Local Anesthetics M5 Flashcards
Local depends on … for onset, potency, and duration?
Potency= lipid solubility
Duration of action = protein binding
Onset= pika
Drug absorption sites from fastest (toxicity) to slowest (low toxicity risk).
I I I Can’t Possibly Enjoy Slow Sloppy Sex
Inhaled IV Tracheal Intercostal Caudal Paracerebral Epidural Bracheal/Spinal Sciatic/Femoral Subcutaneous
Why epinephrine added to local?
1) to limit local systemic toxicity;
2) increases block density
Induced vasoconstriction which decreases vascular absorption leading longer block (more time neuron exposed to local) and increasing its toxic dose.
2 locals that are not added with epinephrine because it won’t benefit?
Bupivicaine & Ropivincaine
Rip won’t enhance or prolong their action because their duration based on protein binding.
Ester vs amide
Ester
- has one i,
- metabolized by psudocholinesterase to PABA
Amides (it has an i already)
- 2 i
- metabolized by liver to methylparaben.
Methemoglobinaemia common with 2 locals?
Benzocaine & prilocaine, and less so lidocaine
Which neuronal state that local has greatest affinity?
Open (active, that sending more signals) or inactived voltage gated channels (no Na influx)
Lowest affinity when gates at resting phase.
Locals binds to alpha or beta subunits ?
It binds to aplpha subunit of voltage gated sodium channels on the intercellular surface and prevent AP
Which local causes methemoglobinenimia through a mechanism involving o-toluidibe?
Prilocaine
Local that associated with AClS- resistant ?
Bupivacaine
The R + isomer binds to cardiac Na channels as well as K and Ca channels and dose not let go quickly like lidocaine.
It has a great long duration because of protein binding and it’s high lipid soluble makes it a good choice for neuraxaul.
How to calculate ?
How much volume u need of 1:1000 epi should be added to 20 cc to end up with 1:200,000
1% = 10 mg/ml = 1:100
0.1% = 1 mg/kg = 1:1000 (epi vial)
Dilution difference b/ starting and ending concentration ( 1:1000 to 1:200,000 = 300 fold different) next divide the final volume you want by this # ( 20 cc needed then 20/200 = 0.1 cc epi to be added in 20 cc)
Local that metabolized by psudocholinesterase?
Ester. (one “i”) except cocaine metabolized by liver carboxylsterase
having higher or lower pKa associated with faster onset?
low pKa = faster onset.
so the molucule/local needs to be in neutral form in order it can cross the cell membrane and bind to intracullurar voltage gated Na channels.
if the pKa is high, less local avaliable to be cross the membrane and therefore, slower onst.
What is pKa?
it is the pH wher the half of molecule (local anesthetic) in ionized form and the other half is non-ionized
What type of protein that basic and acid drugs bind too?
Acidic drugs (like barbiturates) binds to albumin
Basics (like local IV) binds to alpha-1-acid glycoprotein.
Why lidocaine given before succinylcholine?
For bronchial smooth muscle relaxation that succinylcholine blocks them at the nicotine receptors. (It dose with all locals except cocaine)
What is the cause of anaphylaxis with lidocaine?
Some amides contain preservative called methylparaben which is structurally similar to PABA (that is ass. With ester locals)
Cauda equina syndrome is classically associated with which local and route of administration?
High doses of Lidocaine & terracaine esp with continuous/repeated infusions through small bore microcatheters in intratgecal space.
What are symptoms of TNS and when excpected to appear?
Sever buttocks pain, leg burning, dysethesias that occur following lidocaine spirals esp with lithotomy positions
Bupivacaine vs procaine?
Local anesthetics exist in solution in both uncharged base and charged cationic forms. The base diffuses across the nerve sheath and membrane and then re-equilibrates within the axoplasm. It is intracellular penetration of the cation into, and attachment to a receptor at a site within the sodium channel, that leads to inhibition of sodium conductance and ultimate conduction blockade. Bupivacaine is typical of amide-linked local anesthetics with high anes- thetic potency and long duration of action (class III). Procaine is typical of class I agents that are ester linked and have low anesthetic potency and short duration of action. Important features of group III compounds include: (1) high degree of lipid solubility or high partition coefficient that aid in penetration of the drug, (2) high degree of protein binding that aids in attachment of the drug once it has penetrated the cell, and (3) pKa closer to pH = 7.4 so that more of the drug is in the unionized form and is free to penetrate the membrane.
Ester- linked anesthetics, such as procaine, are rapidly metabolized by pseudocholinesterases, whereas bupivacaine is slowly degraded by hepatic enzymes.
