Basic Drug Pharmacology SN

Understand the concept of a drug target and definition of a receptor.
Comprehend the principles of drug-receptor interaction.
Identify basic definitions in pharmacology (e.g., agonist, antagonist, affinity, efficacy, potency).
Recognize the classification of drugs.
Distinguish mode of action from mechanisms of action.
Understand the basics of receptor theories (to be covered in the next lecture).

Four main kinds of regulatory proteins commonly involved as primary drug targets:
- Receptors: Proteins that bind ligands such as neurotransmitters or hormones.
- Enzymes: Proteins that catalyze biochemical reactions and can be inhibited or activated by drugs.
- Carrier molecules (transporters): Proteins that facilitate the movement of ions or molecules across cell membranes.
- Ion channels: Proteins that form pores in cell membranes, allowing ions to pass through.

Definitions according to different scientific disciplines:
- Pharmacologist: A target molecule through which soluble physiological mediators exert their effects.

General Concept: Interaction between a ligand and receptor forms a ligand-receptor complex which triggers biological responses.
Components:
- Ligand: A molecule that binds to another (usually larger) molecule.
- Receptor: The target that the ligand binds to.

Ligand-gated ion channels: e.g., cholinergic nicotinic receptors.
- Function: Changes in membrane potential or ionic concentration within the cell.
G protein-coupled receptors: e.g., α and β adrenoceptors.
Enzyme-linked receptors: e.g., insulin receptors.
Intracellular receptors: e.g., steroid receptors influencing gene expression.

Structural Specificity: Majority of drugs show high structural correlation to produce pharmacological effects.
Three-Point Attachment: A minimum of three points of attachment is required for effective drug-receptor binding.
Chemical Structure Specificity: Changes in the drug's molecular structure can drastically alter its specificity.

Covalent Bonds: Strong and usually irreversible; rarely involved in regular drug-receptor interactions except for toxic scenarios.
Temporary Bonds: Various chemical forces can lead to temporary binding.

Estimate affinities of selected ligands for receptors, including associated errors.
Analyze mechanisms of interaction of ligands with receptors in various concentrations.

Kinetic Experiments: Measure binding of radioligand concentrations over time.
Saturation Experiments: Measure binding of increasing concentrations of a radioligand.
Competition/Modulation Experiments: Measure binding in presence of both radioligand and non-labeled compounds at equilibrium.

A simple method to measure drug binding to receptors:
- Components include unbound labeled drug, unbound test drug, and receptor preparation.

Agonist: A substance that activates a receptor to elicit a biological response. Can be endogenous (produced by the body) or exogenous (from outside the body).
Partial Agonist: Activates the receptor but cannot produce the maximal biological response of a full agonist.
Inverse Agonist: Binds to the same receptor as the agonist but produces the opposite effect.
Antagonist: Inhibits the effects of an agonist; can act competitively or non-competitively, and may either bind to the same site or an allosteric site.

Dose-Response Relationship: Graphical representation of the relationship between drug dose and its pharmacological effect:
- Efficacy: Maximum effect produced by a drug.
- Potency: Amount of drug needed to produce a specific effect (e.g., 50% of the max).

Ceiling ED50: The effective dose that produces 50% of maximal response.
Threshold ED50: The minimum effective dose that begins to elicit a response.
Comparative Examples: Comparing effects of various therapeutic drugs through cumulative responses, including additive, antagonistic, and synergistic effects.

Heteroreceptor: A receptor that regulates the synthesis and/or release of different mediators from its ligand.
Autoreceptor: A macromolecule that regulates the release of its own ligand.
Receptor Up-Regulation: Increase in receptor number in response to an agonist.
Receptor Down-Regulation: Decrease in receptor number due to prolonged stimulation by an agonist.

Affinity: Ability of a drug to bind a receptor;
- Proportional to the binding equilibrium constant $K_D$ .
- Low-affinity ligands require higher concentrations.
Efficacy: Measure of biological effect following drug binding.
Potency: The dose of a drug required for a specific effect, influenced by both affinity and efficacy.

Ligands: Molecules binding with receptors (e.g., neurotransmitters).
Agonists: Ligands that activate receptors, producing specific biological responses. They must possess:
- Affinity for receptors.
- Capability of intrinsic activity to activate receptor-mediated responses.

Actions: Biochemical or physiological mechanisms caused by drugs.
Effects: Observable outcomes of drug actions.
- Example: The action of penicillin is to disrupt bacterial cell wall synthesis (leading to effect: bacterial death).