The Effects of Long Term Heroin Use on the Immune System - Essay Example

The Effects of Long Term Heroin Use on the Immune System The following paper is based on the case study ‘The Effects of Long Term Heroin Use on the Immune System’. It discusses the adverse effects of long term heroin abuse, including its deleterious impact on the immune system, as a consequence of which even fairly innocuous infections, like tooth infections, can eventually cause mortality. The following paper is divided into five main sections. The first section gives a brief introduction to substance abuse and its epidemiology with particular reference to heroin addiction. This is followed by an overview of the medical sequelae of heroin abuse in the second section. The third section gives a basic understanding of the key players involved in immunological processes with regard to their specific role in combating different types of micro organisms. The following section then describes how each of these cell lines is affected by the long term use of heroin and other opioids and what are its consequences. In the last section, all the main points are summarized and discussed in reference to the example give in the case study. INTRODUCTION AND EPIDEMEOLOGY Substance abuse is a global health issue that has become increasingly prevalent in recent years. According to the Diagnostic (DSM IV) substance dependence is defined as: A maladaptive pattern of substance use leading to clinically significant impairment or distress as manifested by one (or more) of the following, occurring within a 12-month period: (i) significant functional and occupational impairment (ii) use of the substance when physically hazardous (iii) recurrent legal problems (iv) recurrent social and interpersonal problems. (DSM-1V-TR c. 2002) Among other psychoactive substances, the use of heroin has also increased over the past years and in 1996 it was shown to be the most common opiate of abuse in the US (Kreek 1996 cited in Brick 2003:219). The annual global prevalence of opioid dependence has been estimated to be around 0.14% (Van Der Burgh C. 1999 cited in Madoz 2003:263). The DAWN survey conducted by the National Institute on Drug Abuse showed that approximately two million people in the United States were heroin abusers and amongst them 500,000 fell into the category of “hardcore” addicts of heroin (Kreek 1990:199). The term “hardcore” has been defined as “repeated use of heroin three to six times a day for over 1 year, with development of tolerance, dependence, and drug-seeking behavior” by the National Institute on Drug Abuse (Kreek 1987b, National Institute on Drug Abuse 1983 and National Institute on Drug Abuse 1987 cited in Kreek 1990:199). Heroin abuse is a serious concern not only because of the effect it has on the individual who abuses it but also because of the impact it has on the society as a whole. In addition to being a major health issue, it is increasingly becoming an economic burden since it not only contributes towards health related costs but also impairs a person’s productivity both at home and at work. HEROIN ABUSE AND ITS MEDICAL CONSEQUENCES Heroin is a psychoactive drug belonging to the class opioids. It is synthetically derived from morphine, which is extracted from the seeds of the opium poppy plants (National Institute on Drug Abuse c. 2008). Opioid drugs have a wide range of uses the most important one being their use as analgesic compounds, however they also have several adverse effects including physical dependence to the drug. Heroin can be administered in several forms i.e. via smoking, snorting or injections. There are two different methods of heroin administration via injection: (i) “skin-popping” i.e. injecting directly under the skin or intramuscularly or (ii) “mainlining” i.e. injecting it into the bloodstream via veins. Among other possible hazards, both these modes of injection have been found to increase ones susceptibility to HIV infection (South Carolina Department of Alcohol and Other Drug Abuse Services c. 2001). Heroin is commonly available in three different forms in the United States viz. pharmaceutical heroin (i.e., diamorphine), white heroin and brown heroin (Strang et al. 2001:575) Once heroin has been administered, it is transported to the brain, where it is metabolized to morphine which interacts with opioid receptors (National Institute on Drug Abuse c. 2008). Opioid receptors have been found throughout the human tissues and organs including the central nervous system where three main kinds of opioid receptors are found viz. the µ (Mu), κ (Kappa) and δ (delta) receptors (Vallejo 2004:355). Amongst other