Pharmacodynamics Flashcards
Pharmacodynamics
What drug does to body
Effects of drug on the body
Receptor Theory
Receptors are macromolecular complexes (usually proteins) embedded in the phospholipid bilayer of a cell membrane.
There are receptors in the body for every physiologic event that occurs and multiple receptors have different actions.
Receptors have active and inactive states.
Binding results in a conformational change in the receptors.
Receptor types
Ligand-gated ion channel
G protein couple receptor
Transmembrane with linked enzymatic domain
Intracellular receptor
Ion Channels
Ligand vs voltage gated Time frame to respond: seconds Examples: -nicotinic -GABA
G-Protein Coupled Receptors
Family of receptors Activation of GTP binding proteins • GTP exchanged for GDP • G-⍺ separates from B andY • Activates effector Examples • Muscarinic/cholinergic • Adrenergic • Dopaminergic • 5-HT • Opioid Ligand on receptor -> conformational change-> 2nd messenger-> CAMP-> physiological effect
Take time more time when compared to ion channel
Transmembrane Enzymatic
Transmembrane embedded enzyme-linked receptors
-Activation of kinase enzyme
-Phosphorylates a signal molecule to activate
-Biological effects result
Usually involved in growth and development
-Target chemotherapy drugs
Examples:
-Tyrosine receptor kinase (most common)
-Insulin
Intracellular receptors
Proteins found inside the nucleus Ligands typically hydrophobic Modify gene transcription Onset Duration of action Examples: steroid hormones and vit d
Drug and receptor interaction
Chemical substances that bind to receptors are called ligands.
-Endogenous
-Exogenous (drugs)
Drugs cannot make the body do something it is not already capable of
Agonists
Bind to a receptor and stimulate the function that receptor serves (shift to activate state)
Affinity for receptor
Causes intrinsic activity
Antagonists
Bind to receptor and block the function that receptor serves (stabilizes inactive state)
Affinity for receptor
Competitive vs noncompetitive
Competitive antagonist
Reversible (most drugs)
Non-competitive antagonist
Non-reversible or binds allosteric site
Allosteric
Binding site different than endogenous ligand
Covalent bonding
Sharing electron, strongest bond
Ionic bonding
“pitchers and catchers”
Transfer of electron
Hydrophobic
“oil in water”
Van der Waals
Transient attraction b/t stable molecules (weakest type of bond)
Think drug binding to proteins
Can drugs act without a receptor?
Yes, but not many.
Antacids
Osmotic diuretics
Chelating agents
Potency (affinity)
How much drug to get an effect?
Efficacy
Does drug produce desired effect
Variability
“nothing is exactly the same”
Slope
Margin of safety of the drug, the steeper the slope, the narrower the therapeutic window and smaller the margin of safety
Therapeutic index
How much more drug required to cause adverse effects
LD50/ED50
ED50
Effective dose in 50% of the population
