Pharmaceutical drug

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A pharmaceutical drug, also referred to as a medicine or (loosely) medication, officially called medicinal product, can be loosely defined as any chemical substance — or product comprising such — intended for use in the medical diagnosis, cure, treatment, or prevention of disease.[1][2] The word pharmaceutical comes from the Greek word Pharmakeia. The modern transliteration of Pharmakeia is Pharmacia.

Classification[edit]

Medicines can be classified in various ways,[3] such as by chemical properties, mode or route of administration, biological system affected, or therapeutic effects. An elaborate and widely used classification system is the Anatomical Therapeutic Chemical Classification System (ATC system). The World Health Organization keeps a list of essential medicines.

A sampling of classes of medicine includes:

  1. Antipyretics: reducing fever (pyrexia/pyresis)
  2. Analgesics: reducing pain (painkillers)
  3. Antimalarial drugs: treating malaria
  4. Antibiotics: inhibiting germ growth
  5. Antiseptics: prevention of germ growth near burns, cuts and wounds
  6. Mood stabilizers: lithium and valpromide
  7. Hormone replacements: Premarin
  8. Oral contraceptives: Enovid, "biphasic" pill, and "triphasic" pill
  9. Stimulants: methylphenidate (Ritalin)
  10. Tranquilizers: meprobamate, chlorpromazine, reserpine, chlordiazepoxide, diazepam, and alprazolam
  11. Statins: lovastatin, pravastatin, and simvastatin

Types of medicines (type of pharmacotherapy)[edit]

For the gastrointestinal tract (digestive system)[edit]

For the cardiovascular system[edit]

For the central nervous system[edit]

See also: Psychiatric medication and Psychoactive drug

Drugs affecting the central nervous system include: Psychedelics, hypnotics, anaesthetics, antipsychotics, antidepressants (including tricyclic antidepressants, monoamine oxidase inhibitors, lithium salts, and selective serotonin reuptake inhibitors (SSRIs)), antiemetics, anticonvulsants/antiepileptics, anxiolytics, barbiturates, movement disorder (e.g., Parkinson's disease) drugs, stimulants (including amphetamines), benzodiazepines, cyclopyrrolones, dopamine antagonists, antihistamines, cholinergics, anticholinergics, emetics, cannabinoids, and 5-HT (serotonin) antagonists.

For pain and consciousness (analgesic drugs)[edit]

See also: Analgesic

The main classes of painkillers are NSAIDs, opioids and various orphans such as paracetamol. Other drugs such as anesthetic medication can also be used to reduce pain or numb a person's feeling to it.

For musculo-skeletal disorders[edit]

The main categories of drugs for musculoskeletal disorders are: NSAIDs (including COX-2 selective inhibitors), muscle relaxants, neuromuscular drugs, and anticholinesterases.

For the eye[edit]

For the ear, nose and oropharynx[edit]

sympathomimetics, antihistamines, anticholinergics, NSAIDs, steroids, antiseptics, local anesthetics, antifungals, cerumenolyti

For the respiratory system[edit]

bronchodilators, NSAIDs, anti-allergics, antitussives, mucolytics, decongestants
corticosteroids, Beta2-adrenergic agonists, anticholinergics, steroids

For endocrine problems[edit]

androgens, antiandrogens, gonadotropin, corticosteroids, human growth hormone, insulin, antidiabetics (sulfonylureas, biguanides/metformin, thiazolidinediones, insulin), thyroid hormones, antithyroid drugs, calcitonin, diphosponate, vasopressin analogues

For the reproductive system or urinary system[edit]

antifungal, alkalinizing agents, quinolones, antibiotics, cholinergics, anticholinergics, anticholinesterases, antispasmodics, 5-alpha reductase inhibitor, selective alpha-1 blockers, sildenafils, fertility medications

For contraception[edit]

For obstetrics and gynecology[edit]

NSAIDs, anticholinergics, haemostatic drugs, antifibrinolytics, Hormone Replacement Therapy (HRT), bone regulators, beta-receptor agonists, follicle stimulating hormone, luteinising hormone, LHRH
gamolenic acid, gonadotropin release inhibitor, progestogen, dopamine agonists, oestrogen, prostaglandins, gonadorelin, clomiphene, tamoxifen, Diethylstilbestrol

