Diamorphine - Oxford Medicine 10.1093/med/9780199236640.003.0016 Page of PRINTED FROM OXFORD MEDICINE ONLINE ( © Oxford University Press, 2015. All Rights Reserved. Under the terms of the licence agreement, an individual user may print out a PDF of a single chapter of a title in Oxford Medicine Online for personal use (for details see Privacy Policy ). Subscriber: University of Washington; date: 20 January 2017 Chapter 16 discusses Diamorphine (di-acetyl morphine, heroin), a semisynthetic derivative of morphine. It is not an active drug in its own right, but a pro-drug or opioid delivery system. The active metabolites 6-monoacetylmorphine (6-AM) and morphine are responsible for the analgesic effects of the drug. Diamorphine was first produced commercially in the late 1890s as a treatment for a variety of respiratory conditions including dyspnoea, pharyngitis, laryngitis, bronchitis, asthma, and tuberculosis.

It was marketed by the Bayer Company under the trade name ‘heroin’. It was also recommended as a remedy for morphine dependence. In 1924 it was banned from medicinal use in the USA when its potential for abuse and addiction was recognized. Diamorphine is used widely and remains the parenteral opioid of choice for the treatment of chronic cancer pain in the UK, but is not used elsewhere because of these concerns. Access to the complete content on Oxford Medicine Online requires a subscription or purchase. Public users are able to search the site and view the abstracts for each book and chapter without a subscription. Please subscribe or login to access full text content. If you have purchased a print title that contains an access token, please see the token for information about how to register your code. For questions on access or troubleshooting, please check our FAQs , and if you can''t find the answer there, please contact us . Morphine & Heroin Opium, Morphine and Heroin Opium - the first Painkiller Opium is obtained from the opium poppy (papaver somniferum) by scraping the unripe seed capsule, and then collecting and drying the rubbery exudate.

The name opium comes from the Greek opion, or poppy juice. It is important as a painkilling drug in its own right, but it is also the source of other analgesic drugs such as morphine and heroin . The opium poppy, papaver somniferum The seed pod, showing the exudate Mankind had discovered the use of opium by the time of the earliest written records. In fact, the first recorded use of opium as a painkiller was around 6000 years ago by the Sumerians, and Babylonian and Egyptian writings contain many references to the value of opium preparations for the relief of pain. Later on, in Eurasia there emerged a legend that Buddha cut off his eyelids in order to prevent sleep overtaking him, and where they fell there grew a herb which bore a nodding violet flower which was to give sleep and tortured dreams to all mankind. Thomas Sydenham, the 17th-century pioneer of English medicine wrote: "Among the remedies which it has pleased Almighty God to give to man to relieve his sufferings, none is so universal and so efficacious as opium".

Nowadays, although opium is no longer regarded as a universal analgesic, it is still very important as the source of morphine, the drug that is still the most commonly prescribed by physicians for the relief of severe pain. Morphine - the first alkaloid Raw opium contains some 20 alkaloid substances, one of which is morphine , in a typical yield of 10%. Morphine was first isolated in 1805 by Friedrich Sertürner, an apothecary's assistant in Paderborn, Germany, however its basic structure was not correctly determined until 120 years later. In the 1800s morphine (known then as laudanum) was a popular panacea and was available from grocers and markets. Later on its addictive qualities led to its use and availability being severely restricted. Morphine is isolated from opium in large quantities (over 1000 tons per year), although most commercial opium is converted into codeine by methylation. Morphine acts as an anesthetic without decreasing consciousness, and it is one of the most powerful analgesics known.

However it also suppresses the respiratory system, and high doses can cause death by respiratory failure. Its analgesic properties are related to the ability of the molecule to fit into and block a specific receptor site on a nerve cell. This eliminates the action of the pain receptor, preventing the pain signals reaching the brain. This is similar to the way in which the body's natural painkillers (endorphins and enkaphalins) work. The shape of the morphine molecule is crucial to its ability to exactly fit into the active site on the receptor - the 'lock-and-key' mechanism. The benzene group of the morphine molecule fits snugly against a flat section of the receptor protein, whilst the bent neighbouring group of carbon atoms fits into a nearby groove. This allows the positively charged nitrogen atom to attach to a negatively-charged group on the receptor, so locking the two molecules together. Morphine blocks deep aching pain, but has no effect on the fast pain that results from injury. One side effect of the analgesic action is that the patient often gets a feeling of detachment from the world, along with euphoria and sometimes pleasure.

