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Prototype drugs: Local Anesthetics (5)
- Procaine
- Benzocaine
- Tertacaine
- Lidocaine
- Bupivicaine
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Most LA's are weak _____, with pKa of _____
bases, 8-9
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What are the two types linking bonds that determine the disposition of an LA?
ester and amide
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Esters are hydrolyzed by ______________ in the _____ AND _____
butyrcholinesterase, plasma and liver
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Amides are resistant to ________; they are ________ in the _________
hydrolysis, N-alkylated in the liver
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which type of LA is up to 95% protein bound, and which protein is it bound to?
amides, a1-acid glycoprotein
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What is the mechanism of action for LA's?
reversible block of nerve impulse conduction by binding and blocking voltage dependent Na channels.
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what is the order of blockage of LA's (neuro types)
pain, sensory, motor
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Is the major site of action INSIDE the cell membrane?
YES
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What factors influence nerve blocks?
- Size of nerve fiber
- Position of nerve
- pKa
- Inflammation
- Blood flow
- Firing rate
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Why is inflamed tissure resistant to LA's?
inflammation causes a reduction in pH. This reductions causes the LA, which is a weak base, to be in the ionized form which is less available to pass into the cell.
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how does firing rate effect LA's?
LA's work more rapidly on nerves that fire more rapidly. Example is Sympathetic nerves
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Which type of LA has a higher tendency to cause systemic toxicity?
AMIDES (Bc longer half life in blood)
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Which type of LA is more likely to cause an allergic rxn?
ESTER
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Procaine is a _____-acting ______, used mainly for infiltration due to ______ potency and _____ T1/2.
short, ESTER, LOW, short
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Benzocaine is _____-acting Ester, used mostly _______.
short, topically
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tetracaine is _______-acting _______, used for _______ anesthesia.
Long, ESTER, spinal
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Does tetracaine have a high toxicity?
YES
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Which LA Esters has the slowest hydrolysis?
tetracaine
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Lidocaine is an _______, with longer duration that procaine, used for ________, and for people with allergy to Esters
AMIDE, anti-arrythmia
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Bupivicaine is an _______, with ______-acting action, and has ______ toxicity than lidocaine.
AMIDE, Long, Higher
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Proparacaine has replaced ______ for anesthesia of the ________. Why?
cocaine, cornea. Less irritating
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What is the advantage of admin epi with local anesthetics?
increases duration of action by causing vasoconstriction and slower clearance time
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