Pharmidynamics Flashcards
Molecular response
Modulation of enzyme activity/movement of ions across the plasma membrane
Cellular response
Modulation of secretion of hormone or NT or the modulation of cell motility
Organ response
Smooth muscle contraction (ACH)
Whole animal response
Behavior changes/ response can be lethal
Therapeutic range
Dose/ response curve
Dose range expected to achieve desired therapeutic effects
Therapeutic Index (TI)
TI= TD50 (toxic dose)/ ED50 (effective dose)
Or
TI = LD50 / EC50
Efficacy
Expresses level of response with a maximal possible effect (y, Emax)
Potency
Strength related to dose
Function of drugs affinity for receptor and ADME factors (x)
EC50 measure drug potency
(Closer to the y axis)
Full agonist
Greatest possible response
IA=1
Ex: isoprenalin
Partial Agonist
Partial response
IA<1
Ex; buprenorphine
Antagonist
Inhibit action of an agonist
IA=0
Also called blockers because they bind to receptor so agonist won’t
Ex: ranitidine, H2 antagonist
Inverse Agonist
Produces opposite response to that of an agonist
IA=0 to -1
Agonist- Antagonist
Acts simultaneously as an agonist on one set and as an antagonist on another set of receptors
Ex: nalorphine activates K opioid receptor but blocks mu-opioid receptor
Types of Antagonism
Chemical (antacids)
Functional/ physiological (insulin and glucagon on blood sugar)
Dispositional
Receptor (competitive and non competitive)
Competitive Antagonism
Reversible receptor binding
Antagonist will bind with the same receptor site as the agonist
Antagonist usually resembles in structure with the agonist
Non competitive antagonist
Irreversible receptor binding
Antagonist could bind with the same receptor site as the agonist or to an allosteric site
Efficacy and slope will decrease
Terms for drug interaction
Potentiation (increased drug response, drug A enhancing activity of drug B)
Additivity
Synergism (2 active drugs enhancing each other)
5 major cross-membrane signaling mechanisms (receptors)
Steroid
Tyrosine kinase
JAK-STAT
Ion channel
GPCR
Ionotropic-Receptors Ligan Gated Ion-channels
Ligand binds to ion channel for ions to pass inside cell
Cationic channels: K, Na and Ca, excitatory
Anionic: Cl, Inhibitory
Quick response
G-protein coupled receptor
Membrane bound, regulates effector proteins through mediation of tranducers (nucleotides like GTP and GDP- G-proteins)
Medium response
G-proteins
Heterotrimerica molecules with 3 subunits: a, b, g attached to the inner surface of plasma membrane
They have homologous guanine nucleotide binding domain
Effector systems
Adenylate cyclase:cAMP system
Phospholipase C: IP3-DAG system
Phospholipase A2: AA system
Tyrsoine Kinase receptor
Ligand binds to both binding sites and forms a dimer –> TK activated inside the cell –> ATP converted to ADP –> Phosphorylation –> activated other down stream signaling proteins –> activate transduction signals
Ex: growth hormone, cytokines, insulin
Nuclear receptors
Intranuclear receptors are located in the cytoplasm or nucleus
Signal molecule lipophilic to cross membrane
Long lasting effect
Up-regulation
Body increases the # of receptors
Seen when receptors are continuously deprived of their ligand or continued use to antagonist (continuously blocked) —> supersensitization
Down-regulation
Cell decreases the quality of receptor or protein population
Causes diminished drug effects
When tissue continuously exposed to agonist –> over-activation
What does down-regulation lead to?
Desensitization/ refractioness
Won’t get the desired effect