It is this which makes morphine, and the other drugs related to it (such as heroin), attractive to those who want to use drugs for 'recreational' reasons. However all of these drugs are highly addictive, and the body rapidly gets acclimatised to their use, such that increasingly large dosages are required for the same effect. Morphine - replacing the -OH group shown in red with -OCH3 produces codeine . Replacing the both the red and blue -OH groups with OCOCH3 produces heroin. Codeine - the methoxy addition is shown in red. Pethidine - the parts of the molecule resembling the morphine structure are shown in red. The isolation of morphine was the beginning of alkaloid chemistry, which has yielded many important medicinal substances. Although a satisfactory theory of analgesic structure or action still eludes us, experimenters have developed a number of synthetic analgesics related to morphine. The oldest is pethidine (also known as meperidine, Demerol and about 40 other names). It was synthesised in 1939 by the German chemist Otto Eisleb.

It is less potent than morphine, but is still widely used for the relief of post-operative pain. By replacing one of the -OH groups with a methoxy group, morphine is converted into codeine , another powerful painkiller. When mixed with paracetamol it goes by the trade name Tylenol. When ingested, the -OCH3 group is converted back to -OH, regenerating morphine. Heroin The most notorious derivative of morphine is heroin . It is synthesised by acetylation of the two hydroxyl groups of morphine with acetyl chloride, hence its other names, diacetylmorphine or diamorphine. Heroin was first isolated from morphine in 1874 and was originally used as a 'safe' (i.e. non addictive) cure from morphine addiction. This was later found to be incorrect and in the 1900s heroin abuse and addiction became common. Heroin was first restricted in the UK in 1868 due to 'unprofitable diversion of workers' and an international ban followed after the first world war. It is now classified as a Class A drug and possession or trading in it results in heavy penalties in most countries.

Heroin The -OCOCH3 groups that replaced the -OH groups in morphine are shown in red. Replacing the hydrogen-bonding -OH groups with -OCOCH3 makes heroin much less soluble in water than morphine, but more soluble in non-polar solvents, like oils and fats. Therefore heroin has to be injected directly into the bloodstream, but once there it can pass rapidly through the blood-brain barrier which normally prevents the passage of water-soluble and large molecules. As a result it is much more potent than morphine, but its effect does not last as long. Again, once the heroin molecule is absorbed into the body, the acetyl groups are removed, reforming morphine. Methadone Methadone hydrochloride is an opioid (a completely synthetic molecule), as opposed to an opiate, which is the name given to drugs which derive directly or indirectly from the opium poppy, such as morphine and heroin. It was originally synthesised by the German pharmaceutical company Axis during the second world war. It was first marketed as 'Dolophine' (to honour Adolph Hitler) and was used as an analgesic for the treatment of severe pain.

It is still occasionally used for pain relief, although it is more widely used now as a substitute drug for people addicted to opiates (primarily heroin). Methadone - the parts of the molecule resembling the morphine structure are shown in red. Levorphan and Dextrorphan The fact that painkilling activity depends greatly upon the exact geometry of the molecule is strikingly illustrated by the drugs levorphan and dextrorphan. They are very similar in structure to morphine, except that they are both mirror images of one another. The left-handed molecule, levorphan, is several times more potent than morphine and is strongly addicting. But the right-handed molecule, dextrorphan, has no analgesic ability and is non-addicting. This is also true for morphine, which is naturally left-handed. There is no naturally occurring right-handed form of morphine, but the Japanese chemist Kakuji Goto has synthesised it and found that it possesses none of morphine's biological properties.

Diamorphine: the return of an old friend | Hospital Pharmacy Europe Diamorphine: the return of an old friend Related articles CLINICAL REVIEW: DIAMORPHINE 2 March, 2009 10:07 AM In late 2004, a shortage of diamorphine injections forced prescribers to find alternatives. Now that supplies have been restored, it is time to reappraise the role of diamorphine Christine Clark Contributing Editor HPE Diamorphine has been extensively used in British medicine, and a wealth of experience has been accumulated. The sudden, unexpected shortage of supply in the UK in recent years caused difficulties for practitioners and patients and resulted in calls for better systems to anticipate and cover such events. In many ways the outcry itself was testimony to the value of diamorphine in clinical practice. In this article I explore the reasons for the supply problems and present a brief overview of the properties of diamorphine and its clinical applications. The shortage of supply In December 2004, Chiron, one of two UK manufacturers of diamorphine, discontinued production.

