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58 Cards in this Set
- Front
- Back
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What is the resting membrane potential of a nerve? What maintains RMP? |
-70 mV -Na/K/ATPase pump |
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Why doesn't K Leak out to create RMP less than -70? |
Relative negative charge created by K leaking prevents positively charged K from leaking out more |
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What is threshold? |
-50 mV |
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Describe depolarization of a nerve. |
-electrical impulse applied to nerve causes increased Na permeability -activation gate opens allowing influx of Na -at 20 mV Na channels close -inactivation gate closes a few 10000ths of a second -channel cannot reopen until membrane potential returns to RMP |
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How does repolarization occur? |
-K channels start to open as Na channels begin to close -K efflux -K channels close -RMP is restored, Na/K pump maintains it |
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What state are sodium channels in at rest? |
Sodium channels in rested-closed state and inactivated closed state are in equilibrium |
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What receptors do local anesthetics bind to and in what state? |
Preferentially bind to sodium channels in open or inactivated states...NOT CLOSED STATE -it is speculated LAs bind to specific sites on inner portion of Na channels to maintain inactivated-closed state |
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What effect does repetitive depolarization of Na channels have on speed of action of LAs? |
LAs work faster -the more frequently the channel is depolarized, the more time it's available in the open and inactive states for LA binding |
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How do LAs get into cell to work? |
-Unionized LA diffuses through cell membrane -Ionized LA binds to Na channel from inside the cell membrane (and small amount of unionized LA) |
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What LA is permanently non-ionized? |
Benzocaine |
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What is Cm? |
-minimum effect concentration -lowest concentration of LA that blocks impulse conduction within a specified time -measure of potency -Cm higher in larger diameter fibers -Cm is lower in alkaline pH and high frequency nerve stimulation |
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Rank different nerve fibers from fastest to slowest conduction. |
-A alpha fibers, A beta fibers -A gamma fibers -A delta fibers -B fibers -C fibers |
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What function do A alpha/A beta fibers have? A gamma? A delta? B? C? |
A alpha/beta: afferent/efferent for m. and joints A gamma: efferent to muscle spindle A delta: Afferent sensory nerve B: preganglionic sympathetic C postganglionic sympathetic/ afferent sensory |
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What is the order of blockade? |
1. preganglionic sympathetic B fibers (vasodilation) 2. Small C fibers and medium sized A fibers (loss of pain and temperature) 3. Other A fibers (pressure, touch, proprioception, motor) |
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What is the order of blockade as described by Nagelhout? |
loss of autonomics, then superficial pain, touch, temperature, motor function and proprioception |
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How many nodes of Ranvier must be blocked to halt implulse transmission? What length of unmyelinated fiber must be blocked? |
-at least 2 and preferably 3 nodes -5-6 mm |
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What are the 3 characteristic segments of LAs? |
-aromatic ring (lipophilic) -intermediate chain (hydrocarbon group) -Amine (hydrophilic) |
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What part of the LA is responsible for classification? |
intermediate chain |
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Which type of LA is more likely to cause allergic reaction? Why? |
-Ester LAs due to one of their metabolites, para amino benzoic acid (PABA) |
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Drug must remain in the local area to be effective. Higher concentration (# of molecules) present in area = what? |
faster onset |
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What causes termination of action of LA? |
-systemic absorption slower absorption = longer duration, lower blood levels, lower incidence of LA toxicity |
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What are the ester LAs? |
-Procaine (Novocaine) -Chloroprocaine (Nesacaine) -Tetracaine (Pontocaine) -Cocaine |
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What LAs are amides? |
Lidocaine (Xylocaine) Mepivacaine (carbocaine, polocaine) Prilocaine (Citanest) Bupivacaine (marcaine, sensorcaine) Levobupivacaine (Chirocaine) Ropivacaine (Naropin) Etidocaine (Duranest) Articaine (Septocaine) |
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What determines onset? |
pKa (also concentration) |
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What determines duration of LA? |
systemic absorption...primarily protein and lipid binding determines duration -also vascularity of area of injection and addition of vasoconstrictors effects duration |
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What protein binds LAs? What does more highly protein bound say about a LA? |
alpha 1-acid glycoprotein -more protein bound = longer DOA because bind to membrane proteins in vicinity of Na channels |
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What increases likelihood of toxicity? |
Low abounts of AAG (higher fraction of free drug) -pregnancy, neonates, cancer |
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What is the primary determinant of potency? |
Lipid solubility -bind to Na channels with greater affinity -higher tendency for severe cardiac toxicity |
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Are LAs weak or strong bases? What occurs when they are placed in an environment with acidic pH? Alkalotic pH? |
-Weak bases -acidic environment = more water soluble -alkalotic environment = more lipid soluble (work better) |
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What do you get when you place acid drug in acid environment? Acid drug in basic environment? Base drug in basic environment? Base drug in acidic environment? |
-Acid in acid = more unionized -Acid in base = more ionized -base in base = more unionized -base in acid = more ionized |
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Why are LAs packaged with weak acid? |
forms neutral salt making more water soluble and makes epi more stable if added -mixed to pH of 6.5 in bottle, epid degrades with pH > 5.5 and optimal is <4 |
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Describe what causes the diffusion of LA into a cell and what happens inside the cell? |
