m and m 16 - local anes Flashcards
What is the ratio of the sodium potassium ATPase
3 Na out for 2 K+ in
What is the composition of the sodium channel?
1 large alpha, 1 or 2 smaller beta
What subunit of the sodium channel do LA’s bind to?
The alpha subunit, prevent sodium influx
LAs have the least affinity for the sodium channel in which of the 3 possible state?
During resting phase. More affinity during the open or inactivated state
What is use-dependent block?
The concept that LA has more affinity for sodium channels that are more frequently depolarized
LAs bind to the sodium channel on the intracellular or extracellular surface?
Intracellular
What are 3 other types of channels that local anesthetics can also bind to?
Calcium channels, K+ channels and TRPV1
Name 5 agents that can non-specifically bind to sodium channels
TCAs (Amytriptyline) Meperidine Volatile anesthetics Calcium channel blockers Ketamine
What agent is able to bind and block the action of sodium channels from the extracellular surface?
tetrodotoxin
When discusses purely A type fibers, what characteristics increase sensitivity to LAs? Larger or smaller diameter?
The smaller the diameter of the A fiber, the more sensitive it is to LA e.g. A-delta is more sensitive than A-alpha
Which is more sensitive to LAs - Small unmyelinated C fibers or large myelinated A fibers?
Large myelinated A fibers are more sensitive, Small unmyelinated C fibers are relatively resistant
In what order does inhibition of nerve function by LA occur i,e. what goes first? Motor, autonomic, sensory
Autonomic -> Sensory -> Motor
What are the functional groups on a typical local anesthetic?
Lipophilic group (Benzene ring) + Hydrophilic group (tertiary amine) separated by ester or amide linkage
At physiological pH, local anesthetic is [weak/strong] [acid/base] with [+ or -] charge on the tertiary amine
Weak base with + charge on amine
What is an easy trick to separate amide vs ester local anesthetics (what letter?)
Amides all have “I” before the “caine”
How does octanol solubility affect LA function? How can you alter octanol solubility of an LA?
The more octanol soluble, the more permeable to lipid membrane an LA is
Increase octanol solubility (an potency) by increasing size of the alkyl group
[Acidic/Basic] conditions antagonize local anesthetic
[hypo/hyper]-kalemia antagonizes local anesthetic
[hyper/hypo] -calcemia antagonizes local anesthetic
Acidic conditions antagonize
Hypokalemia and Hypercalcemia antagonize block
What is pKa?
The pH where the fraction of ionized and non-ionized are equal
Generally speaking - which have faster onset - more potent or less potent LA?
Less potent (and less lipid soluble) will have faster onset of action
Majority of local anesthetics have pKa greater than 7.9. At pH 7.4 are most of the molecules in the ionized or non-ionized form?
Majority in the ionized form
What form of the LA [ionized/non-ionized] binds the sodium channel more avidly? Remember it is the non-ionized that crosses the epineurium
The ionized binds better. The non-ionized crosses then becomes ionized
True / False - onset of action is directly correlated with pKa?
False. This would mean that as pKa increases, onset of action should decrease. The agent with the fastest onset of action - chloroprocaine - has the highest pka of clinically used agents
Epinephrine is unstable In alkaline environments. How does this affect “packaging” of local anesthetics?
LAs that are prepared epinephrine free have higher pH (6-7) vs those that have epinephrine (4-5). Epi free will have faster onset of action (more of the non-ionized form available)
How does infection (in tissues) alter the effectiveness of local anesthetics?
Infected tissues more acidic, slower onset of action of LA in infected tissues
What is a possible explanation for tachyphylaxis with local anesthetics?
Repeated dosing into the same tissue exhausts the buffering capacity of said tissue, the LA remains acidic and cannot function
What is the theoretical effect of alkalinization of LA? What is the agent used?
Should speed onset of action. Can use sodium Bicarb
How does lipid solubility correlate with duration of action? What is proposed mechanism?
More lipid soluble, longer duration of action. Mechanism is that the more lipophilic, the longer before the drug gets into blood stream
What are the 2 major plasma proteins that bind LA?
Alpha-1 acid glycoprotein (Main) and albumin
What are the 2 LAs that display some selectivity for sensory vs motor block?
Ropivacaine and Bupivacaine
What absorbs LA easier - mucous membranes or intact skin?
Mucous membranes
What is EMLA? What is the use of EMLA?
Oil in water emulsion of 5% lidocaine and 5% prilocaine. Used for anesthesia on intact skin. Don’t use on mucus membranes
What is the major factor that determines systemic absorption of a local anesthetic?
Blood flow. Vascularity decreases as follows:
intravenous (or intraarterial) > tracheal > intercostal > paracervical > epidural > brachial plexus > sciatic > subcutaneous.
Epinephrine is more likely to increase the quality of block achieved with which of the following and why? Bupivacaine vs Lidocaine?
Improves lidocaine more. Shorter acting, will prevent its diffusion away from the site. Bupivacaine is already longer acting, not augmented by more epinephrine
Epinephrine and clonidine can augment analgesia by what mechanism?
Activation of alpha-2 adrenergic receptors
What are the alpha and beta phases of tissue distribution of LA?
Alpha phase - rapid uptake by highly perfused organs (brain, heart, lungs, kidneys, liver)
Beta phase - slower redistribution of LA to moderately perfused organs (gut, muscle)
What organ system in particular extracts significant amounts of LA from circulation? What is significance on LA toxicity?
