Local anesthetics - Dersh Flashcards
When are tertiary amines charged?
They are charged at low pH (active form of the local anesthetic)
They are uncharged at high pH
At what pH are quaternary amines charged?
THey are always charged (active form of the local anesthetic molecule)
What conclusions where made about the active form of the local anesthetic molecule?
It is the protonated amine (which is charged)
The local anesthetic molecule blocks conduction from inside the axon
The local anesthetic molecule traverses the axonal membrane in the unprotonated (uncharged) form
What is the target for the action of local anesthetics?
The voltage gated Na channel
This transmembrane protein consists of four subunits surrounding a central pore
An action potential causes depolarization of hte nerve membrane and a conformational change that results in the pore opening and permitting Na ions to pass.
Within a few milliseconds after opening, a polypeptide chain between two of the subunits moves to occlude the central pore and prevent further ion conductance
At what point of the Na channel activation/deactivation cycle do local anesthetics block it?
What determines the degree of block?
They block the Na channel during the open state
The degree of blockade depends on both the resting potential of the nerve and the rapidity with which it has been stimulated
A resting nerve is less sensitive to local anesthetic blockade
A higher stimulation frequency and a more positive resting potential cause a greater degree of block
When a local anesthetic is injected near a compound nerve containing many fiber types, what is the first modality to be blocked?
2nd blocked?
3rd blocked?
First to be blocked is the efferent sympathetic activity fibers
First objective sign of block is –> vasodilation and increase in skin temperature
Second blocked - pain and temperature so there is loss of these sensations
Third blocked - motor strength and the senses of proprioception and light touch (these are the slowest in onset)
As local anesthetic wears off, list the functions you gain back first to last.
You get back motor strength, proprioception and light touch
Second to come back - sensations of pain and temperature
Last to come back - sympathetic tone
What type of nerve fibers are most easily blocked?
Generally, smaller nonmyelinated nerve fibers are more easily blocked than larger, myelinated fibers.
What is a differential block?
This is when you use concentration levels of local anesthetics to block nerve fibers
A low concentration of a local anesthetic solution may block only the sympathetic nerves. A slightly higher concentration may also block the sensations of pain and temperature. Motor blockade is usually achieved only with the highest concentration of the local anesthetic that is clinically available.
Many chemical species have local anesthetic effects. Give examples of these
Phenothiazines - used to treat major psychiatric illnesses
Histamine H1 antagonists - used to treat allergies
Local anesthetics used clinically are all similar in structure, describe this structure
One end has a substituted aromatic ring, the other end has a substituted amine (with one exception)
These ends are linked by an ester or an amide linkage
What are the ester local anesthetics?
BP-PT (Blood pressure physical therapy)
Benzocaine
Procaine
Proparacaine
Tetracaine
Ester anesthetics have higher hypersensitivy reaction in patients due to the high prevalence of hypersensitivity to PABA (product of metabolism of such drugs) in the general population
Methylparaben and/or propylparaben are preservatives that demonstrate cross-reactance with PABA in many people
What are the amide local anesthetics?
L-BMR
Lidocaine
Bupivacaine
Mepivacaine
Ropivacaine
Procaine
Onset and duration?
Metabolised to what?
First synthetic local anesthetic, rarely used today
Not used because of slow onset and short duration
It is metabolized to p-aminobenzoic acid (PABA) - causes allergic reaction in many people
PABA is commonly found in many skin lotions (includig sunscreens) and creams
Lidocaine
Onset and duration?
AE?
Use?
How long is the blockade with a spinal block?
What’s the only site it is not used as a local anesthetic?
Metabolism?
Commonly used anesthetic
Fast onse, short duration and low toxicity
Use:
- Local infiltration
- Nerve blocks IV regional anesthesia - Bier block
- Spinal and epidural anesthesia
- Topically on mucous membranes
Blockade is 1-3 hours
Not used on the cornea
Metabolized by hepatic cytochrome P450 system and subsequently by hepatic amidases:
The tertiary amine is first N-dealkylated to a secondary
amine, and then the amide linkage is hydrolyzed yielding ethylglycine and xylidide. Most of the xylidide thus formed is oxidized by cytochrome P450 to 4-hydroxy-2,6-dimethylaniline which is excreted in the urine
How do you prolong the duration of lidocaine?
By giving epinephrine which will cause vasoconstriction and therefore decreases local blood flow and absorption of lidocaine
Bupivacaine
Onset and duration?
AE?
What is the use of Epinephrine simultaneously with this drug?
Use?
How long is the blockade with a spinal block?
