Pharmacology for Anaesthesia and Intensive Care

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Section IICoredrugs in anaesthetic practice

pKareflects a higher fraction present in the unionized form and, therefore, a faster

onset of action as more is available to cross the phospholipid membrane.


The intrinsicvasodilator activityvaries between drugs and influencespotency

andduration of action.Ingeneral, local anaesthetics cause vasodilatation in low

concentrations (prilocaine > lidocaine > bupivacaine > ropivacaine) and vasocon-

striction at higher concentrations. However, cocaine has solely vasoconstrictor

actions by inhibiting neuronal uptake of catecholamines (uptake 1) and inhibiting

MAO.

However, total dose and concentration of administered local anaesthetic will also

have a significant effect on a given clinical situation.

Local anaesthetics are generally ineffective when used to anaesthetize infected tis-

sue. The acidic environment further reduces the unionized fraction of drug available

to diffuse into and block the nerve. There may also be increased local vascularity,

which increases removal of drug from the site.

Lidocaine: pKa=7.9

At pH7.4

pH=pKa+log

{

[B]

[BH+]

}

7. 4 = 7. 9 +log

{

[B]

[BH+]

}

− 0. 5 =log

{

[B]

[BH+]

}

0. 3 =

{

[B]

[BH+]

}

so 75% ionized and 25% unionized.

At pHof 7.1

7. 1 = 7. 9 +log

{

[B]

[BH+]

}

0. 16 =

{

[B]

[BH+]

}

so 86% ionized and 14% unionized (i.e. less available to penetrate nerves).

Other effects


Cardiac – lidocaine may be used to treat ventricular arrhythmias, while bupi-

vacaine is not. Both drugs block cardiac Na+channels and decrease the max-

imum rate of increase of phase 0 of the cardiac action potential (cf. Chap-

ter 14 ). They also have direct myocardial depressant properties (bupivacaine

>lidocaine). The PR and QRS intervals are also increased and the refractory

period prolonged. However, bupivacaine is ten times slower at dissociating from