Lecture 1 — Principles of Pharmacology and Receptors
1. What pharmacology studies
• Pharmacodynamics (PD): the relationship between drug concentration and biological response—what a drug does to the body. The lecture also considers how drug action changes over time.
• Pharmacokinetics (PK): factors governing absorption, distribution, binding, metabolism, and elimination—what the body does to the drug.
• Structure–activity relationship: a drug’s chemical structure affects its biological activity. Structural changes can influence potency, duration, and toxicity.
• With repeated drug use, biological changes may include tolerance (a reduced response after repeated use), addiction, adverse reactions, and altered drug metabolism.
• Drug antagonism: one drug reduces or blocks the effect of another.
2. Receptor theory
Most drugs act by interacting with a specific cellular target, usually a protein, called a receptor. A receptor can be on the cell surface or inside the cell.
Drug + receptor → molecular change in receptor → chain of cellular events → biological response.
Naturally occurring hormones and neurotransmitters also bind to receptors. Some drugs mimic these endogenous substances by acting at the same receptors.
Example from the lecture: discovery of receptors responsive to morphine helped identify endogenous morphine-like peptides called endorphins. Morphine mimics some of their effects by interacting with the same receptor system.
3. Receptor selectivity
• Receptors are molecules or macromolecules in tissues that chemically interact with drugs.
• Most drugs exhibit selectivity: they bind preferentially to a limited range of structurally related or complementary receptors.
• Receptor activation can trigger cellular reactions; simply occupying a receptor does not necessarily activate it.
4. How acetylcholine causes skeletal muscle contraction
The lecture’s key example is the skeletal muscle motor end plate:
1. The motor nerve releases acetylcholine (ACh).
2. ACh binds nicotinic receptors in the postsynaptic end-plate membrane. These receptors are part of ion channels.
3. Receptor activation opens the channels, permitting Na⁺ influx.
4. Sufficient channel opening causes local depolarization (the end-plate potential).
5. Voltage-dependent sodium channels activate, generating an action potential.
6. The action potential leads to release of intracellular Ca²⁺.
7. Calcium interacts with contractile proteins, producing muscle contraction.
Sequence of events: ACh + receptor → Na⁺ influx → action potential → increased free Ca²⁺ → contraction.
5. Agonists and antagonists
Important distinctions
• Binding is not the same as activation.
• An agonist activates the receptor’s response; an antagonist can block the response by occupying the receptor.
• The same receptor-based principle applies to endogenous signaling molecules and drugs.
