Local Anesthetic Drugs Flashcards
What is the elimination half life of prilocaine, lidocaine and bupivacaine?
Prilocaine: fastest (elimination ½ t 96 min) versus lidocaine (96 min) versus bupivacaine (210 min)
What is the onset of lidocaine?
Rapid onset
What is the duration after inflitration of lidocaine?
60-120 min
What is the pKa and protein binding of Lidocaine?
Protein binding 70%; pKa 7.9
What is the max dose of lidocaine?
300 mg (5mg/kg plain; 7 mg/kg with epi)
What is the clinical concentrations of lidocaine?
- Topical spray 4%
- Topical gel 2%
- Infiltration 0.5-1%
- Tracheal (LTA) 4%
- Spinal 5%
- Epidural 1-2%
- IV Bier block 0.5%
What is the metabolism of lidocaine?
liver mainly CYP 34A (dealkylation) to main active metabolite monoethylglycinexylidide (MEGX) and lesser metabolite xylidide (10% active)
What accounts for the prolonged antidysrhythmic properties of lidocaine?
active metabolite monoethyl
What impact does hepatic disease have on lidocaine?
Affected by hepatic disease/⬇️ hepatic blood flow (5 fold)
Why has use of lidocaine with spinals decreased?
Use for spinal anesthesia has declined due to concerns about neurotoxicity and transient neurological symptoms (TNS)
What is the most concern with lidocaine?
Causes vasodilation at most concentrations
What can be added to lidocaine to prevent the vasodilation?
The addition of epinephrine can significantly reduce absorption of lidocaine by nearby vessels, allowing more of the initially administered dose to enter the neural compartment, thereby prolonging the duration of action by as much as 50%
What is true about clearance of lidocaine and pregnancy?
Maternal clearance of lidocaine is prolonged in the presence of pregnancy-induced hypertension
What is prilocaine similar to?
Similar clinical profile as lidocaine
What are the uses of prilocaine?
Used for infiltration, peripheral nerve blocks (PNB), spinal, and epidural anesthesia
What is different with prilocaine then with lidocaine?
Causes significantly less vasodilation than lidocaine
What is not needed with prilocaine?
Addition of epinephrine is not necessary to prolong duration of action
What characteristic is specific to prilocaine?
Least systemic toxicity of all amide local anesthetics
What can prilocaine cause?
Can cause methemoglobinemia (>600 mg dose) due to its metabolite orthotoluidine (Limits its clinical usefulness)
What is orthotoludiine?
converts hemoglobin to its oxidized form, methemoglobin
How will a patient present with methemoglobinemia?
Patient may appear cyanotic and oxygen carrying capacity is decreased
What is the treatment for Methemeglobinemia?
readily reversed by administering methylene blue 1-2 mg/kg IV over 5 minutes (do not exceed 7-8 mg/kg)
What shift will occur on the oxyhemoglobin curve with Methemeglobinemia?
Left shift of oxygen-dissociation curve
What other substances are associated with Methemeglobinemia?
- Topical local anesthetics (benzocaine, prilocaine, lidocaine)
- NTG
- Phenytoin
- Sulfonamides
Central cyanosis occurs when methemoglobin concentrations exceed ________%
15%
When is Methemeglobinemia
suspected?
Suspect when oxygen “saturation gap” between arterial blood saturation and pulse oximetry; dx w/ co-oximetry
How does Methylene blue treat Methemoglobinemia?
acts as electron donor and nonenzymatically reduces methemoglobin to hemoglobin
When should normal Normal levels of methemoglobin be reached after methylene blue administration?
20-60 minutes
What is true regarding the effects of methemoglobinemia as methylene blue is cleared?
Effects is short-lived as methylene blue cleared before total conversion
What is the pharmacological properties of mepivacaine (Carbocaine)?
Pharmacologic properties similar to lidocaine-Longer duration of action
Why should mepivacaine (Carbocaine) not be used for obstetric anesthesia?
