Pharmacology of Methamphetamine Research Paper

Introduction

The deliberate misuse of a drug to derive a different effect from which it was originally intended is a menace and prevalent in many societies around the world, particularly those in the developed world including the United States of America.. Drug misuse is the bane of such societies, as individuals’ who misuse drugs invariably become dependent on drugs, destroying personal relations and their health, putting themselves and others in danger, and running the potential risk of ending up serving a penitentiary sentence. Controlling and preventing the misuse of drugs has this multi-dimensional perspective to it (Wasilow-Mueller & Erickson, 2001).

Wesson & Smith 1999, p.614, define the misuse of medicinal drugs as “a nebulous construct whose common denominator is that medicinals manufactured by the pharmaceutical industry are being used in ways that were not intended by regulatory agencies and in ways that were not approved by the mainstream culture”. The National Institute on Drug Abuse (NIDA) has classified three types of drugs that are the most frequently abused or misused. These are Opioids, Central Nervous System (CNS) depressants, and CNS stimulants. Stimulants find a role in the treatment of mental disorders including attention-deficit hyperactivity disorder in children (Prescription Drug Abuse Chart).

Methamphetamine is chemically closely related to the commonly used decongestants ephedrine and phenylpropanolamine. It belongs to the drug class of stimulants. Routes through which methamphetamine is ingested into the body are by injection, by smoking, by snorting, or through the oral or rectal route. Methamphetamine produces feelings of euphoria and increased energy that last for up to twelve hours and is the cause of its misuse (Colfax, 2005).

History and Details of Methamphetamine

The medical history of methamphetamine extends back in time by nine decades when methamphetamine was synthesized by a Japanese pharmacologist in 1919. The initial use of methamphetamine for widespread medical use was in the form of a nasal decongestant that led to its use in inhalers for the treatment of rhinitis and asthma in the 1930s. It was not long before its stimulant, euphoric and anorectic effects were understood, leading to the abuse of methamphetamine. Methamphetamine produces euphoria and stimulant effects that are similar to cocaine, but over a longer duration, and the ease with which it can be made available has led to its widespread misuse, such that emergency departments witness a similarity in the rate of methamphetamine-intoxicated patients and cocaine-intoxicated patients. The background of individuals misusing methamphetamine is very broad across the whole panorama of age, socio-economic status, and ethnic background. Misuse of methamphetamine has increased rapidly because it is more readily available, less expensive, and works longer than cocaine (Derlet & Albertson, 2008).

Methamphetamine ranks high on the list of drugs that are misused. Cannabis is the most frequently abused substance and methamphetamine ranks just below it with over 35 million users worldwide. The United States National Survey on Drug Use and Health in 2005 has reported that about 10.4 million (4.3%) Americans in the age group of twelve and older had tried methamphetamine. Methamphetamine misuse is costly to the society, as it leads to violence, economic non-productivity, and harm to the health of the individual (Gupta, Bailey & Lovato, 2009).

Methamphetamine has two enantiomers namely dextrorotary (d) methamphetamine and levorotatory (l) methamphetamine. d-Methamphetamine is a schedule II controlled substance that is available through prescriptions and in the trade name of Desoxyn in different colored tablets on the basis of strength under the drug class of CNS stimulant, sympathomimetic and appetite suppressant. The 5mg tablets are white, the 10 mg tablets pink and the 15 mg tablets yellow. Medical uses of methamphetamine include the treatment of narcolepsy, attention deficit disorder (ADD), and attention deficit hyperactivity disorder (ADHD) (Methamphetamine and Amphetamine)

d-Methamphetamine is one of the commonly abused prescription drugs. The l isomer of methamphetamine is available over the counter (OTC) and is a misused over the counter drug. l-Methamphetamine is the active ingredient of levmetamfetamine in the commonly used Vicks Vapor Inhaler manufactured by Proctor and Gamble and available as an over the counter product and is an example of methamphetamine available in drugs sold over the counter. The Vicks inhaler contains approximately 50 mg of l-methamphetamine, which when used as directed is estimated to deliver doses that range between 1.9 to 7.2 mg of the drug on a daily basis (Mendelson et al, 2008).

