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41 Cards in this Set
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1. indicate which one of the following is most likely to be cardiotoxic; which is most widely used clinically; which is most likely to cause CNS sedation; which is limited to surface or topical anesthesia only; which is most likely to produce vasoconstrictor effects.
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Cocaine:
Ester - Type LA euphoria (unique in its ability to stimulate CNS) Most LA cause Hypotension due to Arteriolar dilations.....but NOT cocaine cocaine is exception: produces vasoconstriction****, blocks NE reuptake Most LA decrease cardioexcitability and contractility....NOT cocaine --> stilumates the heart Cocaine: (Schedule II substance) Medical use limited to surface or topical anesthesia (corneal or nasopharyngeal) Avoid epinephrine because cocaine already has vasoconstrictor properties. (EXCEPTION!!!) A toxic action on heart may induce rapid and lethal cardiac failure. A marked pyrexia is associated with cocaine overdose. |
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Lidocaine:
AMIDE - type LA Most widely used LA**** Effective by all routes. Faster onset, more intense, longer lasting, than procaine. Good alternative for those allergic to ester type More potent than procaine but about equal toxicity More sedative than others |
Benzocaine:
(pKa ~ almost 100% in nonionized form) Topical use ESTER - type LA pKa ~ 3, essentially all non-ionized.... mechanism may be non-specific Most limited to surface or topical anesthesia only!***** Benzocaine - Available in many OTC preps for relief of pain and irritation for surface anesthesia (topical) only ... ointments, sprays, etc. - Used to produce anesthesia of mucous membranes and to suppress gag reflex during endoscopy - methemoglobinemia |
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Mepivacaine:
AMIDE - type LA Effective by all routes except topical Similar onset and duration as lidocaine More toxic to neonates so not used in obstetrical anesthesia (fetus poorly metabolizes mepivicaine)****** |
Procaine:
Procaine and Lidocaine have most effect to cause Hypotension via Arteriolar dilation. Procaine: Topically ineffective Used for infiltration because of low potency and short duration but most commonly used for spinal anesthesia Short local duration ......produces significant vasodilation. Epinephrine used to prolong effect systemic toxicity negligible because rapidly destroyed in plasma |
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Bupivacaine:
No topical effect Slower onset and one of longer duration agents Unique property of sensory and motor dissociation can provide sensory analgesia with minimal motor block has been popular drug for analgesia during labor More cardiotoxic than other LA **** |
Tetracaine:
topical, infiltration and spinal anesthesia Frequently used for topical ophthalomogical anesthesia slow onset and more prolonged effect than procaine (longest duration of the esters) ~10X more toxic and more potent than procaine***** Prilocaine: Similar clinical profile to that of lidocaine Does cause significantly less vasodilation than lidocaine Less vasoconstrictor need be added Most popular clinical application is for topical anesthesia as in combo with lidocaine in a eutectic mixture*** Because of rapid systemic metabolism considered least toxic of amide LA likely to cause Methemoglobinemia***** |
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Ropivacaine:
Is structurally similar to bupivacaine (propyl group instead of butyl) and exists only as S stereoisomer No topical effectiveness Clinically ~ equivalent to bupivacaine Similar sensory versus motor selectivity as bupivacaine with significantly less CV toxicity**** |
Most likely to cause CNS sedation:
Lidocaine - sedation even at non-toxic doses |
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2. describe the nature of ‘differential nerve sensitivities’ to local anesthetics
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Most sensitive to LA block are?
Type A Delta Type B Type C - Dorsal root and sympathestic fibers |
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What are Type A delta fibers?
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1st pain
temperature |
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What are Type B fibers?
Preganglionic autonomic vasomotor fibers |
What are Type C dorsal root fibers?
2nd pain temperature |
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What are Type C Sympathetic fibers?
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Postganglionic
vasomotor |
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3. describe the site and proposed mechanism(s) of action of local anesthetics.
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There are Both Specific and Non-specific effects
Specific: (No effect on RMP - Resting Membrane Potential) bind to specific receptors at the INTRACELLULAR end of the voltage gated sodium channel prevent axonal conduction by a functional blockade LA have greatest affinity for sodium channel in open and inactivated states and slows its reversion to the resting state. |
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MOA:
**LA have low affinity for closed or resting state but have a high affinity for the open and inactivated forms. |
action is voltage dependent
This may be due to Voltage changes induce changes in form of Na+ channels LA have a higher affinity for Na+ channel in the open and inactivated states slowing return to resting form (prolonged refractory period) Increased entry into neuron through opened Na channel action is also frequency dependent Because high affinity forms of Na+ channel (e.g. inactivated) are more frequently presented in neurons that are firing more frequently (increased binding and effect) This provides a degree of LA selectivity Frequent firing pain neurons more affected than slow firing motoneurons |
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LA are WEAK BASES and access to receptor site is dependent on:
pKa lipid solubility molecular size and level of neuronal activity LA ACT IN CATIONIC FORM (charged) |
Non-Specific Action:
LA appear to have some non-specific actions Appear to ‘dissolve’ in the membrane Distorting the membrane and altering function Ex: Benzocaine (pKa ~ almost 100% in nonionized form) Topical use |
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4. indicate the clinical significance of distinquishing between the two general chemical classes of local anesthetics in respect to elimination processes, duration of action, and allergic phenomenon.