- Metabolism is prolonged (leading to a decrease in clearance) in the fetus and newborn
- pKa 7.6 – crosses placenta
What is not needed with mepivacaine (Carbocaine)?
Lacks vasodilator activity – no need to add epinephrine (alternative when epi is not recommended)
What is the onset of Bupivacaine (Marcaine)?
Slow Onset
What is the duration after infiltration of Bupivacaine (Marcaine)?
240-480 min
What is the protein binding and pKa of Bupivacaine (Marcaine)?
Protein binding: 95%; pKa 8.1
What is the max dose of Bupivacaine (Marcaine)?
175 mg (2.5 mg/kg plain; 3mg/kg with epi)
What is the chemical structure of Bupivacaine (Marcaine)?
Racemic mixture of both the R and S enantiomers, provides prolonged and intense sensory analgesia which often outlasts the motor block
What is Bupivacaine (Marcaine) used for?
Used in infiltration, PNBs, spinals, epidurals
What is the concentration of epidural analgesia and anesthesia with Bupivacaine (Marcaine)?
Epidural analgesia and anesthesia: used in concentrations of 0.25-0.5% with a 2-5 hour duration of action
What the duration of PNBs with Bupivacaine (Marcaine)?
12-24 hours
What is the characteristics of the intrathecal use of Bupivacaine (Marcaine)?
- provides 2-3 hours of anesthesia and 4-6 hours of analgesia
- Epinephrine sometimes added as a marker for intravascular injection and to prolong duration of action
What are the metabolisms of Bupivacaine (Marcaine)?
Possible pathways for metabolism include aromatic hydroxylation, N-dealkylation, amide hydrolysis, and conjugation
What is the most important plasma protein binding site of Bupivacaine (Marcaine)?
Alpha 1 –acid glycoprotein,
96% protein bound
What has been reported with Bupivacaine (Marcaine)?
- Reports of sudden cardiac arrest associated with significant morbidity and mortality
- Due to high affinity for Na+ channels and high lipid solubility
When is the 0.75% concentration of Bupivacaine (Marcaine) not used?
in labor epidurals because of the associated mortality/toxicity
What is liposomal local anesthetics?
incorporating local anesthetic into liposomes for the purpose of prolonging the duration of action and decrease toxicity
What is the goal of liposomal local anesthetics (bupivacaine)?
to upload higher amount of local anesthetic into the liposome molecule and have a consistent release of local anesthetic in the tissues;
What are the pk of liposomes?
liposomes are hydrophobic-based polymer particles which are then combined with a LA
What medications can be incorporated into liposomes? What effect does this have?
bupivacaine, lidocaine, & tetracaine have been incorporated into liposomes to prolong the duration of action and decrease toxicity
What is liposomal bupivacaine?
is then released from the liposome particles over a period of 96 hours
What is not recommended with liposomal bupivacaine?
mixing liposomal bupivacaine with nonbupivacaine-based LA incl lidocaine, is not recommended
What is the name for the bupivacaine liposome injectable suspension?
Exparel
What are some indications for Exparel (bupivacaine liposome injectable suspension)?
- Local infiltration of surgical site
- Peripheral Nerve Blocks (interscalene brachial plexus block, transversus abdominis plane [TAP] block)
What is the max does of Exparel(bupivacaine liposome injectable suspension)?
Dose not to exceed 266 mg (20 ml)
How long can Exparel(bupivacaine liposome injectable suspension) provide analgesia?
Provides 48-72 hours of analgesia
What are not routes of Exparel(bupivacaine liposome injectable suspension) delivery?
Not for IV, epidural, or intrathecal administration
What is Exparel(bupivacaine liposome injectable suspension) commonly coadministered with?
0.25-0.5% bupivacaine
What can Exparel(bupivacaine liposome injectable suspension) not be administered with?
NOT lidocaine: Lidocaine will alter the release of drug from DepoFoam structure
What led to the development of ropivacaine?
