
rapid
(at a pka< 7.4, the LA will be in the nonionized, neutral form, it can easily move across membranes and attach to NA channels on the intercellular side → rapid onset)
Increasing lipid solubility facilitates the penetration through lipid membranes, potentially — onset of action.
hastening
the more lipid soluble the greater the potency of a drug
the lower the lipid solubility, the — the potency
lower
Higher protein binding is associated with — duration of action
increased
only free, unbound drug is active, if most of the drug is bound to protein, it will take a long time to use up the drug
lidocaine, procaine, and tetracaine have what chirality?
achiral
what are some S-enantiomer LA
Left: leviosomers
levobupivacaine and ropivacaine
they are less toxic then their Right versions (bupivicane)
what is differential blockade
Some LA can produce vasodilation →loss of sensory → motor loss based on dose of med given
Ropivacaine > Bupivacaine > Lidocaine = Mepivacaine
Local anesthetics with an amide group, high pKa, and lower lipid solubility show greater differential blockade
if you give low dose ropivacaine what will happen
differential blockade
at low does will have vasodilation and some sensory loss, but motor still intact
if you increase dose will lose all three
what length exposed to drug is important for differential pattern
three or more nodes of Ranvier
Therefore, larger fibers with greater internodal distances are less susceptible to local anesthetic blockade
decremental conduction
usually need 3 nodes of ranvier for effect
DC: describes the diminished ability of successive nodes of Ranvier to propagate the impulse in the presence of a local anesthetic. This principle explains why the propagation of an impulse can be stopped even if none of the nodes has been rendered completely unexcitable, as occurs for example with low concentrations of local anesthetics.
which type of nerve fiber is blocked first with LA
B > C = A-δ > A𝛄 > Aβ > A⍺
Systemic absorption depends on several factors including
site vascularity: ↑ vessels= ↑ absorption
intrinsic vasocativity: vasodilators ↑ absorption, constrictors (ropivacaine and levobupivacaine) ↓ absorption
lipid solubility, protin binding, dose
the lower the systemic absorption the safer the med, increased systemic absorption can be toxic
which LA injection site has increased vascularity
intercostal > epidural > brachial plexus > sciatic/femoral
which LA are vasoconstrictive
ropivacaine and levobupivacaine
constriction will lead to slower systemic absorption →less toxicity
if you add epi to lidocaine will it dilate or constrict vessels
lidocaine- dilate
epi- constrict
constriction wins= less systemic absorption of LA
what type of LA is widely distributed throughout body
amino-amides
amino-ester LA are rapidly hydrolyzed = ↓ distribution
explain 1st pass pulmonary uptake
amino-amides LA are widely distributed throughout the body
amino-amides will go through 1st pass pulmonary uptake = lung will absorb a lot of the lipid-soluable, ↓pKa drugs (bupivacaine> lidocaine)
increased risk of toxicity if R-L cardiac shunt (drug doesn’t get to lungs to be cleaned out)
increased risk if ↓ blood pH, cause that will ↑ ionized form of meds and lungs abdorb the unionized version
what happens when LA amino-amides get into placenta
ion trapping
maternal pH is higher then the baby, the lower pH makes more ionized form of LA, that can not cross back out of baby
use — LA in pregnant pts to prevent ion trapping
lidocaine > bupivacaine
breakdown of benzocaine and procaine can produce —
PABA → rare allergic reaction
amino-ester LA that are hydrolyzed by plasma pseudocholinesterases
Prilocaine is broken down by — and forms —
prilocaine is an amino-amide
metabolized in liver by CYP450
makes toxic metabolite methemoglobin
lidocaine is broken down by — and makes —
Lidocaine= amino-amide LA
broken down in liver by CYP450
produce MGEX toxic
The dose of a local anesthetic causing systemic toxicity will depend on the —
route and speed of administration (rapid intravenous administration will be more likely to cause high plasma levels),
the species involved
patient factors (such as acid–base balance, serum potassium levels)
more lipid soluble drugs will be more potent
R-enantiomers more toxic
what are signs of LA toxicity
CNS: excitation, seizure, depression and coma
cardiac: ↓Na into a cell= prolonged PR and QRS intervals = bradycardia, ↓BP, ↓ contractility, asystole
↑potassium = toxic
how does increased PaCO2 lead to ↑ risk of seizures with LA
↑PaCO2= vasodilation in the brain= more LA into the brain = ↑ toxicity → seizures
how does increased PaO2 protect from seizures from LA
hypoxemia increases the CNS and cardiovascular toxicity of local anesthetics
high O2 vasoconstrictive?
