Terms in this set (65)
What are the three reasons that we use local anesthetics?
1. Best method to prevent pain
2. versatile (site of administration)
3. Relatively inexpensive
Why are local anesthetics the best method to prevent pain?
They are the only anesthetics that block transmission completely. Other analgesics just modulate pain
What is Nerve conduction?
Electrical signal generated by rapid movement of sodium and potassium across the membrane
What is the potential when a cell is at resting state?
In normal resting state leakage of Potassium out of the cell results in a net negative charge of -60 to -70 mV potential inside the cell.
What is an action potential?
When a nerve is activated by receptors, the cell membrane becomes less negative. If the threshold potential (-50 mV) is reached the nerve cell with depolarize and an action potential is generated as sodium rapidly enters the cell through specific channels.
What is the mechanism of local anesthetics?
They stop conduction by blocking voltage gated sodium channels
What three parts form the structure of local anesthetics?
1. Lipophilic group
2. Hydrocarbon chain
3. Hydrophilic group
What does the lipophilic group of an anesthetic determine?
The lipophilic group affects the drug's affinity for sodium channels, potency and duration of action. It also affects the drugs therapeutic index - increasing the risk for systemic toxicity.
What does the hydrophilic group of an anesthetic determine?
The hydrophilic group affects the drug's degree of ionization at a given pH and the onset time of the drug (unionized can cross the cell membrane)
Also affects how readily it will bind to sodium channels (only ionized form blocks channels)
What is the order of blockage of local anesthetics?
Pain -> cold -> warm -> touch -> pressure -> motor
How does diameter of the nerve affect anesthetic action?
The smaller the diameter of a nerve fiber the more likely it is that the local is going to block it - just less distance to travel.
How does the structure of the peripheral nerve affect the order of blockage?
In mixed nerves motor fibers are usually located in the outer portion of the nerve bundle so in this circumstance they are blocked first.
Are locals soluble or insoluble?
Locals are relatively insoluble molecules, so they are produced as water soluble salts (HCl)
Why do you often cut locals with bicarb?
Locals are acidic (pH 5-6) so they will sting a lot when injected. You can prevent this by cutting them with bicarbonate.
What happens when pKa of a drug is close to pH of tissues?
When pKa of a drug is close to pH of tissues, more of the drug will be unionized and is able to cross the cell membrane (leads to faster onset)
What is the pKa of lidocaine, what % is unionized in plasma?
pKa = 7.9
% unionized at pH 7.4 = 24%
What is the pKa of mepivacaine, what % is unionized in plasma?
% unionized at pH 7.4 = 39%
What is the pKa of bupivacaine, what % is unionized in plasma?
% unionized in plasma at pH 7.4 = 17%
What are the onset times for each local anesthetic?
Lidocaine, fast < 5 min
Mepivacaine, fast < 5 min
Bupivacaine, slow 10-15 minutes
Why is bupivacaine so much slower than lidocaine and mepivacaine?
Once you go under the 20% threshold of unionized there is not enough of that drug to cross the membrane to work quickly.
True or False, Locals do not bind to proteins
locals are highly bound to plasma and tissue proteins. Binding decreases as pH of tissues decreases (important in patients with acidosis)
How does protein binding influence drug duration?
The fraction that is bound to proteins correlates with the duration of local anesthetic activity.
What is the protein binding of each lidocaine, mepivacaine and bupivacaine?
What is the duration of action for each drug?
Lidocaine: 1-2 hours
Mepivacaine: 1.5-2.5 hours
Bupivacaine: 4-6 hours
Why is duration linked to protein binding?
The sodium channels themselves are proteins so it makes sense that the drugs that have the highest degree of protein binding will last the longest.
What would you do if you needed to provide both immediate and long term pain relief?
You would combine locals. Say, lidocaine and bupivacaine.
What is important to consider when injecting a local?
How much blood flow their is and how the local affects surrounding blood flow. This will affect absorption which will influence toxicity.
Which two locals induce local vasodilation and therefore increase their own uptake?
Lidocaine and Bupivacaine
What two organs are at the most danger if you were to get a local anesthetic toxicity?
Your heart and your brain both have tissues that spontaneously depolarize so if you give a high enough dose of these drugs you can block these channels.
Toxicity of locals is rare, they are low risk drugs.
What determines toxicity?
It relates to the rate of drug uptake (absorption), not necessarily the total dose that is administered.
Locals can be used to treat what two other things?
