Term
|
Definition
nonspecific inhibitors of peripheral sensory, motor, & autonomic pathways via inhibition of AP conduction
no loss of consciousness or vital functions |
|
|
Term
|
Definition
| specific inhibitors of pain pathways via action on primary nociceptors & in the CNS |
|
|
Term
| How do local anesthetics block AP conduction? |
|
Definition
| block voltage-dependent sodium channels |
|
|
Term
| What are the 3 conformations of the sodium channel? |
|
Definition
1) b/w impulses: resting (closed)
2) after stimulation(depolarization): activated (open)
3) transition from an open to closed conformation (inactive) => back to resting once membrane repolarizes |
|
|
Term
| How do local anesthetics block voltage-dependent sodium channels? |
|
Definition
| reducing the influx of sodium ions (=> prevention of depolarization of membrane => blocking AP conduction) |
|
|
Term
| When is the local anethetic pharmacologically active? |
|
Definition
|
|
Term
| What does the Local Anesthetic (LA) do to the calcium channel? |
|
Definition
| binds open state & stabilizes the inactive state => blockade of sodium current (=> increase of threshold excitability, decreased rate of AP, decreased conduction) |
|
|
Term
|
Definition
aromatic ring connected to ionizable group (s.a. amines), connected by ester or amide bond
[image] |
|
|
Term
| Why is the hydrophobic aromatic ring & amino nitrogen substituents needed for LA? |
|
Definition
| increase potency & duration of action |
|
|
Term
| When will LA have a more rapid onset & a more concentration of nonionized base that can pass thru cell membrane? |
|
Definition
the closer pKa of a LA is to physiological pH
most LAs are weak bases (pKa b/w 8 & 10) |
|
|
Term
| Why is the presence of an ester bond or amide bond important in a local anesthetic? |
|
Definition
| suceptibility to metabolic hydrolysis |
|
|
Term
| What inactivates the ester-containing LA? |
|
Definition
|
|
Term
| Who are at an increased risk for LA toxic side effects with ester LA? |
|
Definition
| patients with genetically abnormal pseudocholinesterases => slower metabolism |
|
|
Term
| What metabolizes the amide-containing LA? |
|
Definition
|
|
Term
| What does rate of amide metabolism depend on? |
|
Definition
| drug itself (overall slower than ester hydrolysis) |
|
|
Term
| What can reduce the metabloic rate and predispose patients to systemic toxicity with amide LA? |
|
Definition
| decreases in hepatic function or liver blood flow |
|
|
Term
| What is needed for a LA to be effective? |
|
Definition
1) partition into
2) diffuse across
3) dissociate from
membrane in the cytosol
moderate hydrophobicity = more effective
(not enough hydrophobicity - can't penetrate membrane, too much - sticks in membrane) |
|
|
Term
| Do amide or ester LA have longer durations of action? |
|
Definition
|
|
Term
Where are ester LA excreted?
amide LA? |
|
Definition
|
|
Term
| Do ester or amide LA have more potential SE? |
|
Definition
|
|
Term
| What determines the therapeutic effect & extend of toxicity of LAs? |
|
Definition
|
|
Term
| What are the 6 clinical uses of local anethetics? |
|
Definition
1) Topical
2) infiltration
3) field block
4) nerve block
5) spinal
6) epidural |
|
|
Term
|
Definition
| short term pain relief when applied to skin or mucous membranes |
|
|
Term
| What must topical LA traverse to reach nerve endings of Aδ & C fibers of the dermis? |
|
Definition
|
|
Term
|
Definition
| numb an area of skin via injection intradermally or subcutaneously without considering course of cutaneous nerves |
|
|
Term
| Why is intrafiltration LA faster than topical LA? |
|
Definition
| doesn't have to cross epidermal barrier |
|
|
Term
| What is the disadvantage to infiltration LA? |
|
Definition
| large amount of LA for a sm. area |
|
|
Term
| How can duration of action be increased & amount of LA needed be decreased? |
|
Definition
| specifically block nerves that innervate area of interest |
|
|
Term
| How can specific nerves be blocked? |
|
Definition
1) subcutaneously at major nerves
2) level of spinal roots |
|
|
Term
|
Definition
| subcutaneous injection to anesthetize region distal to injection |
|
|
Term
|
Definition
| injection of LA into or around individual peripheral nerves or nerve plexuses |
|
|
Term
|
Definition
| injection into the CSF in the lumbar space usually b/w 3 & 4 lumbar vertebrae |
|
|
Term
|
Definition
| injection into the epidural space to produce anesthesia above & below injection site |
|
|
Term
Function
therapeutic nerve block |
|
Definition
| used to treat painful conditions |
|
|
Term
Function
diagnostic nerve blocks |
|
Definition
| used to determine source of pain |
|
|
Term
Function
prognostic nerve blocks |
|
Definition
| predict outcomes of current treatment |
|
|
Term
def
preemptive nerve block |
|
Definition
| prevent subsquent pain from a procedure than can cause problems |
|
|
Term
| What determines the degree of toxicity of a LA? |
|
Definition
| amount of LA that enters systemic circulation (absorption) |
|
|
Term
| Where does rapid absorption of LA occur? |
|
Definition
|
|
Term
| How can duration of local anesthetic action be prolonged & reduce toxicity of LA? |
|
Definition
| reduce blood flow to area via administration of a vasocontrictor s.a. epinephrine to reduce blood flow to the area |
|
|
Term
When is epinephrine use with LA contraindicated?
