Receptors and Drug Actions Intro Flashcards
What are the key properties of receptor-ligand interactions?
Modulation of receptor sensitivity and responsiveness during drug treatment, Repeated or chronic drug exposure can lead to “adaptive” changes in receptors
Due to cellular mechanisms for maintaining homeostasis
What are the differences among receptor subtypes?
may be differentially expressed in various tissues and cell types or exhibit differential regulatory properties, exhibit different drug selectivity or couple to different signaling pathways and effects
What is desensitization and when can it occur?
during repeated or chronic agonist drug exposure via transient reversible covalent modification, often phosphorylation or involve receptor “endocytosis” or “internalization” into the cell, away from its extracellular ligands or lead to degradation and loss of the receptor protein, termed “down-regulation”
What is sensitization? cause?
Chronic antagonist can lead to receptor up-regulation and/or increased functional responses
What are the properties of ligand-receptor binding?
reversible, Ligand-receptor complex mediates effects of the ligand, Ligand-receptor complex is transient, exhibits saturation, and exhibits remarkable specificity
What are the properties of an intracellular transcription factor receptor?
Dimers of cytosolic or nuclear proteins; ligand must get inside cell, Agonist binding to “ligand binding domain” (LBD) allows “DNA binding domain” (DBD) to bind specific DNA sequences and “activation domain” then increases or decreases transcription of associated genes
effects over hours or days or longer; transcription effects cell growth (cancer), expression, and development
What are the properties of receptors with intrinsic enzyme effects?
Cell surface, dimer of two single-transmembrane proteins
Binding to extracellular domain activates enzymatic activity of intracellular domain (tyrosine kinase activity) phosphorylated substrates then mediate effects some within minutes but more commonly hours and lasting much longer (via regulating transcription), cell growth, cancer, differentiation, or gene expression
What are the properties of GPCR?
Agonist binding inside transmembrane domains activates associated GTP-binding proteins which regulates effector enzymes that generate intracellular second messenger molecules, Effects seconds to minutes; metabolism, secretion, contraction, migration, more;Targets for over half of all drug prescriptions!
What are the properties of ligand gated ion channels?
plasma membrane; 5 subunits, 4 transmembrane domains each; Agonist binding to extracellular domain opens transmembrane ion pore allowing Na+ ions to enter cell, membrane potential changes; Effects within milliseconds, Neurotransmission, muscle cell contraction
What are the three main targets for drugs?
receptors, enzymes and ion channels
Drugs targeting receptors has to account for what?
the properties can change with disease or with drug treatment: expression, localization, ability to respond
When drugs target enzymes what are some general rules?
typically inhibitors; can be a human, bacterial, or viral enzyme
What are some general rules about ion-channel targeting drugs?
usually channel blockers or transport inhibitors (diuretics, SSRIs)
What is drug specificity?
how specific a drug interacts with its target
What is drug selectivity?
effect the chosen target with minimal side effects
