Term
| what characterizes the object of general anesthesia? |
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Definition
| induction of a drug-induced coma |
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Term
| what characterizes the object of local anesthesia? |
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Definition
| block nerve conduction in one area w/no loss of consciousness |
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Term
| what is the history of local anesthetics? |
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Definition
| peruvian indians would chew coca leaves, the german dr niemann isolated the alkaloid in 1860 - found that it numbed locally on contact, van anrep injected himself in 1880 and became numb, freud used cocaine in 1884 to wean morphine addicts, and kohler in the same year started using it as a topical anesthetic for opthalmologic sx (still FDA approved for this purpose). |
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Term
| what gives the majority of the pharmacokinetics in local anesthetics? |
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Definition
| the alkyl chain which links the hydrophobic and hydrophilic ends together of the molecule which are either esters or amides. if there is an ester = shorter acting b/c esterases exist in all tissues. if there is an amide = longer acting b/c has to be metabolized by the liver. |
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Term
| how does the dissociation constant (pKa) affect the onset, activity, and pharmacokinetics of local anesthetics? |
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Definition
| most local anesthetics are weak bases (poorly soluble) so they are modified and put in low pH solution (like hydrochloride salt) w/pKa ranges 8-9. with this better pKa, the local anesthetic can switch easier to the free base form, which is necessary to penetrate the membrane. the free base form however is not active, so once inside the cell the local anesthetic needs to shift back into its cationic form (active form). |
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Term
| what is the local anesthetic mechanism of action? |
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Definition
| prevention of voltage-dependent increases in Na+ conductance -> blocks initiation and propagation of action potentials. |
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Term
| is the membrane expansion theory purported for local anesthetics well-supported? |
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Definition
| this older theory that the local anesthetic molecules intercalate between the molecules of the membrane causing a membrane expansion and disrupt the function of the Na+ channels is less supported currently. |
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Term
| what is the specific receptor theory for local anesthetics? |
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Definition
| the active local anesthetic cation binds in or near the Na+ channel - blocking its conductance. this theory is more currently supported. |
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Term
| what is the concept of differential blockade? |
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Definition
| small fibers (less myelin/smaller diameter) are more susceptible than larger fibers to local anesthetics. therefore: starting w/the smallest to largest - pain, cold, warmth/touch, deep pressure, proprioception; local anesthetics will have less of an effect at the same dose on each subsequent type of fiber. also more myelinated the nerve the more saltatory conduction - less constant Na+/K+ conductance to interfere with. narahashi demonstrated that a Na channel was involved and have to block a sequential number of channels to block the conduction. |
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Term
| what factors influence the effect of local anesthetics? |
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Definition
| frequency/use dependence (drug will be more active, quicker onset and effects in active channels rather than inactive channels) and vasoconstriction/dilatation (affect perfusion). |
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Term
| what are the routes of local anesthetic administration? |
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Definition
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Term
| where is local anesthetic topically administered? |
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Definition
| skin, eye, ear and mucus membranes: tracheal, nasal, vaginal, rectal, and oral. |
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Term
| where is local anesthetic parenterally administered? |
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Definition
| infiltration (intradermal/subcutaneous), nerve block, spinal (subarachnoid/intrathecal), and epidural/peridural |
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Term
| why do most local anesthetics have a vasoconstrictor (usually epinephrine)? |
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Definition
| to reduce hemorrhage at the site, increase duration of action, and prevention of spread (**via alpha1 receptors**). |
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Term
| what are the uses of local anesthetic? |
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Definition
| pain, soreness, irritation, itching, corneal/conjunctival anesthesia, local anesthesia and cardiac arrhythmias (lidocaine). |
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Term
| what are the ester-type local anesthetics? (just know if it is in this group or not and the procaine relative potency [prp]) |
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Definition
| procaine (prp:1), chloroprocaine (prp:4), tetracaine (prp:16), cocaine, benoxinate, benzocaine, butaben, proparacaine, and cyclomethycaine |
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Term
