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313 Cards in this Set
- Front
- Back
Parasympathetic Effects
HR: BP: GI: blood volume: |
Parasympathetic Effects
HR: slow and regular BP: normal GI: high motor/secretory, extracting nutrients blood volume: most in dilated visceral vascular bed |
|
Sympathetic effects
HR: BP: GI: blood volume: |
Sympathetic effects
HR: increased BP: GI: decreased digestion, motility, and secretion blood volume: vascular vasoconstriction |
|
Parasympathetic
anatomical |
craniosacral
|
|
Sympathetic
anatomical |
thoracolumbar
|
|
Parasympathetic
neurotransmitters |
Ach
|
|
Sympathetic
neurotransmitters |
Ach
Norepi |
|
Parasympathetic
Preganglionic fiber: Postganglionic fiber: Effector organ receptor: |
Parasympathetic
Preganglionic fiber: cholinergic Postganglionic fiber: cholinergic Effector organ receptor: muscarinic |
|
Sympathetic
Preganglionic fiber: Postganglionic fiber: Effector organ receptor: |
Sympathetic
Preganglionic fiber: cholinergic Postganglionic fiber: adrenergic Effector organ receptor: adrenergic |
|
Somatic
neurotransmitter: effector organ receptor: |
Somatic
neurotransmitter: Ach effector organ receptor: nicotinic muscle |
|
Noradrenergic junction
synthesis: blocked by: |
Noradrenergic junction
synthesis: tyrosine, dopa, dopamine, norepi blocked by: metyrosine (tyrosine hydrolase inhibitor) |
|
Noradrenergic Junction
storage blocked by: |
Noradrenergic Junction
storage blocked by: reserpine |
|
Noradrenergic junction
release blocked by: |
Noradrenergic junction
release blocked by: guanethidine |
|
Noradrenergic junction
outcomes: |
Noradrenergic junction
outcomes: bind adrenergic receptor diffuse to synapse reuptake/recycle degraded by monoamine oxidase |
|
Cholinergic junction
synthesis: blocked by: |
Cholinergic junction
synthesis: choline, AcCoA, Ach blocked by: hemicholiniums |
|
Cholinergic junction
storage blocked by: |
Cholinergic junction
storage blocked by: vesamicol |
|
Cholinergic junction
release: blocked by: |
Cholinergic junction
release: voltage-dependent changes blocked by: botulism toxin |
|
Cholinergic junction
outcomes: |
Cholinergic junction
outcomes: bind nicotinic or muscarinic receptor diffuse to synapse reuptake/recycle degraded by acetylcholinesterase |
|
Increase in arterial BP
effect on baroreceptor: efferent sympathetic nerve activity: efferent parasympathetic nerve activity: |
Increase in arterial BP
effect on baroreceptor: stretches efferent sympathetic nerve activity: decreases efferent parasympathetic nerve activity: increases |
|
Decrease in arterial BP
effect on baroreceptor: efferent sympathetic nerve activity: efferent parasympathetic nerve activity: |
Decrease in arterial BP
effect on baroreceptor: unloads efferent sympathetic nerve activity: increases efferent parasympathetic nerve activity: decreases |
|
Adrenergic Receptor Agonists
alpha 1 >> alpha 2 |
phenylephrine
methoxamine |
|
Adrenergic Receptor Agonists
alpha 2 >> alpha 1 (alpha) |
detomidine
medetomidine clonidine xylazine |
|
Adrenergic Receptor Agonists
alpha 1 = alpha 2 B1 >> B2 (alpha and beta) |
norepinephrine
|
|
Adrenergic Receptor Agonists
alpha 1 = alpha 2 B1 = B2 (alpha and beta) |
epinephrine
|
|
Adrenergic Receptor Agonists
B1 > B2 >>>> alpha (beta) |
dobutamine
|
|
Adrenergic Receptor Agonists
B1 = B2 >>>> alpha (beta) |
isoproterenol
|
|
Adrenergic Receptor Agonists
B2 >> B1 >>>> alpha (beta) |
terbutaline
albuterol |
|
Adrenergic Receptor Agonists
D1 = D2 >> B >> alpha |
dopamine
|
|
Adrenergic Receptor Antagonists
alpha 1 >>>> alpha 2 (alpha) |
prazosin
|
|
Adrenergic Receptor Antagonists
alpha 1 > alpha 2 (alpha) |
phenoxybenzamine
|
|
Adrenergic Receptor Antagonists
alpha 1 = alpha 2 (alpha) |
phentolamine
|
|
Adrenergic Receptor Antagonists
alpha 2 >> alpha 1 (alpha) |
yohimbine
tolazoline atipamezole |
|
Adrenergic Receptor Antagonists
B1 = B2 >_ alpha 1 > alpha 2 (mixed) |
labetalol
carvedilol |
|
Adrenergic Receptor Antagonists
B1 >> B2 (beta) |
metoprolol
atenolol |
|
Adrenergic Receptor Antagonists
B1 = B2 (beta) |
propranolol
|
|
Adrenergic Receptor Antagonists
B2 >>> B1 (beta) |
butoxamine
|
|
Cardiovascular responses
mean arterial pressure NE: Epi: Iso: |
Cardiovascular responses
mean arterial pressure NE: inc Epi: inc Iso: dec |
|
Cardiovascular responses
femoral blood flow NE: Epi: Iso: |
Cardiovascular responses
femoral blood flow NE: dec Epi: inc Iso: inc |
|
Cardiovascular responses
renal blood flow NE: Epi: Iso: |
Cardiovascular responses
renal blood flow NE: dec Epi: dec Iso: inc |
|
Cardiovascular responses
peripheral resistance NE: Epi: Iso: |
Cardiovascular responses
peripheral resistance NE: inc Epi: inc Iso: dec |
|
Cardiovascular responses
myocardial contractile force NE: Epi: Iso: |
Cardiovascular responses
myocardial contractile force NE: inc Epi: inc Iso: inc |
|
Cardiovascular responses
heart rate NE: Epi: Iso: |
Cardiovascular responses
heart rate NE: dec Epi: inc Iso: inc |
|
Cardiovascular responses
cardiac output NE: Epi: Iso: |
Cardiovascular responses
cardiac output NE: NA (inc) Epi: inc Iso: inc |
|
receptor
def |
component of cell that interacts with a drug (neurotransmitter) and initiates a chain of biochemical events (pharm effects)
|
|
PNS responses are primarily subserved by ________ receptors
|
PNS responses are primarily subserved by MUSCARINIC receptors
|
|
ganglionic transmission is mediated by _________ receptors
|
ganglionic transmission is mediated by NICOTINIC receptors
|
|
cholinergic fibers
def. nervous system location |
