Local Anesthetics I (Exam IV) Flashcards
What was the first local anesthetic?
Cocaine
S3
Is cocaine an ester or amide?
Cocaine is an ester.
S3
What was cocaine first used for and what was the effect?
Ophthalmology (1884)
Local vasoconstriction: shrink nasal mucosa.
S3
What was the first synthetic ester developed in 1905?
Procaine
S3
What was the first synthetic amide developed in 1943?
Lidocaine
Gold Standard
S3
What are the uses for Local Anesthetics (LAs)?
- Treat dysrhythmias
- Analgesia: Acute and chronic pain
- Anesthesia- ANS Blockade, Sensory Anesthesia, Skeletal Muscle Paralysis
S4
What antiarrhythmic Drug Class is lidocaine in?
Class I: Sodium Channel Blockers
S4
MAGA: What is the intra-op infusion dose of lidocaine?
1 mg/kg over an hour
S5
What is the IV dose of Lidocaine?
- 1 to 2 mg/kg IV (initial bolus) over 2 - 4 min.
- 1 to 2 mg/kg/hour (drip)
S7
When should lidocaine be terminated?
Terminate within 12 - 72 hours
S7
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 1-5 mcg/ml.
Analgesia
S8
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 5-10 mcg/ml.
- Circum-oral numbness
- Tinnitus
- Myocardial depression
- Systemic hypotension
- Skeletal muscle twitching
S8
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 10-15 mcg/ml.
- Seizures
- Unconsciousness
S8
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is 15-25 mcg/ml.
- Apnea
- Coma
S8
Dose Dependent Effects of Lidocaine if plasma lidocaine concentration is >25 mcg/ml.
- Cardiovascular Depression
S8
Describe the components that make up the molecular structure of lidocaine.
Lipophilic Portion (Aromatic Section)
Hydrocarbon Chain
Hydrophilic (Amino Group)
Bond between the lipophilic portion and the hydrocarbon chain will determine if LA is an ester or an amide.
S9 VERIFY!!!!
What structural component of a LA determines if it is an ester or an amide?
Bond between the lipophilic portion and the hydrocarbon chain will determine if LA is an ester or an amide.
What type of local anesthetic would you anticipate from the figure below?
Ester due to the ester bond between the aromatic and the intermediate chain
S10
What type of local anesthetic would you anticipate from the figure below?
Amide due to the amide bond between the aromatic and the intermediate chain
S10
Local anesthetics will typically have a pH of _____ and are weak _______. ?
pH of 6; weak bases
A majority of LA are weak bases
S11
Increased potency generally correlates to increased __________.
duration
S12
What is the potency, onset, DOA, Max single dose of each LA?
Which ester is the most potent?
Tetracaine
S12
Which local anesthetics will exhibit the highest degree of protein binding?
- Bupivacaine
- Levobupivacaine
- Ropivacaine
S12
Which two local anesthetics will have the most rapid onset?
Chloroprocaine
Lidocaine
S12
Which 3 LA will have the highest protein binding?
Levobupivacaine (>97%)
Bupivacaine (95%)
Ropivacaine (94%)
S12
Lipid solubility correlates to _______ of the drug.
Which LA has the highest lipid solubility?
- potency
- Tetracaine
S12
Lipid solubility
pK values closer to a pH of ___________ will have the fastest onset of action.
7.35 - 7.45
S13
Which three local anesthetics have pK values closest to 7.35-7.45 ?
- Lidocaine (pK = 7.9)
- Prilocaine (pK = 7.9)
- Mepivacaine (pK = 7.6)
S13
Which ester has the greatest degree of lipid solubility?
Tetracaine
S12/13
Which amide has the greatest degree of lipid solubility?
Bupivacaine
S12/13
How do liposomes and local anesthetics interact?
What is the result?
- Liposomes unload LA’s into tissue at a controlled rate.
- Prolonged duration of action & decreased toxicity
S15
The FDA released this local anesthetic that contains liposomes and can last up to 96 hours.
Exparel ER (Bupivacaine)
S15
What is the mechanism of action of Local Anesthetics?
- Binds to inactivated, closed voltage-gated Na+ channels@ inner gate
- Block/inhibit Na+ passage in nerve membranes
LA must be non-ionized and lipid-soluble to go through the cell membrane and block the Na+ gated channel from within the cell.
S16
What two things will cause a local anesthetic to not work anymore?
Becoming water-soluble and ionized.
??
What factors affect the degree of blockade seen from local anesthetics?
- Lipid solubility or non-ionized form
- Repetitively stimulated nerve (↑ sensitivity)
- Diameter of the nerve (↑ diameter, ↑ LA need)
S18
What happens when you expose LA (a weak base) to an acidic environment?