For the skin[edit]

emollients, anti-pruritics, antifungals, disinfectants, scabicides, pediculicides, tar products, vitamin A derivatives, vitamin D analogues, keratolytics, abrasives, systemic antibiotics, topical antibiotics, hormones, desloughing agents, exudate absorbents, fibrinolytics, proteolytics, sunscreens, antiperspirants, corticosteroids

For infections and infestations[edit]

antibiotics, antifungals, antileprotics, antituberculous drugs, antimalarials, anthelmintics, amoebicides, antivirals, antiprotozoals

For the immune system[edit]

vaccines, immunoglobulins, immunosuppressants, interferons, monoclonal antibodies

For allergic disorders[edit]

anti-allergics, antihistamines, NSAIDs

For nutrition[edit]

tonics, electrolytes and mineral preparations (including iron preparations and magnesium preparations), Parental nutritional supplements, vitamins, anti-obesity drugs, anabolic drugs, haematopoietic drugs, food product drugs

For neoplastic disorders[edit]

cytotoxic drugs, therapeutic antibodies, sex hormones, aromatase inhibitors, somatostatin inhibitors, recombinant interleukins, G-CSF, erythropoietin

For diagnostics[edit]

contrast media

For euthanasia[edit]

See also: Barbiturate#Other non-therapeutical uses and barbituates

An euthanaticum is used for euthanasia and physician-assisted suicide.

Euthanasia is not permitted by law in many countries, and consequently medicines will not be licensed for this use in those countries.

Administration[edit]

Administration is the delivery of a pharmaceutical drug to a patient. There are three major categories of drug administration; Enteral (taking medication orally), Parenteral (introducing the medication directly to the circulatory system), and Other (which includes introducing medication through intranasal, topical, inhalation, and rectal means).[4]

It can be performed in various dosage forms such as pills, tablets, or capsules.

There are many variations in the routes of administration, including intravenous (into the blood through a vein) and oral administration (through the mouth).

They can be administered all at once as a bolus, at frequent intervals or continuously. Frequencies are often abbreviated from Latin, such as every 8 hours reading Q8H from Quaque VIII Hora.

Statistics[edit]

The "gray market" for cancer and other drugs has been started due to a short supply of pharmaceutical drugs. The data from a statistical graph observed shows that the wholesale acquisition price of 7 prescription drugs are better sources. The drug primarily used to treat breast cancer, called Paclitaxel costs $695 on the gray market where as the wholesaler costs about $52.78.[5]

Legal considerations[edit]

Depending upon the jurisdiction, medications may be divided into over-the-counter drugs (OTC) which may be available without special restrictions, and prescription only medicine (POM), which must be prescribed by a licensed medical practitioner. The precise distinction between OTC and prescription depends on the legal jurisdiction. A third category, behind-the-counter medications (BTMs), is implemented in some jurisdictions. BTMs do not require a prescription, but must be kept in the dispensary, not visible to the public, and only be sold by a pharmacist or pharmacy technician. Doctors may also prescribe prescription drugs for off-label use - purposes which the drugs were not originally approved for by the regulatory agency. The Classification of Pharmaco-Therapeutic Referrals helps guide the referral process between pharmacists and doctors.

The International Narcotics Control Board of the United Nations imposes a world law of prohibition of certain medications. They publish a lengthy list of chemicals and plants whose trade and consumption (where applicable) is forbidden. OTC medications are sold without restriction as they are considered safe enough that most people will not hurt themselves accidentally by taking it as instructed. Many countries, such as the United Kingdom have a third category of pharmacy medicines which can only be sold in registered pharmacies, by or under the supervision of a pharmacist.

For patented medications, countries may have certain mandatory licensing programs which compel, in certain situations, a medication's owner to contract with other agents to manufacture the drug. Such programs may deal with the contingency of a lack of medication in the event of a serious epidemic of disease, or may be part of efforts to ensure that disease treating drugs, such as AIDS drugs, are available to countries which cannot afford the drug owner's price.