nerve fibers that synthesize and release acetylcholine
parasympathetic, sympathetic, and somatic 3 types: pregang, postgang, somatic |
|
adrenergic fibers
def. nervous system location |
nerve fibers that synthesize and release norepinephrine
sympathetic |
|
3 endogenous catecholamines
|
dopamine
norepinephrine epinephrine |
|
only NANC postganglionic neurotransmitter:
|
nitric oxide NO
|
|
arterial smooth muscle is generally not innervated by the ___
|
arterial smooth muscle is generally not innervated by the PNS
|
|
cholinergic receptors in most arterial beds are not associated with ___________ nerves
|
cholinergic receptors in most arterial beds are not associated with PARASYMPATHETIC nerves
|
|
in skeletal muscle arteries, _____ receptors are more sensitive than _____ receptors
|
in skeletal muscle arteries, BETA receptors are MORE sensitive than ALPHA receptors
|
|
in visceral blood vessels, ____ receptors are more important than ____ receptors
|
in visceral blood vessels, ALPHA receptors are more important than BETA receptors
|
|
agonist
|
bind to and activate the receptor
|
|
antagonist
|
by binding to a receptor, prevent binding by other molecules
|
|
alpha 1 receptor
agonist |
Epi = NE >> Iso
|
|
alpha 1 receptor
antagonist |
Prazosin
|
|
alpha 1 receptor
tissue: response: |
tissue: vascular smooth muscle
liver genitourinary smooth muscle response: contract, glycogenolysis, gluconeogenesis |
|
glycogenolysis
|
breakdown glycogen
|
|
alpha 1
subtypes |
1A
1B 1D |
|
alpha 2 receptor
agonist |
Epi = NE >> Iso
|
|
alpha 2 receptor
antagonist |
yohimbine
|
|
alpha 2 receptor
tissue: response: |
tissue: presynaptic nerve terminals
vascular smooth muscle pancreatic islets response: decreased release NE contract decreased insulin release |
|
alpha 2 receptor
subtypes |
2A
2B 2C |
|
beta 1 receptor
agonist |
Iso > Epi = NE
|
|
beta 1 receptor
antagonist |
metropolol
|
|
beta 1 receptor
tissue: response: |
tissue: heart
juxtaglomerular cells response: increased contractility, HR, conduction velocity increased renin secretion |
|
beta 2 receptor
agonist |
Iso > Epi >> NE
|
|
beta 2 receptor
antagonist |
no specific drug
ICI 118551 in industry |
|
beta 2 receptor
tissue: response: |
tissue: smooth muscle
liver response: relax/ dilate skeletal arterioles glycogenolysis |
|
beta 1 receptor
antagonist |
metropolol
|
|
beta 1 receptor
tissue: response: |
tissue: heart
juxtaglomerular cells response: increased contractility, HR, conduction velocity increased renin secretion |
|
beta 2 receptor
agonist |
Iso > Epi >> NE
|
|
beta 2 receptor
antagonist |
no specific drug
ICI 118551 in industry |
|
beta 2 receptor
tissue: response: |
tissue: smooth muscle
liver response: relax/ dilate skeletal arterioles glycogenolysis |
|
beta 3 receptor
agonist |
Iso = NE > Epi
|
|
beta 3 receptor
antagonist |
ICI 118551
|
|
beta 3 receptor
tissue: response: |
tissue: adipose
response: lipolysis |
|
cholinergic receptors
|
nicotinic muscle
nicotinic neural muscarinic |
|
nicotinic muscle receptor
agonist |
Ach
|
|
beta 3 receptor
agonist |
Iso = NE > Epi
|
|
beta 3 receptor
antagonist |
ICI 118551
|
|
beta 3 receptor
tissue: response: |
tissue: adipose
response: lipolysis |
|
cholinergic receptors
|
nicotinic muscle
nicotinic neural muscarinic |
|
nicotinic muscle receptor
agonist |
Ach
|
|
nicotinic muscle receptor
antagonist |
tubocurarine
|
|
nicotinic muscle receptor
tissue: response: |
tissue: neuromuscular junction
response: endplate depolarization skeletal muscle contraction |
|
nicotinic neural receptor
agonist |
Ach
|
|
nicotinic neural receptor
antagonist |
trimethaphan
|
|
nicotinic neural receptor
tissue: response: |
tissue: autonomic ganglia
adrenal medulla CNS response: depolarization secretion catecholamines firing postganglionic neurons |
|
muscarinic 1 receptor
agonist |
Ach
|
|
muscarinic 1 receptor
antagonist |
atropine
|
|
muscarinic 1 receptor
tissue: response: |
tissue: autonomic ganglia
CNS response: depolarization undefined |
|
muscarinic 2 receptor
agonist |
Ach
|
|
muscarinic 2 receptor
antagonist |
atropine
|
|
muscarinic 2 receptor
tissue: response: |
tissue: heart
myocardium response: decrease HR (dec contractile force, not as prominent) hyperpolarization (SA node) |
|
M1 primarily __________
|
M1 primarily PARASYMPATHETIC
|
|
muscarinic 3 receptor
agonist |
Ach
|
|
muscarinic 3 receptor
antagonist |
atropine
|
|
muscarinic 3 receptor
tissue: response: |
tissue: smooth muscle
secretory glands (vascular endothelium) response: dilate BV increased secretion |
|
smooth muscle receptors
|
alpha 1
alpha 2 beta 2 M3 |
|
pressure = _____ x _______
|
pressure = cardiac output x resistance
|
|
cardiac output = ____ x _____
|
cardiac output = heart rate x stroke volume
|
|
cardiac sympathetic-mediated responses are _______
|
cardiac sympathetic-mediated responses are EXCITATORY
increase HR |
|
cardiac parasympathetic-mediated responses are ______
|
cardiac parasympathetic-mediated responses are INHIBITORY
decrease HR |
|
change in bladder tension
muscarinic agonist |
contract body
|
|
change in bladder tension
alpha agonist |
contract neck and base
|
|
change in bladder tension
B agonist |
relax body
|
|
bladder
B: alpha: |
B: dilation
alpha: contraction |
|
Bladder Filling
external sphincter ______ by ______ nerves internal sphincter _______ by _______ nerves, _______ receptors bladder body ______ by ________ nerves, _____ receptors ________ receptors inhibiting ________ _________ PNS outflow inactive |
Bladder Filling
