Drug abuse

Drug abuse refers to self-administration of a drug in chronically excessive quantities, in a manner that deviates from approved medical or social patterns in a given culture, resulting in physical or psychological harm. There are three important aspects to this definition:

Drug abuse has been known throughout history as one expression of an individual’s search for relief of physical, psychological, social or financial problems; it is not confined to any particular country, socioeconomic, cultural or ethnic group. Drug abuse may take a variety of forms:

Drugs commonly abused

The drugs that are most commonly abused in Western societies are caffeine, nicotine and ethanol (alcohol). There are double standards in terms of what is considered acceptable: for example, most governments condemn abuse of alcohol and tobacco products but do not ban the drugs, both for civil liberty reasons and because enormous amounts of revenue are received from taxes on the products. (In 2004/05, the Australian Government collected over A$6.7 billion from the importation and sale of tobacco products [AIHW 2008].) However, the revenue received falls far short of the amount required in health care for treatment of adverse reactions and chronic health and social problems arising from abuse of these two drugs. It is estimated that, for every 1000 Australian males who quit smoking, the savings over the next 10 years in health-care costs associated with heart attack, chronic obstructive pulmonary disease, lung cancer and stroke would be approximately $0.4 million (Hurley & Matthews 2008).

Apart from caffeine, nicotine and ethanol, drugs that are commonly abused are opioid analgesics (‘narcotics’, e.g. morphine and heroin), other CNS depressants (benzodiazepines, inhaled solvents), other CNS stimulants (cocaine, amphetamines) and psychotomimetics or hallucinogens (cannabis, lysergic acid diethylamide [LSD]). Aspects of these drug groups relevant to drug abuse or dependence will be considered in detail in this chapter; therapeutic uses are discussed in other chapters.

Sociocultural factors

Societies use and accept certain drugs as legal, while they may restrict or ban the use of other drugs, depending on the particular society’s religious rules, typical ethos (aggressive or meditative), history, traditional medicine practices and experiences with the drugs. In many Middle Eastern societies cannabis is considered a legal drug, encouraging introspection and meditation and decreasing sex drive, whereas alcohol is usually a forbidden substance. By contrast, in most Western cultures use of alcohol is allowed despite its adverse effects on individuals, families and societies, while cannabis is illegal and may be considered an aphrodisiac (enhancing sex drive)! In highaltitude regions such as the South American Andes and Peru, coca leaves (the source of cocaine) are brewed as a tea or chewed to decrease hunger sensations, improve work performance and enhance a feeling of wellbeing.

As Rang et al (2007) memorably pointed out: ‘… drug-taking is clearly seen by society in a quite different light from other forms of addictive self-gratification, such as opera-going, football or sex’. In smaller units of society, whether or not a drug is ‘popular’ may depend on its availability, ease of sharing and peer-group pressures. Where particular drugs are illegal and in short supply, criminals may be motivated to obtain and sell the banned substances for profit.

Personality factors

The usual reason a person initially takes an illicit drug is belief that a desirable pharmacological effect will result. The drug generally is used as a (maladaptive) mechanism to provide relief from anxiety or from personal problems, to achieve pleasure or gratification or to alter the state of mind. Clinical Interest Box 21-1 summarises some theories on why people abuse drugs.

Psychological studies on people dependent on or abusing drugs have shown the three most important predictors to be rebelliousness, tolerance of deviance and low school performance. Other implicated factors include curiosity; impulsiveness; a low threshold of frustration; boredom; peer pressure; alienation; hedonism (pleasure-seeking behaviour); affluence; feelings of fear, inadequacy, shame or failure; personal conflicts; a predisposition to depression, which may result in emotional and behavioural problems; aggressiveness in childhood; the need to escape; and the widely publicised attention to drug abuse in the mass media. In particular, the ‘alcoholic personality’ has a higher than average incidence of depression and antisocial tendencies plus a genetic predisposition to dependence on the drug. Organisations such as Alcoholics Anonymous have been developed to help individuals overcome their depend ence in a supportive, non-judgemental environment.

Pharmacological factors: CNS effects

All drugs likely to be abused have three characteristics: they act fast, make you feel good or stop you feeling bad. Obviously there would be little temptation to abuse a drug that took several hours to act—deferring gratification is not a common attribute among drug abusers.

Euphoria

Desirable CNS effects include producing euphoria (‘feelgood’ effects), enhanced alertness, relief from anxiety or pain or hallucinations. Tolerance and/or physical dependence and a withdrawal syndrome may develop. Table 21-1 summarises several aspects of the main drugs of abuse. Other drugs that may induce altered states of perception, thought and feelings and drug-induced psychoses include the methylxanthines (caffeine and theophylline, found in coffee, tea, chocolate and colas), anticholinergics, corticosteroids, psychotropic agents and levodopa. The pharmacological effects of some of these mind-altering drugs are graphically illustrated in Figure 21-1, showing the webs woven by spiders sprayed with amphetamine, caffeine, chloral hydrate or marijuana (NASA 1995).

Table 21-1 Selected drugs commonly abused and symptoms of abuse

Figure 21-1 Effects of mind-altering drugs on spiders. In a technique developed to test the toxicity of chemicals, household spiders were sprayed with solutions of the chemicals and the shapes of the webs subsequently spun were analysed using techniques of statistical crystallography. The figure shows the effects on web-spinning prowess of marijuana (a drug causing relaxa tion and impairment of motor coordination and memory), amphetamine and caffeine (CNS stimulants) and chloral hydrate (a sedative drug). The technique was developed as an alternative to toxicity testing in higher animals, which is expensive, timeconsuming and subject to ethical concerns. The head of the research team, Dr David Noever, was quoted as saying that he did not expect complaints from animal rights groups: ‘We’re all concerned about tests on warm and fuzzy creatures, but in this case they are only fuzzy.’

(Quoted in The Sunday Age, 7 July 1995.) Reproduced from NASA Tech Briefs 1995; 19(4): 82, with permission.

The scale of trafficking in drugs

It is estimated that worldwide the trade in drugs amounts to 10% of all international trade. The global trade in illicit drugs—the big four groups being opioids, cocaine, cannabis and amphetamines—comprises a US$320 billion-a-year industry, making drugs one of the most ‘valuable’ commodities in the world. Law enforcement agencies cannot prevent the supply of illicit drugs, despite enormous operating budgets, which leads to the conclusion that prohibition is simply not working. However, the United Nations (2009) concluded that ‘illicit drugs continue to pose a health danger to humanity. That’s why drugs are, and should remain, controlled’.

