Central nervous system cocaine effects

A model for the action of cocaine and amphetamine at a dopaminergic synapse in the central nervous system. Cocaine (right side) blocks the dopamine reuptake transporter (DAT). Amphetamine (left side) has several effects. It enters the nerve ending via reverse transport by the DAT and displaces dopamine (DA) from vesicles by altering their pH. It also inhibits dopamine metabolism by MAO in the nerve ending. The increased intraneuronal dopamine causes reversal of the DAT and dopamine floods into the synapse. 

Because of its peripheral adrenergic and central nervous system stimulatory effects, cocaine should be used with caution in patients with cardiac disease or hyperthyroidism. 

Only one of these therapeutic uses has turned out to be valid, and that is the use of cocaine as a local anesthetic. When cocaine makes direct contact with peripheral neurons, it prevents neural firing, which has the effect of numbing the area. This action is unlike cocaine s effects on the central nervous system. Cocaine was the first local anesthetic and revolutionized surgery. Now, of course, related -caine drugs such as procaine and xylocaine are used more frequently, but because cocaine also constricts blood vessels, it is still used for surgery on areas such as the face, due to the fact that it reduces bleeding as well as pain. 

The various stimulants have no obvious chemical relationships and do not share primary neurochemical effects, despite their similar behavioral effects. Cocaines chemical strucmre does not resemble that of caffeine, nicotine, or amphetamine. Cocaine binds to the dopamine reuptake transporter in the central nervous system, effectively inhibiting dopamine reuptake. It has similar effects on the transporters that mediate norepinephrine and serotonin reuptake. As discussed later in this chapter in the section on neurochemical actions mediating stimulant reward, dopamine is very important in the reward system of the brain the increase of dopamine associated with use of cocaine probably accounts for the high dependence potential of the drug. 

Many simple molecules have profound effects on the central nervous system. Several of these are drugs of abuse methamphetamine, cocaine, and heroin, among others. 

Substance-Induced Anxiety Disorder. Numerous medicines and drugs of abuse can produce panic attacks. Panic attacks can be triggered by central nervous system stimulants such as cocaine, methamphetamine, caffeine, over-the-counter herbal stimulants such as ephedra, or any of the medications commonly used to treat narcolepsy and ADHD, including psychostimulants and modafinil. Thyroid supplementation with thyroxine (Synthroid) or triiodothyronine (Cytomel) can rarely produce panic attacks. Abrupt withdrawal from central nervous system depressants such as alcohol, barbiturates, and benzodiazepines can cause panic attacks as well. This can be especially problematic with short-acting benzodiazepines such as alprazolam (Xanax), which is an effective treatment for panic disorder but which has been associated with between dose withdrawal symptoms. 

Cocaine readily penetrates mucous membranes and is an effective topical local anaesthetic that demonstrates intensive vasoconstrictor action. It has stimulant effects on the central nervous system and is a drug of addiction. It causes agitation, dilated pupils, tachycardia, hypertension, hallucinations, hyperthermia, hypertonia, hyperreflexia and cardiac effects. 

Although this drug is categorized as a local anesthetic, I have chosen to put it in with the hallucinogens because of the psychotomimetic effects that it produces. Cocaine is not a phenylethyl-amine, but it produces central nervous system arousal or stimulant effects which closely resemble those of the amphetamines, the methylenedioxyamphetamines in particular. This is due to the inhibition by cocaine of re-uptake of the norepinephrine released by the adrenergic nerve terminals, leading to an enhanced adrenergic stimulation of norepinephrine receptors. The increased... 

Pani L, Kuzmin A, Diana M, et al Calcium receptor antagonists modify cocaine effects in the central nervous system differently. Eur J Pharmacol 190 217-221, 1990... 

Other drugs may increase the effects of dextroamphetamine. For example, bicarbonate and other alkalin-izing agents increase the amount of amphetamines absorbed in the digestive system. Thiazides (potassium-depleting diuretics) decrease the amount of amphetamines that leave the body in urine. Also, other central nervous system stimulants, such as cocaine and nicotine, can amplify the stimulating effects of dextroamphetamines. 

Cocaine is a local anesthetic with a peripheral sympathomimetic action that results from inhibition of transmitter reuptake at noradrenergic synapses (see Chapter 6 Introduction to Autonomic Pharmacology). It readily enters the central nervous system and produces an amphetamine-like effect that is shorter lasting and more intense. The major action of cocaine in the central nervous system is to inhibit dopamine reuptake into neurons in the "pleasure centers" of the brain. These properties and the fact that it can be smoked, "snorted" into the nose, or injected for rapid onset of... 

This effect is not surprising Amphetamines are potent psychomotor stimulants. Whether sniffed, swallowed, snorted, or injected, they induce feelings of power, strength, exhilaration, self-assertion, focus, and enhanced motivation. Amphetamine intake causes a release of the excitatory neurotransmitters dopamine and noradrenaline (norepinephrine) in the central nervous system (CNS). The release of dopamine typically induces a sense of aroused euphoria that may last several hours unlike cocaine, amphetamine is not readily broken down by the body. After taking amphetamines, feelings are intensified, the need to sleep or eat is diminished, and the user may feel as though he or she can take on the world. ... 

In humans, a prominent effect of cocaine consists in increased vigilance and elevated mood. While cocaine itself is not used clinically, several catecholamine and serotonin reuptake blockers are used as antidepressants. Imipramine (Figure 10.13) is a classic but not so very specific in addition to inhibiting the reuptake of serotonin and of norepinephrine, it also has antihistaminic and antimuscarinic activity. This will lead to side effects in both the central nervous system and the peripheral autonomic system. A prominent one is the causation or deterioration of cardiac arrhythmias due to its antimuscarinic action. 

Cocaine exhibits several pharmacologic effects. After local application it acts as an anesthetic by blocking the initiation and conduction of nerve impulses. In addition, it has been shown to block neuronal reuptake of norepinephrine, thus potentiating adrenergic activity. Moderate doses increase heart rate and cause vasoconstriction. The most striking systemic effect of cocaine is central nervous system stimulation. 

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