Pharmacokinetics of Methamphetamine

Methamphetamine differs from amphetamine by the presence of a methyl group. This makes methamphetamine more easily absorbed into the central nervous system (CNS) than amphetamine and has an extended half-life of approximately twenty hours. The enhanced toxicity of methamphetamine over amphetamine is thought to be the cause for this increase in speed of absorption into the CNS and the potency for dopamine and glutamate absorption. The toxicity of methamphetamine arises from the mediation through the mitochondria in the production of free radicals. This process is inhibited by glutathione and l– carnitine (Ballas, Evans & Dinges, 2004).

Methamphetamine belongs to the group of noncatecholamine, sympathomimetic amines that have CNS stimulant activity, which results in catecholamine efflux with inhibition to the reuptake of these neuro-transmitters. Methamphetamine is extremely soluble in lipids and peak levels are quickly achieved in less than two hours. This extreme solubility of methamphetamine in lipids is responsible for methamphetamine being quickly distributed into the tissues and across the blood brain barrier (Ballas, Evans & Dinges, 2004).

Methamphetamine is a weak base and this makes it possible for alterations in its elimination from the human body. Excretion of Methamphetamine takes place through urine, in which it can be detected, and the half life varies between sixteen to thirty hours. When the urine is acidic the speed of excretion of methamphetamine is increased, while if the urine is alkaline the speed of excretion of methamphetamine is decreased. Usually about thirty percent of the methamphetamine ingested is secreted unaltered. In a further twenty percent is the amine group is removed to convert the methamphetamine to phenylacetone and to a very small extent into parahydroxyamhetamine. The phenyl acetone is gets oxidized to benzoic acid and is excreted from the system as hippuric acid. A very small amount of phenylacetone is metabolized (hydroxylation) by the cytochrome P4502D6 enzyme (Ballas, Evans & Dinges, 2004).

Pharmacodynamics of Methamphetamine

The stimulation of the CNS by methamphetamine is responsible for the clinical effects of euphoria, enhanced emotions, and alteration in self esteem, increased alertness, aggression, and sexual appetite seen in the abuse of methamphetamine. Methamphetamine that is quickly absorbed into the system crosses the blood brain barrier to have its effect on the brain and the CNS. Presynaptic intake of the catecholamines dopamine and norepinephrine are blocked, leading to hyper stimulation at selected postsynaptic neuron receptors. The indirect sympathomimetic seen with methamphetamine is also due to the dual mechanisms of the blocking of the presynaptic vesicular storage and the reduction in the cytoplasmic destruction of catecholamines through the inhibition of mitochondrial monoamine oxidase, which is responsible for this action. In an indirect way these hyperstimulated neurons lead to stimulation of several other noncatecholaminergic central and peripheral pathways. To a lesser extent than seen with ephedrine methamphetamine can also directly cause stimulation of the central and peripheral pathways. It is believed that the changes in mood, excitation, motor movements, sensory perception, and appetite are the result of central dopaminergic alterations, while the serotonin alterations are responsible for the mood changes, psychotic behavior, and aggressiveness associated with methamphetamine. The enhanced psychological and cardiac effects that are seen in combining methamphetamine with alcohol consumption and other drugs like cocaine is essential due to the pharmacodynamic impact of methamphetamine (Derlet & Albertson, 2008).

The initial “rush” experienced with methamphetamine is due to its action of causing the release of neurotransmitters like dopamine, serotonin and epinephrine. Methamphetamine causes an increase in the synaptic level of dopamine through the actions of inhibiting the activity of the reuptake of transporters and enhancing the release of vesicular dopamine stores. Studies of images of the brain confirm that methamphetamine increases the levels of dopamine, with particular reference to the nucleus accumbens, which is the reward center of the brain. The Nucleus Accumbens is believed to be the cornerstone to the mediation of addictive behavior (Colfax, 2005).

