PHSC1613 Pharmacology - Lecture 1 Introduction to Pharmacology: Basic Principles pt 1

Pharmacology

defined as the study of substances that interact with living systems through chemical processes

Activation or inhibition

What can happen to normal biological processes as binding of a drug to a receptor occurs?

Beneficial effect on patient, toxic effect on infecting microorganism

two things that the goal of modifying a biological process may be done to achieve

Antihypertensives

example of medications with a beneficial effect on process within the patient

Antibiotics

example of medications with a toxic effect on process within the microorganism infecting the patient

Pharmacokinetics and pharmacodynamics

two major branches of pharmacology

Pharmacokinetics (PK)

absorption, distribution, metabolism, and excretion of drugs ("what the body does to the drug")

Absorption, distribution, metabolism, and excretion of drugs

What does pharmacokinetics involve?

Body, drug

Pharmacokinetics is the study of what the _______ does to the _______

Pharmacodynamics (PD)

Molecular, biochemical, and physiological effects of drugs ("what the drug does to the body")

Molecular, biochemical, and physiological effects of drugs

What does pharmacodynamics involve?

Drug, body

Pharmacodynamics is the study of what the _______ does to the _______

Toxicology and pharmacogenomics

two subcategories of pharmacology that include both PK and PD aspects

Toxicology

pertains to the undesirable effects of chemicals on living systems

Pharmacogenomics

pertains to the relationship between an individual's genetic makeup and drug response

Ligand

a substance that forms a complex with a biological molecule called a receptor

Endogenous or foreign molecules

two general types of molecules that can be ligands

Endogenous

molecules that can act as ligands and originate in the body (ex. hormones, neurotransmitters)

Foreign

molecules that can act as ligand and are taken in (ex. drugs)

Xenobiotics

another name for drugs, since they are foreign molecules acting as ligands

Receptor

a biological molecule that regulates some biological function upon binding to a ligand

Molecules that mimic biomolecules, other small organic molecules, inorganic molecules

different types of molecules that can serve as drugs

Lithium, iron

inorganic molecule examples

Regulatory proteins, transport proteins, enzymes, immune related proteins

4 primary types of molecules that serve as drug targets

Regulatory proteins

classical "receptors" such as cell surface, intracellular, and ion channels that most drugs bind to as a drug target

Structural

proteins that can also be drug targets, but less common

Cell surface receptors, intracellular receptors, ion channel receptors

types of regulatory proteins usually targeted by drugs and used as classical "receptors"

Receptors

proteins that translate an extracellular signal (a ligand) into an intracellular response

Appropriate size, charge, composition like functional groups, shape/spatial orientation (stereochemistry)

four things a drug molecule must have to interact chemically with its target

Covalent, electrostatic, hydrophobic

chemical forces/bonds that drugs use to interact with their targets

Ionic bonds, hydrogen bonds, Van der Waals forces

examples of electrostatic interactions of drugs and targets

Covalent

bonding of drugs to their targets that is relatively rare in comparison to non-covalent interactions

Non covalent

most common type of interactions between drugs and their targets

Imatinib

a BLC-Abl tyrosine kinase inhibitor, cancer drug

Activation of effector molecule

a key step that links receptor activation to a cellular response

Effector molecules

proteins that translate drug-receptor interaction into a change in cellular activity

Enzymes that produce another signaling molecule or ion channels

What are effector molecules usually?

Second messengers

another signaling molecule that an effector enzyme might produce; small molecules generated in large numbers to amplify a signal

Coupling molecules

intermediary molecules that connect drug-receptor binding to effector molecules

Receptor and effector activations

What does a coupling molecule connect?

G-proteins

classic examples of coupling molecules

Receptor and effector are same molecule, separate but connected molecules, or separate and require coupling molecule

example relationships between receptor and effector molecules

Ion channel

example where the receptor and the effector are the same molecule

JAK-STAT receptor

example where the receptor is a separate molecule from the effector, but the receptor directly activates the effector because they are in contact

GCPR

example where the receptor and effector are separate molecules, and they require a coupling molecule to carry the activation signal from the receptor to the effector

Action on receptor, permanence of receptor binding, influence on receptor confirmation, receptor binding site

4 basic characteristics used to categorize receptors

Agonist and antagonist

2 basic categories of ligands based on their action on a receptor

Agonist

a ligand that activates the receptor when bound and increases cellular response

Receptor activation

What do agonist ligands do when bound to a receptor?

Increased

What happens to cellular response when an agonist binds to a receptor?

Antagonist

a ligand that prevents receptor activation when bound and decreases cellular response

Prevent receptor activation

What do antagonist ligands do when bound to a receptor?

Decreased

What happens to cellular response when an antagonist binds to a receptor?

Almost always temporary and reversible

Is agonist binding usually temporary or permanent?

Temporary or permanent

Is antagonist binding usually temporary or permanent?

Receptor pool

a term sometimes used when referring to a group of receptors