Prescription practice[edit]

Drugs which are prescription only are regulated as such because they can impose adverse effects and should not be used unless necessary. Medical guidelines and clinical trials required for approval are used to help inform doctors' prescription of these drugs, but errors can happen. Reasons to not prescribe drugs such as interactions or side effects are called contraindications.

Errors include overprescription and polypharmacy, misprescription, contraindication and lack of detail in dosage and administrations instructions. In 2000 the definition of a prescription error was studied using a Delphi method conference; the conference was motivated by ambiguity in the what a prescription error and a need to use a uniform definition in studies.[6]

Development[edit]

Main article: Drug development

Drug development is the process by which a drug is created. Drugs can be extracted from natural products (pharmacognosy) or synthesized through chemical processes. The drug's active ingredient will be combined with a "vehicle" such as a capsule, cream, or liquid which will be administered through a particular route of administration. Child-resistant packaging will likely be used in the ultimate package sold to the consumer.

Blockbuster drug[edit]

A blockbuster drug is a drug generating more than $1 billion of revenue for its owner each year.[7] Cimetidine was the first drug ever to reach more than $1 billion a year in sales, thus making it the first blockbuster drug.[8]

A report from URCH Publishing estimated that about one third of the pharma market by value is accounted for by blockbusters. About 125 products are blockbusters. The top seller currently is Lipitor, a cholesterol-lowering medication marketed by Pfizer with sales of $12.5 billion. In 2009 there were a total of seven new blockbuster drugs, with combined sales of $9.8 billion. Beyond this purely arbitrary financial consideration,

"In the pharmaceutical industry, a blockbuster drug is one that achieves acceptance by prescribing physicians as a therapeutic standard for, most commonly, a highly prevalent chronic (rather than acute) condition. Patients often take the medicines for long periods."[9]

The birth control pill Enovid was the first modern drug taken by those not ill for a highly prevalent chronic condition. The focus on highly profitable drugs for chronic conditions and resulting de-emphasis of one-time acute treatment drugs has led to occasional shortages of antibiotics or vaccines, such as the influenza vaccine shortage in the United States.

Leading blockbuster drugs[edit]

Drug Trade name Indication Company Sales[10] ($billion/year)*
Atorvastatin Lipitor Hypercholesterolemia Pfizer 12.5
Clopidogrel Plavix Atherosclerosis Bristol-Myers Squibb
Sanofi		 9.1
Fluticasone/salmeterol Seretide Asthma GlaxoSmithKline 8.7
Esomeprazole Nexium Gastroesophageal reflux disease AstraZeneca 8.3
Rosuvastatin Crestor Hypercholesterolemia AstraZeneca 7.4
Quetiapine Seroquel Bipolar disorder
Schizophrenia
Major Depressive Disorder		 AstraZeneca 7.2
Adalimumab Humira Rheumatoid Arthritis AbbVie 6.6
Etanercept Enbrel Rheumatoid Arthritis Amgen
Pfizer		 6.5
Infliximab Remicade Crohn's Disease
Rheumatoid Arthritis		 Johnson & Johnson 6.4
Olanzapine Zyprexa Schizophrenia Eli Lilly 6.2

*Sales are for the 12 months preceding June 30, 2011.

Environmental impact[edit]

Main article: Pharmaceuticals and personal care products in the environment

Since the 1990s water contamination by pharmaceuticals has been an environmental issue of concern.[11] Most pharmaceuticals are deposited in the environment through human consumption and excretion, and are often filtered ineffectively by wastewater treatment plants which are not designed to manage them. Once in the water they can have diverse, subtle effects on organisms, although research is limited. Pharmaceuticals may also be deposited in the environment through improper disposal, runoff from sludge fertilizer and reclaimed wastewater irrigation, and leaky sewage.[11] In 2009 an investigative report by Associated Press concluded that U.S. manufacturers had legally released 271 million pounds of drugs into the environment, 92% of which was the antiseptics phenol and hydrogen peroxide. It could not distinguish between drugs released by manufacturers as opposed to the pharmaceutical industry. It also found that an estimated 250 million pounds of pharmaceuticals and contaminated packaging were discarded by hospitals and long-term care facilities.[12]