Overall, the economic cost of drug misuse and abuse in Australia, including tangible and intangible costs, was estimated at more than A$56.1 billion in 2004/05. Of this, about 56% was due to tobacco, 27% due to alcohol and only 15% due to illicit drugs. Thus it is the licit drugs (alcohol and tobacco) that cause the most medical and economic harm in our community.

In the USA, alcohol is generally estimated to play a role in 40% of assaults reported, 50% of crimes, 50% of all traffic accidents, 35% of suicides and 50% of unintentional injury fatalities. Over 70% of all prison inmates are imprisoned for drug-related crimes.

Individual, family and society problems

Substance abuse is a major medical, social, economic and interpersonal problem, affecting people from all economic backgrounds and across the lifespan. The craving for further doses may come to dominate the individual’s life, leading to an unacceptable lifestyle or a life of crime to support the drug dependence. Clinical Interest Box 21-2 describes some of the myths related to drug abuse.

While deaths from overdose of heroin or other illicit drugs are tragic and newsworthy, the vast majority of non-prescription drug-related deaths in Australia are due to tobacco (72%) or alcohol (25%). In the state of Victoria, around 10% of hospital bed-days are used to treat conditions associated with the use of alcohol, tobacco or illicit drugs. Of clients attending specialist drug treatment services, about 50% of problems were related to alcohol, 25% to opioid abuse and 7% each to amphetamines or cannabis. Over 12% of clients reported multiple drug use and 38% admitted injecting drugs.

The harm done may be directly to the individual, from adverse drug reactions or interactions such as liver cirrhosis from chronic alcoholism, psychosis from amphetamines or lung cancer and cardiovascular disease from smoking. The signs and symptoms of acute drug intoxication are summarised in Table 21-2. There are indirect effects as well; for example, IV drug abuse may lead a person into the subculture of ‘shooting up’, with the risk of sharing of non-sterile needles and hence of blood-borne infections such as HIV–AIDS and hepatitis, or into a life of crime and possible imprisonment. As a consequence of all the above factors, the life-expectancy of people who are dependent on drugs is generally lower than normal.

Table 21-2 Signs and symptoms of acute drug intoxication

Families of drug-dependent persons may have to cope with aggressive behaviour, reduced earnings and resources, increased medical expenses, destructive relationships and increased dependence on state welfare for support. Physical injury and abuse as a result of drug-related incidents is suffered by 6.6% of Australian men and 3.5% of women (AIHW 2008).

At the society level there may be escalating crime in the community, with consequent requirements for increased policing, court procedures and prisons to deal with offences related to production, supply and possession of illicit drugs; and alcohol-related intoxication, violence and drink-driving (see Clinical Interest Box 21-3), with DRUGS AND ROAD SAFETY increased risk-taking and deaths. It is estimated that approximately 55% of prison inmates in Australia are there due to offences related to illicit drugs or alcohol. Abuse of injectable drugs (opioids, amphetamines and cocaine) leads to spread of infections such as viral hepatitis and HIV–AIDS. The most frequent ‘perpetration of drug-related harm’ reported in the 2007 Australian survey (AIHW 2008) was driving while under the influence of alcohol: 16.2% of men and 8% of women admitted to this. Alcohol is implicated in 40%–70% of all violent crimes.

Withdrawal syndromes

As well as acute adverse pharmacological effects and toxicity, there are longer-term problems of withdrawal after chronic administration. In many cases, the withdrawal syndrome is due to or manifests as a rebound in the systems affected by the drug. Thus withdrawal from chronic use of benzodiazepines (antianxiety agents and CNS depressants) is likely to lead to feelings of anxiety and agitation, while withdrawal from amphetamines (CNS stimulants) leads to depressed mood and drowsiness. Characteristics of individual withdrawal syndromes will be discussed in later sections under specific drug groups.

Problems among health professionals

Career pressures, long working hours and easy accessibility to drugs place health-care professionals, particularly doctors, pharmacists, nurses, anaesthetists and dentists, at greater risk of drug abuse. Studies among health professionals in the USA have shown that misuse of combined alcohol and other drugs was quite prevalent, especially with doctors and nurses. Health-care professionals who abused medications generally used more than four substances, including prescription drugs (opioid analgesics and benzodiazepines), alcohol, tobacco and nitrous oxide.

History of legislation against drugs of abuse

Opium, as a source of active alkaloids with analgesic, sedative (narcotic) and antidiarrhoeal activities, has been used in various cultures for thousands of years. An international Opium Convention was set up in 1912 to curb the trade; this was ratified after World War I. Other drugs of addiction were added to the charter, including cannabis in 1925 (see Chapter 4; and United Nations Office on Drugs and Crime [2009]).

The responsibility for worldwide control of ‘narcotics’ (by then defined to include cocaine and cannabis) was handed over to the United Nations after World War II (1946). The main international treaties are:

Narcotic Drugs and Psychotropic Substances.

Most countries now attempt to keep their official drug regulation legislation in line with that of the UN, but this can be problematic if a country wishes to trial an alternative policy (e.g. supervised injecting facilities).

Patterns of drug abuse worldwide

The United Nations’ latest report (2009) noted that, overall, growth in drug trafficking had flattened out: major markets for opium (Europe and Southeast Asia), cocaine (North America) and cannabis (North America, Oceania and Europe) were declining; however, consumption of synthetic stimulants was increasing, especially in East Asia and the Middle East. In 2008 there was a reduction in opium poppy cultivation in Afghanistan of 19% and a reduction in coca cultivation in Colombia of 18%; the other main producers of opium are Myanmar and Laos and of cocaine are Peru and Bolivia. It is more difficult to estimate production and trafficking in cannabis and amphetamines, as these can be grown or synthesised (respectively) virtually anywhere.

By UN estimates, between 172 and 250 million persons used illicit drugs at least once in 2007. However, the more important estimate is of ‘heavy or problematic users’ who consume the vast bulk of the supply, may be dependent on drugs, would benefit from treatment and whose level of use impacts on public health and public order—in 2007 there were probably between 18 and 38 million problem drug users worldwide.

Extent of drug abuse in Australia

To estimate the extent of drug abuse in Australia, large-scale population surveys on household drug use patterns, attitudes and behaviours have been carried out regularly every 3–4 years since 1985. The data collected from these surveys have formed the basis for the development of policies for Australia’s response to drug-related issues. Results from the 2007 survey are available from the Australian Institute of Health and Welfare (AIHW), Drug Statistics Series no. 22 (2008).