external sphincter CONTRACTION by SOMATIC nerves internal sphincter CONTRACTION by SYMPATHETIC nerves, ALPHA 1 receptors bladder body RELAXATION by SYMPATHETIC nerves, B2 receptors ADRENERGIC (ALPHA 2)receptors inhibiting PARASYMPATHETIC GANGLIA SACRAL PNS outflow inactive |
|
Bladder Filling - Adrenergic inhibiting parasympathetic
____ from postganglioc sympathetic activates presynaptic ______ activated ______ inhibits ____ release from preganglionic parasympathetic _____ muscle contraction bladder fills |
NOREPINEPHRINE from postganglioc sympathetic activates presynaptic ALPHA 2 RECEPTORS
activated ALPHA 2 inhibit ACH release from preganglionic parasympathetic DECREASED muscle contraction bladder fills |
|
Bladder emptying
inhibition of ____ ____ activity and _____ ____ outflow activation of _____ _____ outflow by ________ receptors M3 stimulation by ____ leads to _______ contraction B stimulation by ______ leads to ______ relaxation M2 stimulation by _______ leads to _______ contraction by inhibiting _________ |
inhibition of EXTERNAL SPHINCTER activity and SYMPATHETIC NERVE outflow
activation of PARASYMPATHETIC NERVE outflow by MUSCARINIC receptors M3 stimulation by ACH leads to ACTIVE contraction B stimulation by NOREPI leads to ACTIVE relaxation M2 stimulation by ACH leads to INDIRECT contraction by inhibiting RELAXATION |
|
Bladder Emptying
M3 stimulation causes contraction by _____ _______ and accumulation of _____ |
M3 stimulation causes contraction by PHOSPHOINOSITOL HYDROLYSIS and accumulation of CALCIUM
|
|
Bladder Emptying
M2 activation indirectly leads to contraction by inhibiting _________ ________ and _____ receptors |
M2 activation indirectly leads to contraction by inhibiting ADENYLATE CYCLASE and B2 receptors
|
|
NANC transmitters and Bladder Function
______ is a NANC transmitter |
ATP
|
|
NANC transmitters and bladder function
_____ _______ _______ is localized in nerve fibers of trigonal and urethral tissue |
Nitric Oxide Synthase NOS
|
|
NO may influence bladder tone by modulation of ____ release
|
ACH
|
|
Overactive bladder
M3 receptors stimulation by: leads to: receptors also located: |
M3 receptors
stimulation by: Ach leads to: smooth muscle contraction, bladder emptying receptors also located: salivary glands |
|
Overactive bladder
Tolterodine effect: type of drug: |
Tolterodine
effect: greater bladder than salivation inhibition, no dry mouth type of drug: competitive muscarinic receptor antagonist, bladder selectivity |
|
Overactive bladder
Oxybutynin effect: type of drug: |
Oxybutynin
effect: greater effect on salivation, dry mouth type of drug: selective muscarinic receptor antagonist |
|
Overactive bladder
Atropine effect: |
Atropine
effect: same effects on bladder and salivation |
|
Overactive bladder
selectivity for ___ receptors over other muscarinic subtypes is not necessary for effective inhibition of bladder ______, may result in more pronounced effects on _______ |
selectivity for M3 receptors over other muscarinic subtypes is not necessary for effective inhibition of bladder CONTRACTION, may result in more pronounced effects on SALIVATION
|
|
Stressed urinary incontinence
Onuf's nucleus location/pathway |
Onuf's nucleus in sacral spinal cord
alpha motor neurons/somatic motor neurons out to external urethral sphincter |
|
Onuf's nucleus
glutamate |
excitatory amino acid
power ON button, raises synaptic cleft levels of NE and serotonin |
|
Onuf's nucleus
Duloxetine |
NE and serotonin/5-HT reuptake inhibitor
increases receptor activation |
|
Food safety regulatory agencies
pharmaceuticals: biologics/vaccines: pesticides: nutritional supplements: |
pharmaceuticals: FDA
biologics/vaccines: USDA pesticides: EPA nutritional supplements: none |
|
Food safety
FARAD |
Food Animal Residue Avoidance Databank
establish appropriate withdrawal times in cases of extralabel drug use |
|
Drug residues
Tolerance TOL |
maximum level of drug residue allowed in edible tissue
|
|
Drug residues
Withdrawal time WDT |
length of time from the last treatment for drug residues to deplete to or below TOL
minimum length of time that must be waited prior to slaughtering |
|
Drug residues
Extralabel drug use ELDU |
administering drug in manner different than label directions
|
|
AMDUCA
|
Animal Medicinal Drug Use Clarification Act
|
|
ELDU allowed under certain conditions:
|
valid DVM-client-patient relationship
not permitted by lay person adequate info available to establish WDT ELDU of feed additives strictly prohibited ELDU due to cost not allowed all approved drugs are ineffective careful diagnosis "substantially extended" WDT is established ensure ID of treated animals assure WDT is followed |
|
drugs prohibited from ELDU under AMDUCA
|
diethylstibestrol (DES)
chloramphenicol nitroimidazoles (metronidazole) sulfonamides in dairy >- 20mo clenbuterol dipyrone fluoroquinolones glycopeptides nitrofurans phenylbutazone in dairy >- 20mo |
|
ELDU
Grade A Pasteurized Milk Ordinance PMO |
FDA regulatory ordinance
prohibits use of: dimethyl sulfoxide DMSO colloidal silver |
|
_______ should be contacted for appropriate _____ in cases of ELDU
|
FARAD should be contacted for appropriate WDT in cases of ELDU
|
|
Thalidomide
prohibited b/c: |
concern of human exposure and birth defects
|
|
Causes of illegal residues
|
failure to follow WDT
failure to identify treated animals failure to follow label directions |
|
route of administration effects
|
IM and SC not always identical
poor technique - inject into fascial plane instead of IM, poor vascular supply, delayed/incomplete absorption improper location - SC in ear b/c discarded at slaughter |