-Unionized portion diffuses in -More acidic environment inside cells causes equilibrium to shift back toward ionized -ionized portion binds with Na channel |
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With LAs, lower pKa relates to what? What is the exception to this? |
-greater proportion of LA in unionized for -faster onset -2-chloroprocaine, because high concentration (3%) |
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What determines onset? Potentcy? Duration? |
Onset- pKa -Duration- percent protein binding -potency- partition coefficient (lipid solubility) |
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How does carbonation effect LAs? |
-speeds onset, increases intensity -CO2 rapidly diffuses into nerve -pH lowered inside nerve causing drug to ionize more easily -more ionized drug available to block Na channels |
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How do LAs effect vascular tone? What are the affects of this? |
-Produce vasodilation (except cocaine, vasoconstriction) -increased BF to tissue, drug absorption -decreased duration -increased likelihood of toxicity |
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What is the order of Most to least likely to cause vasodilation leading to increased chance of toxicity? |
lidocaine > mepivacaine, prilocaine > Bupivacaine, Etidocaine, Levobupivacaine |
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Where is absortion speed fastest? List regions in order. |
In time, I can please everyone but susie and sally -IV -tracheal -Intercostal -Caudal -Paracervical -Epidural -Brachial plexus -Sciatic-femoral, spinal, then subcutaneous |
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What determines peak plasma concentration? |
dose, not volume or concentration -400 mg of lido whether 1% or 2% will give you same peak plasma concentration |
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What are some additives that can be added to blocks? |
-alpha 1 agonists -alpha 2 agonists (prolong sensory block, reduce dose of LA) -opioids (increase quality, intensity) -bicarb (speeds onset) -hyaluronidase (increases spread) -Vasoconstictors |
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What is the purpose of added vasoconstrictors to LA? |
-reduces rate of vascular absorption -increases availability of drug for neuronal uptake -longer block -more profound block -decreased peak plasma levels -decreased systemic toxicity |
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What is the best vasoconstrictor to add? |
epi better than phenylephrine and NE |
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What areas of the body should not be injected with LA with epi? |
fingers, nose, toes, ears, penis = Gangrene |
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What does Hyaluronidase do when added to LA? |
-increases spread of LA (breaks down hyaluronic acid which prevents diffusion of foreign substances) -can cause allergic reaction, shortened duration, increased toxicity |
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What is the point of mixing different LAs? |
-can get quicker onset from one, longer duration from another -toxic dose 1/2 of one + 1/2 of the other |
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How are ester LAs metabolized? |
Ester hydrolysis, primarily in plasma (also in RBCs and Liver) -very rapid, 1/2 life 1 minute -decreased risk/duration of toxic effects -tetracaine most toxic because slowest hydrolysis -atypical pseudocholinesterase and other plasma hydrolysis dependent meds could decrease metabolism |
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How are amide LAs metabolized? |
in liver by cytochrome p450 -slower than ester bupiv
determinants of rate: hepatic enzyme activity, hepatic BF, 1-5% eliminated unchanged in urine |
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what is the major metabolite of any tertiary amine amide LA? |
2,6 xylidine -less toxic than parent compund but metabolite accumulation + LA levels can increase risk of seizures |
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What LA is know to cause methemoglobinemia? |
-prilocaine, metabolized to o-toluidine which oxidizes hemoglobin (not until doses >600mg) S&S include: brownish gray cyanosis, metabolic acidosis, HA, LOC changes, chocolate colored blood Rx: methylene blue 1-2mg/kg IV over 5 min, 2nd does 1 hour later if needed -DO not give prilocaine in OB (fetal methemoglobin) -Benzocaine can also cause (rare) |
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How does pregnancy effect LAs? |
-increased sensitivity -greater segmental spread of epidural LA during 1st trimester |
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What is the order in which LA toxicities occur? |
1. lightheadedness, tinnitus, cicumoral and tongue numbness 2. visual disturbances 3. muscular twitching 4. convulsions 5. unconciousness 6. coma 7. resp arrest 8. CVS depression |
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Why does respiratory and metabolic acidosis increase propensity for LA toxicity? |
-increase dilates cerebral vessels = more drug delivery to brain -CO2 diffusion across brain cells decreases intracellular pH and increased ionized intracellular LA -Acidosis decreases plasma protein binding |
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What is ion trapping? |
LA cross placenta (esters dont cross) -more acidotic on fetal side, LAs ionize and will not cross back |
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What happens with CV LA toxicity? |
-prolongation of conduction time (prolonged PR, QRS, AV block, Sinus brady, Cardiac arrest, Depressed automaticity) -May also elevate pacing threshold making pacing difficult -all due to block of Na channels |
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What is the LA that is known for being most cardio toxic? |
Bupivacaine -if injected IV, protein binding sites saturated quickly and lots left for diffusion into heart -causes precipitous hypotension, cardiac dysrhythmias, AV heart block -inhibits fast Na channels and slow Ca channels Ropiv < levobupiv < bupiv and etidocaine |
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Which patients are at increased risk for CV effects of bupivacaine? |
-Parturients -Patients on Beta blockers |
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What is the treatment for Local anesthetic systemic toxicity? |
-prompt airway management -ventilate with 100% O2 -circulatory support -treat seizures with benzos -NMBs will aid in ventilations but not stop Sz |
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What is the treatment for bupivacaine induce cardiac arrest? |
-lipid emulsion 1.5ml/kg 20% bolus -followed by 0.25 ml/kg/min infusion continued for at least 10 min after circulatory stability is attained -may rebolus and increase infusion to 0.5 ml/kg/min Max 10 ml/kg for 30 min -CPB if unresponsive to treatment -avoid vasopressin and CCBs and beta blockers |