2 classes are: Ester linkage Amide linkage |
Cross sensitivity (allergy):
Occurs with drugs in the same chemical class Esters are metabolized to common metabolite PABA Some preps have the preservative methylparaben (chemically similar to PABA) Allergy rarely occurs with amide linkage class***** Biotransformation/duration of action: ESTERS are rapidly metabolized in the plasma by a cholinesterase – succinyl choline AMIDES are more slowly destroyed by liver microsomal P450 enzymes. |
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5. indicate which drug characteristics best correlates with rate of onset of local anesthesia. Indicate the relationship between local duration of anesthesia, lipid solubility, vasodilation and protein binding. Explain how local inflammation might adversely influence the effectiveness of local anesthetics.
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Rate of Onset:
FACTORS INFLUENCING LA ACTION~ Hydrogen ion concentration ~ at pH 7.4 80 - 90% is ionized and can’t enter cells non-ionized (lipid-soluble) form needed for penetration cationic form required for binding to receptor rate of ONSET is related to pKa (because it determines the % of LA in a LS form)***** |
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The lowest pKa is fastest!
Exception is Chloroprocaine......... is given in high dose why it is fast |
FACTORS INFLUENCING LA ACTION~ LIPID SOLUBILITY ~
Potency and systemic toxicity directly correlate with LS (lipid solubility) Ex: The more lipid soluble you are the more potent you are Local duration positively correlated with LS and protein binding but inversely related to vasodilation Ex: The more Vasodilation you have the Quicker the duration of the drug |
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% Protein Binding:
The More Protein bound you are the LESS effect you have Ex: 5% Protein bound is Fast duration Ex: 94% Protein bound is Long duration |
FACTORS INFLUENCING LA ACTION~ Hydrogen ion concentration ~
INFLAMMATION inflammation tends to produce lower pH in tissues therefore LA are more ionized don’t penetrate very well decreased ability of LA to produce effects******* For over 100 years, LA solutions have been alkalinized to hasten onset of neural block |
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6. explain the rationale for inclusion of vasoconstrictors in local anesthetic preparations and the potential risks associated with this drug combination
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ABSORPTION:
Effects of vasoconstrictors Decrease rate of systemic absorption and decrease systemic toxicity Increase local drug concentration and increase neuronal uptake of LA Increase local duration of action (e.g. lidocaine’s duration my increase two fold with epi) Epinephrine or alpha 2 agonists may enhance and prolong spinal anesthesia by acting on alpha 2 receptors to reduce substance P release |
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Potential adverse effects of vasoconstrictors
DON’T use in areas of toes, fingers, ear lobes, penis (ischemia) May produce tissue necrosis May produce systemic toxicity (cardiovasc) |
7. indicate which physiological system is most sensitive to systemic effects of local anesthetics and which system is second most sensitive.
1st: CNS 2nd: Cardio |
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CNS (More sensitive than cardio)
Dose-related spectrum of effects and All effects are due to depression of neurons First an apparent CNS stimulation (convulsions most serious) Followed by CNS depression (death due to respir depression) Premonitory signs include: ringing in ears, metalic taste, numbness around lips |
Cardiovascular System
HYPOTENSION: Arteriolar dilation is a result of: Direct effect (procaine and lidocaine have most effect) Block of postganglionic sympathetic fiber function CNS depression Avoid by adding vasoconstrictor to prep |
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8. indicate in what ways cocaine differs from most local anesthetics with regards to CNS and vascular effects.
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Note: cocaine is exception: produces vasoconstriction, blocks NE reuptake
Cocaine - euphoria (unique in its ability to stimulate CNS) |
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9. compare procaine, lidocaine, bupivacaine, and tetracaine regarding onset and duration of action, lipid solubility, and chemical classification.
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Procaine:
LOW lipid soluble Low % Protein Binding High Vasodilation Short Duration of Action |
Lidocaine:
sort of lipid soluble % sort of protein bound high vasodilation Bupivacaine high lipid solubility High Percent Protein binding LOW vasodilation Long Duration anethetic moderate anethesthic duration tetracaine: High lipid solubility high % protein bound LOW vasofilation |
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10. list two agents that are not classified as local anesthetics but have local anesthetic properties.