Pharmacoenvironmentology is a branch of pharmacology and a form of pharmacovigilance which deals entry of chemicals or drugs into the environment after elimination from humans and animals post-therapy. It deals specifically with those pharmacological agents that have impact on the environment via elimination through living organisms subsequent to pharmacotherapy, while Ecopharmacology is concerned with the entry of chemicals or drugs into the environment through any route and at any concentration disturbing the balance of ecology (ecosystem), as a consequence. Ecopharmacology is a broad term that includes studies of “PPCPs” irrespective of doses and route of entry into environment.[13][14][15]

Ecopharmacovigilance is the science and activities associated with the detection, evaluation, understanding and prevention of adverse effects of pharmaceuticals in the environment. This is close to the WHO definition of pharmacovigilance, the science aiming to capture any adverse effects of pharmaceuticals in humans after use.[16]

The term Environmental Persistent Pharmaceutical Pollutants (EPPP) was suggested in the 2010 nomination of pharmaceuticals and environment as an emerging issue to Strategic Approach to International Chemicals Management (SAICM) by the International Society of Doctors for the Environment (ISDE).

History[edit]

Prescription Drug History[edit]

The pharmaceutical business is the most profitable in the nation. People have turned to prescription drugs to ease physical and psychic pain, combat infection, induce sleep, or stop the spread of disease. The top prescription drugs in history consist of antibiotics, mood stabilizers, hormone replacement, oral contraceptives, stimulants, tranquilizers, statins, and Viagra.

Antibiotics first arrived on the medical scene in 1942; coined the "wonder drugs." Antibiotics inhibits the growth or the metabolic activities of bacteria and other micro organisms by a chemical substance of microbial origin. Penicillin was the first antibiotic to be widely used. Streptomycin found in 1942, proved to be the first drug effective against the cause of tuberculosis and also came to be the best known of a long series of important antibiotics. A second generation of antibiotics were introduced in the 1940s: aureomycin and chloramphenicol. Aureomycin was the best known of the second generation. Antibiotics can be administered through injection; developing countries such as Indonesia, Pakistan, Ghana, Uzbekistan were of fans. The injection of antibiotics was popular in the countries of Africa and Asia also; Africa thought of antibiotics as a cure all for all conditions.[17]

Lithium was discovered in the 19th century for nervous disorders and its possible mood-stabilizing or prophylactic effect; it was cheap and easily produced. As lithium fell out of favor in France, valpromide came into play. This antibiotic was the origin of the drug that eventually created the mood stabilizer category. Valpromide had distinct psychotrophic effects that were of benfit in the treatment of both acute manic states and in the maintenance treatment of manic depression illness. Psychotropics can either be sedative or stimulant, Sedatives aim at damping down the extremes of behavior. Stimulants aim at restoring normality by increasing tone. Soon rose the notion of a tranquilizer which was quite different from any sedative or stimulant. The term tranquilizer took over the notions of sedatives and became the dominant term in the West through the 1980s. In Japan, during this time, the term tranquilizer produced the notion of a psyche-stabilizer and the term mood stabilizer vanished.[17]

Premarin (conjugated estrogens, introduced in 1942) and Prempro (a combination estrogen-progestin pill, introduced in 1995) dominated the hormone replacement therapy (HRT) during the 1990s. HRT is not a life-saving medication, nor does it cure any disease. HRT has been prescribed to improve one's quality of life. Doctors prescribe estrogen for their older female patients both to treat short-term menopausal symptoms and to prevent long term diseases. In the 1960s and early 1970's more and more physicians began to prescribe estrogen for their female patients. between 1991 to 1999, Premarin was listed as the most popular prescription and best selling drug in America.[17]

