local anesthetics 2
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- LAs reversibly block the _____ and _____ of nerve impulses
- generation and propagation
- bi-directional blockade
- LAs can alter both sensory and motor function because LAs can block function in ALL excitable cells
- LAs used to decrease what?
-
1) pain
2) temp
3) touch perception
4) skeletal muscle tone - level of effect depends on what?
-
1) agent used
2) route of administration
3) drug concentration at site
4) lipophilicity - route of LAs
-
1) topical (skin, MM)
2) parentetral (peripheral, cnetral, spinal)
3) rectal
4) ophthalmical - many of LAs also used as:
- antiarrhythmics
- What control the compounds ability to penetrate the nerve sheath and enter the nerve membrane?
- the lipophilicity of the aromatic group
- most of LAs are:
- ionizable weak bases
- ionizable weak bases can exist as:
-
1) the freebase or
2) the positively charged form
which will alter their action at the site - all agents act to decrease:
- the permeability of the membrane to sodium ions
- LAs bind to sites in the:
- Na channel of the voltage gated Na channels (inhibit Na inflow during depolarization)
- low concentration of LAs decreases:
-
both 1) the rate of rise and
2) the height of the action potential
(higher conc. can abolish it totally) - LAs increase:
-
1) firing threshold
2) total propagation time - in myelinated fibers, this occurs only at the:
- Nodes of Ranvier
- K outflow
- may also be inhibited somewhat, but not nearly to the extent of Na
- most of LAs act by binding to:
- inner portion of Na channel
- Which nerves are affected first?
-
1)small diameter nerves
2) more rapidly stimulated fibers
3) autonomic fibers - Why are small diameter nerves affected first?
- small diameter nerves are affected first, then larger diameter nerves due to the # of channels to be blocked (greater in large fibers)
- Why are more rapidly stimulated fibers blocked first?
-
due to 1) more frequent opening of Na channels and
2) the ability of the LAs to get into channel to bind - the order of fibers get affected
-
1st: autonomic fibers
2nd: sensory
3rd: motor - selsective Na channel blockers
-
1) tetrodotoxin
2) saxitoxin - tetrodotoxin
- from pufferfish
- saxitoxin
- from red tide microorganisms (paralytic shellfish poisoning)
- Where selective Na channel blockers block?
- OUTER mouth of Na channel
- LAs use as antiarrhythmic agents is due to the:
-
1) blockade of Na channels in myocardial tissues
2) effective decrease in firing rate
3) effective decrease in passage of signals through conductive fibers - topical
- decrease pain of wound, burn, MMs
- infiltration
- injected around area (ie. for Sx)
- regional nerve block
- injected close to nerve that innervates the area to be anesthetized
- spinal
- injected into lumbar subarachnoid space to get to nerves in that area going to various body sites)
- epidural
- given under the dura mater - keeps agent from rising higher up spinal column)
- intravenous
- usually for Sx on a specific limb
- selection of LAs minly based on its:
- pharmacokinetics
- fast onset
-
1) lidocaine
2) prilocaine - slow onset
-
1) procaine
2) tetracaine - short duration (15-30 min.)
-
1) procaine
2) chloroprocaine - intermediate duration (30-90 min.)
-
1) lidocaine
2) prilocaine - long duration (2-3 hrs)
- tetracaine
- epi.