| what are the amide-type local anesthetics? (just know if it is in this group or not and the procaine relative potency [prp]) |
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Definition
| lidocaine (prp:4), mepivacaine (prp:4), bupivacaine (prp:16), etidocaine (prp:16), prilocaine (prp:3), and dibucaine |
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Term
| what untoward effects are associated w/local anesthetics? |
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Definition
| antihistaminic, anticholinergic, and antiarrhythmic actions which may develop after absorption from site or inadvertent injection into the vessel. these actions are harder to reverse in the longer action local anesthetics such as bupivacaine and tetracaine. |
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Term
| what are the effects of local anesthetics on the CNS? |
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Definition
| stimulation (tremors/convulsions - disinhibition) followed by depression and h/a |
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Term
| what are possible effects on the peripheral nervous system due to local anesthesia? |
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Definition
| nerve damage (needle) and neurotoxic (large doses) |
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Term
| what are possible effects on the CV system due to local anesthesia? |
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Definition
| cardiac depression (decreased force of contraction/cardiac output), cardiac arrest, and vasodilation (hypotension) |
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Term
| what are possible effects on the skin due to local anesthesia? |
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Definition
| hypersensitivity/allergic rxn |
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Term
| what other agents will local anesthetics interact with? |
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Definition
| local anesthetics will increase the effects of neuromuscular blocking agents, quinidine, propranolol, and phenytoin. ester type local anesthetics are increased by cholinesterase inhibitors. |
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Term
| what are the coolant local anesthetics? MOA? what are they used for? |
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Definition
| chlorofluoroalkanes, ethyl chloride, and chlorofluoroalkane+ethyl chloride. MOA: rapid and deep cooling of the skin surface - route of administration: 2-12 in above the skin. they can be used for injections, bruises, contusions, minor sprains, dermabrasion, minor sx, muscle spasms, myofascial pain, restricted motion, and sports injuries. |
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Term
| what ADRs exist for the coolant local anesthetics? |
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Definition
| hypersensitization of tissue, altered pigmentation, reduced resistance to local infection, slow rate of healing, and thawing of the skin is often painful |
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Term
| what cautions specifically exist for ethyl chloride? |
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Definition
| ethyl chloride: nephrotoxic and hepatotoxic. inhalation can produce: narcosis, GA, coma, respiratory arrest, and cardiac arrest. |
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Term
| what contraindications exist for the coolant local anesthetics? |
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Definition
| known hypersensitivity and vascular impairment of the extremities |
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Term
| when are local anesthetics (LAs) used to reversibly block pain pathways? |
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Definition
| acutely: during various surgical procedures. chronically: in a CA victim w/persistent pain. |
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Term
| what are neurolytic agents? who are they used for? |
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Definition
| drugs used to destroy the pain pathway - used for pts w/persistent, chronic, and intractable pain. these pts are considered to have altered or non-intact nervous systems (faulty conduction/disrupted modulating mechanisms). |
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Term
| what are targets for pain control? |
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Definition
| receptors/NTs (increase inhibition/decrease excitation), nerve fibers |
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Term
| what are the specific NTs in the pain pathways? |
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Definition
| opioids, glutamate, substance P, somatostatin, vasoactive intestinal peptide (VIP), cholecystokinin (CCK), antiotensin II, and bombesin |
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Term
| what characterizes glutamate? |
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Definition
| this is the major pain transmitter and its blockage = pain transmission blockade. there are no glutamate antagonists available for clinical use and it is impossible to deplete glutamate stores. |
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Term
| what characterizes substance P? |
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Definition
| there are no clinically available substance P antagonists, but it is possible to deplete substance P stores. |
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Term
| what is the effect of capsaicin? |
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Definition
| this chemical is present in chili peppers and stimulates the release of substance P (produces a burning sensation). with repeated application, the substance P levels can be lowered (in the spinal cord) - reducing pain transmission (generally takes several days). |
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Term
| what nerve fibers are targeted for blocking in pain management? |
