A tip from "Local anaesthesia for dental professionals"

I can't resist tips that use letters like this...

An easy method to identify the classification of dental local anesthetic drugs is to observe that the word amide, as well as all names for these drugs, contain a letter "i" in the first and second syllable of the name. In contrast the word ester has no letter "i," nor does the first syllable for any of the ester drugs. Esters and amides do share the common ending "-caine."

AMI DES	ESTERS
L i do-caine	Co-caine
Bup i va-caine	Pro-caine
Mep i va-caine	Benzo-caine
Pr i lo-caine	Tetra-caine
Art i caine*	Chloropro-caine
Metabolism: primarily in the liver	Metabolism: by cholinesterase
*Articaine is primarily metabolized by cholinesterase.

Also included was a neat explanation on the pharmacology of Local anaesthetics. Assume LA are weak bases in their neutral form (RN) which becomes charged with Hydrogen ions by the HCL acidified in the solution (RNH+)

1. To diffuse into the nerve fiber, the LA must be in its neutral form (RN)

2. To bind to receptors, the LA must be in its charged form (RNH+)

Consider the equilibrium: RN + H+  <>  RNH+

Injected into the tissues, more RN molecules will develop allowing diffusion into the nerve fiber. This decreases the concentration of RN in the extracellular matrix causing a shift of the equilibrium to the left causing a cascading affect increasing the bioavailable LA molecules. Once inside the nerve fiber, the axoplasm pH of ~7.4 causes conversion to charged molecule RNH+ which allows the LA to work on the nerve fiber.

If you consider the decrease in pH (Increase in tissue H+) in inflamed tissue, the equilibrium will shift to the right causing less available RN molecules to be present. Therefore, less LA will diffuse into the nerve preventing profound anaesthesia.

Localised edema and circulation also contributes to faster removal of LA solution from the site resulting in shorter acting and less effective anaesthesia.

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All LA in dentistry are weak vasodilators. Articaine, bupivacaine, lidocaine, and procaine are potent vasodilators and systemic uptake will be more rapid compared with mepivacaine and prilocaine, which are weak vasodilators. This limits their duration of action and increases their toxicity.  Some amides, such as prilocaine and mepivacaine, are successfully used without vasoconstrictors because of their weak vasodilative properties. Others, such as lidocaine, are not particularly useful in dentistry without the addition of vasoconstrictors because of their potent vasodilative properties that lead to rapid uptake into the circulation.

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LA toxicity:

CNS effects
The symptoms of CNS depression have been characterized as biphasic (occurring in two phases) and are consistent with a progression from early signs of CNS excitation (phase I) to signs of CNS depression (phase II) that can lead to tonic-clonic convulsions, coma, and respiratory arrest.

 The initial phase of excitation (phase I) may be explained as an early depression of the normal inhibitory pathways of the CNS. If the excitation represents an early phase of overdose and the excitation is replaced by signs and symptoms of CNS depression, it is due to an overdose. This means that the excitatory pathways of the CNS are being depressed by the drug, leaving only signs and symptoms of CNS depression.

Similar to the CNS effects of local anesthetic drugs, typical CVS events are biphasic. Initially, heart rate and blood pressure may increase. As dosing continues, vasodilation occurs, leading to depression of the myocardium, which may result in a fall in blood pressure. The contractility of the myocardium may be so impaired that cardiac output is reduced. When combined with CNS seizure activity, cardiac and respiratory arrest may result.

The presentation of symptoms of lidocaine and procaine overdose is the notable exception to the biphasic progression of local anesthetic overdose of the CNS. Often patients do not present with phase I signs and symptoms of excitability; instead, they present with initial signs and symptoms of phase II depression only.

CVS effects
Similar to the CNS effects of local anesthetic drugs, typical CVS events are biphasic. Initially, heart rate and blood pressure may increase. As dosing continues, vasodilation occurs, leading to depression of the myocardium, which may result in a fall in blood pressure. The contractility of the myocardium may be so impaired that cardiac output is reduced. When combined with CNS seizure activity, cardiac and respiratory arrest may result.

Fortunately, most overdoses are self-limiting. The drugs are continuously biotransformed. Their effects on the CNS and CVS, similar to those on the skin, mucosa, periodontium, pulp, and other tissues are transient, and disappearing rapidly once their concentrations fall below depressant levels. This explains why many mild overdoses may go unnoticed.

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Pharmacodynamics of LA

ADME (Absorption, distribution, metabolism, excretion)

Absorption through blood vessels into systemic circulation. 

Distribution preferring high blood flow organs e.g lung, heart, brain, kidneys.

Metabolism reduces the toxicity of available drug by breaking the drug down into a metabolite
-Liver--> cytochrome p450 enzyme system which is slower than
-Blood--> plasma cholinesterase enzyme --> breaks down esters and articaine

Amide LA metabolism:
Lignocaine, Mepivacaine, bupivacaine are metabolised in the liver in order of decreasing effectiveness. Additionally, prilocaine is metabolised in the liver, kidney and lungs. Only about 5-10% of articaine is metabolised by liver enzymes beause although it is a true amide, the majority of solution is metabolised by plasma cholinesterases.

Benzocaine, procaine, and tetracaine are esters. Similar to other esters, they are biotransformed in the blood via cholinesterase. Procaine undergoes rapid metabolism by cholinesterase, while tetracaine's metabolic pathway is similar, but slower, compared with procaine and benzocaine.