Lecture 7 Flashcards
pharmacodynamics - dose response relationships (19 cards)
What is pharmacodynamics?
- study of what the drug does to the body
- we study biochemical and physiological effects of drugs and the mechanisms by which drugs produce these effects
What is a dose response curve?
- these are monotonic: the response increases as the dose increases
- are not linear, have a semi-logarithmic plot
Phases of the semi-logarithmic dose-response curve
phase 1: doses are too low to elicit a clinically relevant response
phase 2: the response is graded and nearly linear
phase 3: larger doses do not lead to greater response, may cause toxicity
What is efficacy?
- measure of how effective a drug is at a given dose
- maximal efficacy: maximum effect that a drug is capable of achieving, represented by max. height on curve
Do we always choose the drug with the highest efficacy to treat patients?
- no, choose drug and dose that are therapeutically effective with the fewest side effects
What is potency?
- amount of a drug required to elicit a pharmacological response
- high potency does NOT = more therapeutically active
- drugs must produce the same effect to compare potency
- more potent drugs require smaller dose to achieve the desired effect
What is the ED50 (potency)?
- potency is determined by comparing the dose required to produce the half maximal response (the ED50)
- lower ED50 = more potent (shifted to the left on dose response curve)
How do drugs produce effects?
- act on cellular macromolecules like receptors (majority), enzyme, ion channels, and transport proteins
- involves binding the drug molecule to the macromolecule target in which the complex then produces a biological effect (typically mimic an endogenous compound)
Do all drugs act on cellular targets?
- No, for example antacids
- neutralize stomach acid and therefore dont bind to any cellular target
What is a receptor?
- protein that a drug binds to and produces a measurable response
- majority are proteins that are able to translate extracellular signals into biological responses
What are the 4 most important types of receptors?
- ligand gated ion channels
- G-protein coupled receptors
- enzyme linked receptors
- intracellular receptors (transcription factors)
Ligand Gated ion channels
- ions cannot directly cross cell mem so they use specialized channels
- ligands (drugs or endogenous molecules) control the opening and closing of ion channels
ex. many neurotransmitters bind to these types of receptors like the GABA receptor
the GABA receptors
- GABA (a neurotransmitter) binds to the GABA receptor, causing the opening of the channel that allows choride ions to flow into the cell
- benzodiazepine drugs are able to bind this receptor for the same result
- causes sedation and muscle relaxation very rapidly (milliseconds)
G-protein coupled receptors (GPCRs)
- 50% of currently marketed drugs mediate effects through this receptor
- binding of ligand to GPCR causes activation of G-protein resulting in response that lasts from seconds to minutes
- endogenous neurotransmitters like norepinephrine, serotonin, and histamine mediate effects by binding GPCRs
3 components of GPCRs
- a seven transmembrane spanning protein receptor
- a g-protein which has 3 subunits
- an effector molecule (i.e an enzyme)
What are enzyme linked receptors?
- these span the cell mem with the ligand binding domain on the outside of the cell and the enzymes catalytic site on the inside
- binding outside activates the enzyme on the inside of the cell
- responses to these occur very rapidly (seconds)
Insulin receptor
- an enzyme linked receptor whereby the binding of insulin to the receptor causes enzyme mediated phosphorylation and activation of an intracellular effector
- results in increased translocation of glucose transporters to the cell mem = increased cellular glucose uptake and utilization
What are intracellular receptors?
- completely inside the cell (also called transcription factors)
- ligands must cross cell mem (diffusion or protein transport)
- binding of ligand = translocation of complex to the nucleus and binding to DNA where transcription of messenger RNA is stimulated
- protein synthesis then occurs hours or days later
- ligands to these receptors usually lipid soluble
ex. testosterone and estrogen
Drug receptor selectivity
- lock and key hypothesis: lock is the receptor, which requires a key (drug) with a specific size and shape to open it
- selective drugs will bind to only one receptor and less likely to produce side effects (although they could still have side effects bc the same receptors can be located many different areas)
