Pharmacology - Local Anesthetics (Exam 3) Flashcards
1
Q
Agents used to block pain sensation; absence or loss of sensation in a circumscribed area of the body
A
Local anesthetics
2
Q
Local anesthetics depress _________ of nerve potentials and inhibit ___________ process in peripheral nerves
A
excitation; conduction
3
Q
T/F local anesthetics can act on any part of the nervous system and on every type of nerve fibers by reversibly blocking the action potentials responsible for nerve conduction
A
True
4
Q
Aqueous solutions, sprays, ointments, or gels for topical penetration
A
Topical anesthesia
5
Q
Inject through skin using an electrical current
A
Inotophoresis
6
Q
Inject directly into the area being anesthetized
A
Infiltration anesthesia
7
Q
Inject closer to a larger terminal nerve branch; subcutaneous or submucosal
A
Field block anesthesia
8
Q
Inject close to nerve trunk, but proximal to intended area of anesthesia
A
Nerve block anesthesia
9
Q
Mechanism of action of local anesthetics
A
Reversible block of peripheral nerve conduction by inhibiting movement of nerve impulse
10
Q
What 4 things can local anesthetic act on?
A
Fibers
Sensory endings
Myoneural junctions
Synapses
11
Q
What prevents the local current from flowing across the membrane?
A
Myelin sheath
12
Q
What does the current travel down?
A
Nodes of Ranvier
13
Q
What has a high concentration of ion channels?
A
Nodes of Ranvier
14
Q
What term describes an action potential jumping along the nerve fiber?
A
Saltatory conduction
15
Q
Depolarization
A
Voltage gated Na+ channel opens
(- outside, + inside)
15
Q
Resting potential
A
Na+/K+ pump
(+ outside, - inside)
16
Q
Repolarization
A
Voltage gated K+ channel opens
(+ outside, - inside)
17
Q
What 2 things allow peripheral nerve conduction to occur?
A
- Concentration of electrolytes in ECF and axoplasm
- Selective permeability of membrane to Na+ and K+ channels
18
Q
What do local anesthetics bind to in order to block the generation/conduction of action potentials?
A
Voltage gated Na+ channels
19
Q
What region does local anesthetic bind to? Where is this located?
A
Inactivation region, located between alpha subunits III and IV
20
Q
What are the properties of local anesthetic? (8 things)
A
- Compatible w/ tissue
- Reversible
- Absence of local and systemic rxns
- Absence of allergic rxns
- Potent (high solubility)
- Rapid onset
- Effective in low doses far below toxic level
- Sufficient duration of action for procedure
21
Q
What are the 2 types of local anesthetics?
A
Esters
Amides
22
Q
First group of LA, commonly used topically
A
Esters
23
Q
What are ester LAs metabolized to?
A
Para-amino benzoic acid (PABA)
24
What has the highest association of allergic reactions to LA?
Para-amino benzoic acid (PABA)
25
What are ester LAs metabolized in the tissue by?
Pseudocholinesterase
26
Allergic reactions are extremely rare in which type of LA?
Amides
27
Where are amide LAs metabolized and eliminated?
Metabolized: in liver
Eliminated: through kidneys
28
Which LA has better lipid solubility, potency, duration of action, and ionization constant?
Amides
29
What do amide LAs bind to?
Plasma proteins
RBCs
30
Where are amide LAs distributed to?
All tissue types
31
Which 2 factors affect LA properties?
Lipophilicity
Hydrophilicity
32
The aromatic residue is _________
lipophilic
33
The amino terminus is _________
hydrophilic
34
Which factor is essential for the drug to permeate the nerve sheath and nerve membrane?
Lipophilicity
35
_________ drugs gain access by crossing hydrophobic route (lipid bilayer/hydrophobic domains of Na+ channels)
Lipophilic
36
Which factor allows drugs to be dissolved in aqueous solutions and prevents the drug from precipitating in interstitial fluids?
Hydrophilicity
37
__________ drugs can access site of action via the aqueous route within Na+ channels?
Hydrophilic
38
What is the pH of the lipophilic region of LA?
7.4 - alkaline
39
What is the pH of the hydrophilic region of LA?
4.5-6 - acidic
40
Which region is uncharged and non-ionized?
