Flashcards in Local Anesthetics DSA Deck (51):
What are local anesthetic drugs?
Describe general binding and action of local anesthetics
Local anesthetics bind reversibly to sodium channels in nerves and block ion movement through channel pore, blocking action potentials responsible for nerve conduction
When applied locally to nerve tissue in appropriate concentrations, they can act on any part of the nervous system and on every type of nerve fiber
A local anesthetic in contact with a nerve trunk can cause both sensory and motor paralysis in the area innervated
Since the development of the first drug in 1905 (procaine), local anesthetics have been used for both systemic and local effects
Which local anesthetics are amides?
Which local anesthetics are esters?
Ester-types only have one "i," while amide-types have at least 2 "i's"
Which local anesthetics have medium duration of action?
Which local anesthetics have long duration of action?
Which local anesthetics have a short duration of action?
Which local anesthetic is used for surface use only?
Compared to procaine which has a potency of 1, which local anesthetics have a potency of 16?
Which local anesthetic has a potency of 4?
Which local anesthetics have a potency of 2?
What is the chemistry of local anesthetics?
Typical local anesthetics contain both hydrophilic (amine) and hydrophobic (aromatic ring) moieties that are separated by an ester or amide linkage.
Those with ester linkages (benzocaine, cocaine, procaine, tetracaine) are more prone to hydrolysis than those with amide links (lidocaine, mepivacaine, bupivacaine, ropivacaine, articaine), and as a result, generally have a shorter duration of action
Describe absorption and distribution of local anesthetics
Dosage, site of injection, drug-tissue binding, local blood flow, use of vasoconstrictors, and physiochemical properties of local anesthetics all play a role in determining systemic absorption
The use of vasoconstrictor substances (epinephrine) will reduce systemic absorption of agents and are useful for drugs with intermediate or short durations of action
How is cocaine unique concerning absorption/distribution?
It is unique due to its intrinsic sympathomimetic vasoconstrictive properties
Compare distribution of amide local anesthetics with ester local anesthetics
Amide local anesthetics are widely distributed after intravenous bolus administration, while tissue distribution of ester-type agents have not been extensively evaluated due to their extremely short plasma half-lives
Describe the metabolism and excretion of local anesthetics
Ester-type agents are metabolized in plasma, while amide-type agents are metabolized in liver and then excreted in urine as charged substances
Ester-type compounds are hydrolyzed by circulating butyrylcholinesterase enzymes (plasma cholinesterase)
Amide linkage of amide-type agents are hydrolyzed by liver cytochrome P450 enzymes. Toxicity from these is more likely to occur in patients with hepatic disease
Describe the mechanism of action of local anesthetics
They block voltage-gated sodium channel currents and stop the spread of action potentials across nerve axons (receptor site for local anesthetics is at the inner vestibule of sodium channel)
They block nerve conduction by decreasing or preventing the large transient increase in permeability of excitable membranes to sodium that normally is produced by a depolarization of membrane
Describe the structure and activity of local anesthetics
The smaller and more lipophilic the local anesthetic, the faster the rate of the interaction with the sodium channel and the more potent the agent's actions
Ex: Tetracaine, bupivacaine, and ropivacaine are more lipophilic than lidocaine, procaine, and mepivacaine and are therefore more potent and have longer durations of action
Describe fiber diameter
Local anesthetics preferentially block small fibers because the distance over which such fibers can passively propagate an electrical impulse is shorter
Myelinated nerves tend to become blocked before unmyelinated nerves of the same diameter, so preganglionic B fibers are blocked before the smaller unmyelinated C fibers
Describe firing frequency
Fibers that fire at higher frequencies of depolarization are blocked before those that fire slower
Ex: Type A delta and C fibers are blocked earlier than large A alpha fibers
Describe fiber position
In bundles of large mixed nerves in large nerve trunks, it is not uncommon for motor nerve block to occur before sensory block because motor nerves are usually located circumferentially (motor nerves are the first nerves to be exposed to local anesthetic when it is administered into tissue surrounding the nerve)
In extremities, proximal sensory fibers are located in outer portion of nerve trunk and distal sensory innervation is located in core of nerve
Describe function, diameter (um), myelination, and sensitivity block for Type A alpha fibers
Describe function, diameter (um), myelination, and sensitivity block for Type A beta fibers
Describe function, diameter (um), myelination, and sensitivity block for Type A gamma fibers
Describe function, diameter (um), myelination, and sensitivity block for Type A delta fibers
Describe function, diameter (um), myelination, and sensitivity block for Type B fibers
Describe function, diameter (um), myelination, and sensitivity block for Type C dorsal root fibers
Describe function, diameter (um), myelination, and sensitivity block for Type C sympathetic fibers
What are topical routes of administration?