At that time the chief medical, nursing and pharmaceutical officers of the Department of Health[1] and the corresponding authorities for Northern Ireland and Scotland published guidance on conservation of existing stocks and the alternatives available. Chiron had been responsible for approximately two-thirds of all the diamorphine supplied in the UK, so there was a significant shortfall. The other manufacturer, Wockhardt, stepped in to make up the shortfall. However, the issue was not straightforward diamorphine injection is a freeze-dried preparation, and there was no alternative licensed preparation available in Europe in the strengths required. The freeze-drying capacity at Wockhardt was not sufficient immediately to make up the shortfall, but measures were put in place to increase capacity over the next few months. The chief medical officer's guidance indicated that the supply situation was likely to remain uncertain for some time. Many practitioners expected the shortage to last for no more than two or three months. In the event the shortage persisted for much longer. The guidance also made recommendations for alternative injectable analgesics for most common situations in which diamorphine is used.

Therapeutic switches to morphine and oxycodone appear to have worked satisfactorily, but many patients in drug treatment programmes experienced difficulties when they were switched to oral methadone. The problems became so severe that even representatives of the BMA suggested that Afghan opium should be purchased to correct the deficiency.[2] However, the problem was not shortage of the raw material, but shortage of the processing (freeze-drying) capacity. Prescribing patterns showed that there was a marked fall in the use of injectable controlled drugs during the third and fourth quarters of 2004-5, coinciding with the announcement of supply problems. The level of use increased and returned to the previous level by the end of 2006.[3] It is not known what proportion of this is accounted for by diamorphine, but it seems reasonable to suppose that the improved supply position allowed prescribing of diamorphine to increase. Since late 2007, Wockhardt has had the production capacity and sufficient stock to meet 100% of UK diamorphine needs.

The need for diamorphine Some commentators have pointed out that is not available for therapeutic use in many other countries and therefore, they argue, we could also manage without it in the UK. For example, in Switzerland it is used only in the treatment of opioid addiction. Diamorphine is not used in countries outside Europe for historical rather than clinical reasons. The USA banned Heroin (Bayer's trade name for diamorphine) in 1924 due to concerns over its misuse and exerted vigorous pressure to have it banned universally. Britain resisted the pressure, unlike most other countries. However, diamorphine has some properties that make it particularly useful and, in addition, there is a wealth of experience with the therapeutic use of this drug, and many texts and clinical guidelines refer to it specifically. Diamorphine (diacetyl morphine) is a prodrug with no intrinsic activity. In the body it is rapidly de-acetylated in two steps to form morphine. Intramuscular diamorphine has a faster onset of action than intramuscular morphine. This is thought be due to the higher lipid solubility of diamorphine.

The situation is reversed for intravenous administration, which is presumed to be because diamorphine has first to be metabolised to active compounds and it is also protein-bound to a greater extent than is morphine. [[HPE41.54.jpg]] One great advantage of diamorphine is that it is more soluble than either morphine or oxycodone (see Table 1). This makes it particularly suitable for administration in small volumes, such as subcutaneous infusions, epidural infusions or administration to small or emaciated patients who may be unable to tolerate large volumes of fluid. Diamorphine is described as the strong opioid of choice in the UK because large amounts can be given in very small volumes in the Palliative Care Formulary.[4] Diamorphine, unlike morphine, is suitable for intranasal administration because of its higher lipid solubility. It also may cause less nausea and hypotension than morphine.[5] Another advantage is that diamorphine is better tolerated than methadone by many intravenous drug addicts.

Uses of diamorphine It should be noted that a number of the clinical applications of diamorphine that have slipped into common use are still unlicensed indications for this drug. At present, diamorphine is licensed for the treatment of: Severe pain associated with surgical procedures. Myocardial infarction. Pain in the terminally ill. The relief of dyspnoea in acute pulmonary oedema. The intramuscular, intravenous and subcutaneous routes of administration are licensed for diamorphine, but the intranasal, epidural and intrathecal routes are not. [[HPE41.542.jpg]] Acute trauma pain Parenteral opioids are often used to treat pain induced by trauma or injury, and diamorphine has a place here. The provision of pain relief for children can be challenging because young children are often distressed by the use of needles.