Lipophilic
41
Which region is a free-base?
Lipophilic
42
Which region is unstable?
Lipophilic
43
Which region is a charged cation?
Hydrophilic
44
Which region is stable?
Hydrophilic
45
LA agents in solution are ______ _______ in equilibrium between the nonionized (free base) and ionized (protonated) forms
weak bases
46
What is the proportion of drug in each form (nonionized/ionized) dictated by?
pKa and pH
47
Acid dissociation or equilibrium constant for the reaction
Ka
48
pH at which non-ionized and ionized forms of LA are =
pKa
49
What can the pKa of LA be affected by?
pH of tissue
50
Inflamed tissue tends to be more ________ (basic/acidic), which can ionize the LA and prevent __________ into the nerve
acidic; absorption
51
What term defines site of injection and uptake of LA?
Absorption
52
What 6 things are involved with absorption?
Route
Dose
Potency
Hydrophilic vs lipophilic
pH
Reduce systemic absorption and toxicity
53
System absorption is ________, especially with _________
greater; inflammation
54
What does the addition of vasoconstrictors to LA cause? (3 things)
1. Decreased systemic absorption and risk of toxicity
2. Increased duration of action and depth of anesthesia
3. Decreased bleeding
55
What do you have to watch out for when using LA with a vasoconstrictor?
Cardiovascular effects in patients with uncontrolled cardiac history
56
What are 2 examples of vasoconstrictors used with LA?
Epinephrine
Levonordefrin
57
What does the selection of a vasoconstrictor depend on? (3 things)
1. Length of procedure
2. Requirement for post-op pain control
3. Medical status of pt
58
What are the typical ratios of epinephrine in LA in dentistry?
1:50,000
1:100,000
1:200,000
59
What term defines lipid solubility and protein binding?
Distribution
60
Highly vascular organs receive ________ concentration of anesthetics
higher
61
What dictates the potency of LA?
Lipid solubility (free base)
62
What is the duration of action of LA strongly dependent on?
Protein binding
63
What term is defined by metabolism and excretion?
Elimination
64
How are ester LAs metabolized?
Plasma pseudocholinesterase
Liver esterase
65
How are amide LAs metabolized?
Hepatic metabolism
66
Which drug has:
pKa: 8.9
Onset: 2-5 mins (moderate)
T1/2: 40 seconds
Duration: 60 mins (short)
Metabolism: plasma esterases
Adverse rxns: allergy
Low potency, not used in dentistry today
Procaine (Novocaine)
67
Which drug has:
pKa: 2.78
Onset: <1 min
T1/2: 162-210 mins
Duration: 5-10 mins
Formulations: 20% conc, gel, topical
Adverse rxn: methemoglobinemia, contraindicated in children under 2
Poor water solubility
Benzocaine (Orajel)
68
Which drug has:
pKa: 8.4
Onset: 5-10 mins (moderate)
T1/2: 5.2 hrs
Duration: 2-3 hrs
Formulations: nasal spray
Adverse rxns: contact dermatitis, burning, stinging, angioderma
High potency
Tetracaine
69
Which drug has:
pKa: 7.8
Dose: w/ and w/o epi
Onset: 2-3 mins (fast)
T1/2: 80-96 mins
Duration: alone: 40-100 mins; w/ epi: 170-190 mins
Formulations: injections, ointment, spray
Adverse rxns: sedation, hypotension, headache, shivering
Moderate potency
Infiltration, block, and surface anesthesia
Lidocaine
70
Which drug has:
pKa: 7.7
Dose: 6.6mg/kg
Onset: 1.5-2 mins (fast)
T1/2: 114 mins
Duration: alone: 30-160 mins; w/ levonordefrin: 60-190 mins (moderate)
Formulations: plain or w/ levonordefrin
Adverse rxns: dizziness, tremors, blurred vision
Moderate potency
Not topical
Infiltration or block anesthesia
Mepivacaine
71
When is Mepivacaine plain used?
