III.1. Pain and Inflammation Management. Morphine
III.1. Pain and Inflammation Management
Used from the early 1800s to decrease the sensation of pain, morphine was extracted from raw opium. The Hungarian pharmacist Janos Kabay revolutionized morphine production in the 1920s by extracting it not only from the immature poppy-head but from the dry poppy-straw. It was studied in 1923 to determine its chemical structure in an effort to synthesize a potent analgesic free from undesirable properties such as addiction and respiratory depression. Understanding how the naturally-occurring extract worked on the human body allowed a synthetic version of morphine to be developed and subsequent safer drugs to be created, such as nalorphine and naloxone in 1961.
The thomb of Janos Kabay in Budapest, Hungary
In 1890, salicylic acid was being manufactured as a cheap and effective inflammation reliever for rheumatoid arthritis, despite its unpleasant side effects (nausea, gastric catarrh). Acetylsalicylic acid (or aspirin) was synthesized in 1897 by the German chemist Felix Hoffmann at Bayer and tested pharmacologically by Heinrich Dreser. Production started in 1899 and the first pills were sold in 1900. Aspirin soon became popular because it had far fewer side-effects than salicylic acid. Aspirin, the first medicine to be produced at and industrial level, is still manufactured in large quantities today. Aspirin was consumed mainly as an anti-headache drug until the mid-eighties, when its beneficial effects in preventing heart attacks were discovered.
In the 1940s, studies of the adrenal gland cortex identified that certain naturally-occurring hormones (also called steroids) as having anti-inflammatory properties. First isolated from its natural source in 1936, cortisone was later synthesized by the American Lewis Hastings Sarett in 1948. It was already being commercially manufactured in the next year due to its miraculous affect on rheumatoid arthritis. Subsequent clinical studies showed that it did not cure arthritis, and triggered serious side effects, but enjoyed additional uses in asthma and allergy treatments. Further studies of steroid synthesis led to the creation of prednisone, prednisolone, and dexamethasone as better anti-inflammatory agents with reduced side effects.
Lewis Hastings Sarett
Deformity induced by joint inflammation
III.2. Psychotherapeutic Agents
Chlorpromazine (Thorazine, Hibernal) was first used to treat schizophrenia in 1954, after its original creation as an antihistamine anti-allergic. This new therapy proved itself dramatically effective and heralded the modern era of antipsychotic therapy. Controlling mental illness through medication soon supplanted earlier treatment methods, such as electroshock, insulin shock, prefrontal lobotomy (a surgical treatment disconnecting prefrontal hemispheres), and helped to decrease the rate of institutionalization worldwide. Later research shed light on the pharmacological mechanism of chlorpromazine and served as a basis for the development of many other anti-psychotic drugs, such as Haloperidol and Olanzapine.
Pictures from the film: One Flew Over the Cuckoo’s Nest(1975), which portrays the disastrous effects of mental illness
In 1958, a clinical study of Imipramine, a drug which was originally developed as an antipsychotic, revealed its antidepressant properties. It functions therapeutically by affecting the activity of neurotransmitters (stimulus transmitting agents) in the brain. The many subsequent drugs that were developed in this class became collectively known as `tricyclic’ antidepressants. Tricyclic antidepressants soon become the standard of therapy for this dehabilitating disease.
The onset of depression following labour
In 1959, Chlordiazepoxide (Librium) launched a potent new class of anti-anxiety agents, the benzodiazepines. This drug and its subsequent derivatives rapidly replaced barbiturates and Meprobamate, an earlier, moderately successful anxiolytic agent discovered in 1950, and are considered to be some of the most successful drugs of this era. The highly tolerable and safe benzodiazepines also proved successful as hypnotic agents, muscle relaxants, and as a treatment for epilepsy.
Neurotransmitters in the brain
III.3. Hormones and Hormone Regulators
Insulin, a protein hormone produced by special cells of the pancreas, controls the level of blood sugar (glucose) in the body. Lack of insulin leads to the development of type 1 diabetes, a disease that was considered fatal until the early 1920s. Two young Canadian doctors, Frederick Banting and Charles H. Best, isolated and purified a new injectable extract from bovine pancreas in 1921. Their first patient was a dying 14-year-old boy, who was released from the hospital after a few weeks. Insulin was manufactured from bovine pancreas by Eli Lilly and Company in 1922. The first insulin engineered from human sources using recombinant DNA technology was produced in 1982.
Frederick Banting and Charles H. Bestin a painting
Testosterone is responsible for the development of the male sexual organs and secondary sexual characteristics. It is a steroid hormone, structurally similar to cholesterol. Testosterone was first synthesized from cholesterol in 1935 to treat hormone deficiency diseases. Testosterone can be manufactured by chemical and microbiological modification of readily available naturally-occurring materials.
Progestins, estrogens and oral contraceptives
In the 1930s, two female hormones were isolated and produced from natural sources, the urine of pregnant mares and the Mexican sweet root. Progestins (progesterone, luteal hormone) were discovered to maintain gestation, and estrogens (follicular hormones) were understood to affect menstrual cycles. In the 1950s, synthetic versions of these hormones were produced and their effects on human conception and pregnancy were studied. Their excellent contraceptive qualities led to the development of oral contraceptives (birth control pills) for women. Enovid, marketed in the USA in 1960, was the first birth control pill to contain a mixture of estrogens and progestins for maximum effectiveness.
III.4. Gastro-intestinal Agents
Evolution of ulcer therapy
In 1972, James Black, a Scottish pharmacologist, and his colleagues at Smith, Kline & French shed light on the basis of surplus acid secretion in the stomach. This type of pharmaceutical research is now known as “rational drug design”. By 1976, they developed the drug Cimetidine (Tagamet) which inhibits gastric acid secretion with minimal side-effects, and its widespread use for gastric ulcers dramatically decreased the need for surgery. Tagamet soon became medicine’s most frequently prescribed drug.