Core pharmacology

Class Group

Ester Local Anaesthetic

Legacy Cicm Level

-

Indications Uses

topical vasoconstrictor

Chemical Pharmaceutics

ester of benzoic acid (a naturally occurring alkaloid derived
from the leaves of Erythroxylon coca).

Presentation

1–4% solutions and as a non-proprietary paste of varying concentration.

Main Action

Local anaesthesia, vasoconstriction, and euphoria.

Mechanism of action

Local anaesthetics diffuse in their uncharged base form
through neural sheaths and the axonal membrane to the internal surface
of cell membrane Na+ channels; here they combine with hydrogen ions
to form a cationic species which enters the internal opening of the Na+
channel and combines with a receptor. This produces blockade of the Na+
channel, thereby decreasing Na+ conductance and preventing depolarization of the cell membrane.

Cocaine also produces blockade of the uptake-1
pathway of noradrenaline and dopamine, leading to vasoconstriction and
CNS excitation.

Physiological effects

CVS The usual effect of cocaine is to produce hypertension and tachycardia
due to a combination of central sympathetic stimulation and the blockade
of noradrenaline reuptake at peripheral adrenergic nerve terminals, leading to intense peripheral vasoconstriction. Large doses produce myocardial
depression and may precipitate ventricular fibrillation.
RS Therapeutic concentrations of the drug cause stimulation of the respiratory centre and an increase in ventilation.
CNS The principal effect of cocaine is reversible neural blockade; this
leads to a characteristically biphasic effect in the CNs. Initially, excitation
(euphoria, light-headedness, dizziness, visual and auditory disturbances, and
fitting) occurs due to the blockade of inhibitory pathways in the cortex;
with increasing doses, depression of both facilitatory and inhibitory pathways occurs, leading to CNs depression (drowsiness, disorientation, and
coma). Cocaine may also cause hyperreflexia, mydriasis, and an increase in
the intraocular pressure.
AS The drug produces hyperdynamic bowel sounds and marked nausea
and vomiting (a central effect).
Metabolic/other Cocaine causes a marked increase in body temperature
due to increased motor activity combined with cutaneous vasoconstriction
and a direct effect of the drug on the hypothalamus.

Adverse Effects Toxicity

Allergic phenomena occur occasionally with the
use of cocaine. The side effects are predominantly correlated with excessive plasma concentrations of the drug. These include confusion, hallucinations, seizures, cerebral haemorrhage and infarction, and medullary
depression leading to respiratory arrest. Chest pain is common; myocardial
infarction, pulmonary oedema, gut infarction, rhabdomyolysis, and disseminated intravascular coagulation (DIC) may also occur. Cocaine is a drug
of dependence; maternal use may result in neonatal dependence. Nasal
septum necrosis is reported.

Absorption

well absorbed from mucosae, including that of the gut.

BA Intranasally 0.5%

Protein binding

98%

Volume of distribution

0.9–3.3 l/kg.

Metabolism

In common with the other ester-type local anaesthetic agents,
cocaine is predominantly degraded by plasma esterases, predominantly to
benzoylecgonine

Excretion

excreted in the urine, 10% unchanged.

Clearance

26–44 ml/min/kg

Half-life

elimination half-life is 25–60 minutes.

Route And Dose

topically;

the toxic dose is 3 mg/kg.

duration of action of 20–
30 minutes.