Addiction Treatment Blog

Illness is in part what the world as done to a victim but in a larger part is what the victim has done with his world, and with himself.

Karl Menninger, quoted in ‘Illness as Metaphor’ by Susan Sontag.

Drug abuse is a cause for many serious illnesses, including HIV (AIDS).

From time to time the healthcare professional will encounter an individual with a medical condition who abuses drugs. Although not condoning the taking of these substances, it is desirable that those in a position to advise are able to provide information on whether the drug is liable to exacerbate the condition. The sections below provide brief details which may be helpful in advising those with some of the more common medical conditions. The information given should be used as a guide only. The data available are sparse in most cases and while it is hoped that the details in this chapter will be useful, every patient’s particular circumstances will differ and one should be cautious about extrapolating limited information to all situations in which it could be applicable.

It is difficult to find data in the advisability of drug abuse in those suffering from concomitant medical conditions. The data given here are based upon details of side effects that have been reported in the medical literature and knowledge of drug handling by the body. This information is incomplete because none of the drugs of abuse have been subject to large-scale clinical trials at the doses abused. This is the main mechanism by which side effect profiles of therapeutic drugs are determined. This being the case, most of the data on adverse effects from street drugs are derived from small-scale studies, case reports, surveys and anecdotal evidence. Causality can also be difficult to ascertain because many users employ a variety of drugs simultaneously. Many drug abusers have a poor quality of life due to bad living conditions and/or inadequate nutrition; this may make them more susceptible to various diseases.

This blog considers a large number of individual drugs of abuse. For the purpose of this chapter the drugs considered will be those which are most commonly encountered: opioids, LSD, amphetamines and ecstasy, cannabis, cocaine, volatile substances, alkyl nitrites, benzodiazepines, anabolic steroids, caffeine, alcohol, tobacco and antimuscarinics.

Asthma

The drugs which are inhaled or smoked are most likely to cause respiratory symptoms. When taken this way, cocaine can cause cough, bronchospasm, wheezing and even status asthmaticus. It has also been associated with a hypersensitivity reaction which is characterised by breathlessness, cough and pyrexia. Hypersensitivity to any drug of abuse can manifest as bronchospasm – this reaction has even been associated with alcohol – but in many cases it can be difficult to determine whether the individual is hypersensitive to the drug of abuse or to any adulterants or additives present.

When smoked, cannabis and tobacco impair gaseous exchange, deposit tar in the lungs and can cause bronchitis. The inhalation of smoke particles can trigger an asthmatic attack either in the smoker or in those subject to passive smoking. Regular smoking of cannabis or tobacco usually results in a markedly increased metabolism of theophylline, a drug widely used in the treatment of asthma. Increased metabolism of theophylline gives rise to decreased duration of action and reduced concentrations of the drug in plasma.

Overdose of intravenous opioids can cause bronchospasm, respiratory arrest and pulmonary oedema. However, in the absence of overdose, heroin is occasionally reported to cause bronchospasm when injected or vaporised although the role of adulterants in eliciting this response is unclear. Repeated injection of any street drug can cause pulmonary talcosis due to the presence of insoluble excipients or adulterants in the liquid injected. These can accumulate in small blood vessels in the lung and cause respiratory distress.

Theoretically, large doses of benzodiazepines can cause respiratory depression but in practice even large doses fail to have significant effect upon respiration unless the individual has moderate to severe pre-existing respiratory impairment.

Diabetes

Alcohol can cause hypoglycaemia by a variety of mechanisms. It may be delayed up to 36 hours but it usually only occurs after acute ingestion of large quantities of alcohol. Alcohol may also potentiate the effects of insulin or oral hypoglycaemic drugs. Chronic heavy drinking is commonly associated with hyperglycaemia, glucose intolerance or frank diabetes. Drinkin within nationally recommened limits is not likely to have adverse effects on glycaemic control. Cannabis has been reported to cause a slight increase in blood glucose but this is not clinically relevant unless large doses are taken regularly and even then the reaction is very rare. Insulin-dependent diabetics that smoke require up to 30 per cent more insulin than non-smokers. This means that diabetics that start or stop smoking are likely to have to adjust their insulin requirement. Conversely, diabetics given certain anabolic steroids seem to require much less insulin. It is not clear whether this effect can occur with all steroids; it has been reported for nandrolone, stanozolol, methandienone and testosterone.

