Pain and Anxiety Week 2 Flashcards
New FDA law requires LA carpule labeling to say?
1.7 mL
(each carpule contains 1.8 mL but law requires labeling to say 1.7 mL if manufacturer cannot guarantee all carps contain exactly 1.8 mL)
Which LA is no longer available in the US?
2% Lidocaine Plain
LAs are manufactured in _________ ________ cartridges/carpules
single use
What are the 4 possible % solutions LAs can be produced as?
0.5%
2%
3%
4%
What 5 things can be included in LA carpules?
LA drug
Sodium hydroxide (buffering agent)
Sodium chloride (buffering agent)
Vasoconstrictor (epi or levonordefrin)
Vasoconstrictor preservative (sodium bisulfite)
Name 2 buffering agents that can be in the carpule
sodium hydroxide and sodium chloride
The vasoconstrictor present in the carpule
epi or levonordefrin
This vasoconstrictor preservative helps decrease the solution pH (more acidic) to delay the onset of the LA
Sodium bisulfite
If a pt reported that they had an allergic rxn to a LA before 1984, then what were they probably allergic to?
Parabens
Prior to 1984, LA solutions without epi added _________________ as a preservative, which increased ________ _______, so it is no longer added to LAs
methylparaben; allergic rxns
What are the 2 ways LAs cause reversible local anesthesia?
preventing generation and conduction of impulses
LAs provide a ________ _______ between source of impulse and brain (impulse never reaches the brain)
chemical block
LAs are known as “___________ ___________ drugs,” meaning they decrease the rate of depolarization
membrane-stabilizing
What do LAs inhibit the influx of during depolarization?
Na+
LAs bind to Na+ channels inside/outside the cell
LAs bind to Na+ channels INSIDE the cell
What do LAs provide to allow easier binding to Na+ channels that are firing (NOT resting)?
State-dependent blockade
Small diameter nerves are……
More sensitive to LAs
Large diameter nerves require…..
More volume of LAs
Name the 5 actions of LAs
- Diffuse through neuron cell membrane
- Bind Na+ channels (inside cell membrane)
- Prevent Na+ channels from opening
- Prevents conduction of nerve impulse
- Prevents neuron from reaching firing potential
2 major routes of LA delivery
- Topical (applied on mucosa, higher concentration needed to penetrate mucosa, higher toxicity)
- Submucosal injection (more effective, less concentrations needed)
2 groups of LAs
Esters
Amides
Esters are metabolized in the ______ via _____________ while amides are metabolized in the _________
blood (plasma); psuedocholinesterase; liver
ALL injectables LAs are…
Amides
Topical LAs can be…
Esters or amides
Which group of LA has the most allergic reactions?
Esters
Amides have a low _______________ with esters
cross-hypersensitivity
Describe the chemical structure of LAs
1) lipophilic aromatic ring
2) intermediate linkage
3) hydrophilic terminal amine
Characteristics of the lipophilic aromatic ring of LA
Base = inactive form
Determines potency
Penetrates membrane, but CANNOT bind receptors unless it picks up H+
What does the intermediate linkage of LA determine?
If the LA is ester or amide
Characteristics of the hydrophilic terminal amine of LA
Dissociates becoming tertiary amine -> enters nerve -> gains H+ -> ionized -> binds to receptor sites -> ACTIVE form
CANNOT enter neurons until it loses H+, must pick it up again inside
Once the LA has gained a ________ ion, it’s now in it’s ___________ form
H+; active
Cation form of LA
Active
Only binds to sites within nerve
Anionic form of LA
Inactive
Does NOT bind to receptor sites
Physiological effects of drug on the body
Pharmacodynamics
L.A. molecules in the cartridge include anions and cations. How do they differ with their onset?
More anions: low pKa, more base, fast diffusion, rapid onset
More cations: high pKa, less base, slow diffusion, slow onset
All LAs are __________ solutions before injection, meaning there are more __________ than ________ in the cartridge
acidic; cations; anions
Higher pKa means what?
Less base
Slower onset of action
Lower pKa means what?
More base
Rapid onset of action
Infected tissues are __________
acidic
What happens when you inject LA into infected, acidic tissue?
Less molecules cross the membrane = INADEQUATE ANESTHESIA
What happens to the H+ in infected, acidic tissue?
RNH+ molecules cannot dissociate H+, so the active form CANNOT enter the cell membrane
What does RNH+ refer to?
Cation (acid) = ACTIVE form that CANNOT cross membrane
What does RN refer to?