|
aminoglycosides
gentamicin pro: con: |
pro: effective against some resistant gram negative bac, inexpensive
con: renal tubular reabsorption means in the kidneys for prolonged time (18mo) |
|
Food animal drug approvals require:
|
extensive safety evaluation
residue depletion studies regulated by FDA |
|
Extralabel Drug use
|
allowed under AMDUCA
requires specific conditions certain drugs prohibited |
|
illegal residues
|
from failure to follow directions
occur infrequently |
|
Cholinergic receptors
types |
nicotnic
muscarinic |
|
Nicotinic receptors
subtypes |
Nm
Nn |
|
Nicotinic
agonists |
Ach
nicotine |
|
Nicotinic
response |
NMJ
autonomic ganglia adrenal medulla |
|
Nicotinic
antagonists |
Tubocurarine
Trimethaphan |
|
Muscarinic
subtypes |
M1
M2 M3 |
|
Muscarinic
agonists |
Ach
choline esters |
|
Muscarinic
response |
myenteric plexus
heart bladder eye smooth muscle urinary bladder GI sphincters |
|
Muscarinic
antagonists |
Atropine
|
|
Cholinergic stimulants
2 broad categories |
direct-acting
indirect-acting |
|
cholinergic stimulants activate cholinergic receptors
2 types |
muscarinic
nicotinic |
|
muscarinic targets
|
nerve
heart glands |
|
nicotinic targets
|
neuromuscular
ganglionic |
|
cholinergic stimulants
direct acting |
similar to ach
activate cholinergic receptors located on the effector cells |
|
cholinergic stimulants
indirect acting |
(cholinesterase inhibitors)
allow endogenous Ach to accumulate and thereby prolong/augment its action raises Ach levels |
|
2 types of direct acting receptor agonists
|
choline esters
alkaloids |
|
choline esters
|
ach
methacholine carbachol bethanecol |
|
alkaloids
|
muscarine
pilocarpine |
|
nonuniform susceptibility to _________
nonuniform affinities for _______ nonuniform ____ ______ effects |
nonuniform susceptibility to CHOLINESTERASE
nonuniform affinities for MUS AND NIC RECEPTORS nonuniform TARGET ORGAN effects |
|
remove Ach with ______
|
ACETYLCHOLINESTERASE
|
|
Acetylcholinesterase inhibitors
|
neostigmine
physostigmine edrophonium |
|
Acetylcholinesterase inhibitors
mech action |
inhibit acetylcholinesterase leading to increase in conc endogenous Ach
|
|
Acetylcholinesterase inhibitors
target organ effects |
similar to effects of direct-acting cholinergic agonists
|
|
Neostigmine lacks ___________ whereas __________ produces them
|
Neostigmine lacks CNS EFFECTS whereas PHYSOSTIGMINE produces them
|
|
Neostigmine affects _____ more than the _______
|
Neostigmine affects NMJ more than the ANS
|
|
Physostigmine affects ____ more than the ______
|
Physostigmine affects ANS more than the NMJ
|
|
Muscarinic receptor antagonists
|
atropine
glycopyrrolate scopolamine |
|
Muscarinic receptor antagonists
mech action |
cause reversible blockade (comp ant) of actions of cholinomimetics at muscarinic receptors
|
|
muscarinic receptors are generally ________
|
NONSELECTIVE (receptor subtypes)
can be regionally selective |
|
Muscarinic receptor antagonists
target organ effects eye: CV: GI: bronchioles: bladder: sweat glands: CNS: |
eye: pupillary dilation, loss of accomodation
CV: increase HR, may increase CO due to tachycardic GI: relax smooth muscle, decreased secretions bronchioles: decrease secretions, increase luminal diameter bladder: urine retention due to inhibition smooth muscle sweat glands: decrease sweating in humans CNS: excessive doses cause hallucinations/disorientation in humans, mania/excitement in domestics |
|
Biosynthetic pathway for Nitric oxide
location: substrates: enzyme: product: inhibitor: |
location: endothelium
substrates: O2, L-arginine enzyme: NO synthase product: NO inhibitor: L-name (competitively inhibits NOS) |
|
Equine sweating
sympathetic nerves activate _________ in skin to evoke _________ |
sympathetic nerves activate BETA-ADRENERGIC MECHANISMS in skin to evoke THERMOREGULATORY SWEATING
|
|
L-name inhibits __________ and decreases __________
|
L-name inhibits NITRIC OXIDE SYNTHASE (NOS)and decreases SWEAT RATE
|
|
in humans, sweat glands are innervated by ____________
|
SYMPATHETIC CHOLINERGIC FIBERS
|
|
equine sweating
atropine blocked: no sig effect on: suggests: |
blocked: sweating
no sig effect on: blood flow suggests: independent mech |
|
equine sweating
botulism toxin mech: prevents: which suggests: |
mech: presynaptically inhibits Ach release
prevents: sweating and rise in skin blood flow suggests: substance (NO?) cotransmitted with Ach to evoke rise in skin blood flow |
|
neuromuscular blocking drugs
|
specifically block neuromuscular transmission
used with general anesthesia |
|
normal neuromuscular transmission
depolarization of release of binds to opens influx of metabolized by |
depolarization of motor nerve
release of Ach Ach binds to nicotinic receptors on motor end plate opens membrane channel influx of Na and K Ach metabolized by acetylcholinesterase |
|
Nicotinic receptor
def: what binds: result: |
transmembrane protein with ion channel pore that is usually closed
Ach binds to alpha subunits conformation change in protein, ion channel opens, ions flow, membrane depolarizes |
|
Nondepolarizing NMB
|
competitive antagonists to Ach at nicotinic receptors
prevent binding of Ach reversible |
|
cholinesterase inhibitor
|
biases competition in favor of Ach by allowing build-up Ach and displacing NMB
|
|
Nondepolarizing NMB
highly ______ poorly _________ do not cross _________ act _________ |
highly polar
poorly lipid soluble do not cross blood brain barrier act peripherally |
|
Nondepolarizing NMB
side effects |