One study compared the use of intranasal diamorphine with intramuscular morphine in 404 children and teenagers with clinical fractures.[6] Because of its high solubility, the diamorphine dose can be presented in a small volume as a spray in this study the dose (0.1 mg/kg) was delivered in a 0.1 ml volume. This minimises the chance of swallowing a portion of the dose and thereby ensures that first-pass metabolism is avoided as far as possible. The relatively high lipidsolubility of the drug means that it is well absorbed through the nasal mucosa. The results showed that intranasal diamorphine spray (0.1 mg/kg) gave the same degree of pain relief as intramuscular morphine (0.2 mg/kg) but had a faster onset of action and was more acceptable to patients, parents and staff. Acute cardiac pain and left ventricular failure The British National Formulary recommends the use of slow (1 mg/min) intravenous diamorphine in the initial management of suspected acute myocardial infarction.

A dose of 5 mg should be given followed by a further 2.5-5 mg if necessary; in elderly or frail patients the dose should be reduced by half.[5] Many local guidelines have also included diamorphine. The diamorphine not only relieves pain and anxiety but also acts as a venodilator and reduces cardiac preload. This, in turn, reduces acute pulmonary oedema. Cancer-related pain Diamorphine has an established place in the management of cancer pain in patients who are unable to take opioids orally, as it can be used in subcutaneous infusions. Labour pain Epidural infusion of local anaesthetics is an established technique for the provision of pain relief during labour. It has been suggested that diamorphine is particularly suitable for this purpose as it is readily available to the opioid receptors in the spinal cord and can be delivered in a small volume. A recent study confirmed previous findings that epidural diamorphine alone can provide good pain relief during labour.[7] The combined spinal epidural (CSE) technique for initiation of mobile analgesia for labour is now commonly used.

The main reason for this is that it is believed to offer the advantage of rapid onset of analgesia via the spinal route with the flexibility of later topups via the epidural route. A study that used intrathecal diamorphine instead of the usual fentanyl (in combination with bupivacaine) found no increase in side-effects but a faster onset of action.[8] Postoperative pain There is an extensive literature on the use of diamorphine for postoperative pain relief. In addition to intramuscular injection, the high solubility of diamorphine means that it can be prepared in small volumes for delivery by subcutaneous, epidural, spinal (intrathecal) and nasal routes. Patient-controlled epidural and intranasal and subcutaneous administration is also reported. Sedation for ventilation In preterm babies with respiratory failure who require mechanical ventilation, sedation with opiates or opioids is believed to be preferable to paralysis with neuromuscular blockers.

A study that compared diamorphine with morphine for this indication found that the two drugs were equally efficacious, but that diamorphine had a more rapid onset of action and, unlike morphine, was not associated with an initial hypotensive effect.[9] Sickle-cell anaemia The acute pain of sickle-cell disease can be sudden, unpredictable in onset and intense. Severe acute pain can be treated with subcutaneous doses of 2.5-5 mg diamorphine in opioid-naive patients, but opioidtolerant individuals could need doses of 5-10 mg.[10] Opioid dependency Some opioid-dependent individuals tolerate diamorphine better than methadone, and during the shortage many of these were severely disadvantaged.[11] Current guidelines recommend that injectable diamorphine should be available for this small number of individuals. [12] Only doctors who hold a special licence from the Home Office can prescribe intravenous diamorphine for opioid dependency. Conclusions The physicochemical properties of diamorphine, along with its pharmacodynamic profile, make it particularly suitable in a number of situations and comfortably justify its place in present-day formularies.

Moreover, modern methods of administration are enabling more effective use of this tried-and-tested product. Now that the supply problems of the past few years have been resolved, it is time to take a fresh look at the situations where diamorphine can make a positive impact on patient care. References 1. Department of Health. Guidance on use and supply of diamorphine injections. London: DH; 2004 Dec. CEM/CMO/2004/14. 2. Brimelow A. Afghan poppies â€˜could help NHSâ€™. BBC News. 2007 Jan 23 [cited 2008 Oct 3]. Available from: 3. Healthcare Commission. The safer management of controlled drugs â€" annual report 2007. London: Healthcare Commission; 2008 Jul. 4. Twycross RG, Wilcock A, Charlesworth S, Dickman A. Palliative care formulary. 2nd ed. Oxford: Radcliffe Publishing; 2002. 5. British national formulary. 56th ed.

London: British Medical Association and Royal Pharmaceutical Society of Great Britain; 2008 Sep. 6. Kendall JM, Reeves BC, Latter VS. Multicentre randomised controlled trial of nasal diamorphine for analgesia in children and teenagers with clinical fractures. BMJ 2001;322;261-5. 7. McLeod GA, Munishankar B, Columb MO. Is the clinical efficacy of epidural diamorphine concentrationdependent when used as analgesia for labour? Br J Anaesth 2005;94:229-33. 8. Vaughan DJA, Ahmad N, Lillywhite NK, Lewis N, Thomas D, Robinson PN. Choice of opioid for initiation of combined spinal epidural analgesia in labour â€" fentanyl or diamorphine? Br J Anaesth 2001;86:567-9. 9. Wood CM, Rushforth JA, Hartley R, Dean H, Wild J, Levene MI. Randomised double blind trial of morphine versus diamorphine for sedation of preterm neonates.