locations in the central nervous system, opiod receptors are also found in the brainstem. The brainstem is a region of vital importance since it controls various important functions such as respiration, arousal (level of consciousness) and maintenance of blood pressure (National Institute on Drug Abuse c. 2008). By its action on almost all organs and the central and peripheral receptors heroin is known to cause a vast variety of physiological effects some of which maybe pleasurable (e.g.: euphoria) but most of which are detrimental. The effects of heroin abuse can be categorized as short term and long term. Most heroin abusers report experiencing a feeling of euphoria (“rush”) following drug administration. The intensity of this pleasurable feeling depends on the amount and concentration of the drug and also the rate at which it enters the central nervous system and binds to opiod receptors. There are also other accompanying symptoms such as dry mouth, nausea, vomiting, flushing of the skin, and a feeling of heaviness of the extremities (National Institute on Drug Abuse c. 2008 and National Institute on Drug Abuse n.d.). Following this transient euphoric state, the users experience a state of altered level of consciousness, with alternating periods of drowsiness and wakefulness. This is termed as "on the nod". This state is accompanied by slurring of speech, gait abnormalities, ptosis and miosis, impaired night vision and slowing of respiration and cardiac functioning (National Institute on Drug Abuse c. 2008 and National Institute on Drug Abuse n.d.). There is a multitude of well documented adverse sequelae of chronic heroin use the most important ones being dependence and addiction. Previously, these sequelae were accredited to the unhygienic practices and means of self-administration of the drug but later, heroin and its metabolites have also been found to play a role (Vallejo 2004:355). Studies have shown heroin use to be associated with a six to twenty times increase in mortality (Brick 2003:222) and an increase in the risk of committing suicide by fourteen times (Theodorou 2006:258). Other complications commonly manifested in heroin addicts include abscesses, cellulitis, cirrhosis and other chronic liver diseases, , stroke, gynecological and obstetrical problems, renal failure, wheezing, constipation, weight loss and increased susceptibility to infections particularly skin infections, endocarditis, osteomyelitis, pneumonia, Hepatitis B and C and HIV (South Carolina Department of Alcohol and Other Drug Abuse Services c. 2001). These findings are supported by the study conducted by Lazzarin et al. (1984) which showed that viral hepatitis, recurrent dental abscesses, subcutaneous abscesses, phlebitis, and respiratory infections were the major types of infections which were commonly found in heroin addicts (Lazzarin et al.1984 cited in Bhargava 1990:228). Moreover, heroin drug abuse has also been related to a reduction in the level of immunity and this has been an arena of particular interest recently. Some of the important manifestations of heroin abuse deserve special mention due to their potentially serious consequences and are discussed below: Skin Infections The most common infections found in heroin addicts are skin infections (Heverkos 1990 cited in McCann 2000:322). There are several factors which increase the risk of heroin addicts to contract skin infections as compared to normal individuals. These include the practice of ‘skin popping’ as a method of drug administration, use of contaminated injection needles and needle sharing amongst several individuals and concomitant use of heroin and cocaine, which is commonly referred to as ‘speedballing’(Murphy 2001 cited in Theodorou 2006:259). Numerous organisms have been implicated in causing skin infections in drug addicts, the most common ones being Staphylococcus aureus and streptococcal species. However, more recently several uncommon organisms have also started emerging as important disease causing organisms in this vulnerable population. These include Bacillus cereus infection and botulism (Dancer 2002 and Brett 2004 cited in Theodorou 2006:259). The emergence of these organisms has been attributed to the presence of contaminants in heroin (Dancer 2002 and Brett 2004 cited in Theodorou 2006:259). Bacterial Endocarditis and Pulmonary complications. It has been postulated that injection drug use can cause damage to the valvular endothelium and also leads to the formation of platelet fibrin deposits. The presence of endothelial damage and hypercoagulable state makes such individuals susceptible to bacterial endocarditis (Stein 1999 and