LA becomes ionized.
When LA becomes ionized, it will not cross cell membrane to block Na+ gated channels.
??
What other receptors can be targeted by local anesthetics besides sodium channels?
- Potassium channels
- Calcium Ion Channels
- G protein-coupled receptors
S18 - don’t need to truly memorize
Minimum Effective Concentration or Cm (LAs) = _________ (Volatile Agents)
MAC
S20
What component of the local anesthetic is required for the conduction block?
Non-ionized form (equates with lipid solubility)
??
Larger fibers need _____ concentrations of LAs.
higher
S20
The diameter of motor nerve is how many times larger than the diameter of the sensory nerve.
2x
S20
How many nodes of Ranvier need to be blocked to equate to 1 cm of local anesthesia?
At least 2, preferably 3 Nodes of Ranvier to prevent the conduction (Minimum Effect Concentration)
S20
If a LA were given intravascularly, which fibers would be affected the fastest?
What signs and symptoms would you see?
Pre-ganglionic B fibers (SNS)
Hypotension and tachycardia
S21
What fibers are blocked if the patient can’t tell if they are being poked by a sharp needle?
- Myelinated A and B fibers
S21
What nerve types are typically affected last when administering LA through the epidural/spinal?
What sensations are the last to be affected?
- Myelinated A-δ and unmyelinated C-fibers
- Proprioception and Motor
S21
Place in order the fibers that are affected first to last when administering a local anesthetic.
- Preganglionic B fibers
- Myelinated A and B fibers
- Myelinated A-δ and unmyelinated C-fibers
S21
Which patient population will have increased sensitivity and be harder to block?
Pregnancy
Harder or easier?
S21
pKa values closer to physiologic pH result in a _____ rapid onset
more
S22
Because the pKA of LA’s are 8, less than ______% of the drug is in lipid-soluble nonionized form.
50%
S22
If a LA has vasodilator activity, what happens to its potency?
What happens to the duration of action?
LA is less potent
↓ Duration of action
S22
Because Lidocaine is a vasodilator, it will have ________ systemic absorption.
greater
S22
Because Lidocaine has vasodilator activity, there is (greater/less) _______ systemic absorption. Resulting in a (shorter/longer) ________ duration of action at the site of injection.
- greater
- shorter
S22
Factors that influence the absorption of LA.
- Site of injection
- Dosage
- Epinephrine use
- Pharmacologic characteristics of the drug
S23
List the uptake of Local Anesthetics Based on Regional Anesthesia Technique from highest blood concentration to lowest blood conc.
S23
________is the primary determinant of potency
Lipid solubility
S24
The rate of clearance is dependent on what two factors?
- Cardiac output
- Protein binding:
Note: % bound is inversely related to % plasma.
(40% albumin-bound means 60% will float freely in plasma.)
S25
Which ester LA will metabolize the fastest?
Chloroprocaine > Procaine d/t the smallest % of protein binding.
S26
Which amides will metabolize the slowest?
- Bupivacaine
- Levobupivacaine
- Ropivacaine
S26
Why is it important to know the metabolizing rate of LA?
Re-dosing of LA
S27??
Where are Amide local anesthetics metabolized?
Liver via CYP 450’s
S27
Which Amide is most rapidly metabolized?
Prilocaine (lowest protein binding)
Which Amides exhibit intermediate metabolism?
- Lidocaine
- Mepivacaine
S27
Which Amides exhibit the slowest metabolism?
- Bupivacaine
- Ropivacaine
S27
How are esters metabolized?
Hydrolyzed by cholinesterases in plasma
S28
Cocaine, being an ester, is primarily metabolized via plasma cholinesterases. T/F?
False. Primarily hydrolyzed by liver cholinesterases > plasma cholinesterases. All other esters hydrolyzed by plasma > liver
S28
What is the metabolite of esters?
What is the significance of this metabolite?
- ParaAminoBenzoic acid (PABA)
- Common cause of Allergies
S28
Is there cross-sensitivity between an amide allergy to an ester allergy?
No
S28
Are amides or esters, generally slower at metabolizing?
Amides are slower at metabolism.
(CYP450s instead of plasma cholinesterases)
S28
What are the most common LAs that have first-pass pulmonary extraction?
- Lidocaine
- Bupivacaine (dose dependent)
- Prilocaine
S29
The poor water solubility of local anesthetics usually limits renal excretion of unchanged drug to less than ____%
The exception is ____, of which 10% to 12% of unchanged drug can be recovered in urine.
Water-soluble metabolites of local anesthetics, such as ____ resulting from metabolism of ester local anesthetics, are readily excreted in urine.
