Object and branches of pharmacology. Connection with other sciences. Historical review. Sources of drugs.

• The word pharmacology comes from the Greek pharmakon (drug or poison) and logos (science). It studies the fate and actions of drugs at molecular, cellular, organ and whole-body levels, in any animal species.
• Pharmacology is the base of pharmacotherapeutics, which is the treatment of disease with drugs. It overlaps with pharmacy, which is the science of drug production.
• Its main objects are: how the drug acts on the body (pharmacodynamics), how the body acts on the drug (pharmacokinetics), indications and applications, drug interactions, and unwanted (adverse) effects.
• Pharmacology has many branches, for example basic, organ, experimental, clinical, biochemical, immunopharmacology and pharmacogenetics.
• It is linked to physiology, pathology, biochemistry, microbiology, genetics, toxicology, immunology and pharmaceutics.
• The first drugs came from observing plants and animals. Later, active compounds were isolated (morphine from opium, quinine from cinchona bark), and then synthetic and biotechnology methods were developed.
• Drugs come from plants, animals, minerals, microorganisms, chemical synthesis (synthetic and semi-synthetic), biosynthesis (recombinant DNA) and gene therapy.

The word pharmacology is derived from the Greek words pharmakon (drug or poison) and logos (science). Pharmacology deals with the fate and the actions of drugs at various levels, from molecular to cellular, organ and whole body, in any animal species.

The lecture lists five objects of pharmacology:

1. Pharmacodynamics: how the drugs act on the body.
2. Pharmacokinetics: how the body acts on the drugs.
3. Drug indications and application: when and how drugs are used.
4. Drug interactions.
5. Unwanted (adverse) effects.

The student notes add the main objectives: to understand how drugs work (mechanism of action); to study therapeutic uses, side effects and toxicology; to investigate drug interactions with the body systems (pharmacodynamics); and to analyse how the body affects drugs (pharmacokinetics: absorption, distribution, metabolism and excretion).

Pharmacology is the base of pharmacotherapeutics, the treatment of diseases with drugs. It overlaps extensively with pharmacy, the science of drug production.

The lecture divides pharmacology into these main branches:

1. Basic (fundamental) pharmacology.
2. Special (organ) pharmacology.
3. Experimental (animal) pharmacology.
4. Clinical pharmacology.
5. Biochemical pharmacology.
6. Immunopharmacology.
7. Perinatal pharmacology.
8. Geriatric pharmacology.
9. Pharmacogenetics, and others.
10. Chronopharmacology (the effect of biological rhythms on drugs), which is listed on the next slide.

The student notes give a longer list, with a description of each branch:

The student notes describe the links between pharmacology and the other sciences. The lecture does not include this slide.

The ancient human learned from instinct and from watching birds and animals. Early people used plants to treat illness, and the first records of drugs come from the ancient civilisations.

The lecture names these early figures and their contributions:

• EgyptImhotep, and a papyrus with a date of 1550 BC.
• GreeceHippocrates.
• RomeGalen (Claudius Galenus), a Greek physician of the 2nd century.
• Middle AgesAvicenna. The student notes add his Canon of Medicine, which included pharmacological knowledge.
• RenaissanceParacelsus. The student notes quote his saying: "All substances are poisons; the dose makes the poison."

The 18th and 19th centuries: isolation of active compounds

Many important drugs were isolated from plants in this period:

• Digitalis: William Withering (1785) described the foxglove, Digitalis purpurea. Digitoxin was later isolated (the lecture gives Nativelle, France, 1869).

• Opium and morphine: opium is the dried exudate of the poppy, Papaver somniferum. It contains morphine, codeine and papaverine. F. Sertürner (1783 to 1841) isolated morphine in 1806.

• Cinchona: the bark of Cinchona succirubra (South America) gave quinine and quinidine.

• Rauwolfia: Rauwolfia serpentina gave ajmaline and reserpine (1948). Reserpine is used for hypertension.

• Belladonna: Atropa belladonna (deadly nightshade) gave atropine. The belladonna alkaloids were used in the 1920s in Bulgaria by Ivan Raev to treat Parkinson's disease.

The 20th century

• Penicillin: Alexander Fleming (1881 to 1955) discovered penicillin G, from the mould Penicillium notatum.

• Timeline of new drug groups (from the lecture):
  • 1920s: insulin and vitamins.
  • 1930s: modern anaesthetics.
  • 1940s: penicillins.
  • 1950s: antihypertensive drugs.
  • 1960s: neuroleptics.
  • 1970s: H2-blockers and antiasthmatics.
  • 1980s: immunosuppressive and antiviral drugs.
• The student notes add these developments: the discovery of insulin, vitamins and antibiotics; hormones; and vaccines in the 20th century. In the late 19th century, Rudolf Buchheim and Oswald Schmiedeberg founded experimental pharmacology.

• Bulgarian history: the Department of Pharmacology at the Faculty of Medicine in Sofia was founded in 1945 by Professor P. Nikolov (1894 to 1990) and Professor D. Paskov (1914 to 1986). The lecture lists their work on digitalis (Digitalis lanata), galantamine (for Alzheimer's disease) and aminopyridine.

The 21st century

The student notes describe biotechnology, gene therapy, personalised medicine and targeted cancer drugs as the main developments of the 21st century.

The lecture quotes Sir William Osler (1849 to 1919): "One of the features which is thought to distinguish man from other animals is his desire to take medicine." Another quote on the same slides says that good humour helps enormously in both the study and practice of medicine.

