OS Final Flashcards
Which ions are associated with extracellular space?
Na+, Cl-, HCO3-
- more positive
Which ions are associated with intra cellular space?
K+, proteins
- more negative
Where do local anesthetics exert their pharmacological action on nerve (which part of the nerve?)
on the nerve membrane
how do local anesthetics work (which ion channel?)?
LA binds to specific receptors on the Na+ channel to prevent channel from opening (therefore no action potential and no pain for the patient)
“specific receptor theory”
What is the speed of conduction for a myelinated nerve?
120 m/sec
What is the speed of conduction for an unmyelinated nerve?
1.2 m/sec
Where do local anesthesia work on a myelinated nerve?
at the Nodes of Ranvier (abundance of sodium channels located here)
How do local anesthesias work on the nodes of ranvier?
need to have 2-3 nodes (8-10mm) of the nerve blocked
According to the specific receptor theory, where does local anesthesia bind to?
Specific receptor on the Na channel
What is the order of onset for local anesthetic agents?
Cocaine > Articaine > Mepivacaine > Lidocaine > Prilocaine > Bupivacaine > Procaine
What is the duration order of local anesthetics?
Bupivacaine > Mepivacaine > Lidocaine = Prilocaine > Cocaine > Articaine
What is the onset, duration time, and mg/kg of maximum dose for lidocaine?
2-3 min (rapid)
1.6 hours
4.4 mg/kg (300mg)
What is the onset, duration time, and mg/kg of maximum dose for prilocaine?
2-4 min
1.6 hours
6mg/kg (400mg)
What is the onset, duration time, and mg/kg of maximum dose for mepivicaine?
1.5-2min (rapid!!!)
1.9 hours
4.4mg/kg (300mg)
What is the onset, duration time, and mg/kg of maximum dose for bupivicaine?
6-10 min (very slow onset)
2.7 hours (longest duration)
1.3mg/kg (90mg)
What is the onset, duration time, and mg/kg of maximum dose for articaine?
1-2 min (rapid, 2nd fastest)
0.5 hours (shortest duration)
7mg/kg (500mg)
What is the onset and duration time for cocaine?
1 min (fastest onset)
1-1.5 hours
What is the onset for procaine?
6-10 min (slowest)
What pH determines the ease for nerve blockade?
extracellular pH
What tissue is more difficult to get adequate anesthesia? why?
Inflamed or infected tissue because lower pH or increased H+
What increases the shelf life for LA?
Low pH -> 5.5-7
How does pH affect LA?
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
Is local anesthesia hydrophilic or hydrophobic?
Amphipathic (both hydrophilic and lipophilic)
What is the exception of LA being amphipathic?
Benzocaine, which doesn’t have a hydrophilic group–making it great for
topical anesthesia
How do organic components of local anesthetic change from charged form to non-charged form? (in ninja terms)
The ninja has on his backpack (H+) and is injected, he ditches his backpack and become a free base to cross the nerve axon membrane, then gets his backpack back to be able to complete the mission (bind to the sodium channel)
Only the free base form (“ninja”) of the anesthetic can enter the nerve, the sodium channel must be blocked from the inside
Process of anesthesia changing from cation to anion (NOT in ninja terms)
- 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 its ionized version again and bind to the specific receptor to prevent Na channel from opening
What happens once free bases diffuse?
they must dissociate back to cationic form in order to bind to the receptor
How does pKa affect local anesthetic?
lower pKa = faster onset
higher pKa = slower onset (because fewer free base molecules are available to diffuse)
How does lipid solubility influence local anesthesia?
Lipid solubility influences potency
What happens to the drug with increased lipid solubility?
The drug is more potent
(directly related because nerve membrane is 90% lipid)
What happens with decreased lipid solubility?
The drug is less potent
(directly related because nerve membrane is 90% lipid)
What does protein binding influence?
Protein binding influences duration
What happens to the drug with increased protein binding?
the drug has longer duration
(directly related because nerve membrane is 10% protein)
What happens to the drug with decreased protein binding?
the drug has shorter duration
(directly related because nerve membrane is 10% protein)
What is the most used vasoconstrictor?
Epinephrine
Which is the most profound vasoconstrictor?
Cocaine (also ropivicaine)
Which is the most profound vasodilator?
Procaine
Mnemonic for how to tell the difference between an ester and an amide?