The poor water solubility of local anesthetics usually limits renal excretion of unchanged drug to less than 5%
The exception is cocaine, of which 10% to 12% of unchanged drug can be recovered in urine.
Water-soluble metabolites of local anesthetics, such as PABA resulting from metabolism of ester local anesthetics, are readily excreted in urine.
S29
In general, the more lipid soluble the local anesthetic is, the greater the potency. T/F
True
Question slide
Which local anesthetic property is most important regarding the duration of action?
Lipid Solubility (most important)
protein binding is more cellular
Question slide
Place the three factors below in order of importance for affecting duration of action?
- Protein Binding
- Clearance
- Lipophilicity
- Lipid Solubility (most important)
- Clearance
- Protein binding
???
How will pregnancy affect
plasma cholinesterase levels?
Lower levels of plasma cholinesterases
Caution with LA that are esters, bigger impact with normal doses
Ester LAs are still given to pregnant women because the effects of the amide LAs are detrimental to the fetus.
S30
What classification of LAs is more likely to cause ion trapping thus affecting fetal health?
Amides
Ion trapping will lead to LA toxicity in the placenta.
S30
What is ion trapping?
The pH in the fetal environment is more acidic than in maternal circulation.
S30
If there is ion trapping in the placenta, what can be given to adjust the pH?
Sodium Bicarb
S30
Bupivacaine
Protein Bound:
Arterial Concentration:
Bupivacaine
Protein Bound: 95%
Arterial Concentration: 0.32
S31
Lidocaine
Protein Bound :
Arterial Concentration:
Lidocaine
Protein Bound: 70%
Arterial Concentration: 0.73
S31
Prilocaine
Protein Bound:
Arterial Concentration:
Prilocaine
Protein Bound: 55%
Arterial Concentration: 0.85
S31
What is the major metabolite of lidocaine?
Xylidide
S32
What is Lidocaine’s max infiltration dose?
- 300 mg solo
- 500 mg with epi
S32
Lidocaine will have prolonged clearance with ______
Pregnancy Induced Hypertension
S32
What is prilocaine’s primary metabolite?
What is the issue with this metabolite?
Metabolite: Orthotoluidine
The metabolite converts Hemoglobin to Methemoglobin, resulting in Methemoglobinemia.
S33
What is the result of Methemoglobinemia?
Fe3+ (ferric iron) is not capable of carrying O2
Cyanosis
S33
What is the max dose of prilocaine to cause Methemoglobinemia?
600 mgs
S33
What is the treatment for methemoglobinemia secondary to prilocaine overdose?
Methylene Blue
- 1 to 2 mg/kg IV over 5 mins (initial dose)
- Total dose not to exceed 8 mg/kg (over 24 hours)
S33
Mepivacaine is similar to Lidocaine except:
- Longer duration of action
- Lacks vasodilator activity
S34
Can Mepivacaine be given in pregnant patients?
No. Prolonged elimination in fetus
S34
What plasma protein does Bupivacaine bind to?
95% bound to α1-Acid glycoprotein
S34
Ropivacaine
Metabolism:
Metabolite:
Protein Binding
Ropivacaine
Metabolism: Hepatic cytochrome P450 enzymes
Metabolites: Can accumulate with uremic patients
Lesser system toxicity than Bupivacaine
Protein Binding: α1-acid glycoprotein
S35
Dibucaine
Metabolism:
MOA:
Dibucaine
Metabolism: Liver
MOA: inhibits the activity of normal butyrylcholinesterase (plasma cholinesterase) by more than 70%
S35
What is procaine’s primary metabolite?
PABA
S36
Tetracaine metabolism is slower than ______
Procaine
S36
Which of the following local anesthetics will have the highest rate of metabolism through hydrolysis?
Procaine
Chloroprocaine
Tetracaine
Chloroprocaine (fastest level of metabolism) > procaine > tetracaine (slowest)
S36
What is Benzocaine used for?
Topical anesthesia of mucous membranes
Tracheal intubation
Endoscopy,
Transesophageal echocardiography (TEE)
Bronchoscopy
S37
Overdose of Benzocaine can lead to ________.
OD of Benzocaine can lead to Methemoglobinemia
S37
What makes Benzocaine unique?
Weak acid instead of a weak base, like most LA.
pKa = 3.5
S37
How is cocaine metabolized?
Who should receive decreased amounts of cocaine?
Metabolized by liver cholinesterase > plasma cholinesterase
Decrease cocaine use in parturients, neonates, the elderly, and severe hepatic disease
S38
When should one be cautious when administering cocaine?
Cocaine can cause coronary vasospasm, ventricular dysrhythmias, HTN, tachycardia, and CAD.
S38
