Card Set Information
LA pt 1
Briefly describe the history of injections/LA
1850s hypodermic needle, cocaine isolated
1884 Freud cocaine, cocaine in medicine, LA by Halsted & Hall
1905 Procaine (Einhorn)
1921 Cartridge syringe
1947 Aspirating syringe
1959 Disposable needle
What is Local anesthetics?
drugs that reversibly block gen & propagation of nerve impules
depress conduction in all exciteable cells
sensory/motor periph, ANS ganglia, CNS, NMJ, cardiac & smooth muscle
What did descartes discover in 1664?
pain in brain.
What did gate control theory 1965 imply?
rubbing can interrupt pain transmission
What is the IASP definition of pain?
unpleasant sensory & emotional experience associated w/ actual or potential tissue damage or described in terms of such
What are the 2 aspects of pain?
: detection threshold, ID/loc, reproducible, intensity
: escape threshold, reaction, variable, unpleasantness
What are the processes of pain experience?
: physical to electrical
: to CNS
: endogenous opiods
What is nociception?
potentially tissue damaging thermal or mechanical energy impinging upon specialized nerve endings (A-delta & C fibers)
Describe tranmission pathway of nociception.
nociceptor-> dorsal root of spinal cord-> decussation to ascend via anterolateral system to thalamus and cortex vial spinothalmic and reticulothalmic tracts
LA blocks nociceptors
Which nerves are responsible for head pain sensation?
CN (V,VII, IX, X)
Sympathetic nervous system
What are the different nuclei of the trigeminal?
spinal trigeminal nucleus
: nociceptive info, nucleus cauadalis
rostral to caudal (center of face to outside therefore central face is harder to block with anesthesia than outside face)
What are the types of LA applications?
: skin & mucous membranes
: direct injection
regional nerve block
: injected proximal to nerve supplying area
: injection to lumbar subarachnoid CSF
epidural, peridural or extradural
: inject to extradural space where nerve roots pass, less likely to rise to higher segment then intended
: distal to point and interrupted by tourniquet
: reflex symp dystrophies or intractable pain such as carcinoma
What is the difference between spinal and epidural,peri or extradural?
spinal is in subarachnoid CSF which may rise to higher parts
Explain some of the Complex regional pain syndromes that are addressed by sympathetic blockades.
: CRPS upper arm, herpes zoster of H&N
: pancreatitis pain
: CRPS lower legs: acute herpes zoster of legs
What are peripheral nerves?
mixed population of nerve fibers w/different diameters and rates of conduction.
Explain the axon organization.
: individual cell
: surrounds ind axon
: bundles into fascicles
: invests fascicles (vessels, fat cells)
Core(deep) vs. Mantle(peripheral) fibers
What factors speed nerve conduction.
: saltatory conduction
: directly (larger=faster)
What is a A-alpha peripheral nerve?
innervate skeletal muscle
What is a C perpheral nerve?
smallest, slowest nociceptor
What fibers transmit nociception?
A-delta and C
Describe the various types of peripheral nerve fibers.
: skeletal (15um, 100m/sec)
: touch/pressure (8um, 50 m/sec)
: muscle spindles (6um, 20 m/sec)
: nocicpetors (3um, 15 m/sec) (sharp acute myelinated)
: symp preganglionic (3um, 7 m/sec)
: nociceptors (1um, 1 m/sec) (unmyelinated
Symp post (unmyelinated)
Describe the ionophores of the nerve membrane.
very selective Na+, regulated or gated by membrane potential
closed(resting)->depolarize->open(ion-conducting)->inactive->repolarized to closed(recovery)
Na+ influx makes intracelluar more positive
What are the permeabilities of the nerve membrane?
: impermeable, high extracellular (1:14)
: selectively permeable, high intracellular (27:1 in:out)
: 1:11 in:out
gradient = -70mV (inside is negative)
What is the firing threshold?
magnitude of decrese in negative transmembrane potential that is necessary to initiate an action potential(impulse)
ALL or none
: anything less will not initiate
Explain the Na channel gates.
