PHARMACOLOGY OF COCAINE DEPENDENCE AND ABUSE

Free base (crack) vaporizes easier than HCl salt. Can be inhaled as smoke and is more addictive than HCl salt. Pyrolysis products include benzoic acid (a carcinogen), methylester product.

Metabolism: metabolized by acetylcholinesterase (AchE) and pseudo AchE. Products of crack can cause neurotoxicity. The half-life is relatively short. Cocaine has good bioavailability: intranasal 45%, oral 36%, i.v. nearly 100%. Stimulation and euphoria are related to the brain concentration of the drug.

Pharmacological effects: “Sympathetic storm” results from administration of cocaine, refers to a release of catecholamine. Heart rate increases 30-40 beats per minute, and blood pressure (systolic) may increase by 30 mm HG when given i.v. Coronary vasoconstriction can occur, even in pts without prior history of ischemic heart disease – this leads to death. True tolerance results from taking cocaine. High doses can produce a variety of CNS side effects: seizures, stroke, cerebral vasculitis, hyperpyrexia, headache. Psychiatric complicaiotns can include schizopherenic-like psychosis, anxiety, and others.

Experimental treatment: tegretol and various other drugs like TCAs have been tried, but don’t work. Probably the neatest results will come from blocking the dopaminergic D1 receptor and the reward pathway. Anecdotal evidence suggests that pts with Parkinson’s disease, who lack neuronal dopamine, don’t show the typical euphoric effects of cocaine.

There is no conclusive answer on whether cocaine use affects the amount of local anesthetic that we must give to achieve anesthesia.

The acute effect of cocaine use is blockade of the dopamine reuptake; cocaine is a dopamine reuptake inhibitor. Thus, you will find more dopamine in the synaptic cleft. With chronic use however, there seems to be less release of dopamine, even though it has blocked the transporter the dopamine released from the pre-synaptic neuron is less. When the pt stops the cocaine, there is very little dopamine in the synaptic cleft – leads to withdrawal symptoms.

Ads for Marinol (THC) show that it can increase the appetite of pts living with HIV/AIDS. It is a schedule III drug. So Marinol is indicated for AIDS pts who are losing weight, but is still very rarely prescribed because it produces many of the same effects as marijuana.

Category: Pharmacology Notes