Study Guide Flashcards
Know which ions (Na, K, Cl…) are associated with extra or intra cellular space.
Extracellular space Na, Cl
Intracellular space K
Where do local anesthetics exert their pharmacological action on nerve (which part of the nerve?) and how Local anesthetics work (which ion channel?)?
Location: local anesthetics act on the nerve membrane
“How”: they act by the “specific receptor theory” which states the local anesthetic binds to a specific receptor on the Na channel to prevent channel from opening (therefore no action potential and no pain for the patient)
3) Myelinated nerve vs unmyelinated nerve
a. Speed of signal conduction
Myelinated Speed of conduction: 120 m/sec
Unmyelinated Speed of conduction: 1.2 m/sec
3) Myelinated nerve vs unmyelinated nerve
b. Where does local anesthesia work at myelinated nerve?
Location: local anesthetic works at the Nodes of Ranvier (abundance of sodium channels located here)
- To work you need to have 2-3 nodes (8-10mm) of the nerve blocked
4) Know the following local anesthetic agents:
a. Lidocaine
onset time of action (minutes)
duration time (t 1/2 in hours)
mg/kg of maximum dose
2-3
1.6, 1 hour of pulpal and 3-5 hours of soft tissue for 2% solution
4.4
b. Prilocaine
onset time of action (minutes)
duration time (t 1/2 in hours)
mg/kg of maximum dose
2-4
1.6
6.0
c. Mepivacaine
onset time of action (minutes)
duration time (t 1/2 in hours)
mg/kg of maximum dose
1.5-2
1.9, 20-40 minutes of pulpal and 2-3 hours of soft tissue anesthesia
4.4
d. Bupivacaine
onset time of action (minutes)
duration time (t 1/2 in hours)
mg/kg of maximum dose
6-10
2.7, used when more than 90 minutes of pulpal anesthesia needed or to reduce postoperative pain
1.3
e. Articaine
onset time of action (minutes)
duration time (t 1/2 in hours)
mg/kg of maximum dose
1-2
0.5, 0.5 hours of pulpal and 3-5 hours of soft tissue for 4%
7.0
f. Cocaine
immediate onset time of action
g. Procaine
6-10 min onset
4) Know the following local anesthetic agents: a. Lidocaine b. Prilocaine c. Mepivacaine d. Bupivacaine e. Articaine f. Cocaine g. Procaine
Onset order:
Cocaine > Articaine > Mepivacaine > Lidocaine > Prilocaine > Bupivacaine > Procaine
4) Know the following local anesthetic agents: a. Lidocaine b. Prilocaine c. Mepivacaine d. Bupivacaine e. Articaine f. Cocaine g. Procaine
Duration order:
Bupivacaine > Mepivacaine > Lidocaine = Prilocaine > Cocaine > Articaine
5) How does pH influence local anesthesia?
(2)
Low tissue pH (high acidity/H+) is harder to anesthetize (usually associated with inflamed or infected tissues)
Low anesthetic pH leads to higher effective shelf life
- Average pH of local anesthetics 5.5-7
5) How does pH influence local anesthesia?
How pH affects local?
If the pH of the environment does not allow the free base form (what enters the nerve membrane) of the anesthetic to exist, numbing will not occur
- 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
6) Is local anesthesia hydrophilic or hydrophobic?
Amphipathic (both hydrophilic and hydrophobic)
- With the exception of Benzocaine; doesn’t have hydrophilic group. Good topical but not good for injections)
7) Organic components of local anesthesia (how they change from charged to non-charged form)
Only the free base form (“ninja”) of the anesthetic can enter the nerve, the sodium channel must be blocked from the inside
- Anesthesia is injected as an ionized cation that cannot cross the nerve cell membrane (but can become a non-ionized free base, which can diffuse into the membrane)
- Once in the nerve, the free base can become it’s ionized version again and bind to the specific receptor to prevent Na channel from opening
8) Relationship of pKA vs local anesthesia
High pKA slow onset (few free bases available)
Low pKA rapid onset
9) 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
10) What does protein binding have to do?