Mientjes 1996 cited in McCann 2000:322). About half of these cases of endocarditis are right sided and the valve most commonly involved is the tricuspid valve. The most common organism implicated in the etiology of endocarditis in injection drug users is Staphylococcus aureus, although other organisms such as Pseudomonas and certain fungi have also been isolated (Moreillon 2004 cited in Theodorou 2006:260). Since right sided endocarditis is more common, pulmonary manifestations and complications are also very common in heroin abusers. These include pulmonary embolism and infarction, Pneumonia, Tuberculosis and even occasional cases of talc granulomatosis (Stein 1999 and Mientjes cited in McCann 2000:322) Blood borne Viruses – Hepatitis and HIV It is a well established fact that drug abuse is associated with increased incidence of infections with blood borne viruses. Heroin abuse has also been documented to be associated with these consequences. Kuo and colleagues observed that as compared to the general population, injection drug abusers are at a higher risk of infection with hepatitis B (Kuo 2004 cited in Theodorou 2006:260). Similarly the incidence of Hepatitis C is also higher in heroin addicts and it is to such an extent that it can be considered as an endemic within this population. Studies have shown the prevalence of Hepatitis C infection to be between 70 and 90% in injection drug abusers (Abraham 1999 and Garten 2004 cited in Theodorou 2006:260). The risk of hepatitis A infection in drug addicts is also higher as compared with the rest of the population (Franco 2003 cited in Theodorou 2006:261). The most serious and important disease contracted as a result of heroin abuse via injections is HIV infection. It has been well established that one of the major risk factors contributing to the increasing incidence of HIV is injection drug abuse and this risk of transmission multiplies by needle sharing (Khalsa 2004 cited in Theodorou 2006:262) . Some factors which contribute towards the increased incidence and prevalence of the above mentioned complications, in particular infections, and reduced immunity in heroin addicts include: (i) the sharing of non-sterile needles amongst drug addicts which promotes transmission of other blood borne micro-organisms such as Hepatitis and HIV which themselves influence immunity (ii) concomitant use of other psychoactive substances such as alcohol and (iii) the effect of heroin and the drug contaminants on the individuals’ immune status (Lundy et al. 1975 and Patel et al. 1985 cited in Bhargava 1990:228). IMMUNITY Immunity, which is described as the ability of the body to resist or fight disease, is of two types: cell mediated immunity and humoral immunity. Cellular immunity is mediated via two basic cell lines. These include T cells, which are so named because they acquire maturation within the thymus gland, and macrophages. Humoral immunity, on the other hand is mediated via B cells which in response to antigens, on the surface of foreign cells, produce antibodies. T cells carry different markers on their cell membranes. Based on the biochemical properties of these markers, these cells have been divided into two main kinds: CD4 cells, the function of which is to act as helpers and inducers, and CD8 cells, which are cytotoxic in nature (Bhargava 1990:251).The proper interplay and balance between these cell lines is necessary for the proper functioning of the immune system (Mosmantr 1996 and Rmognani 1994 cited in Somiani 2008:40) Other important cells involved in the immune response are macrophages, monocytes and Natural Killer cells (NK cells). Macrophages and monocytes are phagocytes. They serve the purpose of processing antigens and displaying them on their surface so that they can subsequently be recognized and destroyed by CD4 cells. NK cells, on the other hand, are cytotoxic lymphocytes which differ from the T lymphocytes in that they do not carry the T cell receptors. These cells are involved in combating virus infected cells and tumor cells (Bhargava 1990:251). HEROIN USE AND IMMUNOMODULATION The concept of immune modulation by opioids has been in existence since as early as the 19th century, when Cantacuzene demonstrated immunosupression and decreased resistance to bacterial infections in guinea pigs when following opium administration (Vallejo 2004:355). Later, Kreek et al observed lymphadenopathy, lymphocytosis, hyperimmunoglobulinemia, and altered Tcell function found in chronic heroin abusers and proposed that opiate administration had a role in these alterations of the immune system (Brick 2003:227). Opioid receptors have been discovered on the