Arch Dis Child Fetal Neonatal Ed 1998;79:F34-9. 10. Okpala JR, Tawil A. Management of pain in sickle-cell disease. J R Soc Med 2002;95:456-8. 11. White R, Cox D, Charnaud B. Lessons from the UK diamorphine shortage. Psychiatr Bull 2005;29:316. 12. National Treatment Agency for Substance Misuse (NTA). Drug misuse and dependence â€" UK guidelines on clinical management. London: NTA; 2007 Sep. Featured In Issue: Diamorphine Hydrochloride: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing use of monoamine oxidase inhibitors or within two weeks of stopping taking them. Also see list of precautions and interactions STORAGE Do not store above 25°C. DIAMORPHINE HYDROCHLORIDE USES What is it used for? Diamorphine hydrochloride used to relieve pain by acting on the central nervous system.

It is a narcotic analgesic, sometimes known as an opioid analgesic. It is used to relieve moderate to severe pain . In general this drug is used for the relief of pain. Listed below are the typical uses of diamorphine hydrochloride. relief of severe pain associated with surgery, heart attack , terminal illness , cancer ; relief of breathlessness associated with fluid on the lungs ( pulmonary oedema ). On occasion your doctor may prescribe this medicine to treat a condition not on the above list. Such conditions are listed below. None known. HOW TO USE/TAKE How often do I take it? Your doctor or nurse will prepare and give the injection to you. The injection will be into a vein, into a muscle, or under the skin . This medication will only be given to you by your doctor or nurse. It may take some hours before the full benefit of this drug takes effect. Certain medical conditions may require different dosage instructions as directed by your doctor. What dose? Dosage is based on your age, gender, medical condition, response to therapy, and use of certain interacting medicines. Do I need to avoid anything? Diamorphine causes drowsiness and loss of concentration.

If affected patients should not drive or use machines. Consult your doctor or pharmacist for more details. When can I stop? Always complete the full course as administered by your doctor. DIAMORPHINE HYDROCHLORIDE SIDE EFFECTS See information leaflet for other, less common side effects. If any of these persist or you consider them severe then inform your doctor or pharmacist. Tell your doctor immediately if you develop any of the following symptoms: breathing difficulties, circulation difficulties leading to collapse. Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects. A serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction include: rash, itching/ swelling (especially of the face / tongue /throat), dizziness , trouble breathing . This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist. The Yellow Card Scheme allows you to report suspected side effects from any type of medicine (which includes vaccines, herbals and over the counter medicines) that you are taking.

It is run by the medicines safety watchdog called the Medicines and Healthcare products Regulatory agency (MHRA). Please report any suspected side effect on the Yellow Card Scheme website. DIAMORPHINE HYDROCHLORIDE PRECAUTIONS Before taking diamorphine hydrochloride, tell your doctor or pharmacist if you are allergic to it or to other opiod analgesic; or if you have any other allergies . This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist in case of: Allergies to diamorphine or morphine, a tumour on your adrenal gland called a phaeochromocytoma, severe breathing difficulties, if you are a are a child . Before having surgery, tell your doctor or dentist that you are taking this medication. Does alcohol intake affect this drug? You should not drink alcohol while taking diamorphine hydrochloride. The elderly : diamorphine hydrochloride should be used with caution in the elderly as it may affect breathing.

