History and Basics of Pharmacology

History of Pharmacology

• Hippocrates, known as the "Father of Medicine", created the first collection of medical texts, "The Hippocratic Collection", and promoted the importance of observation and examination in medicine.
• The text highlights early practices using willow bark to relieve pain, reflecting an understanding of herbal remedies.
• Amputations in ancient times were often painful, leading to the use of Henbane or mandrake root for anesthesia.
• Celsus used boiled poppy heads with raisin wine to create a form of anesthesia for amputations.

Pharmacology Defined

• Pharmacology is the study of how drugs interact with living organisms, leading to functional modifications within these systems.
• Drugs do not create new conditions but rather modify existing ones.
• Pharmacology examines how drugs work at the cellular level, including their effects on individual proteins, cells, tissues, and organs.

Sources of Drugs

• Plants and natural products:
  • Atropine (from Atropa belladonna)
  • Digoxin (from Digitalis purpurea)
  • Opiates (from Papaver somniferum)
  • Quinine (from Cinchona bark)
  • Cannabis (from Cannabis sativa)
  • Cocaine (from Erythroxylum coca)
• Microorganisms:
  • Penicillin (from Penicillium notatum)
  • Neomycin (from Streptomyces fradiae)
  • Vancomycin (from Amycolatopsis orientalis)
  • Botulinum toxin (from Clostridium botulinum)
  • Cephalosporins (from Cephalosporium acremonium)
• Animals:
  • Insulin (from porcine or bovine pancreas)
  • Exenatide (from Gila monster saliva)
  • Allantoin (from maggots)
  • Human growth factor (from the pituitary gland)
  • Hirudin (from leeches)
  • Teprotide (from snake venom)

Key Factors in Pharmacology

• Mechanism of action: Explains how a drug exerts its effect.
• Dose: Refers to the amount of drug needed to achieve the desired effect, including ineffective, clinically effective, and toxic levels.
• Selectivity: Indicates a drug's ability to target specific biological pathways.
• Side effects: Undesired consequences of drug use.
• Risk/benefit ratio: A balance between potential benefits and potential harm of a drug.

Mechanisms of Drug Action

• Physical mechanisms: Less common, examples include osmosis or adsorption, like osmotic laxatives.
• Chemical mechanisms: Neutralization reactions are an example, such as antacids.
• Biological/Cellular protein targets:
• Ion channels (e.g., sodium channels blocked by local anesthetics)
• Enzymes (e.g., captopril inhibits ACE enzyme, sildenafil inhibits phosphodiesterase)
• Carrier molecules (e.g., sodium-potassium pump)
• Receptors (e.g., insulin receptors, adrenergic receptors, glucocorticoid receptors)

Receptor Types

• Receptors are specialized macromolecules that bind drugs and mediate their effects.
• Key-lock model: A drug's affinity for a receptor determines its ability to bind, while intrinsic activity determines the ability to initiate a response.
• Types of drug actions on receptors:
• Agonists: Fully activate receptors.
• Partial agonists: Partially activate receptors.
• Antagonists: Block receptors

Receptor Classification

• Ligand-gated ion channels: The receptor's effector domain is an ion channel (e.g., nicotinic receptors).
• Enzyme-linked receptors: The receptor's effector domain is an enzyme (e.g., insulin receptors with tyrosine kinase activity).
• G-protein-coupled receptors: The receptor's effector domain is a G-protein (e.g., adrenergic receptors).
• Nuclear receptors: The receptor's effector domain is located in the nucleus, influencing DNA (e.g., glucocorticoid receptors).

Drug Safety

• Teratogenicity: The ability of a drug to cause fetal abnormalities.
  • Examples include Thalidomide (limb malformations) and Rubella (fetal abnormalities).
• Drug regulatory bodies: Ensure drug safety (e.g., CAPA in Egypt, EDA in Egypt, MHRA in the UK, CSM in the UK).

Milestones in Drug Therapy

• 1600 BC: Egyptian medical papyrus - early record of medicine.
• 200 AD: Galen's theory of disease (blood, phlegm, yellow bile, black bile).
• 1516: Van Hohenheim questioned Galen's theory and focused on active principles in natural products.
• 1804: Sertürner isolated morphine, the first pure drug.
• 1909: Ehrlich synthesized arsenical compounds used in syphilis treatment.
• 1935: Domagk developed sulphonamides, the first selective antimicrobials.
• 1945: Fleming, Chain, and Florey discovered penicillin, the first antibiotic.
• 1960s: Black's study on drug function led to the development of beta-blockers (propranolol) and H2 antagonists (cimetidine).
• 2000s: Biologics like antibodies emerged for treating diseases like rheumatoid arthritis (e.g., etanercept, infliximab).