ganglionic blockade at higher dosages
histamine release reversal agents have muscarinic side effects pretreat with atropine |
|
Nondepolarizing NMB
drug interactions augmented by: potentiated by: |
augmented by: inhalation anesthetics
potentiated by: aminoglycosdie antibiotics |
|
Common nondepolarizing NMB
|
gallamine
pancuronium d-tubocurarine atracurium |
|
reversal agents for nondepolarizing NMB
|
neostigmine
physostigmine edrophonium |
|
Effects of NMB
|
muscle paralysis
progression: eye, facial, pharyngeal, limb, torso, diaphragm |
|
CNS transmitters
|
GABA
glycine glutamate and aspartate norepi dopamine 5-hydroxytryptamine (serotonin) |
|
GABA
|
main inhibitory transmitter in brain
|
|
Gaba-a receptors:
Gaba-b receptors: |
Gaba-a receptors: postsynaptic
Gaba-b receptors: presynaptic inhibition |
|
agonists
Gaba-a: Gaba-b: |
Gaba-a: muscimol
Gaba-b: baclofen |
|
antagonists
Gaba-a: |
Gaba-a: bicucullin, picrotoxin
|
|
GABA
receptor mech |
increases chloride conductance, hyperpolarizes
|
|
Glycine
|
inhibitory transmitter in spinal cord
|
|
Glycine
agonist |
taurine
|
|
Glycine
antagonist |
strychnine
|
|
Glycine
receptor mech |
increases chloride conductance, hyperpolarizes
|
|
Glutamate and aspartate
classified as: mediate: anatomy: |
excitatory amino acids EAA
mediate fast excitatory responses in CNS interneurons at all levels: spinal and supraspinal |
|
Glutamate and aspartate
3 main EAA receptor subtypes |
NMDA
AMPA kainate |
|
Glutamate and aspartate
receptor mech NMDA: AMPA: metobotropic: |
NMDA: slow EPSP
AMPA: fast EPSP metobotropic: neural modulation by many mech |
|
Norepi
anatomy |
all levels
long axons from pons and brainstem |
|
Norepi
agonists |
alpha 2: xylazine, medetomidine, clonidine
|
|
Norepi
antagonist |
yohimbine
|
|
Norepi
receptor mech |
G protein mediated effects on generation of second messengers and on activity of ion channels
|
|
Dopamine
anatomy |
all levels
short, medium, and long connections |
|
Dopamine
agonist |
apomorphine
|
|
Dopamine
antagonist |
phenothiazines and butyrophenones (preanesthetics)
|
|
Dopamine
receptor mech 2 types receptors: CNS effects: |
2 types receptors: D1 and D2
CNS effects: mainly inhibition, pre and post synaptic |
|
5-hydroxytryptamine
anatomy |
5-HT neurons concentrated in midline raphe nuclei in pons and medulla
project diffusely to cortex, limbic system, hypothalamus, spinal cord |
|
5-HT
antagonist |
ketanserin
|
|
5-HT
receptor mech effects: functions associated with pathways: |
effects: inhibitory or excitatory, pre or post synaptic
functions: feeding beh, control of mood, emotion, sleep/wake, sensory pathways, nociception, body temp, vomiting |
|
pain
def. |
coupling of an unpleasant stimulus with conscious perception and an emotional response
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nociception
def. |
sensation of an unpleasant stimulus
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nociceptors
def. |
free nerve endings distributed thruout the body which detect nociceptive stimuli
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Why feel pain? (3)
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warning of actual tissue injury
warning of impending tissue injury warning of danger to a social group |
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sensitization
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stimulus which is normally innocuous becomes a nociceptive stimulus
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Sensitization
1. 2. |
Sensitization
1. Central 2. Peripheral |
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Sensitization
Central (3) |
NMDA receptor activation
increase in magnitude and response of stimulus - pain is worse reduced activation threshold of nociceptors - pain occurs w/ less of stimulus decreased endogenous opioids desensitization of opiate receptors |
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Sensitization
Peripheral (2) |
reduced nociceptor activation thresholds
decreased tissue pH, cytokines, bradykinin, serotonin, histamine, ATP, prostaglandins, leukotrienes |
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Peripheral nerves
3 axon types |
sensory afferent
motor efferent autonomic |
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Sensory afferent peripheral nerves
A-fiber: Aalpha, AB: Adelta: C-fiber: |
Sensory afferent peripheral nerves
A-fiber: large myelinated nerves, rapid conduction Aalpha, AB: prorioception, tactile Adelta: nociception; "first" pain, well localized C-fiber: unmyelinated, slow conducting; "second" pain, dull aching, poorly localized |
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Dorsal root ganglion
receptor +, propagate transmission of painful stimulus (3) |
AMPA (glutamate)
NMDA (glutamate) - loses its Mg block after AMPA activated PGE2 (COX-2) |
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Dorsal root ganglion
receptor -, inhibit transmission of painful stimulus (4) |
opiate (u, k, delta)
alpha-2 (norepi) 5-HT (serotonin) GABA (y-aminobutyric acid) |
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pain transmitted primarily by
receptor: neurotransmitter: |
pain transmitted primarily by
receptor: AMPA neurotransmitter: glutamate |
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Second order neuron
_____ to ______ primary projection |
SPINAL CORD to THALAMUS
spinothalamic tract |
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Second order neuron
receptors +: -: |
Second order neuron
receptors +: glutamate, AMPA, NMDA -: GABA, alpha-2, 5-HT |
