Cocaine undesirable effects

The toxicological or cumulative effect of illicit drugs on the ecosystems has not been studied yet. Moreover, their fate and transport in the environment is to a big extent still unknown. Due to their physical-chemical properties (octanol-water partition coefficient, solubility, etc.) some of them, such as cannabinoids, are likely to bioaccumulate in organisms or concentrate in sediments whereas the rest, much more polar compounds, will tend to stay in aqueous environmental matrices. However, continuous exposure of aquatic organisms to low aquatic concentrations of these substances, some of them still biologically active (e.g., cocaine (CO), morphine (MOR) and MDMA) may cause undesirable effects on the biota. 

At higher doses, cocaine can produce undesirable effects, including tremor, emotional lability, restlessness, irritability, paranoia, panic, and repetitive stereotyped behavior. At even higher doses, it can induce intense anxiety, paranoia, and hallucinations, along with hypertension, tachycardia, ventricular irritability, hyperthermia, and respiratory depression. In overdose, cocaine can cause acute heart failure, stroke, and seizures. Acute intoxication with cocaine produces these various clinical effects, depending on the dose these effects are mediated by inhibition of the dopamine transporter and in turn by the effects of excessive dopamine activity in dopamine synapses, as well as by norepinephrine and serotonin in their respective synapses. 

After determining cocaine s structure, chemists could ask, "How is the structure of cocaine related to its anesthetic effects Can the anesthetic effects be separated from the habituation effect " If these questions could be answered, it might be possible to prepare synthetic drugs with the structural features essential for the anesthetic activity but without those giving rise to the undesirable effects. Chem -ists focused on three structural features of cocaine its benzoic ester, its basic nitrogen atom, and something of its carbon skeleton. This search resulted in 1905 in the synthesis of procaine, which almost immediately replaced cocaine in dentistry and surgery. Lidocaine was introduced in 1948 and today is one of the most widely used local anesthetics. More recently, other members of the "caine" family of local anesthetics have been introduced (e.g., etidocaine). All of these local anesthetics are administered as their water-soluble hydrochloride salts. 

D. Chemical Use Classes. This includes the toxicology aspects of the development of new chemicals for commercial use. In some of these use classes, toxicity, at least to some organisms, is a desirable trait in others, it is an undesirable side effect. Use classes are not composed entirely of synthetic chemicals many natural products are isolated and used for commercial and other purposes and must be subjected to the same toxicity testing as that required for synthetic chemicals. Examples of such natural products include the insecticide, pyrethrin, the clinical drug, digitalis, and the drug of abuse, cocaine. 

There are numerous natural substances that have useful therapeutic properties as well as other undesirable properties. From these starting points, medicinal chemists have improved on nature. For example, while extremely useful in the treatment of infection, penicillin is not available by the oral route this shortcoming is overcome in the analogue ampicillin (Figure 8.3A). Similarly, the obvious deleterious effects of cocaine have been eliminated in the local anesthetic procaine (Figure 8.3B). The short activity and weak steroid progesterone is converted to a stronger... 

Hence, the duration and magnitude of the desired stimulant effects, as well as the undesired toxic effects of cocaine use, appear to depend on the content and activity of enzymes responsible for cocaine metabolism. 

For the coca-chewing Indians in South America, on the other hand, the central stimulant effect is the wanted effect, whereas the local anaesthetic action is an undesired side-effect. The dried leaves (which are purchased on the local market, (see Fig. 20) are mixed with alkali (burned bones from llamas, which is called Lliptar) the mixture is kept between the teeth and cheek, without direct chewing, and the saliva is swallowed. Coca chewing gives rise to less dependence and social problems than the use of isolated cocaine in the form of inhaled cocaine hydrochloride or the smoked free-base alkaloid called Crack or Free-base . 

Because of its ability to block pain, cocaine became widely used as a local anesthetic to deaden nerves during various medical procedures, but it was not an ideal anesthetic owing to its undesired side effects. For example, in eye surgery it produces mydriasis, or dilation of the pupil It also has powerful addictive properties and exhibits dangerous effects on the central nervous system. Medicinal chemists thus began a search for substances related to cocaine that would retain its valuable anesthetic properties but would not produce its side effects. 

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