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A few drugs not generally used for local anesthesia have LA effects
May be substituted if patient is allergic to both esters and amide types. propranolol diphenhydramine chlorpromazine corticosteroids |
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11. indicate which local anesthetic is almost 100% uncharged at physiological pH and used in many OTC preparations as a surface anesthetic.
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Benzocaine
pKa ~ 3, essentially all non-ionized.... mechanism may be non-specific Available in many OTC preps for relief of pain and irritation for surface anesthesia (topical) only ... ointments, sprays, etc. Used to produce anesthesia of mucous membranes and to suppress gag reflex during endoscopy methemoglobinemia |
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12. Lidocaine and prilocaine are quite similar in many respects, indicate two advantages that prilocaine has over lidocaine.
Does cause significantly less vasodilation than lidocaine Less vasoconstrictor need be added Because of rapid systemic metabolism considered least toxic of amide LA |
13. Indicate what EMLA is, local anesthetics used in this product, and some of the general uses.
EMLA = eutectic mixture of local anesthetics Eutectic = two solid substances mixed together in equal quanitites by weight form a eutectic mixture the melting point of the mixture is lower than the melting points of the individual components EMLA = lidocaine and prilocaine becomes an oily mixture |
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lidocaine/prilocaine combination is indicated for dermal anaesthesia
Specifically it is applied to prevent pain associated with intravenous catheter insertion, blood sampling, superficial surgical procedures; and topical anaesthesia of leg ulcers for cleansing or debridement it can also be used to numb the skin before tattooing. EMLA cream is also used in the treatment of premature ejaculation It is applied 20 minutes prior to sex |
14. Indicate the chemical relationship between bupivacaine and ropivacaine and indicate the alleged advantage of ropivacaine.
EPIDURAL AND CAUDAL ANESTHESIA Both are Amide Linkage |
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Ropivacaine
Is structurally similar to bupivacaine (propyl group instead of butyl) and exists only as S stereoisomer Ropivacaine Similar sensory versus motor selectivity as bupivacaine with significantly less CV toxicity**** |
15. indicate what methemoglobinemia is and its relationship to local anesthetic agents, which LA are most likely to produce this condition, and what agent is used to treat the condition.
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Methemoglobinemia – rare but life-threatening
Some LA metabolites have significant oxidizing properties This may cause a significant conversion of hemoglobin to methemoglobin and compromize ability to carry oxygen May be a problem if cardiopulmonary reserve is limited |
Treat with oxygen and methylene blue (converts methemoglobin to hemoglobin)
Prilocaine*****, benzocaine, and lidocaine have been implicated Benzocaine most likely to cause methemoglobinemia |
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16. Indicate the earliest signs of lidocaine’s CNS toxicity.
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First an apparent CNS stimulation (convulsions most serious)
Followed by CNS depression (death due to respir depression) Premonitory signs include: ringing in ears, metalic taste, numbness around lips Shit he said to know! |
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know which are esters and which are amides
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ester has the O-C-O
Amide has the NH-C-O |
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Know the groups of drugs as amides and esters
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AMIDE LINKAGE (2 EYES!!)
lidocaine (Xylocaine) mepivacaine (Carbocaine) bupivacaine (Marcaine) etidocaine (Duranest) ropivacaine (Naropin) ESTER LINKAGE procaine (Novocaine) tetracaine (Pontocaine) benzocaine cocaine |
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Know about infections and how this effects the drug
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Infection makes things more acidic
If too acidic get little drug in here and can cause toxicity because you give more drug and causes systemic effects |
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Know which fibers are most susceptible to LA
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A-delta and which are most sensitive to LA block
Type C carries Pain and postganglionic SNS EXAM!!!! |
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Know Protein binding and affinity for the receptor
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Plasma protein binding may be used as an indirect measure of tissue binding tendencies
***HAS GREATER Local duration positively correlated with LS and protein binding but inversely related to vasodilation |
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Hydrogen ion concentration
rate of ONSET is related to pKa (because it determines the % of LA in a LS form) The lowest pKa is fastest! |
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Most LAs affect the Heart:
Cardiovascular System HYPOTENSION: Arteriolar dilation |
Note: cocaine is exception: produces vasoconstriction, blocks NE reuptake
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Methemoglobinemia
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Treat with oxygen and methylene blue (converts methemoglobin to hemoglobin)
Prilocaine*** or Benzocaine*** most likley to cause this |
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Tetracaine
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topical, infiltration and spinal anesthesia
Frequently used for topical ophthalomogical anesthesia 10X more toxic and more potent than procaine***** |
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Mepivacaine
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More toxic to neonates so not used in obstetrical anesthesia (fetus poorly metabolizes mepivicaine)
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Bupivacaine
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Unique property of sensory and motor dissociation can provide sensory analgesia with minimal motor block
has been popular drug for analgesia during labor More cardiotoxic than other LA****** |
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Ropivacaine
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Similar sensory versus motor selectivity as bupivacaine with significantly less CV toxicity
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