Local Anesthetics
Are nonselective voltage-gated sodium channel blockers
that inhibit conduction of APs in all afferent and efferent neurons to and from the CNS
Precautions
Ester LAs
e.g. Procaine
e.g. Tetracaine
e.g. Benzocaine
Adverse Reactions
Toxicity
Allergic & Hypersensitivity Reactions
Idiosyncratic Reactions
high plasma levels due to overdosing, rapid absorption, slow metabolism, unintentional iv injection
Measuring MRD (maximum recommended dose)
MRD in mg = MRD mg/kg X weight in kg
MRD in mL = MRD mg ÷ mg/mL
Can be primary or secondary
Primary: can be from direct trauma to injection site
Secondary: from a lack of function of a nerve (usually lingual nerve)
Signs and Symptoms:
-edema
-skin peeling
-ischemic necrosis
Signs and Symptoms:
-transient anesthesia or paresthesia (lips, tongue)
May take 2-6 months in worst cases
CNS effects
CVS effects
Pregnancy/Breastfeeding
LAs cause CNS depression after stimulation in high doses or accidental iv injection
(-excitation->restlessness->convulsions->unconsciousness)
LAs are cardiac depressants
No significant effects in normal doses
-fall in BP
-local vasodilation
Bupivicaine can be cardiotoxic and cause ventricular tachycardia
Overdose effects on CVS
-low BP
-depress conduction, excitability, and contractility
-may progress to ventricular arrhythmia and AV block
Sympathetic Reactions
With LAs containing Epinephrine or Levonordefrin
-Healthy adults: MRD = 0.2mg epinephrine, 1.0mg levonordefrin per visit
-ASA III patients: MRD = 0.04mg epinephrine
Most allergic reactions happen with Ester type (from PABA) LAs and with atopic patients
Sodium bisulfite an anti-oxidant in LAs containing vasoconstrictors can cause allergic reactions
Reactions:
-Rash
-angioedema
-asthma
-anaphylaxis
Especially with Prilocaine (systemic) and Benzocaine (topical)
Can cause Methemoglobinemia:
-LA metabolites (orthotolwidine) bind hemoglobin and reduce O2 circulation
-Children and patients with G6PD anemia are most susceptible
Signs and Symptoms:
-cyanosis (nails, lips)
-fatigue, weakness
-nausea
-sedation
-seizures
Pregnancy
Only use Lidocaine and Prilocaine in the 2nd trimester
Never use Mepivacaine, Articaine, or Bupivacaine during pregnancy
Breastfeeding
Bupivacaine can cause toxicity to nursing infants
Drug-Drug Interactions
Not taken with other CNS depressants
Use LAs containing vasoconstrictors with caution if the patient is taking:
Amiodarone
-MOA inhibitors (MOA inhib. will be ineffective)
-TCAs
-ergot type drugs (fungi derived) cause increased BP
-non-selective β-adrenergic receptor blocking agents
-Thyroid hormones (epinephrine effects on CVS)
Inhibits Lidocaine metabolism
(Use Articaine instead)
Structure of LAs
Duration of Action
Determined strength of LA bond to protein (Na+ channel)
Stronger bond = Longer duration of action
Pharmacokinetics
Distribution
Clearance
Absorption
Rate and extent of absorption depends on:
-Vascularity
-LAs physicochemical properties
-Vasoconstrictor presence
-Dose of LA
LAs with greater lipid solubility = greater Vd (degree of tissue uptake)
Amide LAs
Ester LAs
Metabolized in liver by cytochrome P450
-to be more hydrophilic for excretion mainly by kidneys (urine) or some by liver (bile)
e.g. Propoxycaine
Effects of Lidocaine overdose
-dizziness, blurred vision, tinnitus, lethargy, abnormal tongue sensation
Metabolized by tissue and plasma pseudocholinesterases into (PABA) and other metabolites to be excreted by kidneys
Mode of Action
Act on Voltage-gated Na+ channels (integral membrane
proteins) on intracellular side, have reversible & concentration-dependent effect
Onset of Action
consist of 3 structural domains:
- Aromatic group
- Linker : ester (COO) or amide (NHCO)
- Secondary or tertiary amine group
Potency
Topical anesthetics
Exert their effect on free nerve endings near to the skin
Come in form of spray, gel, ointment.
Xylocaine & Benzocaine have short anesthetic effect and give surface anesthesia
Amide LAs
e.g. Lidocaine
e.g. Prilocaine
e.g. Mepivacaine
e.g. Articane
e.g. Bupivacaine
Risk of Methemoglobinemia and paraesthesia following mandibular nerve block
Produce parathesia following mandibular nerve block
Most lipophilic, most potent, longest duration of pulpal anesthesia, longest half life, great degree of tissue uptake Vd and higher risk of cardiotoxic
Determined by the aromatic group which gives the LA lipid solubility
High lipid solubility, lower concentration of LA is required
Amine groups give hydrophilic nature, LAs exist as protonated (RNH+) and neutral (RN + H+)
Only neutral form can cross neuronal membranes, this prevents LAs from working in cases of infection (acidic pH)
Low pH (acidic) = more protonated
Higher pH (basic/alkaline) = more neutral
Factors affecting duration of action:
- Protonated LAs: dissociate slower
- Dose administered
- Addition of a vasoconstrictor (slows absorption)
Example: Bupivacaine less likely to diffuse due to its high protein binding capacity
Degree of tissue uptake (Vd)
Higher Vd = higher elimination half-life = longer to eliminate = high toxicity risk
Example: Bupivacaine has a half-life of 5.5 hours, compared to Lidocaine's 2 hours
Cytochrome P450 can have isoenzymes: CYP34A and CYP1A2
PABA may trigger allergic reactions especially in atopic patients