Local Anesthetic Flashcards
What do afferent nociceptors and what fibers do they include?
- Thermal, intense mechanical, chemical stimulation
2. A-delta and C fibers
How do local anesthetics work?
Block voltage gated sodium channels on nerve membranes
- Inhibit generation of AP
- Inhibit conductance of AP
Where do LA’s bind to sodium channels?
on the INTRACELLULAR side of the sodium channel
What types of LAs reach their sites of action more readily?
Lipid Soluble (uncharged) Form Weak Bases
What is a weak base?
Neutral compound that can form into a cation by combining w/ a proton
H+ + B –> HB+
pKa range of LAs?
7.5 - 9.5
Are LAs more effective at low or high pH
High (more basic)
How do lower pKa LAs compare to Higher pKa LAs?
- Lower - closer to physiological pH, more drug is unprotenated/neutral, more drug penetrates the cellular membrane, FASTER ACTING
- Higher - further form physiological pH, less drug unprotonated, less drug penetrating cell membrane, SLOWER ACTING
How does pH at the site of action effect the LA?
If pH is lower, the LA will be less effective
1. Inflammation/infection = lower pH, reduced effectiveness of LA
What are the different types of nerve blocks?
- Fiber diamter/myelination
- Firing Frequency
- Position of fiber in nerve bundle
How does fiber diameter/myelination effect nerve block?
- Large nerves are less suceptible to block than smaller nerves
- Myelinated nerves are less susceptible than non-myelinated nerves
How does firing frequency effect nerve block?
LAs bind active channels more readily than resting channels
LAs have greater effects on more active, frequently firing nerves
How does posiiton of fiber in a nerve bundle effect block?
Superficial fibers in a bundle are more accessible to LA than nerve fibers in the “Core” of the nerve bundle
What is the general order of nerve function loss?
Sympathetic Pain Cold Warm Touch Motor
What is the critical length hypothesis?
- For an LA to be effective, the field of action must include at least 3 nodes of an axon
* the bigger the axon, the longer the myelin segment and the fewer nodes w/in a given field
How are LAs classified
Based on linkage between aromatic group and intermediate chain
- Amides
- Esters
What LAs are Amides? (6)
- Lidocaine
- Mepivicaine
- Prilocaine
- Bupivicaine
- Articaine
- Ropivacaine
What LAs are Esters? (5)
- Cocaine
- Procaine
- Proparacaine
- Tetracaine
- Benzocaine
Facts for Esters (3)
- Rapidly Hydrolyzed by esterases in blood, decreased anesthetic duration
- Esters are esters of PABA, metabolized to PABA derrivatives, yields allergens
- Tend to have higher pKAs than amides (slower onset)
Facts of Amides (2)
- Metabolized by CYP450 in liver (increased duration of action)
- Less allergenic
Durations of action of amide anesthetics and which drugs they include
- Short: prilocaine, lidocaine
- Intermediate: mepivicaines, articaine
- Long: bupivicaine, ropivicaine
Routes of Adminitration of LAs
- Topical
- Infiltration/Nerve Block
- Epidural (ouside dura)/Spinal (into subarachnoid space around SC)
* LA properties vary greatly depending on route of admin
Topical, and what drugs are most common
- Application to the mucous membranes of the mouth, nose, trachea, as gel/spray
- Benzocaine or Tetracaine
Infiltration, and drugs
- Injection under skin or mucosa
2. Lidocaine, Mepivicaine, Prilocaine, Articaine, Bupivicaine (all amides)
Why are vasoconstrictors used w/ local anesthetics?
- Prolong duration of anesthesia by preventing diffusion from site of action
- limit systemic toxicity
- Reduce blood loss for surgical procedures
What drugs produce vasoconstriction, and what drugs produce the least vasodilation?
- Cocaine
2. Mepivicaine and Prilocaine
What types of vasoconstrictors are used in LAs and what do they target?
Agonsists at Alpha-1 Adrenergic Receptors
- Epiniphrine Hydrocholoride: Most common, local injection, only targets alpha 1
- Levonordefrin Hydrochloride: less common, selective alpha 1
Why should alpha 1 agonists be used w/ caution?