Amide local anesthetic
Compared to lidocaine, it is slower in onset, much longer in duration (due to its very slow dissociation from its binding site in the sodium channel. Epinephrine does not prolong its duration), and much more toxic (correlated to its higher lipid solubility as compared to lidocaine –> “Bupivacaine is Bad”
Epinephrine (vasoconstrictor) decreases its toxicity by slowing down absorption of Bupivacaine, decreasing the peak blood concentration, and decreasing bleeding at the surgical site.
AE: cardiotoxic local anesthetic and ventricular fibrillation.
It dissociates so slowly from the sodium channel, once severe cardiotoxicity is manifested, a prolonged period of cardiopulmonary resuscitation is often required until a normal rhythm is restored.
Use:
- local infiltration
- nerve blocks
- spinal and epidural anesthesia
Blockade is 8-24 hours
Mepivacaine
Onset, duration
AE?
Use?
How long is the blockade with a spinal block?
Similar to lidocaine in that it has fast onset and low toxicity
Longer duration than lidocaine and shorter duration than bupivacaine
Use:
- Local infiltration
- Nerve blocks
- Epidedural anesthesia
Blockade is 4-6 hours
Ropivacaine
What is it used for?
The only local anesthetic that is formulated containing one optical isomer
Its primary advantage over bupivacaine is its lower toxicity when used in nerve and plexus blocks in which a large dose needs to be injected (use).
It achieves its lower toxicity primarily by excluding the more cardio- and neurotoxic isomer from the preparation.
It is also slightly less lipid soluble than bupivacaine (compare the length of the side chains on the piperidine nitrogens).
Tetracaine
Duration
Toxicity
Use
It is an ester local anesthetic
Longerst duration of any available local anesthetics and also the most toxic (great lipid solubility because of hte four-carbon free alkyl chain - like bupivacaine) –> its “TetraToxic”
Systemic toxicity is rare due to small doses used in local anesthesia
Use: spinal anesthesia
Proparacaine
Use?
Used for topical anesthesia of the cornea
It causes the least pitting of the cornea
Can be used to anesthesize the cornea for:
- measurement of intraocular pressure
- removal of a foreign body
- surgical procedures
*** Proparacaine should never be given to a patient with ocular pain for self administration –> repeated or chronic use damages that cornea and masks the underlying disease process
Benzocaine
Use?
AE?
Only used topically
Lacks the amino group at the end of the molecule opposite the aromatic ring
Poorly soluble in water
Because the nucleus of benzocaine is aniline (aminobenzene), systemic absorption causes the stoichiometric oxidation of hemoglobin to methemoglobin.
Since benzocaine is typically administered topically on mucous membrane (e.g., mouth, airway), the large doses that may be used to facilitate upper endoscopy or bronchoscopy may cause significant methemoglobinemia.
Other local anesthetics that have a free aromatic amino group (procaine, proparacaine) are not used in sufficient doses to cause a meaningful degree of
methemoglobinemia.
In the lidocaine metabolite with an aromatic animo group (2,6- dimethylaniline), the amino group is sterically hindered from acting as an efficient
oxidizer of hemoglobin.
Systemic adverse effects are common with local anesthetic use when?
Large doses are used
Local anesthetic is injected in well perfused tissues or applied to well-perfused surfaces or mucous membranes
*** There is an excellent correlation between the blood concetration of the local anesthetic and the magnitude of the untorward effects
On what systems are the side effects of local anesthetics?
Rank the loca anesthetics from least to most toxic
Primarily the central nervous and cardiovascular systems
There is a relation between adverse effects and local anesthetic’s duration and lipid solubility
procaine < lidocaine ~ mepivacaine << bupivacaine < tetracaine
The “bad one” and the “tetratoxic one” are obviously on atop the list
What is the initial effect of local anesthetics on the nervous sytem?
Although they inhibit nerve conduction, their initial effect is excitation –> This action may result from a selective effect of local anesthetics upon inhibitory neurons.
The initial CNS effects are:
- restlessness
- tremor
- altered visual perception.
As the blood concentration increases, seizures may result.
Local anesthetic-induced seizures are most often self-limited and followed by a period of CNS depression that may be accompanied by apnea and hypotension.
The appropriate therapy is to administer oxygen by mask and ensure adequate ventilation. If the seizure is prolonged, it may be treated with an intravenous barbiturate or benzodiazepine.
Besides the initial effects of local anesthetics, what are the other effects?
Which spefic ones cause these effects?