As long as the use of methamphetamine is acute, the increase in dopamine levels are seen, but this is altered in chronic use of methamphetamine. Chronic use of methamphetamine leads to depressed dopaminergic activity. It is speculated that the reason for this is that on repeated exposure to methamphetamine, there is a reduction in the axonal transporters, vesicular monoamine transporters, and synthesis pathways in the dopaminergic neurons. Such speculation is supported by animal studies that demonstrate that repeated exposure to methamphetamine causes degeneration and destruction of dopamine axon terminals in the CNS, and depletion in the brain stores of dopamine (Colfax, 2005). Clinical manifestations of the toxicity of methamphetamine are essentially centered on the central nervous system and the cardiovascular system. Cardiovascular impact includes chest pain, ischemia and myocardial infarction, tachycardia and palpitations (Derlet & Albertson, 2008).

Behavioral Aspects with Methamphetamine

The toxic effects of methamphetamine on the central nervous system lead to behavioral changes in the individual. Agitation, anxiety, hallucinations and toxic psychosis are associated with chronic use of methamphetamine. Changes in sexual appetite are also demonstrated. Chronic users of methamphetamine demonstrate agitation, anxiety and acute paranoia, which can gradually degenerate to mimic acute schizophrenia. Little concern for self hygiene is demonstrated by chronic users of methamphetamine, and there is also loss of self esteem. Sexual behavioral changes are common with chronic methamphetamine misuse, which results in high risk sexual behavior. Studies have shown that the high risk sexual behavior includes an having a high number of sexual partners and the practice of unprotected anal intercourse. This leaves methamphetamine open to sexually transmitted diseases like syphilis and the more dreaded HIV/AIDS (Colfax, 2005).

Misuse of Prescription Drugs and OTC Drugs containing Methamphetamine

Lessenger and Feinberg 2008, p.46 describe prescription medications as “those pharmaceuticals dispensed by a pharmacist on the presentation of a prescription written by a physician, dentist, or other health care provider who is legally authorized to write prescriptions”, while “OTC medications are pharmaceuticals that do not require a prescription and are sold on the shelves of markets, stores, and pharmacies”.

Medications are effective in the treatment of various diseases and conditions, when they are used in therapeutic dosages. These same medications become dangerous and addictive, when they are misused in excess of their recommended therapeutic dosages and used for purposes that they were mot intended for. This in essence means that prescription drug abuses are made up of a mix of behaviors by the physician, patient and addict, with the pharmacists the active bystander of the process (Wesson & Smith, 1999).

Desoxyn is a prescription drug containing methamphetamine which is used in the treatment of ADD, ADHD and occasionally for weight loss in obese patients not responding to other weight loss therapies (Medication Guide – Desoxyn). Deliberate misuse of prescription drugs is on the rise in the United States of America. Data contained in the 2005 National Survey on Drugs and Health shows that nearly 6.4 million individuals in the United States of America or 2.4% of the population have used prescription psychotherapeutic drugs for non-medical purposes Among the kinds of drugs thus misused is methamphetamine with about 512,000 individuals indulging in the misuse of prescription drugs containing methamphetamine. This shows the scope of the problem of misuse of prescription drugs containing methamphetamine (Lessenger & Feinberg, 2008).

