History of Drug Use and Development

Module 1: History of Drug Use and Development

• Humans have used drugs since before recorded history.
• Most clinically useful drugs were developed over the past 250 years, thanks to advances in experimental biological sciences (including pharmacology).
• Drug definition: Any substance received by a biological system not for nutritive purposes, influencing the organism's biological function. Chemicals, biological agents, and herbal products are considered drugs.
• Pharmacology definition: The science of drugs, including their uses, effects, and modes of action.

Historical Influences

• Ancient China: Earliest recorded drug experiments (2700 BCE). Emperor Shen Nung classified drugs by taste. Ma Huang, a "medium drug," was used for coughs, influenza, and fevers. Ephedrine, isolated from Ma Huang, treats asthma and a derivative is a decongestant.
• Ancient Egypt: Ebers Papyrus (1550 BCE) offered a textbook on drug use. Included observations on purgatives (drugs causing bowel movements), like senna, which is still used today.
• Ancient Greece: Theophrastus (380 BCE) wrote a therapeutic textbook including opium, a poppy extract containing morphine (1803 isolation by Serturner).
• Ancient Rome: Zinc oxide was a significant topical therapy ingredient.
• Influence of Religion: Medicine men, acting as both physicians and priests, used plant-based intoxicants to alter consciousness and connect with deities. Examples include mescaline from Peyote cactus, inducing hallucinations.
• Influence of Poisons: Paracelsus's quote: "The right dose differentiates a poison and a remedy."
• Nitrous Oxide, Ether, Organoarsenicals, Sulfa Drugs, Penicillin, Streptomycin: Landmark discoveries with important therapeutic applications.

Module 1: Drug Development, Drug Trials, and Drug Advertising

• Two types of preclinical studies:
  • Toxicology studies: Assess the impact of a new drug on non-target organ systems. All drugs have some toxicity at some dose in some people. It can take up to 6 years.

Module 1: Drug Action

Drug Targets

• Most common drug target: Receptors

• Receptors: Molecules or complexes located inside or outside cells, regulating homeostasis. Typically bound by endogenous ligands (hormones, neurotransmitters).

• Receptor location influences drug action and response.

• Other targets: Antacids (acid-base neutralization).

Efficacy and Potency

• Clinically, efficacy is prioritized over potency.
• Maximal effectiveness of a drug is a key factor in choosing treatments.

Therapeutic Range

• Therapeutic range: Doses maintaining drug blood concentration above the minimal effective level but below toxic concentration.

Module 1: Pharmacokinetics

• Pharmacokinetics: The movement of a drug into, through, and out of the body.
• Four major pharmacokinetic processes: Absorption, Distribution, Metabolism, Excretion.

Absorption

• Absorption: Drug movement from administration site to blood.

Distribution/Redistribution

• Distribution: Drug movement from blood to action site and other tissues.
• Blood flow to an organ affects drug speed to the organ.
• Can lead to reduced therapeutic effects.

Metabolism

• Drug metabolism: Drug conversion to a different compound.

• Drug elimination from the body involves getting converted to more water soluble compounds.

• Phase 1 reactions: Add or reveal a functional group, preparing for Phase 2

• Phase 2 reactions add large, water-soluble molecules, making them excretable by kidneys.

Excretion

• Excreting organs: Kidneys, gastrointestinal tract, lungs, breast milk, saliva, sweat.

Variation in Drug Response

• Drug dosage adjustments are common to fit individual responses.
• Factors influencing responses: Genetic factors, environmental factors, other diseases, and altered psychological states (most commonly age and pregnancy).
• Therapeutic index: A measure of drug safety (higher index = safer).

Drug-Drug Interactions

• Interactions can occur at different stages of pharmacokinetics.

Module 2: Physiological and Pharmacological Aspects of the Central Nervous System

• Basic nervous system functions:
  • Recognize: Identify internal/external changes.
  • Process/integrate: Perceive changes, integrate information.
  • React: Initiate responses and actions.
• Two divisions of the nervous system: Central and Peripheral.

Central Nervous System

• Contains brain and spinal cord which perform the listed functions.

• Brain: Receives, processes information, initiates response, stores memories, generates thought/emotion.

• Spinal Cord: Carries sensory information, controls motor outflow, controls sensory input, controls reflex activity.

• Main parts of the brain: Forebrain, midbrain, hindbrain.

Forebrain

• Parts of Forebrain: Dopaminergic reward centers, Pituitary (gland secreting hormones regulating growth, behavior, and metabolism).

Midbrain

• Links forebrain and hindbrain, relay center for visual and auditory stimuli.

Hindbrain

• Parts of the Hindbrain: Pons (connects midbrain and medulla/cerebellum), Medulla (regulates respiration, heart rate, blood pressure), Cerebellum (coordination and posture).

Neurons

• Functional unit of the brain, generating and transmitting electrical signals.

• Estimated 90 billion neurons in the brain.

• Neurogenesis: New neuron generation.

• Neuroplasticity: Constant reshaping of neuronal connections.

• Neuron parts: Cell body (nucleus, cytoplasm), dendrites (receiving antennae), axon (carries information to synapses).

Synaptic Transmission

• The signal passage from one neuron to another, usually chemical. Neurotransmitters are required to transmit signals.

Neurotransmitters and Receptors

• Neurotransmitters are endogenous chemicals that transmit signals between neurons.
• Examples: Glutamate.