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Cerebral cortex
primary projections: |
thalamocortical
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Cerebral cortex
receptors +: -: |
Cerebral cortex
receptors +: glutamate, AMPA, NMDA -: opiate, 5-HT, alpha-2, GABA COX-1 and COX-3 (NSAIDS acetaminophen) |
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opiate
def. |
compound derived from opium plant
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opioid
def. |
endogenous peptide or synthetic compound interacting on opiate receptors
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opioids
primary metabolism: |
opioids
primary metabolism: hepatic phase I and/or II |
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Opiate receptors
(3) |
Mu - endorphin, endogenous ligand
Kappa - dynorphin, endogenous ligand Delta - enkephalin, endogenous ligand |
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Opioid effects
a lot |
analgesia
euphoria sedation antitussive nausea/vomiting dec stomach, biliary, pancreatic, and intestinal secretions dec GI motility dec urine voiding inc tone antrum stomach diuresis miosis - dog mydriasis - cat panting with large doses: dec BP and respiration immunomodulation |
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antitussive effect
depression of: independent of: |
antitussive effect
depression of: cough center in medulla independent of: respiratory effects |
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nausea/emesis effect
direct stimulation of: not protected by: |
nausea/emesis effect
direct stimulation of: CRTZ not protected by: blood brain barrier |
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GI tract (antidiarrheal) effect
decrease: decrease: increase: can cause: |
GI tract (antidiarrheal) effect
decrease: secretions decrease: in propulsive contractions increase: in non-propulsive rhythmic contractions can cause: constipation |
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opiate receptors
mu |
analgesia
resp antitussive dec GI sedation euphoria |
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opiate receptors
k |
analgesia, antitussive, dec GI, sedation, inc diuresis
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opiate receptors
delta |
analgesia
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opioid receptor locations
(3) |
spinal
supraspinal periphery (GI tract) (other - synovium, leukocytes) |
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opioid receptor locations
synergistic analgesia between ______ and ______ receptors |
synergistic analgesia between SPINAL and SUPRASPINAL receptors
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opioid receptor locations
spinal |
pre and postsynaptic at dorsal root ganglion
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opioid receptor locations
supraspinal |
medulla, hypothalamus, periaqueductal gray area, amygdala, cerebral cortex
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opioid drugs classified by:
____ they interact with and the ______ elicited |
opioid drugs classified by:
RECEPTORS they interact with and the EFFECT elicited |
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potency
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concentration which elicits the effect
affects dose |
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efficacy
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magnitude of the effect
affects analgesic effect |
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opiate receptor activation
_______ inhibition of ________ |
opiate receptor activation
G-PROTEIN inhibition of ADENYLYL CYCLASE |
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G-protein inhibition of adenylyl cyclase
dec: inc: dec: net: |
G-protein inhibition of adenylyl cyclase
dec: cAMP inc: receptor linked K currents - inc outward flow dec: voltage-gated Ca currents - dec inward flow net: hyperpolarization of membrane potential |
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tolerance
def: requires: |
tolerance
def: decrease in efficacy over time requires: long term administration, 4-5wk in dog |
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opioids tolerance
mech: |
internalization of receptors: mu, k
protein kinase C: phosphorylation of receptors leading to inactivation: mu, delta inc adenylyl cyclase activity (as result of dec cAMP) |
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dependence
__ days with morphine clinical signs precipiated by opioid ________ |
dependence
7 days with morphine clinical signs precipiated by opioid ANTAGONIST |
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opioids dependence
clinical signs |
hyperactivity
biting digging tremors nausea hyperthermia inc wakefulness |
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opioids for analgesia
moderate to severe pain |
mu agonists
morphine, hydromorphone, fentanyl |
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opioids for analgesia
mild to moderate pain |
mu agonists - morphine, hydromorphone, fentanyl, tramadol
mu partial agonists - buprenorphine k agonists - butorphanol, nalbuphine |
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opioids for analgesia
administer at ___________ or as ___________, not _________ |
opioids for analgesia
administer at RECOMMENDED INTERVAL or as CONSTANT RATE INFUSION, not AS NEEDED |
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________ and _________ pain are poorly responsive to opioids
