Comprehensive Study Guide Flashcards
Label whether the following ions are intra- or extra-cellular:
- K+
- Na+
- Cl-
- Proteins
- HCO3-
- ICF
- ECF
- ECF
- ICF
- ECF
Intracellular ions=
K+ and proteins (more negative)
Extracellular ions=
Na+, Cl-, HCO3- (more positive)
Where do local anesthetics exert their pharmacological action on the nerve?
Nerve membrane
How do local anesthetics work?
Specific receptor theory- local anesthetic binds to specific receptor on the Na+ channel
What does the specific receptor theory state?
States that the local anesthetic binds to a specific receptor on the Na+ channel to prevent the channel from opening (therefore no action potential and no pain)
Which ion channel does the local anesthetics bind to ?
specific receptors of the na+ channel
Speed of conduction of a myelinated nerve:
Speed of conduction of an unmyelinated nerve:
myelinated: 120 m/sec
unmyelinated: 1.2 m/sec
Where do local anesthetics work at the myelinated nerve?
local anesthetics work at the nodes of ranvier (an abundance of sodium channels here)
In order for local anesthetic to work on a myelinated nerve, it needs to block:
2-3 nodes (8-10mm of nerve)
Drug: Lidocaine
Onset:
Half-Life:
Mg/Kg of max dose:
onset: 2-3 min
half-life: 1.6 hrs
(1hr of pulpal and 3-5 hrs of soft tissue for 2% solution)
Mg/Kg of max dose: 4.4 mg/kg (300mg)
Drug: Prilocaine
Onset:
Half-Life:
Mg/Kg of max dose:
Drug: Prilocaine
Onset: 2-4 min (slightly slower)
Half-Life: 1.6 hrs
Mg/Kg of max dose: 6 mg/kg (400 mg)
Drug: Mepivacaine
Onset:
Half-Life:
Mg/Kg of max dose:
Drug: Mepivicaine
Onset: 1.5-2 min (rapid!)
Half-Life: 1.9 hrs
(20-40 minutes of pulpal and 2-3 hrs of soft tissue)
Mg/Kg of max dose: 4.4mg/kg
Drug: Bupivacaine
Onset:
Half-Life:
Mg/Kg of max dose:
Drug: Bupivacaine
Onset: 6-10 min (longer)
Half-Life: 2.7 hours (long!)
Mg/Kg of max dose: 1.3 mg/kg (90mg)
What drug would be used when more than 90 minutes of pulpal anesthesia is needed and is also used to reduce post-op pain?
Bupivacaine
Drug: Articaine
Onset:
Half-Life:
Mg/Kg of max dose:
Drug: Articaine
Onset: 1-2 min (rapid)
Half-Life: 0.5 hours (short!!)
(0.5hrs of pulpal and 3-5 hours of soft tissue for 4%)
Mg/Kg of max dose: 7mg/kg (500mg)
Drug: Cocaine
Onset:
Half-life:
Drug: Cocaine
Onset: immediate- 1 min
Half-life: 1-1.5 hrs
What is the onset of Procaine?
6-10 min (a little slower than lidocaine)
List the following anesthetics in order of fastest to slowest onset:
- Bupivacaine
- Articaine
- Prilocaine
- Procaine
- Cocaine
- Mepiivocaine
- Lidocaine
(Fastest)
1. Cocaine
2. Articaine
3. Mepivacaine
4. Lidocaine
5. Prilocaine
6. Bupivacaine
7. Procaine
(Slowest)
List the following anesthetics in order of longest to shortest duration:
- Bupivacaine
- Articaine
- Prilocaine
- Procaine
- Cocaine
- Mepiivocaine
- Lidocaine
(Longest)
1. Bupivacaine
2. Mepivacaine
3. Lidocaine & Prilocaine (equal)
4. Cocaine
5. Articaine
For maximum recommended dose (MRD) what guidelines do we follow?
ADA & USPC guidelines (NOT manufacturer)
How does low tissue pH influence local anesthesia?
Low tissue pH (high acidity/H+) is HARDER to anesthetize (usually associated with inflamed tissues)
How does low anesthetic pH lead influence local anesthesia?
Low anesthetic pH leads to higher effective shelf life
is the average pH of local anesthetics?
5.5-7.0
If the pH of the environment does not allow the ___ of the anesthetics to exist, numbing will NOT occur.
free base form
In order for the local anesthetic to work, the pH of the environment:
must allow the free base form to exist
What is the free base form of the local anesthetic?