Certain drugs might be expected to affect glycaemic control in other ways. The stimulant drugs amphetamine, ecstasy and cocaine can all cause loss of appetite, which could lead to hypoglycaemia in diabetics who do not reduce doses of insulin or sulphonylurea once food intake declines. Cannabis, on the other hand, can increase appetite. The balance of food intake and dose of hypoglycaemic drug can also be disrupted by vomiting, which is a recognised side effect of most drugs of abuse except LSD, caffeine, benzodiazepines, nitrites and anabolic steroids. The stimulant drugs and anabolic steroids also increase stamina which could result in hypoglycaemia due to overactivity.

The apathy and poor motivation engendered in some individuals by chronic drug dependence may mitigate against adequate control of blood glucose. Non-compliance with diet, failure to administer medication correctly or inadequate monitoring could result from this. Intoxication may prevent a diabetic recognising and/or dealing with a hypoglycaemic episode. The hypoglycaemic episode can also resemble intoxication, so bystanders may not seek medical attention.

In one study, 26 out of 79 adolescent diabetics stated that alcohol or drugs had altered their diabetic control but no further details were provided.

Epilepsy

Very little research has been performed into the effects of drug abuse on epilepsy. However, it is known that certain drugs can cause convulsions and so, as with therapeutic drugs that have proconvulsant properties, one would assume that epileptics would be more prone to this effect and should preferably avoid these drugs.

Of all the illicit drugs, cocaine probably has the strongest association with drug-induced convulsions. Alldredge et al. described 23 cases in San Francisco where cocaine was the sole drug taken; seizures were reported following administration of cocaine by any route. Other reviews have similarly established link between cocaine abuse and convulsions. The reaction is also a well-known symptom of cocaine overdose. However, one study of 308 patients presenting to a casualty department in New York with seizures failed to identify cocaine as a risk factor despite it being commonly abused by patients and by controls.

Amphetamine has been linked to drug-induced fits but the link is less well established. Eight suspected cases in non-epileptics were reported in one US study. Ecstasy would be expected to be capable of causing convulsions because it is an amphetamine derivative. Both ecstasy and amphetamine can cause fits as part of the sequelae of drug-induced hyperpyrexia or hyponatraemia (see Amphetamines and Ecstasy) but, outside these scenarios, ecstasy-induced fits have not been described in the medical literature. Phencyclidine is known to cause seizures after both normal street-level doses and after overdose.

Fits may occur as a sign of heavy alcohol abuse or, more commonly, as a result of alcohol withdrawal. Chronic, regular, high intake of alcohol also accelerates the metabolism of commonly used anticonvulsant phenytoin. Benzodiazepine withdrawal can cause convulsions but this is not common and tends to occur mainly with the shorter acting forms such as lorazepam. Heroin abuse is associated with fitting, as are other opioids when used in high dose therapeutically. However, this effect of therapeutic opioids has been attributed to accumulation of preservatives or to the misdiagnosis of intense opioid-induced muscular rigidity. Opioid withdrawal is not associated with convulsions in adults but seizures have been occasionally described in neonates undergoing withdrawal due to in utero exposure. Overdose with dextropropoxyphene or pethidine is particularly linked to drug-induced fitting. Use of pethidine or pethidine analogues in patients with renal failure has also been associated with convulsions due to accumulation of a neurotoxic metabolite, norpethidine.