The first oral contraceptive, Enovid, was approved by FDA in 1960. Oral contraceptives inhibit ovulation and so prevent conception. Enovid was known to be much more effective than alternatives including the condom and the diaphragm. As early as 1960, oral contraceptives were available in several different strengths by every manufacturer. In the 1980s and 1990's an increasing number of options arose including, most recently, a new delivery system for the oral contraceptive via a transdermal patch. In 1982, a new version of the Pill was introduced, known as the "biphasic" pill. By 1985, a new triphasic pill was approved. Physicians began to think of the Pill as an excellent means of birth control for young women.[17]

Stimulants such as Ritalin (methylphenidate)came to be pervasive tools for behavior management and modification in young children. Ritalin was first marketed in 1955 for narcolepsy; it's potential users were middle-aged and the elderly. It wasn't until some time in the 1980s along with hyperactivity in children that Ritalin came onto the market. Medical use of methlyphanidate is predominately for symptoms of Attention Deficit/Hyperactivity Disorder (ADHD). Consumption of methylphenidate in the U.S. outpaces all other countries between 1991 and 1999. Significant growth in consumption was also evident in Canada, New Zealand, Australia, and Norway. Currently, 85% of the world's methylphanidate is consumed in America.[17]

The first minor tranquilizer was Meprobamate. Only fourteen months after it was made available, meprobamate had already become the country's largest-selling prescription drug. By 1957, meprobamate had become the fastest-growing drug in history. The popularity of meprobamate paved the way for Librium and Valium, two minor tranquilizers that belonged to a new chemical class of drugs called the benzodiazepines. These were drugs that worked chiefly as anti anxiety agents and muscle relaxants. The first benzodiazepine was Librium. Three months after it was approved, Librium had become the most prescribed tranquilizer in the nation. Three years later Valium hit the shelves and was ten times more effective as a muscle relaxant and anticonvulsant. Valium was the most versatile of the minor tranquilizers. Later came the wide spread adoption of major tranquilizers such as chlorpromazine and the drug reserpine. In 1970 sales began to decline for Valium and Librium; but sales of new and improved tranquilizers, such as Xanax, introduced in 1981 for the newly created diagnosis of panic disorder soared.[17]

Mevacor (lovastatin) is the first and most influential statin in the American market. The 1991 launch of Pravachol (pravastatin), the second available in the United States, and the release of Zocor (simvastatin) made Mevacor no longer the only statin on the market. In 1998 Viagra was released as a treatment for erectile dysfunction.[17]

Ancient pharmacology[edit]

Using plants and plant substances to treat all kinds of diseases and medical conditions is believed to date back to prehistoric medicine.

The Kahun Gynaecological Papyrus, the oldest known medical text of any kind, dates to about 1800 BC and represents the first documented use of any kind of medication.[18][19] It and other medical papyri describe Ancient Egyptian medical practices, such as using honey to treat infections.

Ancient Babylonian medicine demonstrate the use of prescriptions in the first half of the 2nd millennium BC. Medicinal creams and pills were employed as treatments.[20]

On the Indian subcontinent, the Atharvaveda, a sacred text of Hinduism whose core dates from the 2nd millennium BC, although the hymns recorded in it are believed to be older, is the first Indic text dealing with medicine. It describes plant-based medications to counter diseases.[21] The earliest foundations of ayurveda were built on a synthesis of selected ancient herbal practices, together with a massive addition of theoretical conceptualizations, new nosologies and new therapies dating from about 400 BC onwards.[22] The student of Āyurveda was expected to know ten arts that were indispensable in the preparation and application of his medicines: distillation, operative skills, cooking, horticulture, metallurgy, sugar manufacture, pharmacy, analysis and separation of minerals, compounding of metals, and preparation of alkalis.

The Hippocratic Oath for physicians, attributed to 5th century BC Greece, refers to the existence of "deadly drugs", and ancient Greek physicians imported medications from Egypt and elsewhere.[23]

Medieval pharmacology[edit]

Al-Kindi's 9th century AD book, De Gradibus and Ibn Sina (Avicenna)'s The Canon of Medicine cover a range of drugs known to Medicine in the medieval Islamic world.