: activation, initial depolarization opens
: inactivation, rapid depolarization closes
4 alpha subunits, 1 beta holds alphas in membrane
With regard to the Na channels what do LA do?
binds to transmembrane segments IS6, IIIS6, and IVS6
S4 segments unwind to open channel, LA prevents unwinding
induce reversible/dose-dependent reduction in rate of rise and height of action potential
causes an elevation of firing threshold and slowing of spread of conduction as conc of LA inc
in myelinated nerves only at nodes of Ranvier
What is critical length?
smaller distance for blockage of smaller fibers
differential sensitivity of nerve fibers therefore smaller are more susceptible to blockacde than larger ones
What is a use-dependent block?
LA action increased by repeated firing which allows more access and affinity for binding site (when channel is open)
aka freqency-dependent, use-dependent, phasic block
Which fibers are more susceptible to blockade?
dull/sharp pain, temperature
: touch, pressure, proprioception
What is the structure of LA?
2. Intermediate chaing
: amide or ester linkage
: tertiary amine group
procaine 8.9 pKa
chloroprocaine 9.0 pKa
tetracaine 8.2 pKa
Factors that affect the onset of LA action
pH of tissue
pKa of drug
How is the Henderson-Hasselbalch equation used to explain ionization.
: lidocaine pKa = 7.9
7.9-7.4 = log [ion/un-ion]
10^0.5 = ion / un-ion = 3/1
Closer pKa to body pH = faster onset time
How does infection affect onset of LA?
tissue pH of infected tissue is lower-> more acidic therefore the ration of ion/un-ion is higher and will have a slower onset time and less efficacy.
What factors affect duration of action of LA
: DIFFUSION (hence vasoconstrictor)
What is the main factor of LA potency?
lipid solubility: ability to move intraneuronally
How are amide LAs metabolized?
: N-dealkylated to monoethyl-glycine-xylidide(MEGX) (80% potency->sedation)
: biotransformed in plasma and kidney->orhtotoludidine->methemoglobinemia
: amide w/ester, ester hydrolysis more rapid
Bupivacain is N-dealkylated
What does toluidine do in the blood?
blocks conversion of Fe2+ to Fe3+ causing methoglobinemia
How are ester LAs metabolized?
plasma cholinesterase (pseudocholinesterase
concern if atypical plasma cholinesterase (deficiency)
Is metabolism of LA a concern?
not really unless severe liver dysfunction or pseudocholinesterase deficiency.
total amount more important
What are the interactions of LA?
other LA (additive)
: stay below max
opioid and phenothiazine
: increases cerebral blood flow -> predisposed to toxicity, stay well below max
What are the indications for vasoconstrictors?
inc depth of anesthesia
inc duration (if LA doesn't vasodilate like prilocaine)
decrease peak blood levels of LA (dec systemic toxicity)
: minimize bleeding (bware of CV effects)
Describe the adrenergic amine structures of vasoconstrictors.
: both H, no B2
: (NH-CH3), all
: alpha-methyl-NE, decreased a1, B2
How is vasoconstriction mediated?
a2-bare extra-synaptic in periphery, (some presynaptic inhibition too)
What are the CV effects of Epi?
inc HR, CO!!
dec periph resistance -> MBP stable
ST-segment depression->myocardial ischemia
What are CV effects of Levonordefrin?
inc dysrhythmia, CO, PR, MBP
no change in HR
What are the CV effects of NE?
inc! PR, MBP
no change in CO
What are the systemic effects of Epi?
vasoconstriction (capacitance veins) a1
increased contractility and HR b1
vasodilation (skeletal muscle) b2
: Bronchodilation (b2)
decrease plasma K+ (a2)
increased lipolysis (b2)
elevated plasma glucose (b2)
What are the features of epinephrine?
rapid onset, short duration (5-10 IV, 10-20 Intraoral)
exogenous epi metabolized by COMT
What are the sympathetic Nervous system receptors?
: vasoconstriction, inc BP
: HR & force, inc HR
: skeletal vasodilation, dec BP
What are the vasoconstricor interations?
Non selective Beta-blockers (hypertension & reflex bradycardia)
: tricyclic, SNRI, SNE-reuptake inhibitors, cocaine & amphetamines