Regulations on prescription drugs do not make it easy for misuse of prescriptions and the larger misuse of drugs containing methamphetamine occurs in the OTC medications, which are not regulated and do not need a prescription. Nasal decongestants sold over the counter like the Vicks inhaler contain the l isomer of methamphetamine and deliver low dosages of methamphetamine each time the inhaler is used. Mendelson et al 2008, found that in spite of widespread use of these inhalers there was hardly any published data available on their pharmacologic effects and scope for methamphetamine addiction and misuse through the use of these inhalers. Studying these aspects of inhalers containing methamphetamine in the opinion of Mendelsen et al 2008, the low dosages of methamphetamine in the inhalers do not demonstrate any of the toxicity of methamphetamine chronic use nor are there any addiction prospects that go towards the misuse of these OTC products. The doses of methamphetamine delivered through these inhalers are low leading to low plasma levels of methamphetamine. Only when the inhaler is used on an hourly basis is the detection of methamphetamine positive in urine tests. Small changes in cardiac measures were observed, but these changes are not clinically significant, despite l-methamphetamine having known cardio-depressant activity. In the opinion of Mendelson et al 2008, though individuals with hypertension and a history of adverse cardiac events may be at risk through the use of nasal decongestants containing methamphetamine, there is no risk for healthy individuals for cardio-vascular effects from inhalers containing methamphetamine and no risk of addiction. The authors however caution that the study has a number of limitations and these findings will have to be confirmed before they are accepted as evidence with regard to the use of inhalers containing methamphetamine sold of the counter for nasal decongestion (Mendelson et al, 2008).

Role of Healthcare Professionals in the Prevention of Methamphetamine Abuse

Deficiencies in the provision of quality healthcare service occur frequently and could lead to serious consequences. Among these deficiencies, which could be prevented, is the overuse and misuse of medications (Mannase, 2000). Methamphetamine abuse has serious health related consequences, making it important for nurses and healthcare professionals to devote attention to the prevention of methamphetamine misuse. It is the very health related consequences that place nurses and healthcare professionals in a position in the community to play a significant role in the prevention of the misuse of methamphetamine. Alterations in physiological and behavioural functioning are clear indicators of methamphetamine misuse, which may be missed out by the family, friends and other members of the community, but easily spotted by the healthcare professionals during the seeking of healthcare services (Venable, 2009).

In the first phase evaluation of the extent of misuse of methamphetamine can be carried out by the nursing professionals and other healthcare professionals to develop a detoxification plan. Dissemination of methamphetamine abuse to the community on the whole and the parents and friends of the affected person in particular to create an understanding of the need for detoxification in the affected individuals and support of the community in these efforts are another role that can be played by nursing and other healthcare professionals. Nursing and other healthcare professionals also play a role in evaluation of the detoxification plan, looking out for withdrawal signs and compensating for them, and return to normal physiological and psychological functioning as signs of success in rehabilitation of the patient. It must be remembered that for such rehabilitated patients even controlled use of methamphetamine must be avoided in the treatment of any ailments. Rehabilitation of many patients may require psychological counselling and appropriate referrals necessary as part of the action taken by nurses and other healthcare professionals. Finally, to be effective in preventing the misuse of methamphetamine nurses and healthcare professionals must make themselves aware of the resources available in the community and keep themselves abreast of the developments in methamphetamine misuse and its treatment (Venable, 2009).

Conclusion

Methamphetamine was initially developed as a medication for nasal decongestion and used in inhalers. However, its euphoric, stimulant and anorectic effects have led to its widespread misuse. Methamphetamine is easily absorbed in the body and has a long half-life in the human body making it one of the chosen drugs for misuse, leading to addiction. Methamphetamine easily crosses the blood brain barrier to have a strong affect on the brain and through that brings about several behavioral changes in the individual that could have severe consequences. For example changes in sexual behavior methamphetamine users at high risk for sexually transmitted diseases that include HIV/AIDS. The effects of chronic methamphetamine addiction include cardiovascular impacts that with severe consequences like myocardial infarction. Drugs containing methamphetamine continue to be sold on prescription and over the counter. Desoxyn contains methamphetamine and sold on prescription for the treatment of ADD, ADHD and narcolepsy and could lead to misuse of the medication. Nasal inhalers like Vicks inhaler continue to be sold over the counter and contain methamphetamine. A study into nasal inhalers containing methamphetamine suggest that the low dosages of methamphetamine present in these inhalers do not pose a health risk and also do not pose a risk for misuse of methamphetamine. Nursing and other healthcare professionals through their provision of healthcare services are in a position to play a significant role in the prevention of methamphetamine misuse. To be effective in this they must equip themselves with communication, evaluation and planning skills, and also know the community resources and the latest developments in methamphetamine abuse and its treatment.

Literary References

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