Some interesting facts and trends since the previous surveys are:

Policy approaches

Treating acute overdose

The first aim of treatment is resuscitation of the patient, if necessary, then elimination of the drug taken, if possible, and treatment of toxic effects and complications. Specific antagonist drugs may be used to block the toxic effects of the drug of dependence, e.g. the opioid antagonists naloxone or nalorphine for opioid overdose or flumazenil for benzodiazepine overdose. Antidepressants such as fluoxetine or bupropion may be useful, particularly for withdrawal syndromes and quitting smoking. Drugs that may potentiate toxicity in the CNS or cardiovascular system should be avoided.

Treating chronic abuse

Initially, a comprehensive assessment of the person is required, for organic diseases, drug screening and a full history—medical, drug, social, family, psychological and psychiatric. The goals of treatment are to achieve total withdrawal from the drug, detoxification and treatment of any withdrawal reactions. Dopamine agonists may help reduce craving for the pleasure reinforcement. Antagonists (e.g. naltrexone on opioid receptors) will suppress the harmful effects of agonist drugs, but also suppress the euphoriant effects and provide no reinforcement, so compliance with them is poor. Naltrexone has moderate efficacy in treating more than one type of drug dependence (see Drug Monograph 21-1); the patient needs to be highly motivated and supported to stop dependence on opioids or alcohol. A multi-disciplinary approach to treatment is required and may be best carried out in a hospital or ‘detox’ facility. (An analogue, methylnaltrexone, is being used to treat opioid-induced constipation in palliative care patients by blocking opioid receptors in the GIT; as it does not pass the blood–brain barrier, it does not reduce the analgesic effects).

Long-term maintenance

The preferred scenario is to achieve abstinence from any drug abuse; however, this is recognised as being very difficult and perhaps unrealistic, as withdrawal causes distress which commonly leads to resumption of drugtaking behaviours. A more reachable goal is harm minimisation, without reliance on pharmacological agents. A substitute drug may help maintain effects while reducing harms, e.g. oxazepam substituted for diazepam, or methadone for morphine or heroin.

A novel approach still undergoing research and trials is that of developing vaccines that stimulate the immune system to produce antibodies against a drug of dependence. Thus far vaccines have been developed against nicotine and cocaine, with some limited success.

Euphoria and tolerance

Because opioids can rapidly relieve pain, change or elevate mood, relieve tension, fear and anxiety, and produce feelings of peace, euphoria, and tranquillity, they are particularly likely to lead to physical and psychological dependence (see Clinical Interest Box 21-6). Tolerance develops to most of the effects, especially to analgesia, euphoria, sedation and respiratory depression, but not to the constipation or miosis. Heroin, morphine, pethidine, methadone and pholcodine are the most frequently abused; as described earlier, health-care professionals who have ready access to opioids are at particular risk.

Heroin abuse

Diacetylmorphine (heroin, diamorphine) is a synthetic morphine derivative with no accepted medical use in Australia. It was initially introduced into medicine as a cough suppressant and to treat morphine addiction, but was banned in most countries because of its high potential for abuse and the increasing number of heroin addicts.

Heroin abuse and dependence is not an easy lifestyle: the drug has a short half-life, requiring frequent doses, and the practice is illegal and expensive, estimated at costing A$50–200 per day. Studies estimate that in 1997/98 there were about 75 000 dependent heroin users in Australia, i.e. about seven per thousand adults. The mortality rate is 1%–2% of users per annum; in 1998 (a year of high use) there were 737 reported deaths from heroin overdose. In 2007, approximately 1.6% of Australians over 13 years old admitted to have ever used heroin, but only 0.2% to have used it recently. In New Zealand a 1998 survey found that about 1% of the population reported using any opiate drug, with 0.6% as current users. These prevalence figures are similar to those in Britain and the European Union. The purity of heroin supplies varies widely—from 25% pure to 90% pure—and users can never be sure of the strength or purity of a sample (often adulterated with sugar, sedatives or amphetamines). It is therefore fatally easy for addicts to overdose. Impurities injected along with the opioid can cause collapsed veins, infections and organ damage.

Pharmacologically, heroin is a prodrug: after an oral dose it is rapidly converted in the liver to morphine. Heroin is highly lipid-soluble and quickly passes the blood–brain barrier, producing a rapid intense ‘rush’. It is highly addictive and tolerance develops rapidly to most effects. Controlled studies comparing heroin and morphine in terms of effects achieved when abused do not support the generally held belief that heroin is ‘better’.

Mode of administration

The opioids generally have low oral bioavailability and so are administered percutaneously (absorbed through the mucous membranes) by sniffing (snorting), by subcutaneous injection (skin popping) or by direct IV injection (mainlining, ‘shooting up’). The rate of absorption is increased by injection, with IV injection producing almost immediate drug effects.

Acute overdosage

Acute overdosage of opioids may result in severe pulmonary oedema and respiratory depression. These outcomes are dose-dependent, and what constitutes a lethal dose also depends on the individual’s tolerance for the drug. Symptoms occur rapidly in most patients: slow, shallow breathing, severe hypoxia, cold clammy skin, miosis, bradycardia, hypotension, muscle spasm and lethargy; urinary retention may also occur. The presence of thrombophlebitis, scarred veins and puckered scars from subcutaneous injections may help identify a patient with opioid dependence. The treatment of choice for acute overdosage is administration of an antagonist (e.g. naloxone) and respiratory and cardiovascular support.

Withdrawal syndrome

In a patient who is physically dependent on opioids, sudden withdrawal of the substance of abuse, or an abrupt reversal of opioid effects with an opioid antagonist, may precipitate an acute abstinence or withdrawal syndrome, with excitation and diarrhoea. While unpleasant, the withdrawal symptoms are not usually particularly dangerous. Milder symptoms (craving and sleep disturbances) may continue for many months, and psychological dependence may continue for the rest of the person’s life.

Babies born to women who are dependent on an opioid may suffer an immediate withdrawal reaction (see Clinical Interest Box 21-7).

Treating opioid dependence

The main aim of treatment is to keep users alive and help them ‘mature out’ of their condition. Treatment programs concentrate on either withdrawal and continuing total abstinence, including ‘rapid detoxification’ programs then an opioid antagonist such as naltrexone (Drug Monograph 21-1); or (more realistically) withdrawal then substitution and ongoing maintenance with another less dangerous opioid such as methadone. Chilling statistics report that, on average after 10 years’ treatment, 30%–40% of former users remain abstinent, 40%–50% are active users or imprisoned, and 10%–20% have died.