Caffeine can probably cause fits, as can the closely related theophylline but only after extremely large doses which would be unattainable by all but the most fanatical imbiber. Cannabis has been described as a cause of seizures in only one published case report. However, Feeney reported 13 epileptics who used cannabis; one stated that the drug decreased his seizure frequency, another said that cannabis caused his seizures and the remainder felt that cannabis had no effect. Most studies suggest that if cannabis has any effect at all on epilepsy, it should protect against convulsions. Some of the constituent cannabinoids have been used for this purpose therapeutically.

Benzodiazepines would be expected to protect against convulsions. However, this group of drugs can have an unpredictable effect upon plasma phenytoin levels. Reports of increased, decreased and unaltered levels have been described.

The following drugs have not been reported to cause convulsions: LSD, nitrites, volatile substances, benzodiazepines (non-withdrawal), tobacco, antimuscarinics and anabolic steroids.

Hepatic Failure

In individuals with impaired hepatic function, it is important to consider the potential toxic effects of drugs of abuse upon the liver as well as the effect of decreased hepatic function upon the clearance of these drugs.

Hepatotoxicity

In terms of the potential to cause hepatotoxicity, the drugs of abuse can be divided into three groups as follows:

Non-hepatotoxic

There is no evidence, or insufficient evidence, for certain drugs of abuse causing liver damage. These drugs are cannabis, LSD, caffeine, tobacco, alkyl nitrites and antimuscarinics.

Weak link to hepatotoxicity

For the drugs in this category, the evidence for hepatotoxicity comes from a small number of case reports, and/or the reaction is very rare, and/or the validity of reported observations have been questioned. The drugs in this category are following:

Benzodiazepines

Cholestasis and hepatocellular injury have been attributed to this group of drugs. In reviewing the literature, the number of cases is small compared to the very wide usage of benzodiazepines and in many cases patients are reported as taking other drugs known to be hepatotoxic at the same time.

Amphetamine

The number of reported cases is small. More cases have been described with the related drug ecstasy (see below).

Volatile substances

Hepatic damage is a rare complication of thrichloroethylene abuse and of toluene abuse.

Cocaine

Cocaine is hepatotoxic in mice. In humans, minor elevation of various liver enzyme levels is quite common in cocaine abusers. Hepatic necrosis has also been reported, including fatal cases, but, in a detailed review, Farrell concluded that there was insufficient evidence for cocaine being directly hepatotoxic in humans. In all published cases, human liver damage could be attributed to hepatic ischaemia as all patients involved were suffering from shock, hypotension, hyperpyrexia, rhabdomyolysis or renal failure. By contrast, in vitro experiments with human liver cells suggest that cocaine can be directly cytotoxic and that alcohol could potentiate the hepatotoxicity of cocaine under the test conditions. However, in turn, these results were not confirmed in a large study of human alcoholics that abused cocaine.

Opioids

Reports of opioid-induced hepatic failure are extremely rare. Liver biopsies have shown that those who inject heroin may have sinusoidal dilatation, and sinusoidal and hepatic vein inflammation. In ex-abusers this inflammation is largely replaced by fibrosis. However the functional significance of these changes is unclear. Studies using cultured human hepatocytes have suggested that alcohol may potentiate the cytotoxic actions of heroin and methadone.

Well-established hepatotoxicity

It has been clearly documented that alcohol, anabolic steroids and ecstasy can cause liver damage.

Alcohol is associated with a range of liver disorders. Fatty liver can occur to some degree in anyone who drinks a large amount of alcohol, even when this is episodic. It appears to be a dose-related phenomenon and is usually completely reversible when alcohol intake ceases. Acute alcoholic hepatitis occurs as a result of chronic high alcohol intake and involves an inflammatory reaction within the liver, often accompanied by fatty change and jaundice. It is probably reversible if the individual survives and stops drinking but may be a precursor to alcoholic cirrhosis. Cirrhosis itself occurs subsequent to many years of heavy drinking and may progress to hepatocellular carcinoma.

Anabolic steroids are known to cause cholestatic jaundice, which is usually reversible but can rarely progress to peliosis hepatis. Adenoma and hepatocellular carcinoma are also potential adverse effects. Ecstasy has been reported to cause acute hepatitis accompanied by jaundice.