Nasal mucosa, wound margins, GU tract, EENT
Describe infiltration anesthesia
Injection of local anesthetic directly into tissue in vicinity of peripheral nerve endings without taking into consideration the course of cutaneous nerves
Can be superficial enough to include only the skin and deep enough to include intraabdominal organs
Describe block anesthesia
Injections of local anesthetics in major nerve trunks
Purpose is to anesthetize a region distal to site of injection
Ex: femoral nerve block for surgery distal to knee, brachial plexus block for procedures on upper extremities or shoulders
Describe spinal anesthesia
Injection of local anesthetic into cerebrospinal fluid in lumbar space
Produces anesthesia over a considerable fraction of body with a dose of local anesthesia that produces negligible plasma levels
Describe epidural anesthesia
Injection of local anesthesia into epidural space
Can be performed in sacral hiatus or in lumbar, thoracic, or cervical regions of spine
Current popularity has arisen from development of catheters that can be placed into epidural space, allowing their continuous infusions or repeated bolus administration
Describe intravenous regional anesthesia (Bier block)
Used for short surgical procedures (
Describe prolongation of action by vasoconstrictors
Duration of local anesthetic action is proportional to time in contact with nerve
Coadministration of local anesthetics and vasoconstrictors (epi to activate alpha-adrenergic receptors and cause vasoconstriction) decreases the rate of anesthetic absorption into circulation, reduces rate at which local anesthetic is metabolized, and reduces systemic toxicity
Describe epinephrine action of prolongation
Epinephrine-containing solutions should not be injected into tissues supplied by end arteries (fingers, toes, ears, nose, penis) because the resulting vasoconstriction may cause gangrene
Use caution when injecting epinephrine-local anesthetic combinations into muscle tissue (epi can activate beta2-adrenergic receptors in skeletal muscle vascular beds and cause dilation, increasing potential for systemic toxicity)
Describe cocaine and prolongation by vasoconstrictors
Cocaine alone potentiates effect NE on alpha-adrenergic receptors by blocking NE transporter and results in localized vasoconstriction, eliminating need for combining drug with epi
What are the two major forms of local anesthetic toxicity?
Systemic effects following absorption of local anesthetics (CV or CNS effects)
Direct neurotoxicity from local effects of these drugs when given in close proximity to spinal cord and other major nerve trunks
Describe undesired effects of local anesthetics on CNS
Low concentrations have the ability to produce sleepiness, light-headedness, visual and auditory disturbances, and restlessness (early signs of toxicity include circumoral and tongue numbness and metallic taste)
High concentrations may result in nystagmus (unintentional jittery movement of eyes), muscle twitching, and convulsions
Central stimulation is followed by depression. Death usually is caused by respiratory failure
When large doses of a local anesthetic are required, premedication with ____ can provide prophylaxis against CNS toxicity. How?
Benzodiazepine (diazepam or midazolam)
Raising seizure threshold (local anesthetics cause depression of cortical inhibitory pathways, thereby allowing unopposed activity of excitatory neuronal pathways)
Describe undesired effects of local anesthetics on CV system
Result of direct effects on cardiac and smooth muscle and from indirect effects on autonomic nervous system
Local anesthetics block cardiac sodium channels and decrease electrical excitability, conduction rate, force of contraction, and arteriolar dilation, leading to systemic hypotension (not the case with cocaine)
Describe cocaine effects on CV system
Inhibits NE reuptake and results in vasoconstriction (which can lead to local ischemia), hypertension, and cardiac arrhythmias
Describe bupivacaine effects on CV system
Most cardiotoxic due to its long durations of action
Describe lidocaine effects on CV system and CNS
Class Ib antiarrhythmic
Suppresses automaticity of conduction tissue by increasing electrical stimulation threshold of ventricle, His-Purkinje system, and spontaneous depolarization of ventricles during diastole by a direct action of tissues
Blocks both initiation and conduction of nerve impulses by decreasing neuronal membrane's permeability to sodium ions, which results in inhibition of depolarization with resultant blockade of conduction
Most common adverse effect of IV lodicaine is CNS toxicity, which is typically mild, dose-dependent, and always resolves upon discontinuation
Describe allergic reactions to local anesthetics
Allergic reactions to ester-type local anesthetics are most common due to metabolism to allergy-causing compounds (allergies to amide-type local anesthetics are extremely rare)
Pts who are allergic to one ester-type agent will most likely be allergic to another ester-type
Poor solubility in water, used only as a topical agent
Used topically for dermatologic conditions, hemorrhoids, premature ejaculation, and as an anesthetic lubricant (nasogastric and endoscopic tubes and catheters)
Agent with long duration of action capable of producing prolonged anesthesia
Has a tendency to provide more sensory block than motor block
Clinically desired properties are blockade of nerve impulses and local vasoconstricting actions secondary to its ability to inhibit local NE reuptake
Euphoric properties are primarily due to inhibition of catecholamine reuptake (mainly dopamine in CNS)
Used primarily as a topical anesthetic of upper respiratory tract
Due to toxicity associated with injections, now used only as a topical cream for use on skin
Prototypical amide local anesthetic
Alternative choice for individuals sensitive to ester-type local anesthetics
Produces faster, more intense, longer lasting, and more extensive anesthesia than an equal dose of procaine
Used as an antiarrhythmic agent