Analgesia for patients with opioid abuse disorders

Providing adequate analgesia to manage acute pain in patients with an opioid abuse or dependence disorder is difficult. Such patients are predisposed to some acutely painful conditions (pancreatitis, traumatic injuries), but may be tolerant to opioids, already using opioids, in remission or withdrawal or showing drug-seeking behaviours to obtain doses. Careful assessment is required, plus maximisation of non-opioid analgesics (paracetamol, NSAIDs), adjuvant therapies and non-pharmacological pain management techniques. Opioids should not be withheld if indicated for acute pain, but doses for patients in methadone programs may need to be higher than usual; opioids cannot be readily used for patients on naltrexone programs (see Drug Monograph 21-1).

Ethanol (ethyl alcohol, ‘alcohol’)

Alcohols are naturally produced from the fermentation of cereals and fruits. Most wines are produced from fermentation of grapes from the plant species Vitis vinifera, while beer has been traditionally brewed from grains with hops added for flavouring. Spirits contain higher concentrations of alcohol as they are distilled to concentrate the alcohol: rum is distilled after fermentation of sugar cane, and other spirits from grains, fruits or vegetables (e.g. whisky from barley or rye).

Uses

Ethanol is the only alcohol used orally extensively in medicine and in alcoholic beverages. Therapeutically, ethanol has been used orally as an appetite stimulant and as a mild hypnotic. It was also used both clinically and traditionally to diminish uterine contractions in threatened spontaneous abortion. It is currently used as an antidote for acute methanol and ethylene glycol poisoning. Ethanol denatures proteins by precipitation and dehydration, which may be the basis for its germicidal, irritant and astringent effects. For local or in-vitro effects, ethanol has been used as a skin antiseptic and disinfectant, in topical pharmaceutical preparations, as a preservative in many formulations, in sclerotherapy (e.g. to cause hardening and closure of varicose veins) and to cause lesions to sensory nerves in neuralgias.

Alcohol is found in many oral pharmaceuticals, as a solvent or as a component of flavoured vehicles. (Table 21-3 lists the ethanol contents of various Australian OTC preparations.)

Table 21-3 Content of ethyl alcohol in some otc products

Ethanol is used in alcoholic drinks, and a low level of alcohol intake (e.g. two glasses of red wine daily for men, one glass for women) has been shown to be protective against some cardiac conditions.³ While ethanol is not usually taken for therapeutic purposes, it is a very commonly taken drug so it is discussed in the usual format (Drug Monograph 21-3).

Drug monograph 21-3 Alcohol (ethanol)

Taken orally, alcohol is a sedative and euphoriant; it is usually taken in the form of alcoholic drinks. Alcohol is the most commonly used and abused drug in Australia.

Pharmacokinetics

Being a very small molecule (molecular weight 46), ethanol does not require digestion before absorption; it readily diffuses through lipid membranes (as does water) and hence rapidly enters cells despite being very water-soluble. A small amount is absorbed from the stomach, while most is absorbed from the small intestine. Peak blood alcohol levels are reached about 30–60 minutes after administration. Alcohol is distributed in every tissue of the body as is water; the volume of distribution is about 35 L for a 70 kg adult. Analysis of the blood alcohol level gives a rough estimate of the quantity consumed and of the alcohol levels in the brain (see Table 21-4).

About 90% of alcohol absorbed is metabolised in the liver by alcohol dehydrogenase to acetaldehyde, then acetaldehyde is oxidised to acetic acid and eventually to carbon dioxide and water. The remainder of the ethanol is primarily excreted by way of the lungs, sweat and kidneys. The amount of alcohol excreted in expired air—as measured by ‘breathalyzers’—is very small: the amount in 2 L expired air is equivalent to that in 1 mL blood; however, this small amount may have considerable forensic importance if it indicates blood levels higher than the legal limit.

As plasma ethanol levels rise, the hepatic alcohol dehydrogenase pathway becomes saturated; the maximum rate of metabolism is about 120 mg/kg/h, and the clearance and half-life are dosedependent. Hence blood alcohol levels remain high if the person keeps drinking steadily. Plasma levels tend to be higher in women than in men after equivalent doses, both because women have lower levels of dehydrogenase enzymes and because they have a relatively smaller volume of distribution for water-soluble drugs. Heavy exercise may slightly increase the rate of elimination of alcohol. Chronic administration (i.e. in alcoholics) initially increases the rate of metabolism by the liver enzyme pathway, but as liver damage and cirrhosis develop, metabolism becomes impaired.

Adverse drug reactions

Alcohol affects many body systems (see Pharmacological effects in text). In particular, it causes euphoria and reduces inhibitions, causes sensorimotor impairment and increases gastric acidity. The ‘therapeutic index’ is estimated at about 4; i.e. while one or two drinks may make you the life of the party, 4–8 may make you raging drunk, comatose or incapable of driving safely. Alcohol has a diuretic effect both because of the increase in fluid intake (although this may be small with wines and spirits) and through inhibition of antidiuretic hormone (ADH) release. If an individual has preexisting renal disease, the kidney may be further damaged.

Chronic alcohol use may result in hyperlipidaemia, fatty deposits in the liver and, ultimately, alcoholic cirrhosis.

Drug interactions

Ethanol interacts with many prescription and OTC drugs, in particular with any other CNS depressant, resulting in frequent adverse drug interactions (see Drug Interactions 21–1).

Warnings and contraindications

Because of the increased risk of fetal alcohol syndrome (mental retardation, craniofacial dysgenesis and growth retardation; see Clinical Interest Box 9-1), pregnant women are advised by the World Health Organization to avoid alcohol throughout pregnancy; there is a 10% risk of fetal malformations if consumption exceeds 2 g ethanol/kg/day during the first trimester. Drinking alcohol is not recommended for breastfeeding women, as ethanol partitions into milk and causes depressant effects on the infant’s CNS and respiration.

Generally, alcohol is not recommended for people with liver disease or psychiatric problems, or patients taking any of the many drugs with which alcohol interacts.

Dosage and administration

The standard ‘measures’ of alcoholic drinks are such that an average drink contains in the range 5–20 grams of ethanol: the stronger the drink, the smaller is the typical container. Thus a beer stein is larger than a wine glass, and a sherry glass larger than a ‘shot’ glass for spirits. It is generally recommended that men drink no more than four standard drinks per day on a maximum of 3–4 days per week, and women no more than two standard drinks.

Pharmacological effects of ethanol

CNS-depressant actions

Contrary to popular belief, alcohol is not a stimulant but a CNS depressant, causing progressive depression in sequence of the cerebrum, cerebellum, medulla and spinal cord. What sometimes appears to be behavioural stimul ation results from depression of the higher faculties of the brain and represents the loss of inhibitions acquired by socialisation. Alcohol impairs transmission of nerve impulses at synaptic connections but the precise mechanism is not known. It inhibits calcium entry into nerve cells, possibly by enhancing γ-aminobutyric acid (GABA)-mediated inhibition and/or antagonising excitatory amino acid transmitters (e.g. glutamate). Other targets for alcohol actions are receptors for NMDA, glycine, 5-HT₃ and acetylcholine (nicotinic), and some potassium channels.