1. can be used as an anticonvulsant to treat seizures
2. can be used to treat heart arrhythmia
What is the order of effects with increasing concentrations of local anesthetics?
What are the four CNS effects you see with local anesthetic toxicity?
How do you treat local toxicity?
2. supportive care - oxygen, ventilation
With which drug do you most often see cardiac effects?
What are the three cardiac effects you see with local anesthetic toxicity?
1. blocked Na channels in pace maker and myocardial cells slows heart rate and decreases contractility
3. cardiac arrest
How do you treat cardiac effects from local anesthetic toxicity?
inotropes, supportive care, fluids,
Intralipid: an IV fat product
Toxicities are additive when more than one drug is adminstered, what are four things you need to consider?
1. expected rate of absorption from site
2. additives (ie vasoconstrictors like epinephrine)
3. Drug characteristics (vasoconstrictors or vasoldilators)
4. Patient (cardiac output)
Why do we often add epinephrine to doses?
It causes vasoconstriction decreasing absorption and increasing your safety margin
In a healthy patient, clearance is...?
Clearance is rapid in a healthy patient when drugs are administered appropriately. The benefits of use far outweigh the risks as long as you are careful with doses
What are the IV convulsive doses for each drug (mg/kg)
Lidocaine: 20 mg/kg
Mepivacaine: 20 mg/kg
Bupivacaine: 4 mg/kg
What are the recommended maximum doses for each drug?
Lidocaine: 5 mg/kg
Mepivacaine: 7 mg/kg
Bupivacaine: 2 mg/kg
How are locals metabolized and eliminated?
Amides are metabolized by the liver - commonly used local anesthetics are considered to be high extraction drugs, clearance is dependent on liver blood flow not on enzyme function. Can see decreased extraction when cardiac output is low.
Water soluble metabolites are lost in the urine and bile.
What are the three types of muscle relaxants?
1. peripherally acting (anti nicotinic at neuromuscular junction)
2. Centrally acting
3. Direct Acting
What is the most common use for muscle relaxants in veterinary medicine?
Intraocular surgery to prevent the eye from rolling under the third eyelid
A peripherally acting depolarizing muscle relaxant
Two ACh molecules bound together generates an action potential when it binds to the receptor. It is metabolized by pseudocholinesterase in plasma so it stays bound to receptors longer.
A peripherally acting non-depolarizing muscle relaxant
acts as a competitive antagonist at the receptor (ACh cannot bind)
Only one ACh binding site on receptor needs to be blocked for these to be effective)
Centrally acting muscle relaxant
Centrally acting muscle relaxant
Centrally acting muscle relaxant
Centrally acting muscle relaxant
Direct acting muscle relaxant - used to treat malignant hyperthermia
How does the neuromuscular junction work?
Skeletal muscles are innervated by myelinated branches of motor neurons. Neuron loses its myelin as it gets close to the muscle cells. The muscle membrane is highly folded at the motor endplate and is really close to the neuron. ACh is stored in vesicles of neuron and is released into neuromuscular junction to stimulate post synaptic nicotinic receptors.
In order to open the ion channels you need?
Two ACh molecules.
muscle relaxants do what?
They induce skeletal muscle relaxation but NOT anesthesia or analgesia.
Peripherally acting non-depolarizing muscle relaxant
Why is patient monitoring and support so critical with neuromuscular blocking agents?
NMBAs paralyze all skeletal muscles in the body including laryngeal/pharyngeal muscles. (diaphragm is more resistant)
You need to monitor ventilation and be able to ventilate the patient or you cannot use them.
How do you monitor the neuromuscular blockade?
You can monitor the depth of neuromuscular blockade to assist with dosing and planning recovery by using a peripheral nerve stimulator to monitor activity of the nerves at the NMJ.
How do you reverse NMBAs?
Recovery from non-depolarizing NMBAs can be spontaneous or we can antagonize their effects using anticholinesterase inhibitor drugs to allow ACh to build up and competitively displace the NMBA.
Anticholinesterase inhibitor, slow onset with long duration
Anticholinesterase inhibitor, fast onset with shorter duration
Why do you have to be careful when using NMBA antagonists? (ie anticholinesterases)
ACh not only builds up at the nicotinic receptors but at the post ganglionic muscarinic receptors. We may produce other effects that we do not want (slowing heart rate, bronchoconstriction, salivation)
What do we usually administer with anticholinesterase inhibitors?
We will usually administer them concurrently with anticholinergic agents like atropine or glycopyrrolate to minimize side effects of NMBA reversal
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