Anion (base) = INACTIVE, lipid soluble form that CAN cross the membrane
L.A. must penetrate _______mm of myelinated nerve length (3-4 nodes of Ranvier) to block a nerve impulse
8-10mm
↑___________ of L.A. is required for large nerves (inferior alveolar n.)
volume
Increased concentration of LA means…
Increased diffusion through membrane
Rapid onset
Low pKa of LA means…
Increased RN molecules (anions)
Increased base
Rapid onset
High lipid solubility of LA means…
Increased potency
Decreased dose needed (enhances diffusion of drug through nerve)
Increased protein binding of molecules in LA means…
Increased duration
(binds more strongly to receptor, prolonging anesthetic presence at site of action)
Increased vasodilation of LA means…
Decreased potency + Decreased duration
Must increase dose!
(vasodilation = increased blood flow = increased removal of LA molecules from site)
Describe the onset if there is a high concentration of the LA and it has a low pKa
Rapid onset
What happens to the dosage if the lipid solubility decreases?
Increase the dose
(to enhance diffusion of drug through the nerve)
What happens to the duration of the LA if there is increased protein binding?
Increased duration
T/F: LAs are vasodilators
True
Period from LA deposit to blocked impulse conduction
Onset of action
What is the primary factor for determining the onset of action of a LA?
pKa!!
low pKa = rapid onset
high pKa = slow onset
What does pKa determine the amount of?
Ionized molecules in solution
What is the secondary factor for determining the onset of action of a LA?
Site!!
small diameter nerves = rapid onset
Diffusion of molecules across membrane
Induction of LAs
What is the primary factor for determining the induction of a LA?
Initial concentration of LA
inc conc = inc diffusion = rapid onset
dec conc = dec diffusion = slow onset
Name some areas in the body where the anesthetic loses concentration from
Tissue fluid
Capillaries
Lymphatics
Anatomic barriers (bone)
Reversal of LA action
Recovery from LA block
What is the primary factor for determining the duration of action and speed of nerve recovery?
Degree of protein binding
(different for each LA, depends on chemicals)
T/F: Recovery is a slower process than induction
True
If you try to reinject LA and the nerve fibers are only partially recovered (pt still numb), what volume of LA is effective and what is the speed of onset of action?
Small volume is effective
Rapid onset of action
If you try to reinject LA and the nerve fibers are fully recovered (no numbness), what can occur?
Tachyphylaxis = tolerance to LA = LA is ineffective!
Potency
Duration of LA
What are the 3 factors that affect the duration/potency of LA?
Protein binding
Vascularity of injection site
Vasoconstrictor in LA
Stronger protein binding means _________ duration and __________ potency
increased; increased
Increased vascularity of injection site means ___________ duration and ___________ potency
decreased; decreased
Presence of a vasoconstrictor in the LA means ___________ blood flow, ___________ duration, and ___________ potency
decreased; increased; increased
After absorption, where are LAs distributed?
Throughout body
Which organs have higher concentrations of LA?
Highly vascular organs
Name 5 examples of highly vascular organs that will have higher concentrations of LA
Brain
Heart
Lungs
Liver
Kidneys
What is toxicity directly related to?
Amount of LA accumulated in tissues
Increased absorption means there is an __________ risk of systemic ___________
increased; toxicity
Increased dose means there is ____________ absorption. All molecules diffused out of _______ channels into ____________
increased; Na+; bloodstream
Increased concentration means there is ____________ absorption
increased
Which route of administration will allow for increased absorption?
Topical
An intravascular injection will cause __________ absorption
increased
Increased vasoconstrictor in the LA will cause ____________ absorption
decreased
T/F: The presence of a vasoconstrictor increases absorption.
FALSE
it decreases bc you’re constricting the blood vessel so less flows into bloodstream
All LAs are _______________
vasodilators!
Biotransformation refers to the ____________ of a drug
metabolism
How is biotransformation measured?
In half-life (time for 50% of drug to be removed)
Increased half life means ___________ risk for systemic toxicity
increased
(the drug is lingering around in tissue for much longer)
Name 3 ester LAs
- Procaine
- Tetracaine
- Benzocaine
What is the route of administration for ester LAs?
Topical
What is the route of administration for amide LAs?
Injectable and topical
Which amide LAs are metabolized in the liver only, and therefore have an increased toxicity in liver disease?
Lidocaine
Mepivacaine
Bupivacaine
Which amide LA is metabolized in the liver AND lungs?
Prilocaine
Which amide LA is metabolized in plasma (90%) and liver (10%)?
Articaine
Which amide LA has the SHORTEST half life?
Articaine
What is the primary excretory organ for all LAs?
Kidneys
Where are a small amount of ester LAs excreted?
Unchanged in urine
Where are a greater % of amide LAs excreted?
Unchanged in urine
(small amount, even tho more than esters)
Why is there an increased risk of systemic toxicity of LAs in patients with severe renal disease?