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Definition
| A delta fibers, B fibers, and C fibers (particularly) |
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Term
| what characterizes the effect of local anesthetics in chronic pain nerve blocks? |
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Definition
| there is prolonged pain relief which outlasts the pharmacological action of the drug (MOA not well understood) |
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Term
| what are targets for LAs? |
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Definition
| peripheral nerves, spinal posterior roots, sympathetic chain, and sympathetic chain ganglia/plexi |
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Term
| what are the specific nerve block LA agents? |
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Definition
| bupivacaine, etidocaine, procaine, chloroprocaine, mixture of LA w/corticosteroids |
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Term
| what are the side effects of nerve block LA agent administration? |
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Definition
| cardiovascular responses (when drug is systemically absorbed) and systemic toxic reactions (from OD) |
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Term
| what complications are seen w/nerve block LA agent administration? |
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Definition
| unintended damage due to needle, damage to needle, residual pain at injection site, punctures of other structures (vessels, viscera, dura, pleura), and local tissue irritation (swelling, cellulitis, abscess, gangrene, and sloughing) |
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Term
| what ADRs are seen w/spinal blocks? |
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Definition
| h/a (CSF leakage), n/v, hypotension (spinal sympathetic block), and backache (needle trauma) |
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Term
| what ADRs are seen w/epidural blocks? |
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Definition
| backache (needle trauma), urinary retention, and extradural hematoma |
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Term
| what ADRs are seen w/intercostal blocks? |
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Definition
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Term
| who are neurolytic blocks intended for? |
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Definition
| the chronic pain population of pts |
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Term
| why are neurolytic blocks considered temporary? |
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Definition
| nerves can regenerate (1 mm/day) and thus pain relief is proportional to the length of damage. |
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Term
| what agents are specifically used for neurolytic administration? |
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Definition
| local anesthetics (high conc. or direct injection into nerve), ethyl alcohol, phenol, glycerol, and ammonium salts |
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Term
| what are the effects of local anesthetics when used for a neurolytic effect? |
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Definition
| endoneurial edema, wallerian degeneration, schwann cell injury, and axonal dystrophy. ADRs generally related to systemic absorption (magnified b/c of larger dose). |
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Term
| what characterizes ethyl alcohol as a neurolytic agent? |
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Definition
| this causes *extraction of cholesterol, phospholipids, and cerebroside as well as *precipitation of lipoproteins and mucoproteins. when *injected intraneurally: demyelination and mild focal changes in meninges. when *topically applied to a peripheral nerve: schwann cell damage (swollen mitochondria), disruption of the myelin sheath, and wallerian degeneration. |
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Term
| what characterizes phenol as a neurolytic agent? |
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Definition
| this will cause coagulation of proteins, powerful degeneration of the posterior columns, degeneration of the posterior roots, demyelination, and wallerian degeneration (at high concentration). |
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Term
| what characterizes glycerol as a neurolytic agent? |
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Definition
| intraneural injection: nerve fibers are destroyed. topical application to a peripheral nerve: localized subperineural damage - inflammatory cells, myelin swelling, and axonolysis |
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Term
| what characterizes ammonium salts as a neurolytic agent? |
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Definition
| these abolish C-fiber (pain) potentials and produce an acute degenerative neuropathy |
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Term
| what are complications specific to most neurolytic agents? |
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Definition
| persistent pain may occur, skin sloughing or formation of a sterile abscesses |
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Term
| what are complications specific to phenol? |
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Definition
| *systemic absorption: decreased consciousness, decreased BP, and renal damage. *intravascular injection: severe tinnitus and flushing. *phenol is a CNS stimulant and can cause muscle tremors and convulsions. |
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Term
| what are complications specific to ethyl alcohol? |
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Definition
| neuritis, severe adhesions at injection site and thrombosis if accidentally intravascularly injected |
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