Pregnancy and breastfeeding - please ensure you read the detailed information below PREGNANCY Diamorphine hydrochloride is not safe to take if you are, or are planning to become, pregnant, unless you have discussed this with your doctor first. It is sensible to limit use of medication during pregnancy whenever possible. However, your doctor may decide that the benefits outweigh the risks in individual circumstances and after a careful assessment of your specific health situation. If you have any doubts or concerns you are advised to discuss the medicine with your doctor or pharmacist. BREAST FEEDING Diamorphine hydrochloride is not safe to take if you are breastfeeding . It is sensible to limit use of medication during breastfeeding whenever possible. However, your doctor may decide that the benefits outweigh the risks in individual circumstances and after a careful assessment of your specific health situation. If you have any doubts or concerns you are advised to discuss the medicine with your doctor or pharmacist. DIAMORPHINE HYDROCHLORIDE INTERACTIONS Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medications because very serious, possibly fatal interactions may occur: Monoamine oxidase inhibitors such as phenelzine used to treat depression . If you are currently using any of these medications, tell your doctor or pharmacist before starting diamorphine hydrochloride. Before using this medication, tell your doctor or pharmacist of all prescription and non-prescription/herbal products you may use, especially of: Heroin, Bayer and Heinrich Dreser Date: 13 September 1998 How aspirin turned hero A hundred years ago Heinrich Dreser made a fortune from the discovery of heroin and aspirin - but he may have ended his days as an addict. RICHARD ASKWITH reports on a chemist who prescribed heroin for coughs THE MAN in the 100-year-old photograph is not, to the modern eye, prepossessing. Balding, bespectacled and clerkish, he scarcely dominates his own portrait, let alone the picture of him with his staff in his laboratory. Yet Heinrich Dreser, chemist and opportunist, was one of the most influential men of his age.

Between 1897 and 1914, Dreser worked for Bayer, the former dye factory that was to become the first of the world's pharmaceutical giants, in Wuppertal, north-west Germany. Friedrich Engels was born there. While Dreser made less of a mark on history, you could argue he had the greater influence on the 20th century. As head of Bayer's pharmacological laboratory, he was responsible for the launch of two drugs that have shaped the way we live: aspirin, the world's most successful legal drug; and heroin, the most successful illegal one. Aspirin, of which the world now consumes 40 billion tablets a year, was launched 100 years ago next February. A fanfare of publicity will mark the centenary. The centenary of heroin is more ambiguous: it was launched in November 1898 but was registered as a trademark in various countries from June that year, most lucratively in the US in August. But whenever the centenary falls, Bayer won't be celebrating. This is understandable; but the stories of aspirin and heroin are intertwined, not least through Dreser.

Born in 1860, in Darmstadt, the son of a physics professor, he showed promise as a chemist from an early age. After receiving his doctorate from Heidelberg University, he worked in various laboratories before becoming a professor at Bonn University in 1893. Four years later he joined the Bayer Company, where he was in charge of testing the efficacy and safety of new drugs. Dreser was admired for his thorough, methodical approach, and for his innovations in testing (he was, for example, the first chemist to use animal experiments on an industrial scale). The credit for originating new products for Bayer belonged, strictly speaking, to the researcher Arthur Eichengruen, but Dreser had the power to decide which new products would be developed. He had also negotiated a special deal which guaranteed him a share of the profits from products he launched. In 1897 the Bayer chemist Felix Hoffmann, acting on Eichengruen's instructions, discovered a new process for modifying salicyclic acid (a remedy for fever and inflammation which unfortunately has excruciating digestive side effects) to produce acetylsalicyclic acid (ASA).

This compound, later to be named Aspirin, had been isolated before and the healing powers of salicylates (derived from willow bark) had been known for centuries. But Hoffmann had created a reliable process for making it. Eichengruen enthusiastically recommended ASA to Dreser in 1898. Dreser, after cursory consideration, rejected it. Ostensibly, his objection was that ASA would have an "enfeebling" action on the heart. "The product has no value," he pronounced confidently. But the real problem was almost certainly that he had another product on his mind whose impending success he was anxious not to jeopardise. This was heroin. Like aspirin, the drug that Bayer launched under the trademark Heroin in 1898 was not an original discovery. Diacetylmorphine, a white, odourless, bitter, crystalline powder deriving from morphine, had been invented in 1874 by an English chemist, C R Wright. But Dreser was the first to see its commercial potential. Scientists had been looking for some time for a non-addictive substitute for morphine, then widely used as a painkiller and in the treatment of respiratory diseases.

If diacetylmorphine could be shown to be such a product, Bayer - and Dreser - would hit the jackpot. Diacetylmorphine was first synthesised in the Bayer laboratory in 1897 - by Hoffmann, two weeks after he first synthesised ASA. The work seems to have been initiated by Dreser, who was by then aware of Wright's discovery, even though he subsequently implied that heroin was an original Bayer invention. By early 1898 was testing it on sticklebacks, frogs and rabbits. He also tested it on some of Bayer's workers, and on himself. The workers loved it, some saying it made them feel "heroic" (heroisch). This was also the term used by chemists to describe any strong drug (and diacetylmorphine is four times stronger than morphine). Creating a brand name was easy. In November 1898, Dreser presented the drug to the Congress of German Naturalists and Physicians, claiming it was 10 times more effective as a cough medicine than codeine, but had only a tenth of its toxic effects. It was also more effective than morphine as a painkiller. It was safe.