The action of alcohol varies with the blood alcohol level, the individual’s tolerance, the presence or absence of extraneous stimuli, the rate of ingestion and gastric contents. Small or moderate quantities produce a feeling of wellbeing (euphoria) and increased confidence. Then finer powers of concentration, judgement and memory are lost, visual acuity is diminished and sensorimotor functions (including driving) are impaired. Many drivers will take chances when under the influence of alcohol that they would never take ordinarily, as accident statistics reveal (see Figure 21-2). Table 21-4 compares the blood alcohol level with clinical observations of behaviour and pharmacological effects.

Figure 21-2 Results of four surveys on the relation between traffic accidents and blood ethanol concentration. The risk factor is the ratio of traffic accidents in subjects with a given blood ethanol concentration to all traffic accidents in the population from which the subjects are drawn. Note that 50 mg/dL equates to 0.05%.

From data reviewed in H Wallgren, M Berry, Actions of Alcohol, Amsterdam: Elsevier, 1970; as shown in Bowman & Rand 1980; used with permission.

Table 21-4 Dependence of pharmacological responses on blood alcohol level

STAGE	BLOOD ALCOHOL (mg/dL)*	EFFECTS ON COGNITION & BEHAVIOUR
Subclinical	30–100	Possible slight deterioration in motor function, coordination, personality or mood and mental acuity
Emotional instability	100–200	Decreased inhibitions, emotional instability, some muscular incoordination, slowing of responses to stimuli, signs of intoxication
Confusion	200–300	Disturbance of sensation, decreased pain sense, staggering gait, slurred speech
Stupor	300–400	Marked decrease in response to stimuli, muscular incoordination approaching paralysis, impaired intelligence
Coma, death	400	Complete unconsciousness, depressed reflexes and respiration, subnormal temperature, anaesthesia, impairment of circulation, coma, possible death

^* Note: A blood alcohol level of 0.05% (the legally safe driving limit in most states of Australia), i.e. 0.05 g/100 mL, equates to 50 mg/dL.

Methanol (methyl alcohol, wood alcohol)

If taken orally, methanol is a CNS toxin: the fatal dose is in the range 100–200 mL and as little as 10 mL has been known to cause permanent blindness. The reason for this severe toxicity compared with the very similar alcohol, ethanol, is that whereas ethanol is metabolised to acetaldehyde and then acetate, methanol is metabolised to formaldehyde (formalin) and formate, which are more toxic. Formic acid is slowly metabolised, with maximum concentrations in the blood 2–3 days after ingestion of methanol, and is the cause of severe metabolic acidosis. The specific ocular toxicity of formaldehyde is because it is a potent inhibitor of respiration and glycolysis in the retina.

Alcohol abuse and misuse

Treating alcohol abuse

Long-term treatment of ethanol withdrawal and abuse needs to be continued for many months or years; it includes the person’s admitting that he/she needs help, plus monitoring health status, symptom relief, preventing or treating complications, psychotherapy to improve coping skills and prevent relapses and developing long-term rehabilitation plans. Supportive care for the acute phase includes fluid, electrolyte and glucose replacement, adequate nutrition, thiamine to prevent development of Wernicke’s encephalopathy, antiemetics and psychotropic agents (if agitation is severe); hospitalisation may be necessary while the patient is on high doses of sedatives or anticonvulsants (oral diazepam). Naltrexone can be used to facilitate abstinence by reducing craving and relapses (Drug Monograph 21-1).

Benzodiazepines and barbiturates

Misuse and abuse of other CNS depressants (benzodiazepines, barbiturates and chloral hydrate-type sedatives) have declined greatly in recent years, probably as a result of the availability of newer agents with greater safety and effectiveness profiles. (General information about these drugs is summarised in Tables 21-1 and 21-2; their pharmacological and clinical aspects are discussed in Chapters 16 and 17.) The general effects are similar to dependence on ethanol but the social setting is different: whereas men tend more to abuse alcohol, women are more likely to become dependent on benzodiazepines (‘mother’s little helpers’).

Benzodiazepines are commonly prescribed for anxiety, insomnia and convulsive disorders. They can cause de pendence and patients may ‘shop around’ among doctors and pharmacists to obtain supplies. Tolerance develops to the sedating and intoxicating effects but not to the respiratory depression. Managing benzodiazepine dependence should include gradual drug withdrawal. Flumazenil is a specific benzodiazepine-receptor antagonist that is administered intravenously to reverse sedation from benzodiazepines used during anaesthesia, and for treatment of benzodiazepine toxicity; it may precipitate seizures. As flumazenil has a short half-life (50 minutes), several doses may be required to treat the patient who has overdosed with a long-acting benzodiazepine.

Temazepam, a short-acting benzodiazepine used for insomnia, was formerly available in Australia in gel capsules containing temazepam in solution. Unfortunately these came to be abused, as injecting drug users injected the contents of the gel-caps, particularly at times of heroin shortage, in order to replace the depressant effects of the opioid or alcohol, to deal with anxiety and stress or to offset the effects of CNS-stimulant drugs. Common complications included abscesses, skin ulcers, deep venous thromboses, burst aneurysm and haemorrhage, ischaemia and gangrene requiring amputation. The gel-caps have now been withdrawn from the market.

Kava

Gamma-hydroxybutyrate (GHB)

Inhalants

Actions and mechanisms

Chemically, amphetamines are similar to the natural catecholamines, adrenaline, noradrenaline and dopamine, but have fewer hydroxyl groups so are more lipid-soluble and CNS-active. They have weak agonist actions on adrenoreceptor sites and are classified as sympathomimetic agents. They increase the release of natural catecholamines and block their reuptake into neurons, which causes a ‘fight or flight’ response; they may also have mild monoamine oxidase inhibitory effects, which contributes to their sympathomimetic and CNS stimulant actions. The three main types of amphetamines (salts of racemic (±)-amphetamines, dextro-amphetamines and methamphetamines) vary in potency and peripheral effects. Dexamphetamine is said to have fewest peripheral effects, such as hypertension and tachycardia. Central effects include increases in mood, energy, alertness and mental and physical capacities and decreased appetite and sleep; euphoria and stereotyped behaviours also occur (see Drug Monograph 19-1).