Concerns about the cardiotoxicity of bupivacaine led to the development of ropivacaine (S-isomer) So is levobupivacaine
What is the structure of ropivacaine?
Structurally similar to bupivacaine, but as a single, less toxic enantiomer
What are the properties of the S-isomer of ropivacaine?
S-isomer = Less lipid soluble, less potent, less cardiotoxic than bupivacaine
How is ropivacaine given?
Given via the epidural route, greater sensory block without significant motor block
What effects the duration and decreased risk of cardiotoxicity of ropivacaine?
Intrinsic vasoconstricting effect augments the duration of action and reduces the incidence of cardiotoxicity
What is the metabolism of ropivacaine?
Metabolized into 2 metabolites by hepatic cytochrome P450 enzymes
What are the two metabolites produced by ropivacaine metabolism?
2,6-pipecoloxylidide and 3-hydroxyropivicaine
What is true about the metabolites of ropivacaine?
Less local anesthetic potency than ropivacaine
What effect does kidney function have on ropivacaine metabolism?
- Only a small fraction of ropivacaine is excreted unchanged in the urine (1%) when the liver is functioning normally
- Dosage adjustments based on renal function not necessary
What is true of uremic patients who receive ropivacaine?
2,6-pipecoloxylidide may accumulate and produce toxic effects
What is the clearance of ropivacaine?
Clearance of ropivacaine is higher than bupivacaine and half-time is shorter
What is the advantage of the higher clearance of ropivacaine?
Higher clearance offers an advantage over bupivacaine in terms of systemic toxicity
What is the lipid solubility of ropivacaine?
Intermediate lipid solubility between lidocaine and bupivacaine
What is the protein binding as ropivacaine?
Highly protein bound to alpha 1-acid glycoprotein (94%)
What are the ester local anesthetics?
- Procaine
- Chloroprocaine
- Tetracaine
- Benzocaine
- Cocaine
What is the metabolism of ester local anesthetics?
undergo hydrolysis by cholinesterase enzyme, principally in the plasma and to a lesser extent in the liver
What is the rate of hydrolysis of ester LA?
Rate of hydrolysis varies
Chloroprocaine > procaine > tetracaine (slowest)
What is the metabolism of cocaine?
undergoes significant metabolism in the liver
What are the metabolites of procaine?
are pharmacologically inactive, although para-aminobenzoic acid (PABA) may be an antigen responsible for allergic reactions
What is the proportion of ester LA and systemic toxicity?
is inversely proportional to the rate of hydrolysis
What is an example of the relationship between ester LA anf systemic toxicity?
tetracaine is more likely than chloroprocaine to result in excessive plasma concentrations
What is true about spinal placement of tetracaine?
Because CSF contains little to no cholinesterase enzyme, anesthesia produced by subarachnoid placement of tetracaine will persist until the drug has been absorbed into the systemic circulation
What effects plasma cholinesterase and hydrolysis rate of ester LA?
are slowed in the presence of liver disease or an increased BUN
When is plasma cholinesterase decreased with ester LA?
may be decreased in parturients and in patients being treated with certain chemotherapeutic drugs
What is true about patients with atypical plasma cholinesterases with ester LA?
Patients with atypical plasma cholinesterase are at increased risk for developing excess systemic concentrations of an ester local anesthetic due to absent or limited plasma hydrolysis
What is the pk of procaine? (3)
Low potency, slow onset due to high pKa (8.9), and short duration of action limit the use of procaine
What causes of allergic reactions with procaine?
possible due to the production of the metabolite PABA
What is the pk of Chloroprocaine (Nesacaine)? (3)
Low potency, extremely low toxicity, extremely short plasma half-life (due to rapid metabolism by plasma cholinesterase)
What is the unique property of Chloroprocaine (Nesacaine)?
Lowest CNS and cardiovascular toxicity of all agents currently in use
What is the common use for Chloroprocaine (Nesacaine)?
epidural anesthesia
What can Chloroprocaine be used in combo with?