cells of the immune system, including lymphocytes and mononuclear phagocytes, and their role in immune modulation via central and peripheral mechanisms has been established. Heroin has been shown to act directly by interacting with opioid receptors located on lymphocytes and macrophages (Stefano, 1996; Nelson et al., 2000 cited in Zajicova 2004:1) while it acts indirectly via its action on the cells of the nervous system (Peterson et al., 1998 cited in Zajicova 2004:24). Experimental human and animal models have shown that opioids affect not only the acquired immunity but also the innate immunity (Einsenstien 1998, Yeager 1996 and Yokota 2000 cited in Somiani 2008:40). Endogenous opioids have been shown to enhance the function and activity of Natural Killer cells (NK cells) and T-lymphocytes. In contrast to this, exogenous opioids have been shown to cause immunosupression by its affect on almost all cell lines including NK cells, phagocytes and lymphocytes (Vallejo 2004:355). Heroin abuse impairs the proper functioning of almost all the important cells of the human immune system. The effects of heroin and other opiates on all the different cell types are discussed below: Effect of long term heroin use on T Lymphocytes. Opiod use has been shown to affect both the count and the function of lymphocytes. A study by McDonough et al demonstrated a decrease in the absolute T lymphocyte count and also a reduced number of active T lymphocytes in heroin addicts (McDonough et al., 1980 cited in Govitrapong 1998:883). It has been further proven that in addition to a decrease in the number of T lymphocytes there is also a reduction in the response of these cells to mitogenic factors (Govitrapong 1998:887).This subsequently leads to decreased proliferation of lymphocytes and macrophages in response to mitogen stimulation (Govitrapong 1998:888). Effect of long term heroin use on Natural Killer cells. It has been proven in literature that NK cells are highly susceptible to the affects of heroin and even acute administration of heroin reduces the activity of NK cells. The onset of action of the effects of heroin on NK cells begins within hours and has been shown to persist even after discontinuation and abstinence from the drug (Brick 2003:228). Studies have proven that opioids via their interaction with receptors in the brain suppress the activity of NK cells although their absolute numbers may remain unaffected (Novick et al., 1989 cited in Govitrapong 1998:888). Effect of long term heroin use on CD4 and CD8 Cell lines. Long term heroin use affects both the absolute number of different T cell subtypes and the proportion of T-helper and cytotoxic T cells (CD4/CD8) leading to a decline in the CD4/CD8 ratio (Donahoe et al., 1987 cited in Govitrapong 1998:888). Effect of long term heroin use on Humoral Immunity. In addition to its effects on the cellular arm of the immune response, heroin abuse also has an impact on humoral immunity. Eisenstien and Peng observed a reduction in the antibody response to antigenic stimuli in animal models following long term exposure to heroin (Eisenstein 1993 and Peng 2001 cited in Schwacha 2008) In a study of 38 heroin addicts, Brown et al, showed that long term heroin abusers had abnormal immunological function as evidenced by increased levels of gamma globulins i.e. increased levels of IgM and IgG. This increase is gamma globulin production subsequently led to false positive tests for syphilis in this population. (Brown et al. 1974 cited in Bhargava 1990:222). Effect on Polymorphonuclear lymphocytes. The prolonged use of opioids also depresses the activity of polymorphonuclear lymphocytes and monocytes and compromises their effective functioning. This was demonstrated by Tubaro et al. who noticed a decrease in the effective functioning of macrophages and monocytes in heroin effects and also found that these cell lines were compromised in their function of producing superoxide ions while encountering stress (Tubaro et al. 1985 cited in Bhargava 1990:222). Influence of long term heroin use on the Autonomic Nervous System and the Hypothalamic Pituitary Adrenal Axis (HPA). Administration of heroin has both acute and chronic effects on the immune system. The acute effects have been shown to be modulated via the autonomic nervous system while chronic administration leads to the activation of the hypothalamic pituitary adrenal axis (HPA) (Vallejo 2004:2). Following heroin administration, the sympathetic component of the autonomic nervous system is activated. This leads to an activation of the adrenal medulla which responds by production and release of epinephrine, nor-epinephrine and