Medieval medicine saw advances in surgery, but few truly effective drugs existed, beyond opium and quinine. Folklore cures and potentially poisonous metal-based compounds were popular treatments. Theodoric Borgognoni, (1205–1296), one of the most significant surgeons of the medieval period, responsible for introducing and promoting important surgical advances including basic antiseptic practice and the use of anaesthetics. Garcia de Orta described some herbal treatments that were used.

Modern pharmacology[edit]

For most of the 19th century, drugs were not highly effective, leading Oliver Wendell Holmes, Sr. to famously comment in 1842 that "if all medicines in the world were thrown into the sea, it would be all the better for mankind and all the worse for the fishes".[24]:21

During the First World War, Alexis Carrel and Henry Dakin developed the Carrel-Dakin method of treating wounds with an irrigation, Dakin's solution, a germicide which helped prevent gangrene.

In the inter-war period, the first anti-bacterial agents such as the sulpha antibiotics were developed. The Second World War saw the introduction of widespread and effective antimicrobial therapy with the development and mass production of penicillin antibiotics, made possible by the pressures of the war and the collaboration of British scientists with the American pharmaceutical industry.

Medicines commonly used by the late 1920s included aspirin, codeine, and morphine for pain; digitalis, nitroglycerin, and quinine for heart disorders, and insulin for diabetes. Other drugs included antitoxins, a few biological vaccines, and a few synthetic drugs. In the 1930s antibiotics emerged: first sulfa drugs, then penicillin and other antibiotics. Drugs increasingly became "the center of medical practice".[24]:22 In the 1950s other drugs emerged including corticosteroids for inflammation, rauwolfia alkaloids as tranqulizers and antihypertensives, antihistamines for nasal allergies, xanthines for asthma, and typical antipsychotics for psychosis.[24]:23–24 As of 2008, thousands of approved drugs have been developed. Increasingly, biotechnology is used to discover biopharmaceuticals.[24] Recently, multi-disciplinary approaches have yielded a wealth of new data on the development of novel antibiotics and antibacterials and on the use of biological agents for antibacterial therapy.[25]

In the 1950s new psychiatric drugs, notably the antipsychotic chlorpromazine, were designed in laboratories and slowly came into preferred use. Although often accepted as an advance in some ways, there was some opposition, due to serious adverse effects such as tardive dyskinesia. Patients often opposed psychiatry and refused or stopped taking the drugs when not subject to psychiatric control.

Governments have been heavily involved in the regulation of drug development and drug sales. In the U.S., the Elixir Sulfanilamide disaster led to the establishment of the Food and Drug Administration, and the 1938 Federal Food, Drug, and Cosmetic Act required manufacturers to file new drugs with the FDA. The 1951 Humphrey-Durham Amendment required certain drugs to be sold by prescription. In 1962 a subsequent amendment required new drugs to be tested for efficacy and safety in clinical trials.[24]:24–26

Until the 1970s, drug prices were not a major concern for doctors and patients. As more drugs became prescribed for chronic illnesses, however, costs became burdensome, and by the 1970s nearly every U.S. state required or encouraged the substitution of generic drugs for higher-priced brand names. This also led to the 2006 U.S. law, Medicare Part D, which offers Medicare coverage for drugs.[24]:28–29

As of 2008, the United States is the leader in medical research, including pharmaceutical development. U.S. drug prices are among the highest in the world, and drug innovation is correspondingly high. In 2000 U.S. based firms developed 29 of the 75 top-selling drugs; firms from the second-largest market, Japan, developed eight, and the United Kingdom contributed 10. France, which imposes price controls, developed three. Throughout the 1990s outcomes were similar.[24]:30–31

See also[edit]

References[edit]