how to treat LA overdose
supportive care: oxygen, ventilation
may need to do CPR, epi and difibrillate
DO NOT USE LIDOCAINE to treat arrhythmias: use amiodarone or IV lipid emulsion
local LA can be neurotoxic to — cells and is — dependent
schwann cells
time and concentration
mepivacaine < lidocaine < ropivacaine < bupivacaine.
local LA can be myotoxic to —- and is — dependent
skeletal muscle: mess up intracellular Ca and mitochondria
concentration dependent
bupivacaine is worse
LA can be chondrotoxic if — and are — dependent
intra-articular injection
time and concentration dependent
mepivacaine < ropivacaine < bupivacaine= lidocaine
which LA can produce methemoglobin when broken down
ester type: benzocaine and amide type prilocaine
chocolate brown colored blood- not responsive to O2 therapy- need to treat with methylene blue or blood transfusions in severe cases
it is recommended that animals known to be allergic to ester‐type local anesthetics be treated with a —
preservative‐free amide‐type agent
procaine: ester: forms PABA when metabolized, can be allergic
procaine
amino ester LA
fast onset
30-60 min duration
CNS stimulant in horse if given IV
metabolism → PABA→allergic reactions
benzocaine
fast acting
topical only
amino ester LA → PABA → allergic reaction
Can also cause Methemoglobinemia in small animal
used for fish
Tetracaine
amino ester LA
rarely used due to very slow onset when administered in the periphery and potential for systemic toxicity
excelent topical anesthetic
lidocaine
amino-amide LA
- fast onset, 1 hrs duration
- inflitration, nerve blocks, epidural and intrathecal blocks, and intravenous regional anesthesia
- EMLA cream, patches
analgesia from action at Na+, Ca2+, and K+ channels and the NMDA receptors.
Class Ib antiarrhythmic drug
some anti‐inflammatory effects
prokinetic in horses: prevent post op ileus by improving GI motility
mepivacaine
amino-amide LA
* fast onset, 1-2 hrs
* infiltration, nerve block
* poor topical
* low neurotoxicity- use for horses
* very slow metabilism in fetus and newborns
bupivacaine
amino-amides LA
* highly lipophilic= 4 x more potent then lidocaine
* slow onset (20-30 mins), long duration 3-10 hrs
* infiltrative, peripheral nerve, epidural, and intrathecal blocks
* poor topical
* NO IV → cardiotoxic
Levobupivacaine: levoisomer or S‐enantiomer of bupivacaine →less cardiotoxic
Ropivacaine
amino-amide LA
* S- enatiomer = ↓ CV toxic
* similar onset to bupivacaine (20-30 mins), duration (6 hrs)
* infiltrative, peripheral nerve, epidural, and intrathecal blocks
* Biphasic effect of vasculature
* > 1% vasodilation
* < 0.5% vasoconstriction
why add epinephrine to local
it causes vasoconstriction → Decreased systemic absorption and longer duration
- decreases local blood flow to nerves and spinal cord → can cause ischemia
- systemic absoprtion will cause CV effects
1: 200,000 (5 mcg/ml)
what will bicarb do to LA
↑pH= ↑ unionized form = shorter onset
* efficacy depends on LA and location
* decreases pain of injection
1 mEq/10ml
what will adding an ⍺2 agonist do to LA
enhances sensory and motor blockade
* receptors not involved- hyperpolarized C fibers
shorter onset, longer duration of sensory and motor block, enhanced block quality, lower pain scores, and decreased systemic opioid requirements
nocita
72 hr analgesia
multivesicular liposomes, that encapsulate aqueous bupivacaine