dopamine. Similarly, these substances are also produced in the sympathetically innervated lymphoid organs (Fecho 1995 and Budd 2004 cited in Somiani 2008:40). Chronic use of opioids effects neuroendocrine functioning in the following way: heroin and its metabolites cause the activation of the HPA axis which leads to the production and release of glucocorticoids including cortisol. Under normal circumstances, the activity of the HPA axis is under control via negative feedback mechanism. Increased levels of glucocorticoids in the bloodstream lead to feedback suppression of the Corticotropin Releasing Hormone (CRH) at the levels of the hypothalamus. Feedback also occurs at the level of the anterior pituitary gland via suppression of the production and release of beta-endorphin and ACTH. Long term heroin use alters this normal regulation via negative feedback resulting in abnormal levels of cortisol in heroin addicts (Kreek 1990:208). Studies have shown that both nor-epinephrine and glucocorticoids negatively affect the immune system by depressing the functioning capacity of leukocytes (Somiani 2008:40). Additionally, opioids have not only been shown to be similar to cytokines in numerous ways but also to influence the production, secretion and action of cytokines (Vallejo 2004:356). All these effects of prolonged heroin use subsequently lead to depression of immunity and hence, increased susceptibility to bacterial and viral infections (Louria et al., 1967 cited in Zajicova 2004:24) DISCUSSION AND SUMMARY Heroin is an opiate which affects the physiological functions of the body in many ways. It has been shown to have both long and short term effects on almost all the organs and systems of the human body. Heroin abuse has a potential for dependence and addiction and its long term use leads to serious consequences. One of the most important implications of heroin abuse is its tendency to increase the vulnerability and susceptibility of its users to a variety of infections including bacterial, viral, fungal and protozoal. This predisposition to infections has been thought to arise from an interplay of several factors the most important one being immune suppression due to prolonged use of heroin. The effects of heroin on the immune system are well documented in literature and discussed above. In summary, chronic heroin use has the following effects on the different cell lines of the immune system: I. Decrease in the number and function of T lymphocytes; II. Attenuation of lymphocyte proliferation in response to mitogenic stimulation; III. Reduced activity of NK cells; IV. Compromised phagocytosis by macrophages; V. Altered proportion of CD4/CD8 cells; VI. Increased levels of gamma globulins i.e. IgM and IgG; VII. Increased production of norepinephrine; and VIII. Activation of the HPA axis. Once all these immune functions are modified in an individual, he/she becomes predisposed to contracting several kinds of infection. Since both the cellular and humoral immunity are compromised the individual is at a risk of contracting both viral and bacterial infections. In the case study, the 35 year old man, had been a heroin addict for almost 10 years. With such a prolonged history of heroin abuse, it is highly likely that his immunity was significantly impaired. Such heroin addicts, due to their impaired immunity and also due to the non hygienic heroin administration practices, are at an increased risk of contracting infections. The gentleman in the case study contracted a tooth abscess. Tooth abscess are commonly caused by bacteria. In normal, healthy individuals, the body mounts an immune response to such innocuous infection. When the body encounters a foreign organism, the antigens displayed on the cell membrane of the offending organism are detected by the immune cells. These antigens are processed and displayed on the surface of macrophages and subsequently presented to CD4 cells which help in the induction of the cellular immune response. Humoral immunity also plays a role b y the production of Ig M and IgG antibodies, which provide short- term and long-term immunity, respectively. The foreign organism is therefore destroyed and the infection contained. This response is augmented and supplemented by the use of antibiotics. In this particular case, however, despite being prescribed antibiotics, the host immune response was not able to counter the microorganisms causing the abscess. 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(2004) ‘The Alterations of Immunological Reactivity in Heroin Addicts and Their Normalization in Patients Maintained on Methadone’ Folia Biologica (Praha) 50:24-28. Read More