It wasn't habit-forming. In short, it was a wonder drug - the Viagra of its day. "What we don't recognise now," says David Muso, professor of psychiatry and the history of medicine at Yale Medical School, "is that this met what was then a desperate need - not for a painkiller, but for a cough remedy". Tuberculosis and pneumonia were then the leading causes of death, and even routine coughs and colds could be severely incapacitating. Heroin, which both depresses respiration and, as a sedative, gives a restorative night's sleep, seemed a godsend. The initial response to its launch was overwhelmingly positive. Dreser had already written about the drug in medical journals, and studies had endorsed his view that heroin could be effective in treating asthma, bronchitis, phthisis and tuberculosis. Now mailshots and free samples were sent out by the thousand to physicians in Europe and the US. The label on the samples showed a lion and a globe.

(There is a notorious brand of Burmese heroin, Double Globe, that uses remarkably similar packaging today.) By 1899, Bayer was producing about a ton of heroin a year, and exporting the drug to 23 countries. The country where it really took off was the US, where there was already a large population of morphine addicts, a craze for patent medicines, and a relatively lax regulatory framework. Manufacturers of cough syrup were soon lacing their products with Bayer heroin. There were heroin pastilles, heroin cough lozenges, heroin tablets, water-soluble heroin salts and a heroin elixir in a glycerine solution. Bayer never advertised heroin to the public but the publicity material it sent to physicians was unambiguous. One flyer described the product thus: "Heroin: the Sedative for Coughs . . . order a supply from your jobber." "It possesses many advantages over morphine," wrote the Boston Medical and Surgical Journal in 1900. "It's not hypnotic, and there's no danger of acquiring a habit." But worrying rumours were surfacing.

As early as 1899, researchers began to report patients developing "tolerance" to the drug, while a German researcher denounced it as "an extremely dangerous poison". By 1902 - when heroin sales were accounting for roughly five percent of Bayer's net profits - French and American researchers were reporting cases of "heroinism" and addiction. The bandwagon took time to stop. Between 1899 and 1905, at least 180 clinical works on heroin were published around the world, and most were favourable, if cautious. In 1906, the American Medical Association approved heroin for medical use, though with strong reservations about a "habit" that was "readily formed". But with the accumulation of negative reports and the steady encroachment on the market by other manufacturers, it was clear heroin would never deliver the riches that Dreser had yearned for. Had heroin been his only pet project, this disappointment could have spelt career disaster. Dreser had the kind of personality that needed commercial results to lend it plausibility.

With his unfashionably formal clothes and his habit of dragging an overweight dachshund to work with him, he was seen as an eccentric loner, a "difficult" man whose ready sarcasm and autocratic manner meant he did not want for enemies. Luckily, although his first "baby" was showing signs of turning into a monster, Dreser had belatedly adopted another: aspirin. Eichengruen, refusing to accept Dreser's rejection of ASA, had continued to investigate it and to lobby for its development. Eventually, Dreser recognised which way the wind was blowing, tested ASA on himself (as well as on his laboratory of rabbits), and finally published an enthusiastic scientific paper recommending it, particularly for the treatment of rheumatism - but omitting to mention the contributions of Eichengruen and Hoffmann. In February 1899, the brand name "Aspirin" was registered, and in June, Dreser presided over its launch. Like heroin, aspirin more or less sold itself. As a painkiller without undesirable side effects, it was - and remained for decades - unique.

By the end of 1899 it was being used all over Europe and the US, and by the time the heroin bubble burst, aspirin had more than filled the gap. Bayer was on its way to becoming an industrial giant. Hoffman and Eichengruen do not seem to have received any special compensation for their efforts. For Dreser, though, the rewards were spectacular. In 1913, Bayer decided to stop making heroin. There had been an explosion of heroinrelated admissions at New York and Philadelphia hospitals, and in East Coast cities a substantial population of recreational users was reported (some supported their habits by collecting and selling scrap metal, hence the name "junkie"). Prohibition seemed inevitable and, sure enough, the next year the use of heroin without prescription was outlawed in the US.