When avoiding vasoconstrictors
72
Which drug has:
pKa: 7.7
Dose: 8 mg/kg
Onset: 2-4 mins (fast)
T1/2: 93-96 mins
Duration: alone: 30-170 mins; w/ epi: 90-205 mins (moderate)
Formulations: w/ or w/o epi
Adverse rxns: paresthesia; methemoglobinemia
Moderate potency
Prilocaine
73
Which drug has:
pKa: 8.1
Dose: 2 mg/kg
Onset: 6-10 mins (moderate)
T1/2: 162-210 mins
Duration: 340-440 mins (long)
Formulations: w/ epi
Adverse rxns: increased risk of post-op injury; higher cardiovascular toxicity
High potency (higher affinity for Na+ channels)
Helps with pain post-op (bc of prolonged duration)
Bupivacaine
74
Which drug has:
pKa: 8.1
Dose: 7.5-15 mg
Onset: 3-15 mins (moderate)
T1/2: 3-7 hrs
Duration: 0.5-8 hrs (long)
Formulations: 0.5% or 0.75%
Adverse rxns: hypotension, nausea, vomiting, bradycardia
High potency
Not available as dental cartridge
Ropivacaine
75
Which drug has:
pKa: 7.8
Dose: toxic dose 7mg/kg
Onset: 2-3 mins (fast)
T1/2: 30-146 mins (majority metabolized in blood)
Duration: 180-230 mins (moderate)
Formulations: w/ epi
Adverse rxns: paresthesia; methemoglobinemia
Moderate potency
Articaine
76
Which drug has:
pKa: 9
Onset: 2-10 mins (moderate)
Duration: 30-60 mins
Formulations: topical
Adverse rxns: CVS and CNS similar to those of other local anesthetics
Slight irritation and sting when applied
No cross-reactivity with other LAs
Dyclonine
77
Reaction due to insertion of the needle
Psychogenic rxn
78
What are the psychogenic reactions?
1. vasovagal
2. hyperventilation
3. anaphylactoid rxn
79
What reactions are involved with vasovagal?
Syncope
Fainting
Bradycardia
Hypotension
80
Name the things involved with idiosyncratic reactions (6 things)
Toxic rxn at small dose
Anxiety induced
Associated w/ vasoconstrictor
Accidental IV injection
Sulfite in vasoconstrictor containing solutions
Ingested, inhaled, and spray formulations in pts with asthma
81
T/F allergic rxns to LA are rare
True
82
What happens when someone is having an allergic rxn to LA?
Rash to anaphylactic shock
83
T/F there is no confirmed allergic rxns in the amide group of LAs
True
84
T/F there most common allergic rxns are in the ester group of LAs due to production of PABA
True
85
What is LA toxicity directly related to?
Rate of LA absorption and elimination
86
What can cause LA toxicity?
Administration of too much LA
Administration to sensitive individuals
Administration in a blood vessel
Drug interactions
87
What are the 2 main systems affected by LA?
CNS
CVS (cardiovascular system)
88
What is the most common form of LA toxicity?
CNS toxicity
89
What are the symptoms of CNS toxicity?
Sedation
Lightheaded
Slurred speech
Drowsiness
Euphoria/dysphoria
Diplopia
Sensory disturbances
Muscle twitching/seizures
90
What are the symptoms of CVS toxicity?
Tachycardia
Hypertension
91
T/F the typical dental dose is enough to cause myocardial depression and cardiac arrest
FALSE, the typical dose is NOT enough to cause this
92
What are the symptoms of Methemoglobinemia?
Shortness of breath
Cyanosis (blue skin)
Mental status changes
Headache
Fatigue
Dizziness
Seizures
Coma, death
93
How is Methemoglobinemia reversed?
Reversed by IV methylene blue
94
How can you prevent LA toxicity?
1. Give lowest possible dose
2. Use proper injection techniques (always aspirate)
3. Use a vasoconstrictor if not contraindicated
95
What reverses LA?
Phentolamine
96
Phentolamine ________ duration of action of LA containing a vasoconstrictor
shortens
97
What is the mechanism of action of Phentolamine?
Blocks alpha-adrenergic receptors of vascular smooth muscle
Causes vasodilation
98
What can cause LA failure?
Inflamed tissue
Incorrect needle
Starting procedure prior to max. LA effect
99
What are the characteristics of inflamed tissue?
Lower pH
Increased blood flow
Alteration in Na+ channel #