Used for PNBs in combination with other long acting, slow onset local anesthetic for the combined effect of of rapid onset and prolonged duration
What can Chloroprocaine be used for in obstetrics?
epidural chloroprocaine with or without bicarbonate is used to rapidly attain surgical levels of anesthesia in preparation for cesarean section
Another advantage in obstetrics is there is virtually __________ to the fetus
no transmission of chloroprocaine
What is the pk of Tetracaine? (4)
Slow onset, high lipid solubility, potent, and intermediate to long acting ester local anesthetic
What is the toxicity of Tetracaine?
may cause neurotoxicity at high doses in animal studies, resulting in cauda equina syndrome with repeated spinal dosing
What is the clinical use of Tetracaine?
clinically as topical anesthesia in ophthalmology
What is the pk of benzocaine? (4)
Slow onset, short duration of action, minimally potent, minimally toxic
What is the clinical use of benzocaine?
Clinical use limited to topical anesthesia to anesthetize mucous membranes prior to tracheal intubation, endoscopy, TEE, EGD, bronchoscopy
What is the unique characteristics of benzocaine?
Unique because it is a weak acid (pKa 3.5) so that it exists primarily in the nonionized form at physiologic pH (Secondary amine: permanently nonionized or neutral)
What is the onset of topical anesthesia with benzocaine?
Onset of topical anesthesia is rapid and lasts 30-60 minutes
A brief spray of 20% benzocaine delivers the recommended dose of _______-________
200-300 mg
What is cetacaine marked as?
marketed as a combination of 14% benzocaine, 2% tetracaine, and 2% butamben
What is excessive use of benzocaine associated with?
methemoglobinemia
What is the only naturally occuring local anesthetic?
Cocaine
What does cocaine cause?
Only local anesthetic that causes intense vasoconstriction
What is the use of cocaine?
Used as a topical anesthetic in ENT surgery [Cocaine Hydrochloride Nasal Solution is provided as a 4% solution, 160 mg/4 mL (40 mg/mL)]
What is the MOA of cocaine?
Inhibits the neuronal reuptake of catecholamines
What are the side effects of cocaine? (4)
Causes HTN, tachycardia, dysrhythmias, and other serious cardiac effects
How is cocaine metabolized?
Metabolized by plasma and liver cholinesterases to water-soluble metabolites that are excreted in urine
When is Plasma cholinesterase activity decreased? (4)
parturients, neonates, the elderly, and patients with severe liver disease
Cocaine abuse and intoxication is ______________
widespread
What determines the onset of cocaine?
Route of administration is important in determining onset
What is the typical onset of cocaine?
Peak venous plasma concentrations of cocaine are reached 30-40 minutes after intranasal administration and 5 minutes following IV and smoked cocaine administration
When does the Maximum physiologic effect after intranasal cocaine occurs?
within 15-40 minutes
What is the duration of cocaine?
approximately 60 minutes or longer after peak effects
What is the elimination half time of cocaine?
60-90 minutes
What is the max dose of cocaine?
3 mg/kg (150-160 mg) 2 soaked cottonoid pledgets into each nare: 40 mg/pledgit (1.3 x 4 cm pledgit) (per FDA)
What are the effects of acute cocaine administration?
has local anesthetic, vasoconstrictive, and sympathomimetic effects
What can be caused from cocaine
coronary vasospasm, myocardial ischemia, myocardial infarction, and ventricular cardiac dysrhythmias
When is caution used with cocaine administration?
CAUTION with HTN/CAD patients (avoid beta blockers- profound CV collapse)
How can cocaine increase myocardial oxygen requirements?
Associated HTN and tachycardia
What is true about Cocaine-abusing parturients?
are at a higher risk of HTN, hypotension, and wheezing
What can cocaine produce in the fetus?
Cocaine produces a dose-dependent decrease in uterine blood flow that results in fetal hypoxemia
What neuro symptoms is a result of cocaine?
seizures (benzodiazepines)