  1. ^ US Federal Food, Drug, and Cosmetic Act, SEC. 210., (g)(1)(B). Accessed 17 August 2008.
  2. ^ Directive 2004/27/EC of the European Parliament and of the Council of 31 March 2004 amending Directive 2001/83/EC on the Community code relating to medicinal products for human use. Article 1. Published March 31, 2004. Accessed 17 August 2008.
  3. ^ www.epgonline.org database of prescription pharmaceutical products including drug classifications [1]
  4. ^ Finkel, Richard; Cubeddu, Luigi; Clark, Michelle (2009). Lippencott's Illustrated Reviews: Pharmacology 4th Edition. Lippencott Williams & Wilkins. pp. 1–4. ISBN 978-0-7817-7155-9. 
  5. ^ Riaz AJOURNAL OF THE NATIONAL CANCER INSTITUTE, V. 104 (3), 02/2012, p. 169-169.
  6. ^ Dean B, Barber N, Schachter M (December 2000). "What is a prescribing error?". Qual Health Care 9 (4): 232–7. doi:10.1136/qhc.9.4.232. PMC 1743540. PMID 11101708. 
  7. ^ ""Blockbuster medicine" is defined as being one which achieves annual revenues of over US$ 1 billion at global level." in European Commission, Pharmaceutical Sector Inquiry, Preliminary Report (DG Competition Staff Working Paper), 28 November 2008, page 17 (pdf, 1.95 MB).
  8. ^ Whitney, Jake (February 2006). "Pharmaceutical Sales 101: Me-Too Drugs". Guernica. Retrieved 2008-07-31. 
  9. ^ Finkelstein, Temin "Reasonable Rx: Solving the Drug Price Crisis" 11 January 2008
  10. ^ "Before the Storm". Chemical & Engineering News 89 (49): 12–18. 2011. 
  11. ^ a b Doerr-MacEwen NA, Haight ME (November 2006). "Expert stakeholders' views on the management of human pharmaceuticals in the environment". Environ Manage 38 (5): 853–66. doi:10.1007/s00267-005-0306-z. PMID 16955232. 
  12. ^ Donn J. (2009). Tons of Released Drugs Taint U.S. Water. AP.
  13. ^ Rahman, SZ; Khan RA, Gupta V, Misbah Uddin (2008). "Chapter 2: Pharmacoenvironmentology – Ahead of Pharmacovigilance". In Rahman SZ, Shahid M & Gupta A. An Introduction to Environmental Pharmacology (1st ed.). Aligarh, India: Ibn Sina Academy. pp. 35–52. ISBN 978-81-906070-4-9. 
  14. ^ Rahman, SZ; Khan, RA; Gupta, V; Uddin, Misbah (July 2007). "Pharmacoenvironmentology–A Component of Pharmacovigilance". Environmental Health 6 (20): 20. doi:10.1186/1476-069X-6-20. PMC 1947975. PMID 17650313. 
  15. ^ Ilene Sue Ruhoy, Christian G. Daughton. Beyond the medicine cabinet: An analysis of where and why medications accumulate. Environment International 2008, Vol. 34 (8): 1157-1169
  16. ^ Ecopharmacovigilance (AstraZeneca)[dead link]
  17. ^ a b c d e f g Tone, Andrea and Elizabeth Watkins, Medicating Modern America: Prescription Drugs in History. New York and London, New York University, 2007. Print.
  18. ^ Griffith, F. Ll. The Petrie Papyri: Hieratic Papyri from Kahun and Gurob
  19. ^ The Kahun Gynaecological Papyrus
  20. ^ H. F. J. Horstmanshoff, Marten Stol, Cornelis Tilburg (2004), Magic and Rationality in Ancient Near Eastern and Graeco-Roman Medicine, p. 99, Brill Publishers, ISBN 90-04-13666-5.
  21. ^ See Atharvaveda XIX.34.9
  22. ^ Kenneth G. Zysk, Asceticism and Healing in Ancient India: Medicine in the Buddhist Monastery, Oxford University Press, rev. ed. (1998) ISBN 0-19-505956-5.
  23. ^ Heinrich Von Staden, Herophilus: The Art of Medicine in Early Alexandria (Cambridge: Cambridge University Press, 1989), pp. 1-26.
  24. ^ a b c d e f g Finkelstein S, Temin P (2008). Reasonable Rx: Solving the drug price crisis. FT Press. 
  25. ^ Miller, AA; Miller, PF (editor) (2011). Emerging Trends in Antibacterial Discovery: Answering the Call to Arms. Caister Academic Press. ISBN 978-1-904455-89-9. 

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