Local anesthetics can also cause:
- decreased excitability
- conduction rate
- force of contraction in the heart
Bupivacaine is the most cardiotoxic local anesthetic
What preservatives used in local anesthetic mixtures have demonstrated cross-reactance with PABA?
methylparaben
propylparaben
A patient describes manifestation of local anesthetic “allergy” with symtoms of sweating and tachycardia after a local anesthetic dose. What could this be a result of?
This could be attributable to epinephrine
When a patient gives a history of local anesthetic “allergy,” the patient should be questioned carefully. Even when the symptoms were those of a true hypersensitivity reaction and the local anesthetic was an amide, the overwhelming probability was that the reaction was due
to the preservative!!
What is local infiltration?
Advantage?
Disadvantage
The process by which the local anesthetic is injected into the tissue in the area in which numbness is desired
Dilute solutions are used since there is no need to block motor neurons
Epinephrine is often used as a vasoconstrictor except at end arteries like toes ears, nose and penis
Advantage - it requires no knowledge of the anatomic course of any nerves and that it usually does not disrupt any physiological functions
Disadvantage
- the impracticality of anesthetizing large areas
- difficulty in anesthetizing certain tissues by local infiltration (e.g. periosteum, peritoneum)
- difficulty in anesthetizing the viscera by this method
What is a peripheral nerve block?
How do you locate the nerve?
Local anesthetic solution is injected in very close proximity to the nerve
Location of nerve:
- Some nerves are known to have very little variation eg median nerve
- Intentionally touch a nerve to induce parasthesia - to prevent intraneural injection which is very painful eg femoral nerve
- Needle connected to motor stimulator an invoke motor activity - only useful for mixed (sensory and motor nerves) eg sciatic nerve
- Needle is visualized in proximity to the nerve via ultrasound
What is a plexus block?
Its similar to a peripheral nerve block but in this case the plexus is blocked proximal to where the peripheral nerves seperate from each other
What is a spinal anesthetic?
How can you anesthesize high thoracic nerves with this method?
What’s the possible AE of spinal anesthesia?
This consists of injecting the local anesthetic solution into CSF after performing an lumbar puncture
Since the spinal cord ends at L1 in about 90% of people and at L2 in the remaining 10%, spinal anesthetics are administered at the L2-L3, L3-L4, L4-L5, or L5-S1 interspaces.
Typically a spinal anesthetic causes a temporary and reversible pharmacological transection of the spinal cord; autonomic, sensory, and motor nerves are blocked below the level of the anesthetic solution.
Even though no injection can be made above L2-L3, blockade of higher thoracic nerves is done by making the local anesthetic solution hyperbaric (having a higher specific gravity that SCF- by adding glucose) then tilting the patient into a head down position. This method can be used in intraabdominal surgery
AE - hypotension due to sympathetic blockade
- hydrate the patient prior to spinal injection
IV administration of vascontrictor - phenylephrine
What is an epidural anesthetic?
The injection of local anesthetic solution into the epidural space - usually through a catheter allowing bolus injections or continuous infusions
Its a segmental block, localized to the dermatomes above and below the site of the catheter insertion
Concentration of the local anesthetic goes along with the degree of block
Intravenous regional (or Bier) block
What is the technique of block?
This is a method of produces anesthesia of the arm (or much less commonly the leg)
Technique of block:
- An intravenous catheter is inserted distally in the extremity.
- The extremity is wrapped tightly, distally to proximally, with an Esmarch bandage to exsanguinate the limb.
- A pneumatic tourniquet is placed proximally on the limb and inflated to a pressure approximately twice the systolic pressure.
- A dilute (usually 0.5%) solution of lidocaine is injected into the i.v. catheter.
This type of block doesnt require much expertise. Limited to procedures less than 1.5 to 2 hours in duration. Pain from the tourniquet usually limits the overal duration of the block
The block dissipates rapidly after the tourniquet is deflated. As long as the tourniquet has been inflated for at least 15 min following lidocaine injection, the risk of
systemic toxicity is low. Conversely, tourniquet failure shortly after lidocaine injection is likely to be associated with systemic toxicity.
What is topical anesthesia?
Most commonly used today to facilitate endoscopic procedures. The pharynx, nares, trachea, and esophagus are all readily anesthetized by topically-applied anesthetics.
Systemic absorption of local anesthetic solution from
mucous membranes is very efficient. Coupled with the fact that high concentrations of
local anesthetic solution are used topically (e.g. 4% lidocaine), it is important to limit the
total volume of local anesthetic solution used to minimize systemic toxicity.
Also recall
that topical benzocaine is associated with methemoglobinemia.
