Flashcards in Local Anesthetics Deck (40):
What do local anesthetics do?
Bind reversibly to Na channels in nerves and block ion movement through the channel pore, blocking APs responsible for nerve conduction
-when applied locally to nerve tissue in appropriate concentrations, they can act on any part of the the nervous system and on every type of nerve fiber
What happens when local anesthetic in contact with a nerve trunk?
Cause both sensory and motor paralysis in the area innervated
What is the chemistry of local anesthetics?
Contain both hydrophilic (amine) and hydrophobic (aromatic ring) moieties that are separated by an Easter or amide linkage
-agents with a ester linkage (procaine) are more prone to hydrolysis than those with amide links (lidocaine) and therefore have shorter duration of action
What are the highlighted local anesthetic?
Benzocaine, Bupivacaine, cocaine, dibucaine, lidocaine, procaine (novacaine)
What factors play a role in determining systemic absorption?
Dosage, site of injection, drug-tissue binding, local blood flow, use of vasoconstrictors, and physiochemical properties of local anesthetics
What does the use of vasoconstrictors (epinephrine) do?
Reduce systemic absorption of agents and are useful for drugs with intermediate or short durations of action
What makes Cocaine unique?
Intrinsic sympathomimetic vasoconstrictive properties
What is a difference between amide and ester-type agents?
Amide ones are widely distributed after intravenous bolus administration ; tissue distribution of ester-type agents have not been evaluated (short plasma half-lives)
How are ester-type and amide type agents metabolized?
Ester-type agents: plasma
Amide-type agents: liver
Excreted in urine as charged substances
-ester-type compounds are hydrolyzed by circulating butyrylcholinesterase enzymes (plasma cholinesterase)
-amide linkage are hydrolyzed by liver CYP450 enzyme; toxicity from amide type agents occur in Pts with hepatic disease
MOA of local anesthetics
Block voltage-gated sodium channel currents and stop the spread of APs across nerve axons (the Rc site for local anesthetics is at the inner vestibule of sodium channel)
-block nerve conduction by decreasing or preventing the large transient increase in permeability of excitable membranes to sodiu that normally is produced by a depolarization of the membrane
Structure and activity
The smaller and more lipophilic the agent, the faster the rate of interaction with the sodium channel and the more potent the agent's actions
-tetracaine, Bupivacaine, and ropivacain are more lipophilic (more potent and longer durations of actions) than lidocaine, procaine, and mepivacaine
Agents preferentially block small fibers because the distance over which such fibers can passively propagate an electrical impulse is shorter
-myelinated nerves end to become blocked before unmeylinated nerves of Same diameter (preganglionic B fivers blocked before smaller unmeylinated C fibers)
Higher firing freq blocked before slower ones
(In bundles of large mixed nerve trunks) Motor nerve block can occur before sensory block because motor nerves are usually located circumferentially (motor nerves are the first to be exposed to the local anesthetic when it is administered into the tissue surrounding the nerve
-in extremities: proximal sensory fibers are located in the outer portion of the nerve trunk and distal sensory innervation is located in the core of the nerve
What are the usual routes of administration?
Topical (nasal mucosa, wound margined, GU tract, EENT procedures), injections, IV
Injection of local anesthetic directly into tissue in the vicinity of peripheral nerve endings w/out taking into consideration the course of cutaneous nerves
-superficial (skin); deep (intraabdominal organs)
Injection of local anesthesia in major nerve trunks; anesthetize a region distal to the site of injection
-femoral nerve block for sx of distal knee; brachial plexus nerve block
Injection of agent into the epidural space
-in sacral hiatus or in the lumbar, thoracic, or cervical regions of spine
Intravenous regional anesthesia (Bier block)
Used for short surgical procedures (
What is the duration of agent proportional to?
The time in contact with the nerve
What is the effect of coadministration of local anesthetics and vasoconstrictors (epinephrine to activat alpha-adrenergic receptors and cause vasoconstriction)?
Decreases the rate of anesthetic absorption into circulation, reduces the rate oat which the local anesthetic is metabolized , and reduces systemic toxicity
Why should epinephrine-containing solutions not be injected into tissues supplied by end arteries (fingers, toes, ears, nose, penis)?
The resulting vasoconstriction may cause gangrene
Why must you use caution when injecting epinephrine-local anesthetic combos into muscle tissue?
epi can activate Beta-2 Adren Rcs is sk m vascular beds and cause dilation, increasing the potential for systemic toxicity
What potentiates the effect of NE on alpha-adrenergic Rcs by blocking the NE transporter and results in localized vasoconstriction, eliminating the need for combing the drug with epinephrine?
What are the two major forms of local anesthetic toxicity?
(1) systemic effects following absorption of local anesthetics (CV or CNS effects)
(2) direct neurotoxicity from the local effects of these drugs when given in close proximity to the spinal cord and other major nerve trunks
What adverse effects are on the CNS due to a low concentration?
Sleepiness, light-headedness, visual and auditory disturbances and restlessness (early signs of toxicity = circumoral and tongue numbness and a metallic taste)
What adverse effects are on the CNS due to a high concentration?
Nystagmus, muscular twitching and convulsions
-with large doses: premedication w/ par enteral BZD (diazepam or midazolam)--> raise the seizure threshold (local anesthetics cause depression of cortical inhibitory pathways, allowing unopposed activity of excitatory neural pathways)
Death caused by______
Depression; respiratory failure
What are the causes of undesired effects on CV system?
Direct effects on cardiac sm m and from indirect effects on the ANS
Adverse effects in CV
Block cardiac sodiu channels and decrease electrical excitability, conduction rate, force of contraction, and arteriolar dilation, leading to systemic hypotension (not with cocaine)
How does cocaine affect the CV system?
Inhibits NE reuptake and results in vasoconstriction (can lead to local ischemia), HTN, and cardiac arrhythmias
Whic drug is the most cardio toxic ?
Bupivacaine due to its long duration of action
Lidocaine is a class Ib anti-arrhythmic
-supresses automaticity of conduction tissue b increasing electrical stimulation threshold of ventricle, His-Purkinje system, and spontaneous depot of ventricles during diastole by a direct action on the tissues
-blocks the initiation and conduction of nerve impulses by decreasing the neuronal membrane's permeability to sodium ions --> inhibition of depot with resultant blackade of conduction
-adverse effects: CNS toxicity
To ester-type local anesthetics: most common due to metabolism to allergy-causing compounds (allergies to amide-type are rare)
Poor water-solubility; used only as a topical agent
-topically used for dermatological conditions, hemorrhoid so, premature ejaculation, anesthetic lubricant (nasogastric and endoscopic tubes and catheters)
Long duration of action--> prolongs anesthesia
-provide more sensory than motor block
Blockade of nerve impulses and local vasoconstriction get actions secondary to its ability to inhibit local NE reuptake
-euphoria: inhibition of catecholamine reuptake (dopamine in CNS)
-topical anesthetic of the UR tract
Topical crease for use on skin
-prototype amide; alternative choice for individuals sensitive to ester-type agents
-faster, more intense, longer lasting, and more extensive anesthesia than an equal dose of procaine
-anti arrhythmic agent