Drug accumulation in hepatic failure

All of the drugs of abuse considered in this chapter except three are largely eliminated via the liver, so hepatic failure may allow any of them to accumulate to a greater or lesser extent. The exceptions are:

• Ecstasy. This is mainly eliminated renally (about two-thirds), so hepatic failure may make little difference to clearance.
• Volatile substances. Most volatile substances are excreted via the lungs, so that even in severe liver failure they will be cleared normally. Toluene is an exception since it is partly liver metabolised.
• Cocaine. This is largely metabolised by pseudocholinesterases which are concentrated in the liver but also found elsewhere throughout the body. Liver failure may therefore not seriously impair cocaine clearance.

Hypertension

Cocaine and amphetamines are known to increase blood pressure and should be avoided by those with hypertension. Anabolic steroids may have a similar effect because they encourage fluid retention. Chronic moderate to high alcohol intake also raises blood pressure in addition, alcohol can exacerbate the postural hypotensive response to many anti-hypertensives. The other drugs considered in this chapter are not likely to worsen hypertension.

Impaired Immunity

The prospect of certain drugs of abuse altering immunity is an important consideration for many abusers, not least those who are HIV positive or who have AIDS. A study in San Francisco, in which HIV-infected individuals were followed for six years, revealed that none of the drugs of abuse taken was associated with increased likelihood of progression to AIDS. These drugs included: cannabis, opioids, alkyl nitrites, amphetamine derivatives, cocaine. This contrasts with a Scottish study suggesting that although other drugs of abuse had no effects, heroin could hasten progression to AIDS.

The potential for opioids to affect immunity has been studied in some detail. Endogenous opioids seem to have an immunoregulatory function in many species, including humans, and the administration of exogenous opioid may disrupt this process. The addition of morphine to cells infected with HIV and cultured in vitro results in increased replication of the virus. A variety of signs of impaired immunity have been detected in both HIV-negative and HIV-positive patients taking methadone, including alterations in lymphocyte phenotype, suppressed lymphocyte function and reduced cytotoxic function of certain lymphocytes. An analysis of the immunocompetence of 220 patients receiving daily methadone as maintenance treatment also revealed detrimental effects upon immunity regardless of HIC status. Specifically, the ratio of CD4 lymphocytes, which bolster immunity, to CD8 lymphocytes, which have a suppressor function, was reduced apparently due to increased CD8 numbers. The study of 156 HIV-infected intravenous drug users in Scotland referred to above, found that those who continued to inject heroin were significantly more likely to progress to AIDS.

Alkyl nitrites are known to have detrimental effects upon lymphocytes in vitro. Both functional deficits and structural alterations have been observed which would be expected to reduce the effectiveness of lymphocytes if reproduced in vivo. Some animal studies have shown no effect, others show a reduced helper T-lymphocyte level. In humans, small studies have suggested that nitrite use can be associated with a decreased helper: suppressor T-lymphocyte ratio or a decreased total lymphocyte count followed by an increase in seven days later. However, it is not clear whether these effects are clinically relevant in humans. Several studies have suggested that a history of nitrite abuse is one factor that can be associated with an increased risk of developing Kaposi’s sarcoma in patients with AIDS. In addition, nitrites might be converted to carcinogenic nitrosamines in vivo by mammalian metabolism. Although the case against alkyl nitrites cannot be said to be proven and it is largely circumstantial, it would be prudent for those who are immunosuppressed to avoid abusing them.

Cannabis has traditionally been held to possess immunosuppressive properties. However, the evidence for this is equivocal. In vitro, studies using very high doses of cannabis have demonstrated adverse effects upon mammalian immunity but clinical studies have not demonstrated a convincing link.