Why? |
|
Definition
| fingers, toes, ears, & nose due to limited collateral circulation => hypoxic damage, tissue necrosis, & gangrene |
|
|
Term
| What are the 3 types of nerve fibers comprising peripheral nerves? |
|
Definition
|
|
Term
| What 3 protective membranes surround the peripheral nerve fibers? |
|
Definition
epineurium
perineurium
endoneurium |
|
|
Term
| What peripheral nerve fibers mediate pain? |
|
Definition
|
|
Term
| What peripheral nrve fibers mediate temperature? |
|
Definition
|
|
Term
| What is mediated by Aα, Aβ, & Aγ nerve fivers? |
|
Definition
| postural, touch, pressure & motor |
|
|
Term
| Which nerve fibers are blocked first in a nerve blockade? |
|
Definition
|
|
Term
| What contributes to the differential sensitivity to LA of nerve fibers in a nerve blockade? |
|
Definition
1) fiber diameter (smaller = faster)
2) firing frequency (higher frequency = faster)
3) location in nerve bundle (periphery = faster) |
|
|
Term
def
differential functional blockade |
|
Definition
the general order in which functional deficits occur
(pain, temp, touch, pressure, motor) |
|
|
Term
| Do sensory or motor fibers have a slower firing rate? |
|
Definition
|
|
Term
| Do sensory or motor fibers have a longer action potential duration? |
|
Definition
|
|
Term
| Why are shorter diameter fibers preferentially blocked by LA over larger diameters? |
|
Definition
| the distance over which these fibers propagate an electrical impulse is shorter |
|
|
Term
| Why are nerve fibers in the periphery preferentially blocked by LA? |
|
Definition
1) exposed 1st
2) exposed to higher concentration |
|
|
Term
| What undesired CNS SE are seen due to LAs? |
|
Definition
1) stimulation (excitatory motor phenomena)
2) restlessness
3) dizziness, drowsiness
4) tremors, convulsions
5) confusion, agitation
6) resp. depression |
|
|
Term
| What is the primary site of action of cariovascular SE due to LAs? |
|
Definition
|
|
Term
| What are the LA cardiovascular SE? |
|
Definition
Myocardium:
decreased electrical excitability
decreased conduction
decreased contraction => decreased CO
Vascular smooth muscle:
relaxation => vasodilation (except cocaine) |
|
|
Term
| What other smooth muscle SE are seen in LA? |
|
Definition
| depress contractions/relaxation (GI, vascular, bronchial) |
|
|
Term
| What are the LA hypersensitivity SE? |
|
Definition
allergic dermatitis
asthmatic attacks |
|
|
Term
Are ester or amide LA more likely to cause hypersensitivity?