What enters the nerve membrane
The further the pH Is from the ideal for that specific anesthetic, the:
lower the percentage of that local anesthetic will be present in the free base form
Is local anesthetic hydrophilic or hydrophobic?
amphipathic (both hydrophilic and hydrophobic)
What is the exception to local anesthetic being amphipathic?
Benzocaine; doesn’t have a hydrophilic group so it is good for topical but not for injections
_____ determines the ease for nerve blockade
extracellular pH
Inflamed or infected tissue is
much more difficult to get adequate anesthesia because:
of increased H+ or lower pH
RNH+ Breaks down into:
Rn (free base) and H+
The low pH in an anesthetic allows for:
increased shelf life
RNH+ —> RN + H+ describes:
the dissociation of local anesthesia
RNH+ —> RN + H+
What does RN represent?
free base
RNH+ —> RN + H+
What does RNH+ represent?
cation
RNH+ —> RN + H+
In this reaction, if there’s excess H+, the equilibrium will shift to the:
left (RNH+ side)
this means that if there is an acidic environment (example- a really infected tooth with lots of bacteria = very acidic) it will be harder to anesthetize because there is less of the free base form RN which is what actually enters the nerve membrane
Only the _____ of the anesthetic can enter the nerve, which is important because the sodium channel must be blocked ____
free base form (“ninja”); from the inside
Anesthesia is injected as a ___ that ___
ionized cation; that cannot cross the nerve cell membrane (until broken down into free-base form)
The anesthesia that is injected must break down from its _____ form into ____ form, which can diffuse into the membrane
ionized cation; non-ionized free-base
Once in the nerve, the free base can become the ionized version again and bind to the specific receptor to:
prevent sodium channel from opening
Once the free base form of the local anesthetic is diffused, it must _____ in order to bind to the receptor
dissociate back into the cationic form
Once the free base form of the local anesthetic is diffused, it must dissociate back into the cation form in order to bind to the receptor- what does this binding t the receptor cause?
prevents sodium channel from opening
Describe the relationship of pKa vs. local anesthesia:
high pKA: slow onset (few free bases available)
low pKA: rapid onset
Local anesthesia are _______- They combine with acids to form local anesthetic salt (HCl)
weak base compounds
pKA influences:
onset; inversely related
Describe why a high pKA would have slower onset?
because there are fewer free bases to diffuse (fewer ninjas without their backpacks that can get through, most ninjas have their backpacks on so they can’t cross to bind)
How does lipid solubility influence local anesthesia?
With increased lipid solubility, the drug is more potent.
With decreased lipid solubility, the drug is less potent.
The relationship of pKA to onset is ____.
The relationship of lipid solubility to local anesthesia potency is ___
inverse; direct
The nerve membrane is ____% Lipid
90%
- What influences the ONSET of local anesthesia?
- What influences the POTENCY of the local anesthesia?
- What influences the DURATION of the local anesthesia?
- pKA
- lipid solubility
- protein binding
With increased protein binding, the local anesthetic has:
longer duration
With decrease protein binding, the local anesthetic has:
shorter duration
The nerve membrane is ____% protein
10%
With increased lipid solubility, the drug is:
more potent
With decrease lipid solubility, the drug is:
less potent
With a high pKA, the onset of the local anesthesia is:
slow (few free bases available)
With a low pKA, the onset of the local anesthesia is:
rapid
Most local anesthetics have a ____ effect
vasodilation
Which local anesthetic has the most profound vasodilation effect?
Procaine
The only local anesthetic to have a vasoconstrictive effect
cocaine
Cocaine is vasoconstrictor (meaning its alpha-1) and works by:
Inhibition of catecholamine re-uptake
Alpha 1 =
vasoconstriction
Beta 2=
vasodilation
What agent has the most potent vasodilation properties?
procaine
The most commonly used vasoconstrictor:
epinephrine
“I” comes before “Caine” if the agent is:
an amide
_____ are readily hydrolyzed in aqueous solutions
esters
List examples of esters (6)
- procaine
- propoxycaine
- tetracaine
- cocaine
- benzocaine
- dyclonine
_____ resist hydrolysis and get excreted in urine as an unchanged form
Amides
List examples of amides (6)
- lidocaine
- etidocaine
- mepivocaine
- bupivocaine
- prilocaine
- articaine
What are the two different classes of local anesthesia?
Amides & Esters
How do amides metabolize in the body?
The liver is the primary biotransformation site
Metabolism of what type of anesthetic can cause cirrhosis/CHF or hypotension?
amides
How are esters metabolized in the body?
Hydrolyzed in plasma by pseudocholinesterase into paraaminobenzoic acid (PABA)
What is a substance in local anesthetic that individuals commonly have a reaction to? Is this in amide anesthetics or ester anesthetics?