Lungs extract a lot of LA. This makes toxicity from arterial admin of LA require a LOT less drug than venous (venous will pass though lung before seeing areas of possible toxicity)
What is the tissue / blood partition coefficient? What is the major relevant factor / property re: LA in determining this coefficient?
This is the proportion of LA that is in blood vs. tissues. The more lipid soluble, the greater ability to bind to plasma proteins and to tissues from blood
What is the tissue that serves as the greatest reservoir for LA?
Muscle
How are esters metabolized? How are they excreted?
Metabolized by plasma cholinesterases and butyrylcholinesterase (both termed pseudocholinesterases). Metabolites excreted in urine
What is PABA? Significance?
p-aminobenzoic acid. Assoc with metabolism of procaine and benzocaine, can cause rare anaphylactic reaction
Cocaine is also an ester. How is its metabolism and excretion different from others?
Partially metabolized in liver, partially excreted unchanged in urine
How are amides metabolized?
Metabolized by microsomal p-450 in liver.
Cirrhosis of liver, CHF, beta-blockers can all affect metabolism of LAs how?
These are all associated with decreased liver function or decreased blood flow through liver. Can slow metabolism of LAs
Which group metabolized faster. Amides or esters?
Esters
What is the significance of methemaglobinemia re: LAs?
Prilocaine (metabolized to o-toluidine) and benzocaine can both produce dangerous levels of methemaglobinemia. Avoid prilocaine in labor (for epidurals)
What are some of the early neurological signs of LA toxicity? 5 lister
Circumoral numbness Tongue paresthesias Dizziness Tinnitus Blurred Vision
Patient who got LA now has muscle twitches. What should you watch out for?
Tonic clonic seizures
LA toxicity can cause coma and respiratory arrest. True or false?
True
What class of medications, and what action, can raise the seizure threshold after LA toxicity? What is the definitive treatment (drug) of a seizure from LA?
Benzos and hyperventilation raise threshold
Propofol is definitive tx. Can also use benzos or barbiturates
What is the effect of metabolic or respiratory acidosis on seizure threshold?
Both will decrease the threshold
What is the effect of infused lidocaine on intracranial pressure?
Infused lidocaine can decrease cerebral blood flow and decrease the rise in ICP associated with intubation
What is the effect of infused LA (lidocaine and prilocaine) on MAC?
Can decrease MAC of volatiles by up to 40 %
OD of which LA can cause restlessness, emesis, tremors, convulsions, arrhythmias, resp failure and cardiac arrest?
Cocaine
A patient who got a spinal complains of dysethesia, burning pain and aching of the lower extremity and buttock. What is the most likely agent used for the spinal?
Lidocaine - thought to be from radicular irritation
What is the effect of lidocaine on hypoxic drive?
It depresses hypoxic drive
What are 3 ways that apnea can occur after Lidocaine admin?
Paralysis of phrenic nerve
Paralysis of intercostal nerves
Depression of the medullary respiratory center
What is the effect of lidocaine on myocardial contractility and conduction velocity? What is the mechanism?
Depresses both by blocking the sodium channels involved
What is the effect of high concentrations of LA on arterioles? Low concentrations?
High - Relaxes smooth muscles, leading to arteriolar vasodilaion
Low - Inhibits nitric oxide, leading to vasoconstriction
What will occur first after LA overdose - seizure or cardiac arrest?
Seizure. Cardiac arrest requires 3x more blood concentration of LA. That said, cardiac symptoms may be the only sign seen in patients undergoing general anesthesia
How do you treat cardiac arrhythmias secondary to LA overdose?
IV amiodarone
Bupivacaine - longer acting LA - can cause what 3 effects on the heart when injected IV?
Heart block
Ventricular depression
Ventricular arrythmias (V tach, V fib)
From a cardiac toxicity stand point, what LA blocks more avidly and dissociates more slowly from cardiac sodium channels?
Bupivacaine
What are the effects of cocaine on the cardiovascular system? What is the mechanism?
Cocaine causes hypertension and ventricular ectopy. The mechanism is that it blocks the re-absorption of norepinephrine
What is the treatment of cocaine induced arrythmias?
Calcium channel and adrenergic blockers
What class of LAs are more likely to cause true allergic reaction? What two agents specifically?
Esters, Especially procaine and benzocaine
True or false, injection of local anesthetic directly into muscle is myotoxic?
True - mildly myotoxic - regeneration occurs in 3-4 weeks
What is the effect of lidocaine on coagulation
Causes reduced thrombosis and platelet aggregation. The latter is why an epidural blood patch is not as effective after LA has been administered
How can toxicity with a substance like organophosphate affect LA administration?
Organophosphates inhibit pseudocholinesterase. This can prolong metabolism of ester local anesthetics
What is the effect of histamine and propranolol on lidocaine? Mechanism?
Can decreases the clearance of lidocaine by decreasing blood flow to the kidneys
How do you treat seizures from LA toxicity?
Midazolam or propofol
Why is bupivacaine particularly toxic when administered intravascularly?
Higher chance of cardiotoxicity because it binds better and inhibits cardiac sodium channels better than other LAs (ventricular disturbances, cardiac arrest)
What is the agent to be used for the treatment of LA induced cardiac arrythmias?
Amiodarone