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CHRONIC and NEUROPATHIC pain are poorly responsive to opioids
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pre-emptive analgesia
def. |
administration of opioids prior to and during surgery
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pre-emptive analgesia
decreases (3) |
decreases in central sensitization
decreases postoperative pain decreases consumption of analgesics |
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morphine
active metabolite: |
morphine
active metabolite: M6G, has variable activity |
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morphine
________ release upon IV administration note minimal: |
morphine
HISTAMINE release upon IV administration note minimal: HYPOTENSION |
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morphine half life
short or long dog: cat: |
morphine half life
SHORT dog: 1 hr cat: 1.3 hr |
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morphine
primary adverse effect is in horses: limit to: |
morphine
primary adverse effect is in horses: ILEUS limit to: SINGLE DOSE |
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morphine
with IV dosing, _______ lag time until max effect |
45 MIN
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morphine
clinically relevant effects in: |
10-20 MIN
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morphine
oral bioavailability: |
morphine
oral bioavailability: poor and erratic 5-20% not recommened, poor efficacy |
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morphine in dogs
clin use: AE: |
morphine in dogs
clin use: analgesia, sedative AE: minimal - vomit, defecation, panting, sedation, dysphoria |
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morphine in cats
clin use: AE: |
morphine in cats
clin use: analgesia, emesis AE: vomit, mydriasis, sedation, dysphoria |
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morphine in horses
clin use: AE: |
morphine in horses
clin use: analgesia AE: ileus |
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oxygmorphone
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10x potency morphine
cost-prohibitive mu agonist less vomiting, quicker onset of action b/c 25x lipophilicity |
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hydromorphone
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7x potency, 2x lipophilicity
mu agonist less vomiting, quicker onset action |
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fentanyl
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80-100x potency, 1000x lipophilicity
short duration b/c redistribution T1/2: 3-4 hr less vomiting, quicker onset |
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fentanyl transdermal patch
lag time: duration dog: duration cat: |
lag time: 12-24 hr
duration dog: 3 day duration cat: 5 day |
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fentanyl transdermal patch in horse
duration: lag: tolerated: |
duration: 36-48 hr, 2 days
lag: 1 hr, rapid absorption tolerated: well tolerated for 9 days |
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buprenorphine
duration: affinity: oral bioavailability: |
partial mu agonist
25-50x potent less vomiting, sedation slowest onset, 1hr to max duration: longer, 4-12hr affinity: high for mu receptors, resistant to naloxone reversal oral bioavailability: <20%, not effective |
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buprenorphine in cats
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transmucosal - cheek pouch
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hydrocodone
use: metabolized in part to: oral bioavailability: duration: analgesia: |
hydrocodone
use: antitussive in dogs metabolized in part to: hydromorphone oral bioavailability: 40-80%, only true opioid can use orally duration: 4-8hr analgesia: not evaulated |
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codeine
metabolized to: bioavailability: still used a lot b/c: |
codeine
metabolized to: 10% to morphine bioavailability: poor, 6%; minimal conversion to morphine in dogs; probably ineffective as analgesic still used a lot b/c: cheap and no AE (b/c not absorbed) |
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oxycodone
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mu and k agonist
poor oral bioavailability high abuse potential probably ineffective use not recommended |
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butorphanol
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5x potency
weak analgesic, short duration 1hr poor oral bioavailability, 20% less GI AE moderate sedative less effective than NSAIDs painful on IM SEDATION, BUT NOT ANALGESIA |
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butorphanol in ruminants may cause _____
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RUMEN STASIS
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nalbuphine
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mu antagonist (used as reversal agent), k agonist
inexpensive, not scheduled similar efficacy to butorphanol |
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naloxone
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opioid antagonist "reversal agent"
reverses exogenous and endogenous - ALL opioid induced analgesia |
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naloxone
primary indication: may cause: duration of reversal: |
naloxone
primary indication: opioid overdose may cause: CV shock due to pain, arrhythmias, hypertension, tachycardia, excitement duration of reversal: short, use multiple doses |