Due to build up of drug when not cleared by kidneys
Although small amounts of both esters and amides L.A.s are excreted unchanged in urine, which is excreted in a greater percent this way?
Amides
At what point can LAs affect the CNS and CV system?
After they are absorbed into blood (before metabolized)
(↑blood levels = ↑toxicity)
Toxicity and adverse reactions of LAs are directly related to what? (9)
1) Nature of specific L.A. (vasodilation)
2) Concentration of drug
3) Route of administration
4) Dose administered
5) Rate of injection
6) Vascularity of site
7) Age of patient
8) Weight of patient
9) Health of patient
Order of selection of LAs (5)
1) duration of pain control needed
2) need for post op pain control
3) patient’s health assessment and current meds
4) allergic to the LA or sodium bisulfite
5) need for hemostasis
What is the highest concentration of epinephrine?
1:50,000
What is the lowest concentration of epinephrine?
1:200,000
If a pt is allergic to wine, dried fruit, or dried potatoes, then we assume they have a ___________ allergy
bisulfite
T/F: Most LAs are short-acting.
FALSE!
Most are intermediate-acting (60 mins of pulpal anesthesia)
Which LA is most commonly used in dentistry for nerve blocks?
Lidocaine
Which LA is good for hemostasis if 1:50,000 epi?
Lidocaine
Which LA is NOT available in US without epi?
Lidocaine
What is the duration of Lidocaine?
60 mins
Lidocaine brand name?
Xylocaine
Which LA is an effective topical and is the only amide topical?
Lidocaine
What is the onset of action of Lidocaine?
2-3 mins
Where is Lidocaine metabolized? What is the 1/2 life?
Liver (half life = 1.6 hrs)
What is the pregnancy category for Lidocaine?
pregnancy = category B; lactation safe
Which LA is a good choice if vasoconstrictor is contraindicated?
Mepivacaine
Which LA is NOT used for hemostasis since there is no epi?
Mepivacaine
Which LA is a WEAK vasodilator? (2)
Mepivacaine
Prilocaine
What is the duration of Mepivacaine (without epi and with levo)?
Duration w/o epi = 20-40 mins
Duration w/ levo = 60 mins
What is the onset of action of Mepivacaine?
1.5-2 mins
Where is Mepivacaine metabolized? What is the 1/2 life?
Liver (half life = 1.9 hrs)
What is the pregnancy category for Mepivcaine?
pregnancy = category C; lactation safe
Mepivacaine brand name?
Carbocaine
Which LA is the LEAST toxic in dentistry?
Prilocaine
Which LA is the BEST choice for pregnancy + CV pts?
Prilocaine
Which LA has a risk of methemoglobinemia?
Prilocaine
What patients should you be worried about for methemoglobinemia risk with Prilocaine?
COPD patients
Which LA has no anticonvulsant properties? (2)
Prilocaine
Articaine
Which LA is an effective topical when combined w/ lido?
Prilocaine
What is the duration of Prilocaine (with and without epi)?
Duration w/o epi = 40-60 mins
Duration w/ epi = 60-90 mins
What is the onset of action of Prilocaine?
2 mins
Where is Prilocaine metabolized? What is the 1/2 life?
Lungs + small amount in liver (half life = 1.6 hrs)
What is the pregnancy category for Prilocaine?
pregnancy = category B; lactation unknown safety
Prilocaine brand name?
Citnest
Which LA has a risk for IA nerve injury?
Articaine
Which LA is highly lipid soluble and has high diffusion thru bone?
Articaine
What is the pregnancy category for Articaine?
pregnancy = category C; lactation unknown safety
What is the duration of Articaine (with 1:100,000 epi and 1:200,000 epi?
Duration with 1:100,000 epi = 60-75 mins
Duration with 1:200,000 epi = 45-60 mins
What is the onset of action of Articaine?
1-3 mins
Where is Articaine metabolized? What is the 1/2 life?
Plasma (90%) + liver (half life = 45 mins)
Which LA is NOT an effective topical? (2)
Articaine
Bupivacaine
Which LA is highly lipid soluble and has high diffusion thru bone?
Articaine
Which LA is a good choice in CV + liver disease pts?
Articaine
Articaine brand name?
Septocaine
Which LA is MOST potent and toxic?
Bupivacaine
Which LA is the MOST potent vasodilator?
Bupivacaine
Which LA is good for long treatment?
Bupivcaine
Which LA has a HIGH toxicity risk?
Bupivcaine
T/F: You MUST give Bupivacaine with a vasoconstrictor (not available w/o epi)
True
What is the duration of Bupivacaine?
1.5-3 hours
What is the onset of action for Bupivacaine?
5-10 mins
Where is Bupivacaine metabolized? What is the 1/2 life?
