Local Anesthetics Flashcards
Most local anesthetic agents consist of a lipophilic group (eg, an ___ ring) connected by an intermediate chain (___ or ___) to an ionizable group (eg, a ___ ___).
aromatic; ester; amide; tertiary amine
Because ester links are more prone to ___ by pseudocholinesterases than amide links, esters usually have a ___ duration of action. Which is favored in dental practices?
hydrolysis; shorter; amides
Why do amides have a longer half life in the plasma?
local anesthetics with an amide linkage will be metabolized by P450 enzymes in the liver, thereby they’ll have a longer half life in the plasma
Which are more allergenic, esters or amides?
esters
T/F. Amides will have an ‘i’ in their name somewhere prior to ‘caine’ (eg, lidocaine) but esters won’t (eg, procaine).
True.
Primary, secondary and tertiary amines will exist in equilibrium between basic and acidic forms. What are type of amine are local anesthetics used in dentistry?
secondary or tertiary amines
Are both forms, acidic and basic, of local anesthetics important for function? Why?
Yes, the uncharged BASIC form will cross the cell membrane. Therefore, local anesthetics produce their block from ‘inside’ the nerve.
Once inside the nerve, the charged acidic form will bind better to the Na+ channel and inhibit conduction of the nerve impulse.
In the case of optically active agents such as ___, the R(+) isomer can usually be shown to be slightly more ___ than the S(-) isomer (___).
bupivacaine; potent; levobupivacaine
Local anesthetics cross the axon membrane and interact with the ___ and ___ forms of the Na+ channel, blocking Na+ conductance.
open; inactivated
Axons are either myelinated or unmyelinated. Which form conducts nerve impulses more rapidly?
myelinated
Peripheral nerves consist of bundles of nerve fibers encased by ___ tissue. Which of these tissue covering is found in the outermost layer, surrounding fasicles, and surrounding individual nerve fibers?
Connective tissue
Epineurium - outermost layer
Perineurium - surrounds fasicles
Endoneurium - surrounds individual nerve fibers
A ___ is a organized bundle of nerve fibers.
fasicle
A-alpha fibers are ___ and involved in somatic ___ and ___ at muscle spindle (Ia) and golgi tendon organ (Ib).
myelinated; motor; proprioception
C fibers are ___-___ and are involved in ___ from the dorsal root or serve as ___ sympathetic fibers.
non-myelinated; pain; postganglionic
What is the relative size and susceptibility to block of nerve fibers?
- pain
- cold
- warmth
- touch
- deep pressure
- motor
Recovery in reverse order.
T/F. Because local anesthetics bind to the open form of the sodium channel, they produce a more rapid nerve block on axons with a more rapid firing rate.
True.
Functions served by ___ and ___ fibers are more readily disrupted by local anesthetics than the motor functions served by (larger) ___ fibers.
B; C; A
Sensory neurons are heterogeneous in size and sensitivity. When senses are most sensitive to least sensitive?
Most sensitive → least sensitive pain cold warmth touch deep pressure
T/F. The slower the fiber is blocked, the longer it takes to recover.
False, the FASTER a fiber is blocked, the longer it takes to recover.
First on, last off
T/F. Local anesthetics block more rapid with rapidly firing nerves.
True.
___ produces sensory anesthesia at ___ the concentration required for motor blockade. ___ shows no selectivity. Which would be favored for epidural anesthesia during childbirth (maintain uterine muscle contractility)?
Bupivacaine; 1/3; Etidocaine
Bupivacaine
T/F. Inflamed tissue is more difficult to anesthetize.
True.
Products released by cells in inflamed tissue lower pH, making it more difficult to get sufficient levels of anesthetic inside the axon.
Anesthetic must be sufficiently ___ to diffuse to its site of action, but once at the site, the more ___ local anesthetics have a longer duration of action (increased protein binding, decreased clearance by local blood flow).
hydrophilic; lipid-soluble
Why can’t the pKa of the anesthetic stray too far from the physiological pH?
