META TUTS | MOD 4

• Graded Dose-Response Curve: Involves 1 patient only
• Dose vs intensity of effect = Graded Dose-Response Curve
• Potency - dose that gives 50% effect
• left-shift = more potent
• taller DRC = more effective
• Ceiling dose - minimum dose with maximal effect
• Full agonist + competitive antagonist = same efficacy
• Full agonist + non-competitive antagonist = efficacy downshift
• Full agonist + partial agonist = partial agonist becomes antagonist
• Quantal-Dose Response Curve aka all or none DRC
• Narrow TI = Less safe
• Higher TI = More safe
• Therapeutic window - Aka therapeutic range
• Concentration range of drug in plasma where the drug shows therapeutic response without causing toxic effects in most people
• Ligand-gated ion receptors - ionotropic
• Ligand-gated ion receptors location = cell membrane
• Ligand-gated ion receptors example is GABA-A
• gaba-a (ion is CL-)
• G-protein coupled receptors aka 7-transmembrane spanning receptor
• G-protein coupled receptors - metabotropic
• G-protein coupled receptors moa is 2nd messenger
• αlpha-1/ GQ → Constriction = (+) PLC = ↑ IP₃ & ↑DAG
• αlpha-2/ GI → Inhibition = (-) Adenylyl Cyclase/ AC = ↓CAMP
• βeta-1/ Gs → Stimulates = (+) Adenylyl Cyclase/ AC = ↑CAMP
• βeta-2/ Gs → Stimulates = (+) Adenylyl Cyclase/ AC = ↑CAMP
• G-protein coupled receptors location is cell membrane
• Type 3: Enzyme-linked receptors aka receptor tyrosine kinase
• Examples of enzyme linked receptors include insulin receptor, EGF receptor, PDGF receptor, etc.
• Enzyme-linked receptors are transmembrane proteins with an extracellular ligand binding domain, a single pass transmembrane region, and intracellular catalytic domains.
• The insulin receptor has two alpha subunits that bind to the insulin molecule and two beta subunits that have tyrosine kinase activity.
• Ligand binding causes dimerization or oligomerization of the receptor
• Dimerization activates the cytoplasmic tyrosine kinases that phosphorylate specific substrate proteins on their tyrosines residues.
• Type 4: Nuclear receptors location is in the nucleus
• Type 4: Nuclear receptors moa is gene transcription
• Type 4: Nuclear receptors
• Glitazones activates PPAR GABA
• Fibrates activates PPAR Alpha
• Modified occupancy theory - Ariens and Stephenson
• Lock and key theory - fischer theory
• Induced Fit theory - koshland theory