1. Kinase-lined receptors
2. Ligand-gated ion channels
3. G protein-coupled receptor systems
4. Nuclear receptors
The site on the receptor at which the drug binds.
How do kinase-linked receptors work?
– Ligand-binding domain is on cell surface
– Drug activates enzyme inside cell, response is initiated
How do ligand-gated ion channels work?
– Channel spans cell membrane
– Channel opens, allowing flow of ions into/out of cell
– Ions are primarily Na+ and Ca++
How do G protein-coupled receptor systems work?
1. Drug activates receptor
2. Receptor activates G protein (binds w/ GTP)
3. Activated G protein initiates effect (either an enzyme or an ion channel)
How do nuclear receptors work?
– Found in cell nucleus
– Activation is through transcription factors
– Activation is prolonged
The better a drug fits at a receptor site…
…the more biologically active the drug is.
Drugs that produce a response.
Drugs that inhibit a response.
How can the effects of an antagonist be determined?
By the inhibitory (I) action of the drug concentration on the receptor site.
What does IC50 describe?
The antagonist drug concentration required to inhibit 50% of the max biologic response.
Why do many agonists and antagonists lack specific, selective effects?
Receptors produce a variety of responses. Drugs that affect that receptor affect all responses.
Drugs that affect various sites. (heart, bladder, eyes, etc)
Drugs that affect various receptors.
What are the four categories of drug action?
1. Stimulation or depression
3. Inhibition or killing of organisms
therapeutic index (TI)
Estimates the margin of safety of a drug.
A ratio that measures the effective dose (ED) in 50% of persons/animals and the lethal dose in 50% of animals. The closer the ratio is to 1, the greater the danger of toxicity..
low therapeutic index
narrow margin of safety.
high therapeutic index
wide margin of safety and less danger of producing toxic effects
therapeutic range (therapeutic window)
The window of plasma concentration between the MEC for a desired action and the MTC.
What values should a therapeutic range provide, when given?
Protein-bound and unboud portions of the drug
peak drug level
The time of highest plasma concentration;
indicates rate of absorption.
trough drug level
The lowest plasma concentration of a drug; measures rate of elimination.
Large initial dose is given to achieve rapid minimum effective concentration in the plasma. When immediate drug response is desired.
physiologic effects of a drug not related to desired drug effects.
some desirable, some undesirable
always undesirable, more severe than side effects.
The scientific discipline studying how the effect of a drug action varies from predicted b/c of genetic factors or hereditary influence.
A decreased responsiveness over the course of therapy.
A rapid decrease in response to a drug.