Lesson 2 Pharmacology of local anesthetics

Lesson 2

Pharmacology of local anesthetics
The first used local anesthetic drugs was the cocain, in the Ink period in Peru. The old "surgeons" were chuwing the leaves of the tree Erythroxylon coca and spited the saliva to the wounds of the patient. Both hade pleasure effects from it.

Anyway, the first isolation of pure kokain in 1884 by Niemann and first analgetic using by Koller was quickly overhelmed by the drug abusibility. First real and less toxic local anesthetic was found Procain (Einhorn, 1904)

Lidokain 1943

mepivakain 1956

bupivakain 1957

etidokain 1971

The molecul of every LA(local anesthetic) has always three parts - lipofil chain, hydrophil chain qand conecting chain. The conecting chain is either with amid (-CO-NH-)or esteric(-CO-O-C-) chain,

Accordding to the molecular structure we divide local anesthetics in two groups: amino-esters and amido-amids.

Esters: Prokain, Amethokain,Chloroprokain

Amidy: Prilokain, Lidokain, Mepivakain, Bupivakain, Etidokain, Ropivakain

The mechanism of the action to the cells is still discussed, however, it is sure, that they influence the Na-chanel of the cell membrane and by the blocade of it they blocate the leading of the information - signal at the neuron or muscle.
The dose of LA depends on the potential action of the anesthetics, on the pH, on the tissue, on the depp of wanted effect and on the space, where we apply the agent.

For example the efect of the anesthetics in the SAB and epidural block is different. For SAB we ned small volume of highly concentrade LA, while to epidural space is needed higher volume with lover concentration. The vascularity of the tissue is playing the big role.

Toxicity

The lokal anesthetic might show the toxic actions, especialy when used not correctly or wrongly applyed.

If LA effect the brain dirrectly, they may cause dissiness, tinitus, headache, speakind disability or on the other hand talkative,vision disturbances. If the concentration is increasing, the convulsions can occur and patient can even die in inconciousness, cardiac and respiratory arrest.

Cardiotoxicity is showing especially bupivacain, we must be extremely carefull, that the LA is not getting in big amount to the blood.

Additive substances

For different reasons we add different substances to modulate the effect of the anesthetics.

Adrenalin - adding the adrenalin to the LA is making the vasoconstriction of sorounding vessels and so the LA is not flowing out so quickly. That prolonging and intensifing the block. As well the bleeding is lower.

KI: Kondraindicated in nestabil angina pectoris, major cardiovasciular problems, hyperthyreoidism, during general anesthesia (higher sensitivity to katecholamins), at the acral parts - danger of necrosis - fingers, ears, penis, ...

Light - iso - heavy anesthetics

LA , when floating in the liquor, can have the same density as liquor, higher or lower. Than, hypobaric , with the lower density are from the place of injection floating up, hyperbaric are floating down and isobaric are staying around. Positioning of the patient can thus highly effect on the action of LA.

Baricity = density LA(t) / liquor density (t)
It would be very dangerous, for instance, to give in SAB Marcain heavy and than position patient head down.
Preparates:
I was choosing just the most offen used LA in anesthesiology, for examp. in stomathology we use another ones.
Lidocain quickly acting anesteticum with medium time of action

start 5min/ action 2-3 hours

regional techniques 4-10%

infiltrations 0.5 - 1%

peripheral blocks 1-2%

epidural 2%

SAB 5%

(Xylocain, Lignocain, EMLA)

Bupivacain quite kardiotoxic LA vith long action and later start

10 min/3 - 4 hours

Epid 0.5%

SAB 0.5%

perif. 0.25 - 0.5%

(Marcain, Marcain heavy, Marcain spinal )

Ropivacain the same action almost like bupivakain, but no kardiotoxicity

15 min/ 6 hod

(Naropin)

Articain very quick start, but also short action, quite big involving in mortoric action

1 min/ 60 min

(Ultracain)