Pharmacokinetics

Oral amphetamine is absorbed from the GI tract and concentrates in the brain, kidneys and lungs. It is metabolised in the liver and excreted via the kidneys. Amphetamine is a basic drug with a pKa (the pH at which half the drug amount is ionised and half un-ionised) of 9.9; therefore, alkaline urine with pH >7 reduces excretion of amphetamine and extends its half-life to about 20 hours. Acidic urine at pH 5, by contrast, increases excretion and reduces the half-life to 5–6 hours. People who abuse this drug are usually aware of the prolonged effect they can achieve by alkalinising their urine (with oral sodium or potassium citrate), whereas prescribers are aware that acidifying a person’s urine (with oral ammonium chloride) to a pH of 4.5–5.5 will enhance amphetamine excretion and help treatment of ampheta mine overdose.

Abuse of amphetamines

Amphetamines were widely used during World War II by servicemen to enhance alertness and reduce battle fatigue, and quickly became popular drugs of abuse, amphetamine as ‘benzedrine’ and methamphetamine or methedrine as ‘speed’. Results from the 2007 National Drug Survey in Australia showed that approximately 7.3% of persons aged 20–29 years had used amphetamines in the previous 12 months, and 11.2% had used the related drug ecstasy; the use of ecstasy increased steadily from 1991 to 2004. Most amphetamines are produced in illegal backyard laboratories, with no controls over the manufacturing practices or the purity or strength of the product, and sold illegally. Due to the unknown strength of street supplies, overdose is common and potentially fatal.

Amphetamines are generally taken orally, but can also be inhaled after vaporisation, inhaled as fine powders (‘snorted’) or injected. Intravenous amphetamine injection results in marked euphoria—a rush accompanied by a sense of great physical strength and clear thinking, and engagement in vigorous activity that may actually be inefficient and repetitious. Parenteral use carries the usual risks of IV drug abuse and associated infections.

The sympathomimetic stimulant properties of amphetamines can cause dramatic effects such as tachycardia, dyspnoea, chest pain and hypertension; infarcts, hyperpyrexia, hepatotoxicity, seizures and circulatory collapse have been reported. Severe anxiety, paranoia, schizophrenia-like symptoms (‘snow lights’), insomnia and weight loss also occur. Amphetamine users often use depressants or ‘downers’, such as large amounts of alcohol, marijuana, benzodiazepines, barbiturates or heroin to offset the overstimulation effects. Detoxification and use of usual treatments for medical complications, including anticonvulsants and antihypertensive agents, are necessary in treating acute toxicity.

There is a rapid fall-off in drug effects, which enhances the intense craving for the drug and rapidly leads to addiction. Drug withdrawal is followed by long periods of sleep and, on waking, the individual often feels hungry, extremely lethargic and profoundly depressed (anhedonia). This phenomenon is known as ‘crashing’ and is typical of the rebound swings after withdrawal of drugs of dependence. Suicide risk is quite possible during this period.

Amphetamine (especially methamphetamine) use is on the rise. Crystal methamphetamine (known as ‘ice’ or ‘crystal meth’) is gaining popularity because a ‘high’ occurs usually in less than a minute when these crystals are heated and the vapour is inhaled. In some instances, oral amphetamine users are also inhaling or smoking methamphetamine concurrently, which vastly increases the intensity and toxicity of the effect, and its duration (a ‘high’ can persist for 12 hours).

‘Designer drugs’

These are drugs designed and synthesised to be amphetamine look-alikes and mimic the CNS-stimulant effects of amphetamines and cocaine; the people designing the drugs are aiming at keeping a step ahead of the drug policy-makers and law-enforcement officers. The classic designer drug is 3,4-methylenedioxymethamphetamine (MDMA, better known as ‘ecstasy’, see Figure 21-4), originally synthesised in 1914 as an appetite suppressant but which has recently found popularity as a stimulant. Related compounds have varying chemical substituents (methoxy-, methyl-, halogen or sulfur) on the phenyl ring of the amphetamine or methamphetamine. They have similar mechanisms of action to amphetamine, interfering with uptake processes (transporters) in CNS neurons or enhancing release, to raise levels of monoamine neurotransmitters and cause CNS stimulation.

Pharmacological effects

Tobacco smoking and nicotine

Tobacco smoke is an aerosol containing about 4 × 10⁹ particles per mL, i.e. in the range 10–80 mg per cigarette; nicotine accounts for about 0.14–1.21 mg. Burning of tobacco also generates around 4000 compounds in the gaseous and particulate phases, including 60 known carcinogens such as tars, formaldehyde, hydrogen cyanide, benzene and nitrosamines, implicated as aetiological factors in cancers of the bladder, lung, buccal cavity, oesophagus and pancreas. Other smoking-related illnesses include pulmonary emphysema, chronic bronchitis, coronary heart disease, strokes, myocardial infarction and chronic dyspepsia. Male smokers have about one-third the sperm count of non-smokers. Cigarette smoking is thought to be responsible for more than 50% of all domestic fires. Smoking is also a considerable financial outlay: it has been estimated that someone who has smoked 10 cigarettes a day since the age of 20 and has the good luck to live to be 50 will be more than A$250,000 poorer than a non-smoker of the same age.

Smokers absorb sufficient nicotine to exert a variety of effects on the autonomic nervous system. In people with peripheral vascular disease such as thromboangiitis obliterans (Buerger’s disease), nicotine is generally believed to be a contributing factor by causing spasms of the peripheral blood vessels. Vasospasm in the retinal blood vessels of the eye, associated with smoking of tobacco, is thought to cause serious disturbance of vision. Most male smokers of 20 years duration are impotent by the age of 50, owing to microvascular damage. Mothers who smoke usually deliver infants with low birth weights and a higher incidence of congenital abnormalities; prematurity and stillbirth are more common.

Dependence on nicotine

Tobacco is Australia’s worst ‘killer’ drug, the most abused and the most harmful, killing ‘more people than alcohol, drugs, murder, suicide, road, rail and air crashes, poisoning, HIV, drowning, fires, falls, lightning, electrocution, snakes, spiders and sharks put together’ (Jamrozik & Le 2001). A 2007 national survey of drug use found that about 16.6% of Australians aged 14 years and over smoked regularly at least daily.

The addictive component of tobacco is nicotine. Monkeys trained to press a bar to receive an IV injection of nicotine will self-administer up to a point, at which the adverse effects presumably outweigh the rewarding effects. Nicotine is also postulated to have an antidepressant action, and ex-smokers who successfully quit and abstain often suffer clinical depression.

