Local Anesthetics Flashcards
In general, the _______ the pKa of the LA, the ________ the proportion of LA in nonionized form at pH= 7.4, and the _______ the onset of the conduction block.
lower; greater; faster
What local anesthetic is the MOST nonionized at pH 7.4?
Mepivacaine b\c some sources say the pKa is 7.6…. some say 7.7…. which if that is the case, then lidocaine and etidocaine have the same
Why does chloroprocaine have a fast onset despite its high pKa?
d\t the high concentration of the drug injected
How do LA’s block nerve conduction?
by blocking (impairing) propagation of the action potential along axons–> by directly acting on sodium channels and inhibiting sodium influx
What determines the SPEED of onset?
pKa
LA’s with a lower pKa will have a faster onset
Remember is you take LSD you’ll have to Pee Pee Pee.
P—–S (pKa=speed of onset)
L—–P (lipid solubility=potency)
P—–D (protein binding=duration of action)
What determines the POTENCY of LA’s?
lipid solubility
a LA with a high lipid solubility is very potent
What determines the DURATION OF ACTION of LA’s?
protein binding
LA’s that are highly protein bound will have a prolonged DOA
The ______ the oil:water partition coefficient, the ______ the lipid solubility.
greater; greater
The _______ coefficient provides a measure of lipid solubility.
oil:water partition coefficient
Why do you need a higher concentration of lidocaine (ex: 2%) vs bupivacaine (ex: 0.25%)?
b\c bupivacaine has a higher oil:water partition coefficient (30 compared to 4)–> so it is more lipid soluble, therefore potent… so you need less of it to provide the effect
______ serve as storage depots for the LA’s; as anesthetic diffuses, more become unbound maintaining the supply of anesthetic to nerve axons.
proteins (protein binding)—> directly correlated to the duration of action
What is responsible for the binding of weak bases?
alpha-1 acid glycoprotein
What is the second factor that determines the duration of action of local anesthetics?
lipid solubility
*when injected, the LA with higher lipid solubility will dissolve to a greater extent into surrounding lipids–> the lipids act as a reservoir for lipid soluble agents
What single change in a property of a LA will result in a more potent and longer acting agent?
increase lipid solubility will increase DOA and potency
Name two short acting LA’s.
1) Procaine
2) Chloroprocaine
Name two moderate acting LA’s.
1) Lidocaine
2) Mepivacaine
Name 4 long acting LA’s.
1) tetracaine
2) etidocaine
3) bupivacaine
4) ropivacaine
Loss of an anesthetic from the injection site is primarily by ________.
vascular absorption
What 2 factors can influence the rate of absorption of LA from injection sites?
1) presence of vasoconstrictor–> EPI may increase the duration of spinal anesthesia by 75-100% (decreases BF and slows removal)
2) high blood flow to tissue where anesthetic is injected–> the greater the blood flow, the faster the agent is absorbed and washed away from the site
Is blood concentration higher after epidural anesthesia or a subarachnoid block?
epidural–> receives higher blood flow–> higher toxicity risk
Rank the tissues from highest to lowest blood flow.
1) IV
2) tracheal
3) intercostal
4) caudal
5) paracervical
6) epidural
7) brachial plexus
8) subarachnoid, sciatic, femoral
9) subcutaneous
* greatest to least for risk of LA toxicity
* I Think I Can Push Each Bolus SSlowly For Safety
What are 3 non-physiochemical properties that prolong conduction blocks?
1) presence of vasoconstrictor
2) concentration of LA injected (>concentration = > DOA)
3) blood flow–> lower blood flow in the tissues = > DOA
Is the ionized or nonionized form of the local anesthetic needed to block nerve conduction?
BOTH= nonionized LA diffuses into the nerve axon—> ionized form binds to receptors on the Na channel when the channel is in the inactivated state–> action potentials cannot be generated
For myelinated axons, ______ nodes of Ranvier must be blocked to stop nerve conduction.
2-3
Conduction block is _______ dependent.
frequency
*the > the frequency of action potentials, the faster the nerve is blocked by LA–> the LA must bind to the Na channel when it is in the inactivated state–> the faster the nerve is firing, the more opportunities the LA will have to catch the Na channel in the inactivated state
Voltage gated Na channels are found only in ______.
the nerve’s axon
Sympathetic block is ____ to _____ dermatomes ______ than sensory block.
2-6 higher than sensory
Motor block is ______ dermatomes _______ than sensory block.
2 lower than sensory
Ester local anesthetics are metabolized by ________.
plasma pseudocholinesterase
Amides are metabolized by the _______.
LIVER
am”I”de–>l”I”ver
What is the MAX dose for chloroprocaine?
12mg/kg (duration 0.5-1hr)
What is the MAX dose for cocaine?
3mg/kg (duration 0.5-1hr)
What is the MAX dose for procaine?
12mg/kg (duration 0.5-1hr)
What is the MAX dose for tetracaine?
3mg/kg (duration 1.5-6hr)
What is the MAX dose for bupivacaine and ropivacaine?
3mg/kg (duration 1.5-8hr)
What is the MAX dose for lidocaine and mepivacaine?
