At what point in the pain pathway do local anesthetic work?
initiation, transmission, perception, or reaction?
transmission of the pain signal
What is a distinguishing characteristic of local anesthetics and how is their goal different from other pain management techniques?
the distinguishing characteristic is that they can provide complete loss of all sensory modalities
they're unique in that other forms of pain control want to try to be systemic, but local anesthetics try really hard to just be local
What are the three structural components of a local anesthetic:
the hydrophobic aromatic ring
the ester or amide linker
the hydrophillic amine
As the hydrophobicity of the aromatic ring increases, what happens to the LA's potentcy, duration of action, and toxicity?
potency goes up
duration of action begins sooner and lasts longer
toxicity also increases unfortunately
What are hte two types of linker bonds in LAs and how are the two classes different?
ester bonds or amide bonds
they are different in that they are metabolized differently
esters are more rapidly broken down in the plasma and also have a higher potential for allergic sensitization
What does the hydrophilic amine of an LA determine?
the pK of the drug - basically how much of the drug will be ionized at physiological pH
Are most local anesthetic weak acids or weak bases? What does this mean in terms of concentration of ionized drug?
weak bases with pK about 8-9
It means that at physiologic pH of 7.4, most of the drug will be ionized
Why are both the ionized and unionized form of the anesthetic necessary for the effect?
in order to enter the cell, the drug must be unionized
but in order to be effective and block the sodium channels, the drug must be ionized
So will a drug with a lower pK or higher pK have faster action?
at lower pK you'll have less of the drug in the ionized form, so more will be able to cross the cell membrane into the neuron
Local anesthetics have higher affinity for the sodium channels when they are n what states? What does this means in terms of what neurons are most affected?
higher affinity for open and inactive states
less affinity for resting states
This means that neurons that are especially active will be affected first.
Why do local anesthetics block pretty much all transmission?
they block sodium channels, and literally all nerves use sodium channels
so it can block anything with a sufficient concentration of the drug
Do LAs preferentially block smaller diameter or larger diameter nerve fibers? Myelinated or unmyelinated?
will block small diameter nerve fibers faster
will block myelinated nerves faster than unmyelinated nerves of the same diameter
In what order are the modalities of sensation and motor function affected by LAs?
5. deep pressure
6. motor function
What effect do LAs have on the cardiovascular system? Why is this a bad thing in terms?
they block Na+ channels in vascular smooth muscle, resulting in vasodilation
this is a bad thing because it counterintuitively promotes removal of the LA form the site of application, which decreases effectiveness and increases risk of toxicity
How do you pharmacologically circumvent the vasodilation effects of the LAs?
you give them with a vasoconstrictor like epinephrine to prolong action, decrease toxicity
also helpful because it decreases bleeding
What are some of the adverse CNS side effects of LAs?
tongue numbness (at even low concentrations)
What cardiovascular adverse effects will the LAs have if they diffuse to the heart?
these are really bad - potentially fatal
decreased myocardial electrical excitability
decreased conduction rate/decreased force of ocntractions
In what type of LAs are hyeprsensitivity reactions more common? Why?
they are metabolized rapidly and one fo the metabolites - PABA - is easy to develop a hypersentivity to
What are the two reasons you don't want systemic distribution of a LA?
distribution decreases teh effectiveness because it dilutes the drug
distribution is associated with toxicity because ou don't want Na+ channels blocked in the CNS or CV systems
What is the negative impact of using a vasoconstrictor like epinephrine with LA when closing significant wounds?
they can have a negative impact by reducing blood flow, which makes healing ultimately harder
Why might LAs be less effective when injected to inflammed/pruritic areas?
inflammaton and pus formation makes the area more acidic, with a pH about 5.5-6.5
this means that the vast majority of the drug will be ionized right away and less likely to enter the neuron, reducing the anesthetic effect
Which form: esters or amides distribute more widely?
the amides, since they take longer to metabolize
What enzyme hydrolyzes the esters and where?
the pseudocholinesterases in the plasma
How and where are the amides metabolized?
they are hydrolyzed in the liver by mixed-function oxidases
How are LA metabolites excreted?
What is EMLA?
It's a eutetic mixture of local anesthetics
lidocaine and prilocaine
it's an oil at room temp, so you put it on intact skin to numb the area over where you're going to do an LP, venipuncture, or skin graft harvesting
What is the most common route of administration for the LAs? What do you need to be careful for with this route?
infiltration anesthesia - injected subcutaneous or submucosal for minor surgery or dental procedures
you need to be careful that you don't inadvertently inject it into the vascular system - you dont want systemic action
How would you administer an LA if you wanted to block nerve conduction in a bigger area like the finger or the arm?
a nerve block
injection into thte brachial plexus will anesthetize the whole extremity
What's another name for an intravenous regional block and when can you use it/what's the danger?
A bier block
You can only use it on the extremities because you need to block the diffusion fo the drug by placing a touniquet and leaving it on for at least 15 minutes
How does an epidural work and what nerves does it primarily work on?
you inject LA into the epidural space of the spinal cord - primarily works on spinal nerve roots
Why is there a concern for systemic distribution with epidural injections?
they can diffuse into the blood stream following absorption from the epidural space
so give with epinephrine and use a dilute solution fo bupivacaine during labor to avoid respiratory depression in the neonate
Why are spinal local anesthetics helpful sometimes?
they are best at anesthetizing very large regions - you inject it into the CSF of the lumbar space
nice because it doesn't really get into the blood at all with this route
Is procaine an ester or amide? What does that mean for it's duration of action and metabolism?
it's short acting because it's rapidly metabolised in the plasma - thus not useful as a topical anesthetic
What is the most widely used local anesthetics?
Is lidocaine an ester or amide?
amide - metabolized in the liver
What is lidocaine used for besides as a LA?
an antiarrhythmic agent
lidocaine OD can produce death due to....
ventricular fibrillation or cardiac arrest
What local aneshetic works very similar to lidocaine, but with a longer duration of action?
What is the major pro to bupivacaine?
it's very potent and long-acting, making it perfect for epidural blocks and prolonged surgery
What is the benefit to ropivacaine over bupivacaine?
it has fewer CVS and CNS toxicities
What LA is common used for topical anesthesia of the eye, nose, and throat?
What is the added benefit that is unusual to cocaine?
It actually has vasoconstrictor action instead of vasodilation - so it's great at numbing areas and stopping bleeding
(especially in the mucosal membranes - so cut lips)