EXAM 1 PDA

What is a Drug?

A drug is a chemical or biological substances that interacts with a living system to alter its biological or physiological functions

Drugs may be used to

prevent, diagnose, treat, or manage diseases and symptoms

characteristic of drugs, chemical or biological

drugs may be small molecules like aspirin

peptides like insulin

proteins like monoclonal antibodies

nucleic acid based therapeutics

characteristics of drugs, biological activity

drug produce effects by interacting with biological systems through specific molecular targets

characteristics of drugs, mechanisms of action

drugs may activate or inhibit receptors, enzymes, ion channels, transporters, or other biological components

characteristics of drugs, therapeutic effects

drugs are used to prevent or treat disease, relieve symptoms, or modify physiological processes

characteristics of drugs, adverse effects

drugs may produce both beneficial and undesirable effects depending on their dose, selectivity, and exposure

FDAs definition of a drug

its an article (other than food) intended to affect the structure or any function of the body, intended for use in the diagnosis, cure, mitigation, treatment, or prevention of a disease

drugs that are small molecule

low MW

compounds MW<900 Da

about 90%

drugs that are biologics (large molecules)

large molecules

MW>1000 Da

about 10%, such as vaccines

small molecule drugs still account for abt

90% of the therapeutics in today’s pharmaceutical market

31 of t50 novel drugs approved by FDA 2024 were small molecules

traditionally small molecule drugs were obtained thru

extraction from medicinal plants, more frequently also by organic synthesis

drug targets

biological macromolecules or structures with which drugs interact to produce therapeutic effects

4 major classes of protein drug targets

receptors: recognize chemical signals ex. beta adrenergic receptor

enzymes: catalyze biochemical reactions ex. angiotensin converting enzymes

ion channels: regulate ion movement ex. L-type Ca2+ channel

transporters: move solute across membranes ex. serotonin transsporter

receptors

drug action thru recognition and carry signal transduction

receptor major types

G protein–coupled receptors (GPCRs)

Ligand-gated ion channels

Nuclear receptors

Enzyme-linked receptors

receptors drug examples

Propranolol → β-adrenoceptor antagonist

Morphine → μ-opioid receptor agonist

Dexamethasone → glucocorticoid receptor agonist

enzymes

drugs frequently inhibit catalytic activity

enzymes target —drug

ACE → lisinopril

Cyclooxygenase (COX) → aspirin

HMG-CoA reductase → atorvastatin

Protein kinases → kinase inhibitors

enzymes mechanisms

Competitive inhibition

Noncompetitive / allosteric inhibition

Irreversible inhibition

Modulation of enzyme activity

ion channels and transporters

control electrical excitability and chemical transport

ion channels

L-type Ca²⁺ channel → amlodipine

Voltage-gated Na⁺ channel → lidocaine

Drugs may block or modulate channel

opening

transporters

Serotonin transporter (SERT) → fluoxetine

SGLT2 → empagliflozin

Drugs often inhibit substrate transport or

reuptake

SGLT2

sodium-glucose co-transporter 2. It is a protein located in the kidneys that normally reabsorbs most of the filtered glucose (sugar) and sodium (salt) back into the bloodstream

additional drug target classes

important targets beyond the four principal protein classes

Structural Proteins

Tubulin → paclitaxel, colchicine

Nucleic Acids

DNA → cisplatin; RNA → antisense drugs

Ribosomes

Bacterial 30S/50S → tetracycline,

azithromycin

Membrane Components

Ergosterol → amphotericin B

some drugs act via physiochemical mechanisms…

without a specific protein target

Examples of drugs acting through physicochemical mechanisms

drug vs. medicine

drug: the active chemical or biological substance that produces an effect

medicine: a drug formulated for administration to achieve a therapeutic or diagnostic purpose

organic chemistry is important

• Molecular structure determines physicochemical properties (e.g. solubility, lipophilicity)

• Functional groups control binding interactions with drug targets

• Ionization and lipophilicity influence drug distribution

• Metabolic soft spots affect duration of action

• Small chemical changes can substantially alter activity

drug-targeting binding forces

• Ionic: attraction of oppositely charged groups

• Hydrogen bonds: directional donor–acceptor interactions

• Hydrophobic interaction: nonpolar surfaces bury from water

• van der Waals: close packing and shape complementarity

• π interactions: aromatic stacking and cation–π contacts

ionic

attraction of oppositely charged groups

hydrogen bonds

directional donor-acceptor interactions

pie interactions

aromatic stacking and cation pie contracts

hydrophobic interactions

nonpolar surfaces bury from water

van der waals

close packing and shape complemtarity