The lecture classifies the sources of drugs as natural (plants, microorganisms, minerals and animals) and synthetic. Drugs are also made by biosynthesis and by gene therapy.

Plant sources

Plants are a biosynthetic laboratory for many compounds, including glycosides, alkaloids and steroids. The active ingredients can be in any part of the plant. The lecture gives these plant drugs:

The student notes add that 25% of drugs come from plants (alkaloids, glycosides, vitamins and bioflavonoids).

Animal sources

The lecture gives these animal sources:

• thyroxine from porcine or bovine thyroid glands;
• heparin from porcine gut or bovine lung;
• insulin from porcine or bovine pancreas;
• omega-3 fatty acids from fish oil (Omacor).

Microbial sources

Microorganisms produce antibiotics and anticancer drugs. The lecture gives penicillin from Penicillium notatum, streptomycin from Streptomyces griseus, gentamicin from Micromonospora purpurea and vancomycin (the source is named in the lecture; see Source errors in the handover). Section 2 of topic I.02 gives the details.

Mineral sources

The lecture gives calcium, magnesium and aluminium salts, and liquid paraffin from petroleum. The student notes add iron, magnesium sulfate and lithium.

Synthetic and semi-synthetic drugs

Synthetic drugs are prepared by chemical synthesis. The lecture gives these examples: sulfonamides (sulfamethoxazole, sulfadiazine); fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin); salicylates (acetylsalicylic acid); barbiturates (phenobarbital); benzodiazepines (diazepam, bromazepam, lorazepam); paracetamol (acetaminophen); and isoniazid.

Semi-synthetic drugs are made by chemical modification of natural drugs. Examples: ampicillin from penicillin G; dihydroergotamine from ergotamine; and dehydroemetine from emetine.

The student notes give marine sources: ziconotide (from a cone snail) and anticancer drugs from sea organisms.

Biosynthetic drugs (recombinant DNA)

Biosynthetic drugs are made by cloning human DNA into bacteria such as E. coli. This is called recombinant DNA technology, or genetic engineering. Examples given: human insulins; human growth hormone (somatropin); human interferons (alpha and beta); tissue plasminogen activator (alteplase and reteplase); and erythropoietin (Eprex). The student notes add monoclonal antibodies.

Gene therapy

Gene therapy introduces functional genetic material (DNA) into target cells, to replace or supplement defective genes. It gives the cell a new function. The lecture lists conditions that might be treated this way: cancers, Alzheimer's disease, Parkinson's disease, diabetes mellitus, arterial hypertension, cystic fibrosis, multiple sclerosis and muscular dystrophy.

Botanicals are plant medicines used in natural or unprocessed form. Their medical use began when the first animals noticed that some food plants changed body functions. The information about their use and effects is very uneven, and much of it is useless or false.

The herbal chapter in the lecture pack makes these points (based on the US textbook chapter):

• Traditional drugs such as morphine, digitalis and atropine come from botanicals too. Herbal products are different because they are sold without a prescription and are legally classed as dietary supplements, not drugs.
• In the USA the Dietary Supplement and Health Education Act (DSHEA) of 1994 let these products be sold without a prescription and without FDA review of safety or efficacy before marketing.
• Dietary supplements follow the Current Good Manufacturing Practice (CGMP) rules for food. These rules are often not enough to guarantee the purity, potency and correct identification of the product.
• Doses recommended for some active botanicals can be much higher than the clinically safe dose. The chapter gives Ma-huang (ephedra) preparations with three to five times the recommended daily dose of ephedrine, which is a serious risk for patients with cardiovascular disease.
• Adverse effects are documented for many botanicals, but the products are rarely chemically analysed. It is therefore often unclear whether the herb or an adulterant caused the effect.
• "Natural" does not mean safe. Products can be adulterated, misbranded or contaminated.
• Purified chemicals such as glucosamine and melatonin are also sold as supplements. Glucosamine and melatonin are of significant pharmacological interest.

The individual herbs are discussed in later topics, according to their use (for example valerian and the sedative herbs in topic II.29).

Homeopathy is an alternative method of therapy, developed in the 1800s by Samuel Hahnemann (1755 to 1843). The lecture gives his idea:

• When a drug is given in a normal (allopathic) dose, it produces a set of symptoms.
• In a patient whose disease symptoms resemble that set of symptoms, the same drug (the simile principle) should cure the disease when given in a very low dose. The lecture calls this potentiation.
• The body's self-healing powers are activated only by minimal doses of the medicinal substance.
• The homeopath's task is not to diagnose the cause of the illness, but to find the drug whose "symptom profile" is closest to the patient's illness. The drug is then given in very high dilution.

The lecture adds that a direct action of homeopathic medicines on the body cannot be demonstrated. Any therapeutic success is attributed to the suggestive powers of the homeopath and to the patient's expectation. When an illness is strongly influenced by emotional (psychic) factors, the lecture accepts that suggestion can be used as a therapeutic tool. It says homeopathy is one of several possible methods of doing so.

The source for the homeopathy slides is Lüllmann, Color Atlas of Pharmacology (2nd edition, 2000).

The lecture defines integrative medicine as the combination of the practices and methods of alternative medicine with conventional medicine. The term is relatively recent, and is mainly promoted by proponents of alternative therapies in the West. Some universities and hospitals have departments of integrative medicine.

Exam tip: Know the three classic plant drugs from the history: digitalis (Withering), morphine (Sertürner) and quinine (cinchona).