Most local anesthetics are prepared as a water soluble HCl salt (pH of solution around 6 or 7). If epi is included, the pH is frequently lowered to 4 or 5 to stabilize the epi. The buffering capacity at the injection site neutralizes this.
What is added prior to injection of an epi-containing preparation to increase the concentration of free base but runs the risk of precipitating the local anesthetic?
NaHCO3
T/F. Local anesthetics can readily pass from the periphery to the CNS and affect the CNS causing light headedness, dizziness to death.
True.
What are the direct effects that local anesthetics have on the heart?
block cardiac Na+ channels
block cardiac Ca2+ channels (much higher concentrations)
Depress pacemaker activity, excitability, conduction
What effects do local anesthetics have on the autonomic nervous system of the heart?
By inhibiting the sympathetic response
- depress contractility
- produce hypotension
What local anesthetic is cardiotoxic?
Bupivacaine
T/F. Allergic reactions are significant for ester local anesthetics not amide local anesthetics. Amides are usually used in dentistry.
True.
What are the benefits and concerns with using Epi as a vasoconstrictor?
benefits: success rate and intensity better, toxicity of anesthetic reduced, less blood loss
concerns: excess dosing or inadvertent intravascular injection possible and can lead to cardiovascular side effects
Give 40ug instead of 200ug in a compromised patient
All local anesthetics will get ___. Lidocaine and procaine produce potent ___ and are more readily absorbed. It is important to supply a ___ with these drugs.
absorbed; vasodilation; vasoconstrictor
Name two plasma proteins that local anesthetics bind to as they are being distributed in the body.
alpha-1 glycoprotein
albumin
Unbound drugs can ___ to various tissues, including the CNS and ___. Absorption (and subsequent metabolism) by ___ is important to keep systemic concentrations of ___ local anesthetics low.
diffuse; placenta; liver; amide
___ local anesthetics are metabolized by a combo of ___ in the plasma and tissue (liver metabolism). The t1/2 for procaine hydrolysis is less than ___ min and less than ___% of the drug leaves the kidneys unhydrolyzed.
Ester; pseudocholinesterase; 1; 2
T/F. Amides with p-aminobenzoic acid hydrolyzed very rapidly by pseudocholinesterase.
False, ESTERS withp-aminobenzoic acid hydrolyzed very rapidly by pseudocholinesterase.
___ local anesthetics undergo complex biotransformation in the liver, which includes ___ by cytochrome P450 isozymes.
Amide; dealkylation
Which two amide local anesthetics are inactivated more rapidly?
prilocaine (secondary amine, dealkylation not required, extrahepatic metabolism)
articaine (inactivated by blood esterase)
What is the cause of the most serious side effects?
operator error
What does operator error result from?
- excessive concentrations in the blood caused by inadvertent intravascular injection
- administration of excessive quantities of drug
What are the results of operator error?
convulsions, respiratory arrest, cardiovascular collapse
What are the three guiding principles when administering local anesthetics?
- administer the smallest dose that is effective
- use proper injection technique
- use a vasoconstrictor-containing solution unless contraindicated
How do you treat convulsions, respiratory distress, hypotension and disrupted cardiac function?
convulsions: benzodiazepine, barbituate (thiopental), succinylcholine (treats symptoms only)
respiratory distress: ventilation, oxygen
hypotension: sympathomimetic agents
cardiac function disrupted: cardiopulmonary resuscitation
What is the dermatological and anaphylactic shock treatment?
dermatological: antihistamines
anaphylactic shock: epi???
What local anesthetics can be used during pregnancy?
lidocaine, prilocaine category B, articaine, mepivacaine, bupivacaine category C
Why are local anesthetics generally safe in dentistry?
doses are low low fatalities adverse effects (pallor, unrest, swating, palpitation, nausea) difficult to quantitate from anxiety.