PABA; Esters
What is the relationship between cirrhosis patient and metabolism of local anesthetics?
Liver function/hepatic perfusion influence biotransformation
(1) Cirrhosis → Late stage of scarring (fibrosis) of
the liver
When is local anesthetics a contraindication for patients with liver issues?
ASA IV to V for patients with liver
dysfunction (or heart failure)
How do cirrhosis and/or CHF interfere with the amounts of your local anesthesia injection?
Amide LAs are chemically modified (metabolized) in the body in the liver, so since the liver is not functioning well (does have full metabolic capacity), then less LA should be administered
If a patient has cirrhosis and/or liver failure, do you give them more or less local anesthetic when injecting?
LESS
Does a patient who has cirrhosis and/or CHF increase the availability of the amide local anesthetic or decrease the availability of the local anesthetic?
Increases the availability because the amide is not being metabolized as quickly and more is left in the body for longer periods of time
Which organ in the body (largest mass and tissue in the body) has the greatest concentration of local anesthesia?
skeletal muscle
What is tachyphylaxis?
The increase in tolerance to drug after repeated administration
Explain how to calculate elimination half-life
Take percentage of leftover, divide that in half, and add it on to what has been eliminated thus far.
What does elimination half life describe?
The amount of time needed for 50% reduction in blood level
List the percentages of elimination of the following elimination half life:
1st half life: 50% eliminated
2nd half life:
3rd half life:
4th half life:
1st half life: 50% eliminated
2nd half life: 75% eliminated
3rd half life: 87.5% eliminated
4th half life: 94% eliminated
DO all local anesthetics readily cost the BBB and placenta?
yes
What is the cause for local anesthesia overdose/ toxicity?
over injection or repeated injections into the bloodstream and systemic circulation
To prevent local anesthesia overdose/toxicity it is important to:
aspirate
What are the initial signs of local anesthesia overdose/toxicity?
Initially: Causes excitatory response (numbness of tongue and circumoral region slurred speech, shivering, AV disturbances, tremor and etc.)
If you ignore the initial signs of local anesthesia overdose/toxicity, what may occur?
patient may go into a seizure and if you continue loading them up with more local anesthesia they will stop breathing
What are the later signs/stages of local anesthesia overdose/toxicity?
Depressive response on CNS with a lesser CV effect as well as agitation, confusion, dizziness, drowsiness, dysphoria, auditory changes, tinnitus, perioral numbness, metallic taste, etc.)
Causes excitatory response (numbness of tongue and circumoral region slurred speech, shivering, AV disturbances, tremor and etc.)
Initial stage of local anesthesia overdose/toxicity
Depressive response on CNS with a lesser CV effect as well as agitation, confusion, dizziness, drowsiness, dysphoria, auditory changes, tinnitus, perioral numbness, metallic taste, etc.)
Later stage of local anesthesia overdose/toxicity
The initial signs/symptoms of CNS toxicity are:
excitatory
Higher levels of initial toxicity from local anesthetic may result in:
tonic-clonic convulsion (seizure)
In later stages of toxicity or where their is further increases in anesthetic beyond the initial symptoms, there will be:
cessation of seizure activity –> respiratory depression —> respiratory arrest
Catecholamines include:
epinephrine, norepinephrine and dopamine
Non-catecholamines include:
amphetamine, ephedrine, and methanphetamine
Epinephrine, Norepinephrine and dopamine are ____ catecholamines
natural
Isoproterenol and levonordefrin are ____ catecholamines
synthetic
Contain hydroxyl group on benzene ring and work directly on adrenergic receptors (alpha 1, 2 and beta 1, 2)
Catecholamines
Do not contain hydroxyl group on benzene ring
non-catecholamines
Catecholamines work directly on:
adrenergic receptors (alpha 1 & 2 and beta 1 & 2)
What is more concentrated
1:100,000 or 1:200,000
1:100,000 because this is equal to 1G or 1000mg/100,000ml of solution
versus
1:200,000 is equal to 1G or 1000mg/200,000ml of solution
Calculate the mg/ml of solution for a 1:300,000 dilution:
1G = 1,000 mg
1000mg/300,000ml = 0.0033mg/ml
The maximum dose of epinephrine in a healthy patient is:
0.20mg (200mcg)
The maximum dose of epinephrine in an unhealthy/cardiac patient is:
0.04mg (40mcg)
If you have a 1.7ml solution of the 1:100,000 dilution of epinephrine, how much epi is present per ml?
1.7 x.01 = .017mg/ml