With increased protein binding, the drug has longer duration
With decreased protein binding, the drug has shorter duration
Nerve membrane = –% lipid
Nerve membrane = –% protein
90
10
11) Vasoactivity of different kinds of local anesthetic agents? (which agent has the most profound vasoconstrictive property and which has the most profound vasodilatation property?)
Alpha 1 = most profound vasoconstriction activity
- Epinephrine is most used vasoconstrictor
- Cocaine is the only local anesthetic with vasoconstrictive effect
Beta 2 = most profound vasodilation activity
- Procaine is the most potent vasodilator
12) Different classes of local anesthesia
a. Ester and Amide (answer)
AMIDES: resist hydrolysis and excreted unchanged in urine
- Trick: drugs with an “I” that comes before “caine” is an amide (i.e. articaine)
ESTERS: readily hydrolyzed in aqueous solution
- Trick: drugs without an “I” that comes before “caine” is an ester (i.e. lidocaine)
13) How esters or amides metabolize in the body? (and their effect on individuals with cirrhosis and CHF)
Amide metabolism
Liver: primary biotransformation site
Can cause cirrhosis/CHF or hypotension
Ester metabolism
Hydrolyzed in plasma by pseudocholinesterase into paraaminobenzoic acid (PABA)
- PABA = usually what individuals have a reaction to
What is the relationship between cirrhosis patient and metabolism of local anesthetics?
Liver function/hepatic perfusion influence biotransformation
How do cirrhosis and/or CHF interfere with the amount of your local anesthesia injection? Does this disease state increase the availability of this drug or decrease the availability?
Amide LAs are chemically modified (metabolized) in the body in the liver, so since the liver is not functioning as well (doesn’t have the full metabolic capacity), then less LA should be administered. This disease increases the available (will be available longer) due to the liver not being able to biotransform the drug. Therefore we give them less LA
14) Which organ in the body has the greatest concentration of local anesthesia?
Skeletal muscle
15) What is Tachyphylaxis?
Increased tolerance to drug due to repeated administration
16) Know how to calculate elimination half-life (t 1⁄2)
Elimination half life = time needed for 50% of the drug to be reduced in blood level
Equation:
(t ½): ln 2/k (where k= reaction rate constant)
Different Half-lives:
1st half-life:
2nd half-life:
3rd half-life:
4th half-life:
50% eliminated
there is 50% of the drug left…half of 50 is 25. Add 25 to the previous 50 you have eliminated 75%
you have eliminated 75%, there is 25% left, 25/2= 12.5 add that to 75=87.5% eliminated
you have eliminated 87.5% up to this point. There is 12.5% left. Half of that is 6.25 add that to 87.5= 94% eliminated
17) Do all local anesthesia readily cross the BBB and placenta?
Yes
18) What are the stages/ signs of local anesthesia over dose / toxicity?
Caused by:
- Initially =
- Eventually =
over injection or repeated injections into the blood stream and systemic circulation (why it’s important to aspirate!)
causes excitatory response (numbness of tongue and circumoral region slurred speech, shivering, AV disturbances, tremor, etc.)
o if you ignore initial signs, patient can go into a seizure
o if you keep loading them up with more local anesthesia, they will stop breathing
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.)
19) Catecholamine vs non-catecholamine?
Catecholamine
Natural: epinephrine, norepinephrine, dopamine
Synthetic: isoproterenol, levonordefrin
Contain hydroxyl group on benzene ring. Work directly on adrenergic receptors (alpha 1,2 and beta 1,2)
19) Catecholamine vs non-catecholamine?
Non-catecholamines
Amphetamine, methamphetamine, ephedrine
Do not contain hydroxyl group on benzene ring
20) What does epinephrine dilution mean? If someone ask you what’s 1:300,000 mean.
___:____ = gram (or mg) of drug: ml of solution (so 1:300,000 would be 1 g (1000 mg) of drug per 300k ml of solution
- To calculate mg/ml of solution, just divide. Here would be 1000mg/300,000ml = 0.0033 mg/ml of solution
- When comparing: the lower the second number (ml of solution), the higher the concentration (i.e. 1:100,000 is more concentrated than 1:200,000)