4.5mg/kg without EPI
7mg/kg with EPI
lidocaine duration= 0.75-2hr
mepivacaine duration= 1-2hr
What is the MAX dose for prilocaine?
8mg/kg
duration= 0.5-1hr
What is the treatment for local anesthetic toxicity?
1) airway
2) breathing
3) circulation
* Drugs:
- lipid emulsion (20% Intralipid) 1.5mL/kg, followed by continuous infusion of 0.25ml/kg/min
- benzo’s to treat seizures, small amount of propofol in benzo are not available, but no propofol in the context of cardiovascular instability
- AVOID vasopressin, CCB’s, beta blockers, and local anesthetics
- muscle relaxants to secure airway
What is the initial dosing of _____% lipid emulsion (Intralipid) in the case of LA toxicity?
20%; 1.5ml/kg
With methemoglobin, Fe2 (ferrous) becomes ________. What is the treatment?
Fe3 (ferric); Tx= methylene blue 1-2 mg/kg
normal Hgb has iron in the ferrous (Fe++) state, oxygen carried by normal Hb is excellent–> Met-Hb has iron in the ferric (Fe+++) state, oxygen carrying capacity Met-Hb is poor
What is the normal (“therapeutic”) plasma concentration of lidocaine?
1-5 mcg/mL= analgesia, therapeutic
What is the plasma concentration of lidocaine where you will begin to see early s/s of toxicity?
x2 of normal, so 5-10 mcg/ml
What are the early s/s of lidocaine toxicity?
lightheaded, tinnitus, visual disturbances, numbness of tongue, muscle twitching
*almost like being drunk and then getting tazed
List the s/s of lidocaine toxicity from early to late.
lightheaded, ears ringing, vision disturbed, numb tongue, muscles twitching, seizures and convulsions–> unconsciousness into coma into respiratory arrest into cardiovascular depression
What plasma concentration of lidocaine is required to reach cardiovascular depression?
> 25 mcg/ml
What plasma concentration of lidocaine is required to reach seizures and convulsions?
10-15 mcg/ml
What plasma concentration of lidocaine is required to reach unconsciousness to coma to respiratory arrest?
15-25 mcg/ml
What plasma concentration of lidocaine is required to reach lightheadedness, tinnitus, visual disturbances, numbness of the tongue, and muscle twitching?
5-10 mcg/ml
_______ is the LA to which all others are compared.
lidocaine
The action of _______ local anesthetics would be prolonged in the patient with atypical pseudocholinesterase.
ester
Chronic therapy with acetylcholinesterase inhibitors (edrophonium, physostigmine, echothiophate) prolongs the action of ______ LA’s b\c these agents depress _________ function.
ester; pseudocholinesterase
What is the end product of ester metabolism?
PABA–> para-aminobenzoic acid
this metabolite may mediate the hypersensitivity reactions to ester LA’s
How does cocaine differ from other local anesthetics?
1) vasoconstrictor
2) naturally occurring
Why is Chloroprocaine a suitable anesthetic for obstetric practice?
1) rapidly metabolized by plasma cholinesterase
this means plasma levels are kept low (important b\c LA’s cross the placenta)–> in order to protect fetus from toxic levels of LA, an agent that has its blood levels kept low is advantageous
______ is hydrolyzed by plasma cholinesterase much more slowly than procaine or chloroprocaine.
tetracaine
Dibucaine is about ____ times more toxic than procaine.
15
If pseudocholinesterase is normal, dibucaine will depress the activity of pseudocholinesterase by _____%.
70-85%= dibucaine number
If the dibucaine # is _____, the individual is a homozygote for the abnormal (atypical) pseudocholinesterase.
20
If the dibucaine # is _____, the individual is a heterozygote for the abnormal (atypical) pseudocholinesterase.
30-70
What is the clinical concern for patients with atypical pseudocholinesterase?
1) the lower the dibucaine number, the slower the hydrolysis of Sux
2) toxicity of ester local anesthetics is MORE likely
Which local anesthetic can lead to methemoglobinemia and why?
prilocaine–> metabolite is O-toluidine which may lead to methemoglobinemia
The dose of local anesthetic administered epidurally should be reduced by _____% in the parturient.
25-50%
What is the cause of hypotension following spinal and epidural anesthesia?
blockage of sympathetic preganglionic nerves–> relaxation of arterial and venous vascular smooth muscle–> decreases SVR and reduced venous return–> decreases arterial BP (the decrease in preload is the biggest factor of hypotension)
If beta effects are not desirable, what can be given instead of EPI with a local anesthetic?
1:20,000 phenylephrine
The risk of aspiration pneumonitis is increased when gastric pH and gastric volume are:_____ and _______.
25mL
What agent consistently reduces gastric volume and the acidity of gastric contents?
ranitidine
Alfentanil is eliminated faster than sufentanil b\c alfentanil has a _______ volume of distribution than sufentanil.
smaller
A drug will be eliminated slowly if its clearance is ______ and volume of distribution is ______.
small; large
What segment of the neuron does local anesthetics work on?
the axon only
Duration of action of local anesthetics is determined by?? (2 things)
BOTH lipid solubility and protein binding