- may be used to increase duration, but is not always effective
- onset on MMs
-
fastest onset: benzocaine
2nd: lidocaine and cocaine
(topical duration: 30-60 min.) - local hypersensitivity more commone with:
- ester type
- examples of preps which increase sensitivity risk:
-
1) tartrazine
2) sulfites - systemic absorption can lead to:
-
1) cardiotoxic risk
2) potential CNS symptoms (sedation, dizziness, disorientation, tremors, seizures, resp. arrest) - the LAs are classified by:
-
their structure
1) ester
2) amide
3) neither - esters
-
1) benzocaine (oragel)
2) procaine (novocaine)
3) chloroprocaine (nesacaine)
4) tetracaine (pontocaine)
5) cocaine
6) cetacaine (cetylite) - amides
-
1) lidocaine (xylocaine)
2) prilocaine (citanest)
3) mepivacaine (carbocaine)
4) bupivacaine (marcaine)
5) articaine (septocaine)
6) ropivacaine (naropin) - not true amides or esters
- pramoxine (proctofoam)
- esters are hydrolyzed by:
- cholinesterases
- 1) Benzocaine (Oragel)
-
1) poorly water soluble
2) topical use only
3) pKa ~3.5 - excessive absorption of Benzocaine may lead to:
- methemoglobinemia
- 2) Procaine (Novocaine)
-
1) 1st synthetic local anesthetic
2) slower onset with short duration
3) weak potency
4) fairly low systemic toxicity
5) use superceded by better agents (amides) - Procaine is best for:
- infiltration and nerve block
- 3) Chloroprocaine (Nesacaine)
-
1) ester
2) rapid onset, short duration
3) low syst. toxicity
4) used in high [ ]
5) for infiltration, nerve block, IV, and epidural use - 4) Tetracaine (Pontocaine)
-
1) ester
2) long duration with slow onset
3) spinal (major use)
4) topical (absorption across MMs limit its use) - potency of Tetracaine
- 10 times more potent than procaine, but also 10 times more toxic
- Why Tetracaine used in spinal anesthesia?
- because the barriers decrease diffusion and decrease toxicity risk
- 5) Cocaine
-
1) ester
2) C-2 controlled substance
3) only use in topical on MMs(too toxic for other uses) - uniquness of Cocaine
-
1) potent vasoconstrictive activity
2) addiction liability in addition to it's LA effect - 6) Cetacaine (Cetylite)
-
1) ester
2) topical for local skin disorders (not for MMs)
3) for opthalmology - Cetacaine is a mixture of:
-
1) Benzocaine
2) Tetracaine
3) Butyl Aminobenzoate - use of Cetacaine
-
1) topically
2) rectally
3) spray to inhibit the gag reflex (during bronc. exam) - amides are metabolized mainly in the:
- liver
- 1) Lidocaine (Xylocaine)
-
1) amide
2) most commonly used LA
3) rapid onset with intermediate duration
4) used for most types of applications - Why many formulations of Lidocaine include Epi?
- because Lidocaine causes vasodilation
- 2) Prilocaine (Citanest)
-
1) amide
2) similar to lidocaine in properties, but LESS vasodilation
3) rapid onset, intermediate duration - toxicity of Prilocaine
- least toxic of the amides, but can still cause methemoglobinemia
- 3) Mepivacaine (Carbocaine)
-
1) amide
2) similar to lidocaine
3) used for infiltration, nerve blocks, epidural
4) not effectively topically - Why Mepivacaine is not used in obstetrics?
- because biotransformation in fetus is prolonged
- 4) Bupivacaine (Marcaine)
-
1) amide
2) long duration, with slower onset
3) high potency
4) used for infiltration nerve block, epidural, and spinal - Is Bupivacaine more toxic than Lidocaine?
- Yes! (cardiotoxic)
- 5) Articaine (Septocaine)
-
1) amide
2) only available in US in combination with Epi
3) similar to lidocaine
4) short duration and rapid onset - use of Articaine
- used for dental and peridontal procedures
- toxicity of Articaine
- low systemic toxicity due to rapid breakdown (it has an ester group in addition to an amide)
- 6) Ropivacaine (Naropin)
-
1) amide
2) long duration
3) similar to Bupivacaine, but less cardiotoxic
4) less lipid soluble, and more rapidly metabolized than Bupivacaine - use of Ropivacaine
-
similar to Bupivacaine
1) infiltration
2) nerve block
3) epidural
4) spinal - Bupivacaine and Ropivacaine
-
1) Bupivacaine: R-isomer
2) Ropivacaine: S-isomer - Pramoxine (Proctofoam)
-
1) not true amide or ester
2) topical agent for relief of hemorrhoids, rectal pain and itching of skin disorders (pruritis) - potency of Pramoxine
- weak potency (will not totally abolish gag reflex)
- Pramoxin mixed in combination with many products such as:
-
1) hydrocortisone
2) calamine - liposomal formulation
- Liposomes are somewhat like cells in that they are round shells of phospholipids, the basic components of human cell walls. Enclosing a drug within a liposome entraps the drug as ‘payload,’ protecting it from early degradation within the body. Liposome encapsulation also improves a medication’s bioavailability (the amount of time and specific distribution within the body), which can extend the treatment effect and reduce dosing.