Term
| any drug ending w -caine is a ______. |
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Definition
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Term
Describe the Structure of LA that influences its:
- lipophilicity
-route of administration
-hydrophilicity |
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Definition
in order:
-Aromatic hydrophobic domain
-Alkyl linker: ester or amide type
-Hydrophilic domain: tertiary amine |
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Term
The more lipophlic the LA, the _________ it will stay at a local site instead of spreading systemically?
Longer/shorter |
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Definition
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Term
| Duration of action of LA is determined by |
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Definition
| its rate of absorption which is determined by its lipophilicity |
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Term
| Rate of absorption of a LA is determined by its |
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Definition
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Term
| wrt duration of action/ lipophilicity/rate of absorption:rank the LAs |
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Definition
Benzocaine >> tetracaine>=bupivacaine>
lidocaine |
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Term
| Toxicity of LA is partially determined by |
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Definition
| rate of absorption because the more lipophilic the drug is, the longer it will stay at a local site and nto spread systemically |
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Term
| Rate of absorption of LA is often reduced by coadministration of |
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Definition
vasoconstrictor
eg epinephrine, phenylephrine
(alpha 1 agonists)
* CANNOT use on places w end arteries eg fingers toes or penis ==> gangrene |
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Term
Name ester-linked LA:
-hydrolyzed by plasma esterases
-there is no esterase activity in the CSF so ester-linked LAs used for spinal anesthesia have a long duration of action (good) |
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Definition
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Term
| Amide-linked LAs like lidocaine, bupivacaine are degraded by |
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Definition
liver microsomal enzyme system
(also bound to plasma proteins)
- therefore toxicity of amide-linked LAs is influenced by hepatic diisease and expression of alpha-glycoproteins |
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Term
| How do LAs work mechanistically? |
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Definition
1) Lipophilic drug crosses cell membrane
2) repartitions into charged/ uncharged forms
3) charged form is responsible for LA action by entering channel VIA INTRACELLULAR side, and plugging the channel physically so that Na+ cannot move in.
***active form of LA is the charged form! |
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Term
| define the "safety factor" of LAs |
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Definition
| the number of consecutive nodes that must be blocked by LA before conduction fails |
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Term
| define critical length of LAs |
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Definition
Critical length = Safety factor x internodal distance
(safety factor is the number of consecutive nodes that must be blocked by LA before conduction fails) |
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Term
What type of fibers is described by this:
-Readily blocked by LA because conduction is continuous not saltatory
-therefore critical length is very short |
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Definition
| Unmyelinated C fibers (pain, sympathetic postganglionic) |
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Term
What type of fibers is described by this:
-readily blocked by LA because their internodal distances and thus their critical lenghts are short (but longer than C fibers) |
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Definition
| A delta: Small myelinated fibers (pain, temperature) |
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Term
What type of fibers is described by this:
Less readily blocked by LA due to long critical lengths
-bcos nodes of Ranvier are far apart |
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Definition
| Large myelinated fibers (motor function, pressure, proprioception) |
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Term
| Describe how LA action is dependent upon frequency and voltage of AP |
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Definition
-the higher the frequency of AP firing and the more positive the membrane potential, the GREATER the degree of block by LA
(because LAs work by binding to and dissociating from the open state of the Na+ channel)
-pain fibers fire at high freq and have prolonged APs, therefore they are preferentially blocked by LAs |
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Term
| Pain is blocked more readily than other modalities in a mixed nerve because: |
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Definition
1) critical length is short
2) pain fibers fire APs at rel high freq
3) pain fibers have rel broad APs |
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Term
| Order of sensitivity to LAs is as follows: |
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Definition
| Pain > Temperature, Sympathetic postganglionic > Touch, Pressure, Motor |
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Term
| Surface anesthesia for mucous membranes such as nose, mouth, throat, bronchi, esophagus, genitourinary tract |
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Definition
Lidocaine, Tetracaine
-superficial effect
-bad: rapid absorption (ie lower lipophilicity)
-therefore use w vasoconstrictors |
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Term
| Surface anesthesia for the cornea: |
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Definition
must be non-irritating, water soluble, not causing mydriasis or corneal injury
-Tetracaine, Proparacaine
-water soluble because nerve endings not v deep, doesn't have to be lipophilic,plus you don't want the drug to get thru cornea into the iris and ciliary muscle disturbing vision |
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Term
| Surface anesthesia for skin |
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Definition
Benzocaine
-most lipophilic because you want to avoid rapid absorption from wounds and ulcerated surfaces and avoid dissemination into systemic circulation |
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Term
| Infiltration anesthesia for minor surgery and dentistry: |
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Definition
Lidocaine, Bupivacaine
(dentist//Lip Balm//Lidocaine Bupivacaine) |
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Term
Nerve block: LA applied directly to nerve trunk that is proximal to where you want the LA action:
-surgical procedures that involve large area eg most of limb |
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Definition
Lidocaine, bupivacaine
(same 2 as infiltrative/dentistry) |
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Term
| Spinal (intrathecal anesthesia) |
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Definition
Lidocaine, bupivacaine, tetracaine
-tetracaine is ester-linked; low esterase activity in CSF (good)
-anesthetizes large fraction of lower body
-bad: blocks sympathetic outflow and can reduce venous return and cause venous pooling--> lower head, administer fluid, give ephedrine/ phenylephrine |
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Term
Epidural anesthesia eg during delivery/labor
-action on spinal nerve roots |
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Definition
| Epidural cannula allows a variety of LAs to be used |
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Term
| Toxicity of Local Anesthetics to the Brain, Heart: |
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Definition
Brain:
-preferential depression of inhibitory circuits causing restlessness and tremor-->clonic convulsions--> CNS depression and respiratory failure
eg cocaine seizures
Heart:
-slowed conduction and reduced excitability AND
- Increased rate (ventricular tachycardia in susceptible individuals)
causing tachy arythmias |
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