It has been suggested that anabolic steroids might have immunosuppressant effects but the evidence for this is poor, being based on a very small number of case reports (see Performance Enhancing Drugs). Similarly it has been suggested anecdotally that ecstasy might have a mild immunosuppressant effect because many users claim to suffer from colds more frequently but there are no formal studies. One author suggests that this effect is due to the milieu which ecstasy is taken: hot crowded dance floors, with lots of body contact, where colds and influenza are readily contracted. Fatigue and loss of appetite induced by ecstasy could also increase susceptibility to these minor illnesses.

Regular smoking of any drug increases the risk of respiratory tract infections. In some cases contamination of the material with fungi has led to the development of fungal chest infections. Those who are immunosuppressed will be more prone to this effect of smoking and to infections derived from injection of non-sterile materials (see Adverse Effects of Drug Injection).

Renal Failure

As with hepatic failure, one must consider the potential effects of the drug upon the disease and of the disease upon the elimination of the drug.

Nephrotoxicity

None of the drugs of abuse are commonly directly toxic to the kidney. However, certain drugs can cause acute myoglobinuric renal failure, secondary to rhabdomyolysis. This occurs when stimulants facilitate over exercise and then hyperpyrexia. The reaction is particularly associated with ecstasy but has also been reported with amphetamine and cocaine (see Amphetamines and Ecstasy). There are two other pertinent ways in which drug abuse can be associated with rhabdomyolysis. Intra-arterial injection of some preparations can cause skeletal muscle ischaemia (see Adverse Effects of Drug Injection) and unconsciousness secondary to intoxication can lead to pressure-related muscle damage. If other organ systems are unaffected, the renal function will normalise within a few weeks.

Acute renal failure may occur subsequent to hypotension caused by overdoses of intravenous heroin. This usually resolves quickly. Cocaine tends to have the opposite effect upon blood pressure. It can cause renal damage secondary to uncontrolled hypertension, usually in the form of nephrosclerosis or glomerulosclerosis.

Heroin-association nephropathy has also been described but this now seems to be more rare than previously. It has been suggested that this is because the condition might have been due to heroin adulteration in the past and the drug is now much more pure at street level. Alternatively, as many intravenous drug abusers have died early of AIDS or other infection, the condition may not have time to develop. Septicaemia itself can also cause acute renal failure. It can occur secondary to non-sterile injections.

Amyloidosis can arise as a result of chronic subcutaneous injection of drugs and this can in turn trigger a form of nephrotic syndrome. Antimuscarinic drugs can cause urinary retention.

Volatile substance abuse has rarely been associated with renal damage, not least because these compounds are excreted very rapidly. However, toluene is eliminated from the body more slowly and has been associated with renal tubular acidosis and glomerulonephritis, although the latter has also been associated with other hydrocarbon solvents.

Drug accumulation in renal failure

With the exception of the opioids and ecstasy, none of the drugs of abuse considered in this chapter are eliminated renally to a great extent. It would therefore be anticipated that these drugs would not accumulate in patients with renal impairment. Ecstasy is eliminated renally.

Morphine and heroin (which is converted to morphine), are metabolised to morphine-6-glucuronide which, although only produced in small quantities, is a very potent opioid agonist. It is known to accumulate in patients with renal failure, with potentially serious consequences, and so heroin should be used with extreme caution in renal failure. It would be important to stabilise any heroin-dependent individual with renal failure on a regular dose of methadone quickly rather than allow continued abuse of street heroin. Pethidine is metabolised to a neurotoxic derivative, norpethidine, which is eliminated renally. This metabolite accumulates in renal failure and causes excitation of the central nervous system (CNS) and even convulsions. The fentanyl-derived opioid designer drugs are probably eliminated hepatically, like the parent compound, and with inactive metabolites. These opioids should not, therefore accumulate in renal impairment.

However, the situation is further complicated by the fact that patients with renal failure typically become more sensitive to the CNS effect of many drugs, probably because of the accumulation of urea. Consequently certain drugs of abuse may seem to exert more powerful effects. Although this field has not been studied adequately, increased sensitivity to CNS depressant drugs such as opioids, benzodiazepines and alcohol is widely recognised.