Why? |
|
Definition
| esters due to PABA dertivatives (known allergen) |
|
|
Term
| What are the 4 ester-derived LA? |
|
Definition
1) Cocaine
2) Procaine (novacaine)
3) Benzocaine
4) Tetracaine |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| amino ester associated with complex cyclic structure |
|
|
Term
| How is cocaine different in SE profile than other LA? |
|
Definition
|
|
Term
|
Definition
| adrenergic phenomenon: HTN, tachycardia, arrythmia, etc. |
|
|
Term
| What causes cocaine toxicity SE? |
|
Definition
| blockage of catecholamine uptake in CNS & PNS |
|
|
Term
SOA (spectrum of activity)
cocaine |
|
Definition
| anesthesia of mucous membranes (topical only) - due to LA & vasoconstriction, can be used to decrease operative bleeding |
|
|
Term
| Why is cocaine so addictive? |
|
Definition
| affects mesolimbic pathway (pleasurable feelings) |
|
|
Term
|
Definition
|
|
Term
CI (contraindications)
cocaine |
|
Definition
| traumatized mucosa & sepsis, heart issues, Tourette's, pregnancy |
|
|
Term
| What was the first synthetic anesthetic? |
|
Definition
|
|
Term
| What is procaine hydrolyzed to? |
|
Definition
|
|
Term
|
Definition
|
|
Term
| Why is procaine anethesia slow to onset(2-5 min)? |
|
Definition
|
|
Term
| Why is procaine duration of action short |
|
Definition
| low hydrophobicity => dissociated rapidly from Na+ channel |
|
|
Term
| What happens once procaine dissociates from Na+ channel? |
|
Definition
| rapid removal from administration site via circulation (not retained in tissue) |
|
|
Term
|
Definition
| infiltration & dental procedures |
|
|
Term
|
Definition
warfarin
MAOIs
anti-HTN
sulfas |
|
|
Term
|
Definition
| liver/heart disease, PABA, low pseudocholinesterase |
|
|
Term
Onset/Duration/Potency
Benzocaine |
|
Definition
| rapid onset(1 min), short acting(15-20 min), low potency |
|
|
Term
| How does bezocaine MOA differ from that of other LA? |
|
Definition
| it's small, so it fits into the pore in the closed state to stabilize the closed form |
|
|
Term
| What are the 3 forms benzocaine comes in? |
|
Definition
1) cream
2) aerosol
3) ointment |
|
|
Term
|
Definition
1) topical pain reliever (sun burn, sore throat, teething, etc)
2) anesthesize mucous membranes
3) lubricant & LA for inserting medical devices s.a. catheters, endoscopic tubes, scopes, etc. |
|
|
Term
|
Definition
| sulfas, supplements, caffeine, EtOH |
|
|
Term
|
Definition
| methemoglobulinemia, enzyme deficiency, COPD, heart disease, infants, Advisory for cosmetic procedures (risk for systemic toxicity if not used appropriately) |
|
|
Term
Duration/Potency
Tetracaine |
|
Definition
| long lasting/high potency |
|
|
Term
| hy is tetracaine so potent & long lasting? |
|
Definition
| high hydrophobiticy due to butyl group =>
a) prolonged interaction with Na+ channel
b) increased time with tissue surrounding nerve |
|
|
Term
| Why can tetracaine cause increased systemic toxicity? |
|
Definition
| more slowly metabolized than other ester LAs since it's released gradually from the tissue to the blood |
|
|
Term
|
Definition
| spinal & topical anesthesia |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
| What are the 3 amide LAs? |
|
Definition
1) Lidocaine
2) Bupivacaine
3) Ropicacaine |
|
|
Term
| What is the most widely used LA? |
|
Definition
|
|
Term
| What are the 5 forms lidocaine is available in? |
|
Definition
| ointment, jelly, patch, aerosol, solution |
|
|
Term
Onset/Duration/Potency
Lidocaine |
|
Definition
| fast onset/moderate duration(1-2 hrs)/medium potency |
|
|
Term
| Why does lidocaine have a fast onset? |
|
Definition
|
|
Term
| Why does lidocaine have a medium duration of action & potency? |
|
Definition
| moderately hydrophobic & metabolites retain a weak anethetic activity |
|
|
Term
|
Definition
infiltration
nerve block
epidural
spinal
topical |
|
|
Term
|
Definition
|
|
Term
|
Definition
| antiarrythmics, vasopressors, hypersensitive, liver failure, breat-feeding |
|
|
Term
Duration/Potency
bupivacaine |
|
Definition
|
|
Term
| Why is bupivacaine so potent? |
|
Definition
| highly hydrophobic due to butyl piperidine group attached to teriary nitrogen |
|
|
Term
| Does bupivacine have more sensory or motor block? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
epidural
infiltration
nerve block
spinal |
|
|
Term
|
Definition
|
|
Term
|
Definition
| liver disease, bleeding/clotting disorder, HTN, hypotension, kidney disease |
|
|
Term
| What is the newest amide local anesthetic? |
|
Definition
|
|
Term
| How does ropivacaine differ from bupivacaine? |
|
Definition
| low cardiotoxiticy & less lipid soluble |
|
|
Term
| What neurons are preferentially blocked by ropivacaine? |
|
Definition
|
|
Term
| Why does epinephrine have no effect on onset, duration, or systemic absorption for ropivacaine? |
|
Definition
| produces vasoconstriction (like cocaine) |
|
|
Term
|
Definition
epidural
infiltration
nerve block |
|
|
Term
|
Definition
|
|
Term
|
Definition
may increase labor
not reccomended for emergency situations
allergies, heart diease, liver disease
maternal/neonatal toxicity |
|
|
Term
| What are the 3 most potent LAs? |
|
Definition
tetracaine
bupivacaine
ropivacaine |
|
|
Term
| What 2 LAs have no parenteral use? |
|
Definition
|
|
Term
| What 2 LAs have no parenteral use? |
|
Definition
|
|
Term
| What 3 LAs have no topical use? |
|
Definition
procaine
bupivacaine
ropivacaine |
|
|
Term
| Do ester or amide LAs tend to havea higher potency? |
|
Definition
| amide (except tetracaine - ester with high potency) |
|
|