The dose of nicotine absorbed from one cigarette is estimated to amount to about 10–40 mcg/kg body weight, and smokers tend to maintain their plasma nicotine concentration at about 10–50 ng/mL. By comparison, nicotine is absorbed more slowly from cigars and pipes but the doses of nicotine achieved are in the same order, about 20–40 mcg/kg (see Figure 21-3).

Figure 21-3 Plasma concentration of nicotine after smoking. Habitual smokers used a cigarette, pipe or cigar; blood samples were taken and plasma levels of nicotine measured. The mean dose of nicotine over the period of smoking was estimated at, for a cigarette, 21 mcg/kg over 8–10 minutes; pipe, 45 mcg/kg over 20–30 minutes; cigar, 41 mcg/kg over 22 minutes.

Source: Bowman & Rand 1980, used with permission; data obtained by Dr MP Giles, Department of Pharmacology, University of Melbourne.

Treating nicotine dependence

Pharmacological properties

Cocaine is an alkaloid related to the belladonna alkaloids atropine and hyoscine; it is an ester-type local anaesthetic (see Clinical Interest Box 14-9) with vasoconstrictor effects. Topically and parenterally it has a limited local anaesthetic use in a few nasal and ophthalmic surgical procedures. Its central and autonomic effects are largely due to inhibition of reuptake of catecholamines back into nerve terminals, thus it potentiates the actions of noradrenaline, adrenaline and dopamine and has sympathomimetic effects. Cocaine has central stimulant properties, causing excitement, talkativeness, tremors, vomiting and increased respiration and blood pressure.

Abuse of cocaine

Cocaine is a powerful reinforcer, rapidly producing sensations of reward and exhilaration, and hence dependence. It is classified as a controlled substance (Schedule 8). While abuse of cocaine in Australia is nowhere near the problem it is in the USA, abuse is increasing: recent use in males aged 14 and older has doubled from 1.1% of the population in 1995 to 2.2% in 2007. Approximately 6% of the Australian population say they have ever used cocaine; the main age group using cocaine is young adults 20–29 years of age. There is no typical withdrawal syndrome, but rebound effects may be manifest as fatigue and depression.

Xanthine alkaloids

Chemically, the xanthines are closely related to the purine bases adenine and guanine (building blocks for DNA and RNA, see Figure 42-1), and they are thought to act through antagonist effects on adenosine receptors. At higher concentrations, the xanthines also inhibit the enzyme phosphodiesterase (PDE), which leads to raised intracellular levels of cAMP and may contribute to some of caffeine’s actions (Figure 28-4). The xanthines have legitimate medical uses, as CNS stimulants (see Chapter 19) and as bronchodilators (Chapter 28); they also have mild diuretic and cardiac-stimulant effects and have been used to treat respiratory failure in premature infants. Caffeine (Drug Monograph 19-2) is the most powerful CNS stimulant of the xanthine alkaloids, and is the xanthine present in many OTC medications and in some prescribed medicines (see Table 21-6). Theophylline (Drug Monograph 28-3) is the most powerful smooth muscle relaxant, so it and its derivative aminophylline are used in asthma.

Social use of caffeine

Caffeine is the most widely used psychoactive substance worldwide; a large proportion of the world’s population have a cup of tea or coffee every day. About half the world’s annual coffee production is consumed in the USA, where the average daily caffeine dose is over 250 mg. By comparison, tea accounts for about 43% of all caffeine consumption; the British tend to drink more tea than coffee, on average over 300 mg caffeine daily. Two to three cups of strong coffee are sufficient to raise the caffeine levels in the plasma or brain to approximately 100 μM, a concentration at which adenosine-receptor blockade and some PDE inhibition occurs.

Source and uses

The cannabis drugs are derived from hemp plants (Cannabis sativa), which were probably originally native to Central Asia. The plants have historically been used for the very strong fibres in the stems, which are fast-growing up to 5 m in length and are used for weaving into fabric (hence the term canvas), for twisting into ropes (hemp) and for making paper. Hempseed is used as birdseed and is a source of oil. There are also dermatological preparations (oils, soaps, lotions etc) and foods and fabrics based on cannabis.

The active drugs used for mental relaxation and euphoria (cannabinoids) are from the resin of the plant, exuded from the leaves, tops of the stems and the flowering tops of the plants. The potency of the main psychoactive ingredient (Δ⁹-tetrahydrocannabinol, THC), is greatest in the flowering tops and varies according to the climatic conditions under which the plant is grown, with the typical leaf containing 3%–10% THC. Marijuana grown under scientifically controlled conditions as a THC source may contain up to 15% THC. The other major ingredient, cannabidiol, does not impair cognition and may even have antipsychotic effects.

Preparations and active constituents

Marijuana (cannabis prepared for smoking) and hashish are the most common forms of cannabis in use. Hashish refers to the powdered form of the plant’s resin, which contains 7%–12% THC. Other forms of cannabis, used in such countries as Jamaica, Mexico, Africa, India and the Middle East, include bhang, ganja and charas. In Morocco kif is used and in South America a cannabis form called dagga.

Marijuana plants contain hundreds of different chemicals, generally termed cannabinoids; they have complex 3-ring structures. Of these, Δ⁹-THC and related compounds and cannabidiol have been most studied in humans to identify their pharmacological effects. Marijuana cigarettes contain about 0.5–2 g marijuana, of which only 0.5%–1% is THC.

Mode of administration and pharmacokinetics

Tetrahydrocannabinols are highly lipid-soluble, so are readily absorbed when administered by oral, subcutaneous or inhaled routes; they are most potent when inhaled. Either the pure resin or the dried leaves of the cannabis plant may be smoked in pipes or cigarettes. The smoke is inhaled deeply⁵ and retained in the lungs as long as possible to achieve maximal saturation of the absorbing surface; about 15%–50% of the THC present in preparations is actually absorbed after smoking.

The peak plasma level of THC after smoking one marijuana cigarette is reported to occur within minutes. THC is highly protein-bound, so only a small proportion enters the CNS; it persists in the body in adipose tissue depots (for over 4 weeks) and in the lungs and liver, with a long half-life. It is metabolised in the liver to various hydroxylation products, some of which are pharmacologically active. The metabolites are excreted in the urine, bile and faeces. Note that the long half-life of marijuana and the consequent prolonged period for detection of cannabinoids in the urine have made it difficult for accurate correlations to be made between blood cannabinoid concentrations and impaired driving performance, whereas with alcohol the correlation between alcohol in expired air (breath-testing) and impaired psychomotor performance is clear (Figure 21-2).

