Flashcards in Pharm - Local Anesthetics Deck (38):
What are some naturally occurring agents that are anesthetic, and what is their difference with local anesthetics?
1. erythroxylum coca - cocaine
2. gymnodinium breve - aka red tide; poisons fish on mass scale
3. puffer fish
4. snake & spider venom
- the difference is these cpds are IRREVERSIBLE, while local anesthetics are REVERSIBLE.
what are the advantages & disadvantages of local anesthetics?
Advantages: simple, safe, inexpensive
Disadvantages: unsuitability, unpredictable surgery, prejudice
What are the 2 mechanisms of action for local anesthetics?
1. open sodium channel block
2. closed sodium channel block (memb expansion theory)
*make sure you understand these concepts
What nerve would be more sensitive to local ane: non-myelinated or myelinated?
Where are opioid receptors located at on a nerve, and what is their purpose?
- on the ends of the nerve fiber; they inhibit action potential generation
Synaptic transmission involves the release of what substances?
Synaptic transmission involves the release of substance P, a neuropeptide (NP) and glutamate and activation of their receptors on the secondary neuron.
Na channels exist in what 3 different states? Which states do local ane prefer?
*activated & inactivated bc the channels are open--enough room for Na to get in!
What forms of the drugs cross the biological memb? What form works on Na channels?
Why does a block run proximal to distal? What happens during recovery of the drug?
- Anesthetic diffuses DOWN concentration gradient
- conc gradient is reversed after diffusion, dispersion, dilution, and absorption of the drug
- so recovery runs proximal to distal!!
What is the effect of the size of the nerve bundle on drug penetration?
(know this is long, but just read it and understand it...)
- fibers on the outside of the bundle see the highest conc quickest while those fibers in the center see the conc rising the slowest.
- fibers in the center serve the distal parts of the anatomy.
- when the conc gradient is reversed, the drug comes back out and the center of the nerve bundle retains the conc the longest so have recovery at the site of injection and then recover from distal areas last of all
ex. inject in upper arm, have loss of sensation there first and then in fingertips last and then stays in fingertips longer than at injection site
What are the 3 parts of a local anesthetic? Describe them.
1. aromatic - allows for passage thru memb
2. intermediate - linking region; either an ester or amide
3. amine - active end; becomes positively charged & binds to Na chnl
What is an exception to the rule of having either an amide or an ester?
Articaine [Septocaine] has BOTH an ester and an amide, but is classified as as amide!
*it also has a thiophene ring (5-membered) rather than a benzene ring.
What is a good way to differentiate agents with amide structure from ones with esters?
"I Rule" - if local anesthetic has an "i" before the suffix caine, it has an amide linkage.
*with the exception that articaine has both...
What is the difference in metabolism of amides & esters?
- amides need to be inactivated by the liver and tend to have a longer duration of action.
- esters are inactivated in situ by esterase enzymes.
There is a genetic subset of the population that have atypical esterase activity (genetic defect) and have a lack of capacity in this enzyme action. What effect would this have on providing them anesthesia?
Administration of an ester drug/local anesthetic would lead to a prolonged effect bc the esters are not breaking down properly.
What are symptoms of minor toxicity?
ringing in ears, metallic taste, numbness of lips & tongue
what would you administer in the event of seizures?
diazepam; succinylcholine if a severe rxn
Why is a vasoconstrictor important to use with a local anesthetic? What are some examples of vasoconstrictors? What can be used to reverse the effects of anesthesia by facilitating blood flow?
- it temporarily shits down the blood supply to provide more time for the local anesthetic to have an effects.
-examples: epi or levonordefrin
- phentolamine (vasodilator)
What type of local ane can inc chances of allergy?
1. Some esters like procaine (through conversion to para-aminobenzoic acid [PABA])
- this metabolite causes more allergies
2. preservatives (sulphites) may produce allergy as well
*if pt is allergic to amide, give them ester. Vice versa.
* if allergic to both, give them diphenhydramine
• How many mg/mL in a 2% solution?
• How many ug/mL epinephrine in a 1:100,000 solution?
20 mg/mL in a 2% solution
*make sure you understand how to solve these type of problems!
What parameter correlates w/ POTENCY?
LIPID SOLUBILITY correlates w/ POTENCY.
- greater lipid solubility enhances diffusion thru membranes, allowing a lower mg dosage.
What parameter correlates w/ TIME OF ONSET?
- determines portion of an administered dose that exists in lipid-soluble, tertiary molecular state at a given pH
- lower pKa = greater portion in tertiary, diffusible state (hastens onset!!)
What parameter correlates w/ METABOLISM?
- esters are principally hydrolyzed in plasma by cholinesterases; amides are primary transformed w/i the liver
What parameter correlates w/ DURATION?
- affinity for plasma proteins also corresponds w/ affinity of drug for protein binding-site w/i the Na chnl
- this prolongs presence of drug
What is methemoglobinemia? What is the TX?
- an oxidized Ferric Hb that has a reduced oxygen carrying capacity produced by toxic metabolites (PRILOCAINE BENZOCAINE)
- an excess amount of methamoglobin = bluish discoloration of mucosal memb & nail beds (life threatening w/ cardiac or pulm diseases)
- Tx: IV Methylene blue (or ascorbic acid)
What local anesthetic has a prolonged drug action that could cause cardiotoxicity? What is a similar, but safer drug to use?
BUPIVACAINE; more potent & cardiotoxic than lidocaine/mepivacaine
- ROPIVACAINE; reduced cardiotoxicity, greater safety margin
What local ane are used for the mucous membranes (mouth, pharynx, larynx, trachea, esophagus, urethra)?
What local ane are used for the skin (NOT mucous membranes)?
What is EMLA cream?
aka eutectic mixture of local anesthetics cream (topical); mix of 2.5% lidocaine & 2.5% prilocaine
***make sure you know this
What is LET?
aka lidocaine-epinephrine-tetracaine OR tetracaine-phenylephrine
- widely used in pediatric emergency rooms
- for suturing situations
*Why would you mix lidocaine & tetracaine?
- lidocaine = rapid onset; tetracaine = slow onset—now you get the durability & rapid onset you want by mixing!
***make sure you know this
What are the rapid intermediate acting local anesthetic(s)?
ARTICAINE, LIDOCAINE, PRILOCAINE
What are the slow intermediate acting local anesthetic(s)?
What are the slow long-acting local anesthetic(s)?
BUPIVACAINE, ROPIVACAINE, TETRACAINE
What are the slow short-acting local anesthetic(s)?
What are the rapid short-acting local anesthetic(s)?
What is lidocaine-oxymetazoline?
an a1/a2 adrenergic agonist that is used by otolaryngologists to provide analgesia & reduce engorgement of nasal passages
IV anesthetics are acidic, so they cause stinging. What can be done to reduce this?
- Neutralize with Na Bicarbonate 0.1-0.2 mEq/mL
- Mix immediately before use, drug stability!
• Can speed up passage across membrane by changing the pH
• If made more alkaline = can inc neutral amt & thus inc amt of going across memb
• Use Na Bicarbonate to neutralize this right before injection (b/c the drugs are unstable in alkaline solutions)