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loperamide (immodium)
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antidiarrheal
mu agonist minimal tolerance to chronic use high efficacy excluded from CNS by p-glycoprotein - NO analgesia sedation in collies |
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tramadol
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tech not an opioid
active metabolite M1 mu agonist fluoxetine (SSRI) inhibits metabolism inexpensive, not scheduled bitter tasting |
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tramadol
avoid co-administration with: |
OTHER 5-HT DRUGS
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tramadol
indication: AE (rare): |
indication: mild-moderate pain, antitussive
AE: sedation, vomiting, dec seizure threshold (contraindicated in epileptics) |
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heroin (diamorphine)
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more lipophilic, faster onset
mu agonist metabolized to morphine legal in europe no more effective than other opioids |
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amantadine
mech action: indications: |
mech action:
NMDA antagonist - dec sensitization, but no analgesia dopamine agonist, inc NT release antiviral indications: no pre-emptive analgesia potentiates other analgesics chronic, acute, or neuropathic pain |
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amantadine
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renal excretion, glomerular filtration
AE: nausea, vomiting well tolerated often combo w/ tramadol, NSAIDs, gabapentin, or fentanyl |
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gabapentin
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GABA analogue
mech: may dec GABA metabolism, inc non-synaptic release, or dec reuptake inc brain GABA conc indications: anticonvulsant, neuralgia, chronic pain |
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hydroxyzine
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H1 - antihistamine
most commonly for atopy trt people: effective sole analgesic, additive analgesia w/ opioids no studies in dogs |
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local anesthetics
mech: |
block Na channels on nerves blocking action potential
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local anesthetics
order of blockade: |
nociceptors
autonomic touch/pressure motor |
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local anesthetics
tachyphylaxis: |
loss of activity with repeated doses
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local anesthetics
routes of administration |
topical, inject in vicinity to peripheral nerves, subcu infiltration, epidural, subarachnoid
IVRA - IV w/ tourniquet systemic - IV infusion, LIDOCAINE only |
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local anesthetics
add _______ to prolong activity |
VASOCONSTRICTORS
epi, phenylephrine |
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local anesthetics
______ absorption following _____ administration potential for ________ |
SYSTEMIC absorption following LOCAL administration
potential for TOXICITY |
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local anesthetics
AE (3) |
1. CNS - dogs, horses, ruminants
2. cardiovascular - cats 3. neurotoxicity - put around nerve, not in nerve sheath |
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local anesthetics
3 |
lidocaine
mepivicaine bupivicaine |
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lidocaine
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quick onset, 10min
short duration, 1-2hr |
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mepivicaine
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used most in horses
onset and duration similar to lidocaine |
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bupivicaine
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longer onset, 30-45min
longer duration, 6hr often combo w/ lidocaine |
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local anesthetics
indications |
pre-emptive analgesia
postoperative analgesia epidurals IV infusion - Lidocaine only |
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topical lidocaine
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EMLA
variable success |
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other medications for pain
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tricyclic antidepressants TCA's
serotonin norepi reuptake inhibitors SNRI's selective serotonin reuptake inhibitors SSRI's NSAIDs |
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TCA's
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norepi and serotonin reuptake inhibitors
amitriptyline clomipramine |
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SNRI's
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venlafaxine
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SSRI's
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fluoxetine - combo w/ opioids
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NSAIDs
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carprofen, meloxicam, deracoxib
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targets for pain management
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opioid agonists
serotonin agonists GABA agonists norepi agonists NMDA antagonists sodium channel blockers COX-1 and COX-2 inhibitors |