Pharmacological effects

The main effects are in the CNS, where the drug has intoxicating and mind-altering properties. The drug experience is highly subjective, with a high placebo reaction. Cannabinoids can affect most systems and organs of the body, as shown below:

Medical uses of cannabinoids

Synthetic cannabinoids (dronabinol, a pure preparation of Δ⁹-THC, and nabilone) have been prepared and tested for the treatment of nausea and vomiting induced by cancer chemotherapy and not responsive to standard therapies. Both products have a high potential for abuse and so are closely regulated; neither is available in Australia. Other potential uses of cannabinoids are as an adjunct in treating patients with wasting conditions such as HIV–AIDS and in chronic pain syndromes, insomnia, epilepsy, opioid withdrawal, glaucoma, asthma and neurological diseases with spasticity. Problems that can be envisaged related to medical use of cannabis are the issues of placebo reactions; consistency of dosing and bioavailability after adminis tration by smoking; and the long half-life and potential prolonged adverse effects on concentration and driving.

Marijuana abuse

Traditionally, marijuana was used in Eastern and African countries in religious ceremonies to enhance meditation and as a mild intoxicant (especially when alcohol was prohibited). Marijuana cigarettes (‘joints’) are illegal in Australia but in some states there is a more lenient attitude to marijuana use than to ‘harder’ illicit drugs such as opioids, amphetamines and cocaine, and a plant may be grown for personal use, despite prohibitions against sale and large-scale production. This has been shown to reduce the black market in marijuana products and the costs of enforcement and the criminal justice system, while increasing individuals’ use and civil liberties. In Australia, marijuana is by far the most commonly used illicit drug:⁶ in a 2007 survey, one-third of the adult population admitted to having used marijuana at some stage. It is now estimated that 40% of young Europeans have tried cannabis at least once in their life. ‘Recent use’ in Australia has been declining, from 18% in 1998 (then much higher than in the USA, UK, Canada or Spain) to 9.1% in 2007. The prohibitions on the use of cannabis are much debated, with arguments both for and against prohibition.

LSD (lysergic acid diethylamide; lysergide)

Lysergide is a very potent hallucinogenic drug that is usually available illicitly in doses of around 200 mcg. LSD is related to the ergot alkaloids (see Drug Monograph 38-4 and Clinical Interest Box 38-4) and thus can affect many body systems and neurotransmitters. It is an agonist at 5-HT_2A receptors. After oral administration, it will cause a central sympathomimetic effect within 20 minutes: hypertension, dilated pupils, hyperthermia, tachycardia and enhanced alertness. Effects on mood are unpredictable, ranging from euphoria to severe depression and panic. The psychoactive effects occur in about 1–2 hours and have been described as heightened perceptions, distortions of the body and visual hallucinations.

Unpleasant experiences with LSD (a ‘bad trip’) are frequent. Clinically, evidence of impaired judgement in the toxic state is common, and altered states of consciousness may progress to psychosis. Feelings of acute panic and paranoia can result in homicidal or suicidal thoughts and actions. Long-term effects include flashback phenomena, in which unfavourable reactions induced by LSD, such as depression and long-term schizophrenic or psychotic reactions, recur weeks or even years after using the drug.

Mescaline

Mescaline is the chief alkaloid extracted from mescal buttons (flowering heads) of the peyote cactus. It produces subjective hallucinogenic effects similar to those produced by LSD but has only about 0.02% of the potency of LSD. The trimethoxy- and dimethoxy-derivatives of mescaline are also hallucinogenic. It is usually ingested in the form of a soluble crystalline powder that is either dissolved into teas or encapsulated. The usual dose of mescaline is 300–500 mg, which produces GI disturbances and sympathomimetic effects then vivid and colourful visual hallucinations. The half-life of mescaline is about 6 hours and it is excreted in the urine.

Psilocybin

Psilocybin and psilocyn are drugs derived from Mexican mushrooms. They produce subjective hallucinogenic effects similar to those produced by mescaline but of shorter duration. Within 0.5–1 hour after ingestion of 5–15 mg psilocybin, a hallucinogenic dysphoric state begins. A dose of 20–60 mg may produce effects lasting 5–6 hours. The mood is pleasant to some users, while others experience apprehension. The user has poor critical judgement capacities and impaired performance ability. Also seen are hyperkinetic compulsive movements, laughter, mydriasis, vertigo, ataxia, paraesthesia, muscle weakness, drowsiness and sleep.

Ketamine and phencyclidine (PCP)

Ketamine (‘K’, ‘special K’) is a dissociative anaesthetic with hallucinogenic properties; overdose can cause CNS stimulation and delirium. Dependence and flashbacks can occur.

PCP (phencyclidine, also known as ‘angel dust’) was originally introduced into medicine as an anaesthetic similar to ketamine, but its use was discontinued because of its hallucinogenic effects. PCP has a history of serious adverse outcomes, including many suicides, assaults and murders. Common peripheral signs include flushing, profuse sweating, nystagmus, diplopia, ptosis, analgesia and sedation. PCP produces a state similar to alcohol intoxication, with other perceptual distortions (visual or auditory) that can recur unpredictably, and symptoms that mimic schizophrenia. Toxic pressor effects may cause hypertensive crisis, intracerebral haemorrhage, convulsions, coma and death.

Non-opioid analgesics (paracetamol, aspirin, ibuprofen)

Paracetamol, aspirin, ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs—see Chapters 15 and 47) are OTC drugs that are readily available in many outlets such as pharmacies and supermarkets. These same ingredients may also be contained in combination formulations (with an opioid such as codeine) and sold with or without a prescription. Thus the potential for intentional and unintentional drug overdose exists with these drugs, although they do not cause dependence. They are particularly risky when combined with CNS depressants such as alcohol or benzodiazepines.

Overdoses from non-opioid analgesics are commonly seen in emergency departments; paracetamol (Drug Monograph 3-1) is especially dangerous when taken in large overdoses, owing to its toxic effects on the liver. In Australia, young teenage girls (aged 10–14) overdose on ‘headache tablets’ at 14 times the rate of boys of the same age. It is thought that the girls are beginning to selfmedicate at a turbulent time in their lives and that, whereas boys tend to use more violent means to harm themselves, girls are more likely to use drugs. About one in 100 females admitted to hospital for analgesic poisoning dies from the toxic effects.

Benzodiazepines

Benzodiazepines are prescribed for insomnia, anxiety or musculoskeletal problems; they are commonly used as tranquillisers or sleeping pills, but people can quickly become dependent on them—it can take as little as two weeks of regular use to become dependent. It is estimated that there are four times more Australians dependent on ‘benzos’ than on heroin (see earlier section under CNS depressants).