(A court ruling in 1919 also determined it illegal for doctors to prescribe it to addicts.) But Dreser was now earning, on top of his "substantial" salary, more than 100 000 marks a year (about By 1914 Dreser was an exceptionally rich 53-year-old - so much so that he decided not to renew his contract at Bayer. When war broke out he moved to Dusseldorf as honorary, unsalaried professor of his own pharmacological institute at the new Medical Academy. Thereafter, the record becomes indistinct. His first wife died, there were no children and, it appears, few friends. There were rumours that he was addicted to heroin himself. Eventually, his health deteriorated. His last years may or may not have been happy. But they were certainly comfortable - which is more than can be said for Eichengruen, who, in his eighties, emerged from a concentration camp to write an unpublished denunciation of Dreser's "discovery" of aspirin. In 1924, health problems forced Dreser to give up his institute and he moved to Zurich, where he remarried.

That year, the US banned the use and manufacture of heroin altogether, even for medical purposes. (In Britain, the medical use of heroin continues to this day, accounting for 95 percent of the world's legal heroin consumption.) The same year, four days before Christmas, Dreser died. The cause of death was given as a cerebral apoplexy, or stroke. It is just conceivable - had anyone known it - that he could have averted this fate by the simple expedience of taking an aspirin a day. If the rumours of addiction were true, the irony is doubled: Dreser, incorrigible in his misjudgment, had spent his twilight years taking a daily dose of the wrong wonder drug. Even before its properties as a prophylactic against circulatory disease became known, aspirin changed the lives of millions, reducing the sum of human misery. It also produced untold wealth for, among others, the shareholders of Bayer, which still earns about R4-billion a year from the drug.

(Those "others" include the generations of lawyers who acted in an 80-year orgy of litigation in which the original Bayer company, having had its American assets confiscated at the end of World War One, fought to reclaim the right to sell "Bayer aspirin" in the US.) The impact of heroin is harder to assess. In 1898, there were an estimated 250 000 morphine addicts in the US - a per capita rate roughly twice as high as today's. In Britain, similarly, opium use was widespread, especially in East Anglia, where it was a more or less necessary antidote to the malaria endemic in the Fens. It was also used as a sedative for babies. (In Britain, however, opium seems to have been superseded not by heroin but by other modern drugs - notably aspirin.) But the appearance of heroin played a crucial role in cementing the link between drug abuse and crime. Pharmacologically, heroin has the same effect as morphine. But you need only about a quarter as much to get the same effect. It is also cheaper, quicker and easier to use.

As national and international legislation against opiates gathered force after 1914, addicts who wished to continue their habit inevitably switched to heroin. By 1924, 98 percent of New York's drug addicts were thought to be heroin addicts. With legal channels of supply closed, criminal gangs - first Jewish, then Italian - began to monopolise the trade. By the end of the 30s, the Mafia was inextricably involved. Today, heroin use in Britain and the US is increasing faster than at any time since the 60s: heroin seizures rose by 135 percent between 1996 and 1997. There are thought to be between 160 000 and 200 000 heroin addicts in the UK, who spend almost R30-billion a year on heroin. And the British government spends R14-billion a year on drug-related policies. The other great change resulting from Dreser's marketing of a faster-acting and more conveniently consumed opiate has been a change in the profile of the average opiate abuser.

In 1898, the typical morphine addict in Britain or the US was a middle-class woman in her forties, whereas today's typical addict is an 18-year-old male. CHEMICAL REACTION: Dreser (seated, right) with his staff at Bayer, where he tested aspirin and heroin on himself As early as 1899, researchers began to report patients developing 'tolerance' to the drug, while a German researcher denounced it as 'an extremely dangerous poison'. By 1902 - when heroin sales were accounting for roughly five percent of Bayer's net profits - French and American researchers were reporting cases of 'heroinism' and addiction * * * Heroin: A Hundred-Year Habit | History Today Heroin: A Hundred-Year Habit Ian Scott traces the hundred-year history of heroin, from cough medicine to underworld narcotic. Bayer's pre-war heroin bottle, originally containing 5 grams of Heroin substance. In 1898 a German chemical company launched a new medicine called ‘Heroin’. A hundred years later, this drug is flooding illegally into Britain in record amounts. The latest Home Office figures show a 40 per cent increase in police seizures of heroin.

The National Criminal Intelligence Service believes that up to 80 per cent of the heroin currently entering Britain is controlled by Turkish organised criminals based in London and the South-East. How, then, did nineteenth-century science come to bequeath this notorious drug of abuse to twentieth-century crime? Want the full article and website archive access? Already a member? Log in now

Question: What trade name did Bayer give to the analgesic drug diamorphine?
Answer: Heroin