They are hypertensive agents, used w/ caution in pt w/ cardiovascular disease:
HTN, angina, history of MI
*Always avoid delivery into systemic circulation, only use via infiltration w/ low doses
Drug Interactions of alpha-1 adrenergic agonists
Sympathomimetic Drugs - MAOi and adrenergic agonists increase effects potentially resulting in HTN crisis
-Antihypertensive drugs that are alpha-1 ANTAGONISTS can block vasoconstriction
What is the most commonly used LA?
How is it used in dentsitry?
Lidodcaine
2% Lidocaine Hydrochloride w/ 1:100k epi
Benefits of lidocaine?
- Safe for children
- Inexpensive
3* Lower toxicity and increased stability (amides in general)
Other than lidocaine, what amides are used in denstirty?
- Articaine : similar to lidocaine
- Mepivicaine: little vasodilation, no need for vasoconstrictor
- Prilocaine: does not need vasoconstrictor
- Bupivicaine: prolonged duration of action
What esters can be used in dentistry?
Benzocaine: used topically as numbing agent
How are LAs supplied?
- 8 mL Cartriage for a syringe
- w/ vasoconstrictor
- w/ anti-oxidant (prevents breakdown of drugs)
How many mg of Lido is there in a 2% carpule?
36 mg Lido
2% = 2g/100mL
= 20mg/mL
1.8mL/carpule X 20mg/mL = 36mg
How much epi is in a carp if it is 1:100k epi
18 micrograms (ug)
1g/100,000 mL
10ug/mL
1.8mg/carp X 10ug/mL = 18ug
What type of drug and what drugs are used to treat pain and itching?
Topical LAs
- EMLA
- LMX-4
- Tetracain/benzocaine
What drug is used in opthamology?
Proparacaine - but repeated admin = corneal damage/blindness
What are the indications for topical LA?
- Pain/itching
- Opthamalogy
- Otolaryngology
- Numbing gel prior to infiltration - benzocaine
- Others = cough drops, ear drops, hemorrhoids, oral lesions
- Lacerations
What topicals can be used to manage minor lacerations?
- Use topical w/ epi
1. TAC (tetracaine, adrenaline/epi, cocaine)
2. LET (lidocaine, epi, tetracaine)
What can be used to treat major lacerations?
Pack w/ agents soaked w/ TAC or LET
What can be used to treat Digital Injury?
Digital Nerve Block - DO NOT ADMIN EPI
W/ epidural/spinal block below L1, where will it be effective?
All regions below the diaphragm
How is an epidural administered?
- Needle inserted through ligamentum flavum into epidural space
- Catheter introduced via needle and inserted into epidural space
- LA (Ropivicaine for child birth) is introduced to produce regional nerve block
What 2 Drugs can be used for epidurals, and what are the difference between them?
- Ropivacaine - long acting for child birth
2. Bupivacaine - more cardiotoxic when delievered epidurally, especially towards pregnant women
Effected systems for systemic toxicity in LAs
- Extremely rare w/ proper administration
1. CNS
2. Cardiovascular
3. Hemoglobin
CNS toxicity w/ LAs
Initially: excitation (talkativeness, lightheadedness, tinnitus, tremors)
Severe: seizures, respiratory depression, coma, death
Cardiovascular toxicity w/ LAs
- Decreased conduction, arrhythmias
- High conc can block calcium channels (reducing cardiac fxn)
- Hypotension from vasodilation
- Reduced autonomic activity; blockade of autonomic nerves
Hemoglobin toxicity w/ LAs
Prilocaine is safer than most other anesthetic drugs w/ administered acutely, it is metabolized in the liver to a compound that converts hemoglobin to methemoglobin = impaired O2 transport
Allergic Reactions associated w/ LAs
- PABA: metabolite of ESTER anesthetics
- metabolite of some preservatives in drug preperations - Amides are relatively non-allergenic
Hypersensitivity Rxns w/ LAs
- Allergic contact dermatitis w/ repeated injections (delayed onset- 24-48 hrs) = localized rash, hives, up to 30% taking ESTER anesthetics
- Rare: acute (30-60min) Type I hypersensitivty (life threatening)
-symptoms: rash, hives, angioedemia, bronchoconstriction, anaphylactic shock
TX: Oral diphenhydramine (benadryl/antihistamine)
Subcutaneous epi (1:1000)