“i” before the “-caine” if an amide
What is the effect of esters in aqueous solutions?
Readily hydrolyzed
What are examples of esters?
Procaine
Propoxycaine
Tetracaine
Cocaine
Benzocaine
Dyclonine
What is the effect of amides in aqueous solutions?
resist hydrolysis; get excreted in urine as an unchanged form
What are examples of amides?
Lidocaine
Etidocaine
Mepivocaine
Bupivocaine
Prilocaine
Articaine
How are esters metabolized in the body?
Hydrolyzed in the plasma by pseudocholinesterase into paraaminobenzoic acid (PABA)
What do people have a reaction to in an ester local anesthetic?
PABA
Where are amides metabolized in the body?
Primary biotransformation process site is the liver
What is the relationship between cirrhosis patient and metabolism of local anesthetics?
A liver with cirrhosis becomes flooded with blood after anesthetic delivery
What is cirrhosis?
Late stage of scarring (fibrosis) of the liver
LA with cirrhosis is a contraindication for what patients?
ASA IV to V for patients with liver dysfunction (or heart failure)
How do cirrhosis and/or CHF interfere with the amount of your local anesthesia injection?
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
Does this disease state increase the availability of this drug or decrease the availability?
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
Which organ in the body has the greatest concentration of local anesthesia?
Skeletal muscle
What is tachyphylaxis?
The increase in tolerance to drug after repeated administration
What is elimination half life?
time needed for 50% of the drug to be reduced in blood level
How do you calculate the elimination of half life?
1st half-life: 50% eliminated
2nd half-life: there is 50% of the drug left…half of 50 is 25. Add 25 to the previous 50 you have eliminated 75%
3rd half-life: you have eliminated 75%, there is 25% left, 25/2= 12.5 add that to 75=87.5% eliminated
4th half-life: 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
Do all local anesthesia readily cross the BBB and placenta?
Yes
What happens initially when a patient has overdose/toxicity to local anesthesia?
causes excitatory response (numbness of tongue and circumoral region slurred speech, shivering, AV disturbances, tremor, etc.)
- if you ignore initial signs, patient can go into a seizure
- if you keep loading them up with more local anesthesia, they will stop breathing
What happens eventually when a patient has overdose/toxicity to local anesthesia?
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.)
What LA’s are catecholamines?
epinephrine, norepinephrine, dopamine
What LA’s are non-catecholamines?
amphetamine, ephedrine, methamphetamine
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
How do you calculate mg/ml of solution?
Just divide. Here would be 1000mg/300,000ml = 0.0033 mg/ml of solution
How to know which dilution formulation is more concentrated when comparing two values?
ex: 1:100,000 and 1:200,000
The lower the second number (ml of solution), the higher the concentration (i.e. 1:100,000 is more concentrated than 1:200,000)
What’s the maximum fose for epinephrine in a healthy patient?
0.2 mg (200 mcg)
What is the maximum dose of epinephrine in a not so healthy patient (cardio patient)?
0.04 mg (40 mcg)
Which agent (catecholamine) lacks significant B2 actions thus produces intense peripheral vasoconstriction with possible dramatic elevation of blood pressure?
Norepinephrine – EXCESSIVE vasoconstriction
- is associated with a side effect ratio 9X higher than that of epinephrine? That’s one of the big reasons why this agent is NOT available in the U.S.
* Levonordefrin closely resembles norepinephrine
What are contraindications for vasoconstrictors?
“memorize them”
- High blood pressure (200mmHg systolic OR 115mmHg diastolic)
- Uncontrolled hyperthyroidism
- Severe cardiovascular disease
- Undergoing general anesthesia WITH halogenated agents
- Other drugs: Patient receiving non-specific beta-blocker, MAOi, tricyclic antidepressants
What are indications of severe cardiovascular disease in which you would not administer a vasoconstrictor?
a) Less than 6 months after myocardial infarction
b) Less than 6 months after cerebrovascular accident
c) Daily episodes of angina pectoris or unstable angina
d) Cardiac dysrhythmias despite appropriate therapy
e) Post-coronary artery bypass surgery (CABG), less than 6 months
4) Undergoing general anesthesia with halogenated agents
What patients are NOT normally considered candidates for elective or emergency dental treatment in the office?
Patients in categories 1 to 3a through 3d are classified as ASA 4 risks