Module 7 Flashcards
Study of what the drug does to the body.
Pharmacodynamics
Study of the biochemical and physiological effects of drugs and the mechanisms by which drugs produce effects.
Pharmacodynamics
To evaluate the pharmacodynamics of drugs, we look at __________.
dose-response curves
Dose-response curves are _______, which means that the response increases as the dose increases.
monotonic
Importantly, dose response curves are not linear, thus we usually look at them as _____________ plots.
semi-logarithmic
What are the phases of the semi-log 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 responses - larger doses may lead to toxicity.
Measure of how effective a drug is at a given dose
Efficacy
Maximum effect that a drug is capable of achieving
maximal efficacy
Maximal efficacy is read off the dose response curve by looking at what?
Maximum height
Healthcare professionals often titrate the dose of a drug. What does this mean?
This means they start with a low dose of the drug and slowly increase the dose while monitoring the patient’s response
Refers to the amount of drug required to elicit a pharmacological response.
potency
In order to compare potency, what is necessary?
Both drugs MUST produce the same therapeutic effect
A more potent drug will require a ______ dose to achieve the desire effect than a less potent drug.
smaller
Potency is determined by comparing the dose required to produce the half-maximal response - the ____.
ED50
Most drugs act on ________ _________.
cellular macromolecules
Give an example of a drug that does not act on cellular targets.
Antacids
Protein that a drug binds to and produces a measurable response.
receptor
What are the 4 most important types of receptors?
1 - Ligand-gated ion channels
2 - GPCR
3 - Enzyme-linked receptors
4 - Intracellular receptors
What is an important example of a ligand-gated ion channel?
GABA receptor
Describe the action of the GABA receptor.
When GABA (NT) binds to the GABA receptor, it causes the opening of a channel that allows the ion chloride to flow into the cell
Drugs that are part of the _______ class are able to bind to the GABA receptor and allow chloride to enter the cell.
benzodiazepine
Activation of the GABA receptor causes _______ and muscle _______ mediated by the increased intracellular chloride.
sedation
relaxation
Describe the time frame of response for ligand-gated ion channels.
Responses to these receptors are very rapid, having a duration of milliseconds
Approximately __% of marketed drugs mediate their effects through actions on GPCRs.
50
What are the three components of GPCRs?
Seven transmembrane spanning protein receptor
G-protein with three subunits
Effector molecule
Describe the timeframe of activation of GPCRs.
Result in a response that lasts from seconds to minutes in duration.
What endogenous NTs mediate their effects by binding to GPCRs?
NE, serotonin, histamine
Describe enzyme-linked receptors.
Receptor side is on the outside of the cell membrane
Catalytic side in on the inside
Describe the time frame of the response for enzyme-linked receptors.
Very rapid - seconds
What is an example of an enzyme-linked receptor in the body?
Insulin binding to the insulin receptor - causes enzyme-mediated phosphorylation and activation of an intracellular effector (causes increased translocation of glucose transporters to the cell membrane)
What is the net effect of insulin binding to its receptor?
Increased cellular glucose uptake and utilization
Intracellular receptors reside completely inside the cell and are also called __________ _________.
transcription receptors
In order for ligands to access intracellular receptors, what must they be able to do?
Cross the cell membrane by diffusion or via drug transport proteins
Binding of the ligand to the intracellular complex causes translocation of this complex to the _______ and binding to ______.
nucleus
DNA
When the ligand-receptor complex binds to DNA, what occurs?
RNA transcription is stimulated, with protein synthesis occurring hours to days later
Ligands to intracellular receptors are typically highly ______ _______. What are some endogenous examples?
lipid soluble
Steroid molecules such as testosterone and estrogen
Drugs that are ________ will bind to only one receptor and therefore will be less likely to produce ______ _______.
selective
side effects
IF a drug binds to only one receptor, can there be side effects?
Yes, the receptor may be located in many different organs.
What is the classical view of drug selectivity?
Lock and key hypothesis