Liver (half life = 2.7 hrs)
What is the pregnancy category for Bupivacaine?
pregnancy = category C; lactation unknown safety
Bupivacaine brand name?
Marcaine
The CNS is very sensitive to high levels of LA because they?
Readily cross BBB
Has this pt suffered from a moderate or high overdose of LAs?
Presents with:
increased HR, RR, BP, and also has muscle twitching with tremors
Moderate
Has this pt suffered from a moderate or high overdose of LAs?
Presents with:
decreased HR, RR, BP, they’re convulsing and experiencing unconsciousness
High!
They are progressing to respiratory arrest due to CNS depression
Has this pt suffered from a moderate or high overdose of LAs?
Presents with:
increased HR, RR, BP, headache and feeling lethargic
Moderate!
They have initial cardiovascular stimulation
Has this pt suffered from a moderate or high overdose of LAs?
Presents with:
decreased HR, RR, BP, slurred speech, disoriented
High!
Progressing to cardiac arrest and cardiac depression
2 vasoconstrictors used in US
Epinephrine
Levonordefrin
4 functions of vasoconstrictors
1) constrict blood vessels @ site
2) increase duration of LA (6x longer)
3) provides hemostasis at injection site
4) decrease absorption rate of LA (and risk of toxicity)
Which vasoconstrictor affects alpha and beta receptors equally?
Epi
T/F: Levonordefrin affects the alpha receptors more.
True! 75% is alpha and 25% is beta
MRD for epi (healthy pt and CV disease)
Healthy MRD = 0.2 mg
CV disease = 0.04 mg
MRD for levonordefrin (healthy pt and CV disease)
Healthy MRD = 1.0 mg
CV disease = 0.2 mg
An overdose usually occurs via which route?
Intravascular injection
How fast due overdose symptoms appear? How long does it take for the body to clear the drug?
Symptoms appear within 60 seconds
Body clears within 5-10 mins
Symptoms of an overdose (6)
1) dysrhytmias
2) increased HR + BP
3) headache
4) hyperventilation
5) tremors
6) anxiety
What does an overdose lead to in patients with CV disease?
Cardiac arrest
Absolute contraindication for LA
Allergy
Relative contraindications of LA (6)
1) H2 receptor blocker
2) Beta blocker
3) CNS depressants
4) Pregnancy
5) Significant liver disease
6) Renal dysfunction
H2 receptor blockers decrease liver metabolism. What do you do when a pt is taking a H2 receptor blocker?
Decrease dosage of lidocaine
Beta blockers decrease amide metabolism. What do you do when a pt is taking a beta blocker?
Decrease dosage of all amides
CNS depressants can decrease metabolism. What do you do when a pt is taking a CNS depressant?
Decrease dosage of all amides
What do you do if your pt is pregnant?
Use prilocaine or lidocaine
Significant liver disease decreases amide metabolism. What do you do if your pt has significant liver disease?
Use articaine and/or decrease dosage of all amides
Renal dysfunction decreases excretion. What do you do if your pt has renal dysfunction?
Use LAs with caution
Absolute contraindications for vasocontrictors (5)
MI/coronary bypass surgery within 3-6 months
Uncontrolled hypertension, angina, arrythmias, hyperthyroidism
Sulfite allergy
Glaucoma
Cocaine/methamphetamine use
(basically anything heart related)
Relative contraindications of vasoconstrictors (4)
CVD pts
Tricyclic antidepressants
Nonselective beta blockers
Digitalis
What is cardiac protocol?
0.04 mg epi
0.2 mg levo
What do you do if your pt has CV disease?
Cardiac protocol
What do you do if your pt is taking tricyclic anti-depressants?
No levo
0.04 mg epi
What do you do if your pt is taking a nonselective beta blocker?
Cardiac protocol
What do you do if your pt is taking digitalis?
Consult physician
MRD stands for
Max recommended dose
What is MRD adjusted to accommodate?
Pts medical status
We use the lowest effective dose for…
Elderly
Children
Medically compromised
MRD is based on…
Maximum dose per appointment
Body weight
MRD is calculated as…
mg/lb or mg/kg
MRD and AMD of Lidocaine
MRD: 3.2 mg/lb
AMD: 500 mg
MRD and AMD of Mepivacaine
MRD: 3.0 mg/lb
AMD: 400 mg
MRD and AMD of Prilocaine
MRD: 4.0 mg/lb
AMD: 600 mg
MRD and AMD of Articaine
MRD: 3.2 mg/lb
AMD: none
MRD and AMD of Bupivacaine
MRD: none
AMD: 90 mg
How many mg of epi per carpule?
0.018 mg
In healthy pts, the ______________ is the limiting drug, but in cardiac pts the _______________ is the limiting drug
LA; vasoconstrictor
