Pharmacology Flashcards
Pharmacodynamics vs pharmacokinetics
Pharmacodynamics is what the drug does to the body
Pharmacokinetics is what the body does to the drug
Medicine vs drug
Used with the intention of a therapeutic effect
Affinity vs Efficacy
Binding step - Affinity, activation - Efficacy
Do antagonists have affinity or efficacy
Affinity
What shape is the curve of dose vs response
Hyperbolic
What is EC50 in a dose response relationship graph
EC50 is the agonist concentration that produces half the maximum response in a cell
What are full agonists
Agonists that can produce a 100% response
What is potency of agonist
Measure of concentration range over which agonist is effective
What is orthosteric binding
Binding of agonist and antagonist is at the same site
What shift is seen in response dose graph with a competitive antagonist
Parallel shift to the right with no depression of maximum respose
What happens in non-competitive antagonist
Receptor cells are blocked and maximum efficacy can’t be reached even with increasing agonist concentration
What is allosteric regulation
Regulation of enzyme by binding an effector molecule to a site other than its enzymes active site
Types of chemical signalling
Autocrine, paracrine (nearby) and endocrine (distant)
What are ion channels
Transmembrane pores formed by glycoproteins that span the membrane to create ion conducting pathway
What do pharmacologists consider true receptors
Ligand gated ion channels as they response to chemical signal
What is second messenger system
Receptor activation modulates activity of an effector that is generally an enzyme or ion channel
GPCR receptor structure
7 transmembrane spans, 3 extra and 3 intracellular loops
Integral membrane protein
What occupies Guanine Neucleotide Binding Site of alpa-subunit
GDP
What anchors G protein to membrane
Alpha and Gamma subunits have lipid chains attached
What two domains does alpha subunit have
Ras and AH, Ras - GTPase component
AH - Alpha helical element
What happens when GPCR is activated by agonist
Conformational change in alpha subunit -
Releases GDP and allows GTP to bind
Dissociates from beta-gamma dimer and receptor
GTP bound alpha and beta-gamma subunits are signalling units
How is GPCR signal turned off
Alpha subunit acts as a GTPase to hydrolyze GTP to GDP and Pi. This turns the signal off. G protein alpha and beta-gamma subunit recombine with receptor.
How is protein kinase regulated via GPCR
Adenyly cyclase can either be inhibited (Gi) or stimulated (Gs). Gs stimulates cAMP production from ATP. This intracellular signal transducer part of the cAMP-dependant pathway which stimulates Protein Kinase A (Serine/Thrombokinase) leading to cellular effects
What is the IP3/DAG pathway
Inositol triphosphate (IP3) and Diacylglycerol (DAG) is a secondary messenger molecule used in signal transuction. Ligand binding to GPCP activates Gq alpha subunit. This activates Phospholipase C (PLC) which converts PiP2 to IP3 and DAG. DAG remains in the membrane, activating Protein Kinase C; phosphorylating other cytosolic proteins. IP3 enters cytoplasm and activates IP3 receptors on smooth ER, causing Ca2+ influx and smooth muscle contraction