Drug targets and mechanisms of action Flashcards
What are the main classes of drug targets?
Drug targets include proteins (e.g., enzymes, receptors, transport proteins, structural proteins), nucleic acids (DNA and RNA), and other targets like protein-protein interactions, lipids, carbohydrates, and antigens/antibodies.
How do enzymes serve as drug targets?
Enzymes act as catalysts, speeding up biochemical reactions. Drugs can inhibit enzymes by binding to their active sites (competitive inhibitors) or allosteric sites (allosteric inhibitors) to block their function.
Describe the structure and function of an enzyme’s active site.
The active site is a hydrophobic cleft where substrates bind, often involving catalytic amino acids that assist the reaction and binding amino acids that stabilize the substrate.
What is a competitive inhibitor, and how does it function?
Competitive inhibitors bind to an enzyme’s active site, competing directly with the substrate, often mimicking the substrate’s structure to block substrate binding.
What are COX inhibitors, and what do they treat?
COX inhibitors, like NSAIDs (e.g., aspirin, ibuprofen) and paracetamol, inhibit cyclooxygenase enzymes, which produce prostaglandins and thromboxanes involved in inflammation, pain, and fever.
How does orlistat work as a lipase inhibitor?
Orlistat irreversibly inhibits lipase by binding to its active site, blocking fat breakdown in the gastrointestinal tract, thus reducing fat absorption.
What are receptors, and how do they function as drug targets?
Receptors are proteins, often on cell membranes, that bind chemical messengers (e.g., hormones, neurotransmitters) to elicit biological responses via signal transduction pathways.
Define agonists and antagonists in the context of receptor targets.
Agonists mimic natural messengers to activate receptors, while antagonists bind receptors to block natural messengers from binding, inhibiting receptor function.
Describe the structure and function of ion channel receptors.
Ion channels are protein complexes that open or close to regulate ion flow across membranes, controlled by ligands like acetylcholine (cation channels) or glycine (anion channels).
How does the GABAA_AA receptor work?
The GABAA_AA receptor is an ion channel that, when activated by GABA, allows Cl−^-− ions to enter the neuron, hyperpolarizing it and reducing neuronal activity (inhibitory effect).
What are G-protein coupled receptors (GPCRs)?
GPCRs are membrane-bound receptors with seven transmembrane domains. Upon activation by a ligand, they interact with G-proteins to initiate intracellular signaling cascades.
Explain the process of G-protein signaling initiated by adrenaline.
Adrenaline binds to the β1-adrenergic receptor, causing the G-protein to exchange GDP for GTP, dissociate, and activate adenylyl cyclase, which converts ATP to cAMP, initiating a signaling cascade.
What are beta-blockers, and how do they function?
Beta-blockers, such as propranolol, are antagonists that block adrenaline’s action on β1 receptors, used to treat hypertension and other cardiovascular conditions.
Describe kinase-linked receptors and their importance in drug targeting.
Kinase-linked receptors act as receptors and enzymes; they bind messengers, undergo conformational changes, and catalyze intracellular reactions. They are important in cancer therapy (e.g., targeting tyrosine kinase receptors).
How do intercalating agents work on DNA?
Intercalating agents slip between DNA base pairs, disrupting the helix and blocking replication and transcription. Examples include proflavin (antibacterial) and doxorubicin (anticancer).
