Cocaine long-term effects

Information about long-term effects of SNA 1b derived from two sources its administration as an anesthetic and Its chronic use as a street drug. As to the latter, It must be noted that PCP rarely occurs in a pure form and commonly Is abused with other substances, such as THC and cocaine. 

As noted in Chapter 3, stimulant drugs such as cocaine and the amphetamines are thought to affect the brain primarily through complex actions on monoamine neurotransmitters dopamine, norepinephrine, and serotonin. For example, both cocaine and the amphetamines block rcuptake of norepinephrine, serotonin, and particularly dopamine (Meyer 8c Quenzer, 2005). In addition, the amphetamines and methylphenidatc also increase the release of dopamine (Sulzer, Sonders, Poulsen, 8c Galli, 2005). Thus, the initial effect of stimulants is to produce a storm of activity in neural pathways that are sensitive to the monoamine transmitters. Because of this increased activity, however, and particularly because reuptake is blocked so that enzymes break down the neurotransmitters, the long-term effects of stimulant use involve depletion of monoamines. If you remember that low levels of monoamines are linked to clinical depression (see Chapter 3), tlien you have the basis for one theory of why the aftereffects of heavy cocaine use involve depression (Dackis 8c Gold, 1985). To explain this hypothesis, we must turn briefly to data from the animal laboratory. 

Acute and long-term effects of what we call illicit drugs have been mostly observed on human subjects. Here we review the effects of cocaine, tetralydrocamiabmol (THC), 3,4-methylenedioxymethamphetamine (MDMA), and morphine as a reference for further discussion of potential consequences on nontaiget organisms. 

Taylor, D., and Ho, B.T. Effect of short- and long-term treatment with cocaine on rat brain tryptophan hydroxylase. Res Commun Chem Pathol Pharmacol 15 805-808, 1976. 

Even when effective in controlling behavior, Ritalin and other stimulants have side effects common with use of amphetamines. These include nervousness, insomnia, and perhaps some more long-term problems such as dependency, slowed growth, or depression. Critics sometimes note the similarity between cocaine and the active chemical ingredient in Ritalin, methylphenidate. Both stimulate the dopamine system of the brain, but cocaine does so quickly and methylphenidate does so slowly. The similarities show in the abuse of Ritalin for its pleasure-inducing qualities. 

Long-term cocaine or amphetamine abuse leads to a deterioration of the nervous system. The body recognizes the excessive stimulatory actions produced by these drugs. To deal with the overstimulation, the body creates more depressant receptor sites for neurotransmitters that inhibit nerve transmission. A tolerance for the drugs therefore develops. Then, to receive the same stimulatory effect, the abuser is forced to increase the dose, which induces the body to create even more depressant receptor sites. The end result over the long term is that the abusers natural levels of dopamine and norepinephrine are insufficient to compensate for the excessive number of depressant sites. Lasting personality changes are thus often observed. 

Recall from our discussion of cocaine and amphetamines that the body responds to the long-term abuse of these stimulants by creating more depressant receptor sites. Likewise, the body recognizes the excessive inhibitory actions produced by alcohol and tries to recover by increasing the number of synaptic receptor sites that lead to nerve excitation. A tolerance for alcohol therefore develops. To receive the same inhibitory effect, the drinker is forced to drink more, which induces the body to create even more excitable synaptic receptor sites. Eventually, an excess of these excitatory receptor sites leads to perpetual body tremors, which can be subdued either by more drinking or, with greater difficulty, by a long-term cessation of alcohol consumption. 

Because they both seem to function as uppers, some people think that cocaine and methamphetamine are essentially the same drug. While it is true that they both have similar mental and physiological effects, the two drugs do act quite differently. In contrast to cocaine, which is rapidly broken down in the body, methamphetamine tends to accumulate in both the body and brain, thereby leading to longer effects and more potential to cause long-term brain damage. Also, cocaine is derived from a natural substance, the coca plant, while methamphetamine is a totally synthetic chemical. 

Ritalin is a mild stimulant. On the contrary, the studies found that Ritalin, although effective in treating the symptoms of ADHD, shows no clear long-term improvement on users and can have dangerous effects on health, including death. Because the effects of Ritalin on humans are virtually identical to those produced by cocaine, amphetamine, and methamphetamine (speed), the researchers noted that its abuse liability is high and can lead to marked tolerance and psychological dependence. 

This only develops to some of the effects of cocaine, for example the euphoric "rush" following intravenous administration and some of the cardiovascular effects, but the degree of tolerance is limited. However, most long-term users do require increasing amounts of the drug to produce the same subjective effects to those experienced initially when taking the drug. 

Deficits in attention and motor skills persisted after 1 year of abstinence from stimulant abuse in 50 twin pairs in which only one member had heavy stimulant abuse with cocaine and/or amphetamines (55). Stimulant abusers performed significantly worse on tests of motor skills and attention, and significantly better on one test of visual vigilance. These findings provide evidence of long-term residual effects of stimulant abuse. 

Cardiovascular effects include tachycardia, hypertension, and increased cardiac irritability large intravenous doses can cause cardiac failure. Cardiac dysrhythmias have been ascribed to a direct toxic effect of cocaine and a secondary sensitization of ventricular tissue to catecholamines (17), along with slowed cardiac conduction secondary to local anesthetic effects. Myocardial infarction has increased as a complication of cocaine abuse (7,8). Dilated cardiomyopathies, with subsequent recurrent myocardial infarction, have been associated with long-term use of cocaine, raising the possibility of chronic effects on the heart (18). Many victims have evidence of pre-existing fixed coronary artery disease precipitated by cocaine (SEDA-9, 35) (19-21). However, myocardial infarction has been noted even in young intranasal users with no evidence of coronary disease (22), defined by autopsy or angiography (23,24). If applied to mucous membranes, cocaine causes local vasoconstriction, and, with chronic use, necrosis. 

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