Local Anesthetic - Dr. Paul Mirdamadi DDS

Multi-dose vials of local anesthetics often contain preservatives such as parabens which are allergenic; this is not the case with single use dental cartridges. The presence of a vasoconstrictor usually is accompanied by an antioxidant such as a bisulfite which also may be allergenic, and should be avoided in cases of atopy
Multi-use vials contain preservatives such as parabens
Vasoconstrictors are usually accompanied by an antioxidant such as a bisulfite

Reversibly block conduction along the nerve distal to the site of application
Once injected into tissue, the local anesthetic is a weak base and equilibrates into two forms: ionized and non-ionized. The non-ionized form is able to freely cross the cell membrane. Once inside the ell, re-equilibration occurs to the ionized form, which bonds to specific sites on the voltage-gated sodium channels, impairing depolarization.
as concentration of the anesthetic increases and more receptors are occupied, actions potentials are progressively slowed and then abolished.

Amide local anesthetics are metabolized mainly by the microsomal P-450 enzymes of the liver. The rate of metabolism can be affected by decreases in liver function or liver blood flow, potentially leading to systemic toxicity.
Ester local anesthetics are very rapidly metabolized by the plasma pseudocholinesterases.

Onset time = pKa
the pKa of a local anesthetic determines the speed of action.
The pKa of a local anesthetic is the pH at which equal concentrations of ionized and un-ionized forms exist. It is the un-ionized form that must cross the axonal membrane to initiate neural blockade.
The closer the pKa of a local anesthetic is to the pH of tissue (7.4), the mor rapid the onset due to the greater amount of un-ionized agent available for diffusion.
Slowest onset (bupivicaine > articaine > lidocaine, prilocaine > mepivacaine)
Greater degree of ionization at physiologic pH = slower onset

Lipid solubility = potency
The lipid solubility of a local anesthetic appears to be related to its intrinsic potency of the local anesthetic.
A greater lipid solubility produces a more potent local anesthetic due to the fact that nerve membranes are most lipid.
Increased lipid solubility permits the anesthetic to penetrate the nerve membrane (which is 90% lipid) more easily. This is reflected biologically in an increased potency of the anesthetic. Local anesthetics with greater lipid solubility produce more effective conduction blockade at lower concentrations (lower percentage solutions or smaller volumes deposited) than the less lipid soluble solutions.

Protein binding = duration
The degree of protein binding determines the duration of the anesthetic.
Sodium channels and receptor sites are mostly protein, thus an agent with a greater degree of protein binding will have a longer duration of action.
Shortest half-life: (articaine 27min> prilocaine > lidocaine 96min > mepivacaine 114min > bupivacaine 162min )

Treatment of hypertension with a non-selective beta blocker will affect both beta-1 and beta-2 receptors. Epinephrine or levonordefrin will normally cause sympathetic stimulation of both alpha and beta adrenergic receptors. Alpha-1 mediated vasoconstriction is unopposed with beta blockade and can result in severe hypertension and possible reflex bradycardia.
Lidocaine has a depressor effect on the myocardium. Lidocaine toxicity causes sinus bradycardia because lidocaine increases the effective refractory period relative to the action potential duration and lowers cardiac automaticity. The bradycardia is followed by impaired contractility, massive peripheral vasodilation, hypotension and possible cardiac arrest. Lidocaine may be used to treat PVC’s and lidocaine toxicity produces hypotension, not hypertension.
Procaine is an ester local anesthetic and metabolized in the blood by plasma cholinesterase. Succinylcholine is a depolarizing muscle relaxant that also requires plasma cholinesterase for hydrolysis. Prolonged apnea or paralysis may result form the concomitant use of these drugs. Bupivicaine, mepivicaine and articaine are all amides and thus metabolized in the liver.

Get help.
Ventilate with 100% oxygen. Alert nearest facility with cardiopulmonary bypass capability
Resuscitation: airway/ventilatory support, chest compressions, etc. Avoid vasopressin, calcium channel blockers, β-blockers, or additional local anesthetic. Reduce epinephrine dosages. Prolonged effort may be required.
Seizure management: benzodiazepines preferred (eg, intravenous midazolam 0.1–0.2 mg/kg); avoid propofol if cardiovascular instability.
Administer 1.5 mL/kg 20% lipid emulsion over ∼1 minute to trap unbound amide local anesthetics. Repeat bolus once or twice for persistent cardiovascular collapse.
Initiate 20% lipid infusion (0.25 mL/kg per minute) until circulation is restored; double the infusion rate if blood pressure remains low. Continue infusion for at least 10 minutes after attaining circulatory stability. Recommended upper limit of ∼10 mL/kg.
A fluid bolus of 10–20 mL/kg balanced salt solution and an infusion of phenylephrine (0.1 μg/kg per minute to start) may be needed to correct peripheral vasodilation.