What are receptors and why are they important for pharmacology?
Drug effects result from interaction with specific sites on or in cells termed receptors. Receptors are drug targets, the sites of action that mediate the pharmacological effects of a drug. The drug-receptor concept is the basis of pharmacology.
What are 2 classes of receptor molecules, and some examples of each?
Specialized receptors include GPCR, receptor gated channels, or RTKs and detect chem signals and initiate response via signal transduction. Generalized receptors include enzymes, lipids, or nucleic acids; some with high specificity (ribosomes) and some with generally lower specificity (lipids, nucleic acids).
What determines the binding affinity of a drug to a specific receptor?
Size, shape, and electrical charge
What is the difference in action between agonists and antagonists?
Agonists bind to a receptor and cause the same action as the normal ligand. Antagonists bind to a receptor and produce NO REACTION. Activity of antagonists is only evident if there is "normal tone" (binding of agonist). A pharmaceutical antagonist has no effect in the absence of the agaonist for the receptor.
What are the three assumptions made by the Drug Receptor Theory?
Interaction follows simple mass action relationships. Binding is reversible. Response is proportional to # of receptors [R] occupied by drug [D]. R + D RD -> RESPONSE. Response is proportional to RD
What are log dose response curves used over dose response curves?
Drug responses a tracked over very wide ranges of concentration. The log dose response curve allows these ranges to be represented in much more concise manners.
What is "Potency"?
Potency is the concentration (EC50) or dosage (ED50) required to produce 50% of the individual drug's Emax. The lower the EC50 (see x-axis), the higher the potency. Potency depends on affinity Kd of receptors/drug, and the eficiency of the complex to produce a result.
What is "Efficacy"?
The maximal efficacy, maximal effect, or power of a drug is the Emax or limit of dose response. It indicates the relationship between receptor binding and ability to initial a response. Efficacy is the most important determinant of clinical utility, as potency only determines what dose will acheive the ends.
What are two classes of agonists?
Full agonists and partial agonists. Full agonists occupy receptor and bring about full or maximal response. Partial agonists occupy the same recpetor as the agonists, but produce less than full response. A drug that is less efficacious, with 100% receptor occupancy = decreased response.
How are potency and efficacy found on the (log) drug repsonse curves, and how are they compared between drugs?
Potency is on the x-axis, efficacy is on the y-axis. The difference in potency or efficacy between two drugs may be easily determined by finding the difference between the EC50's (potency) or Emax's (efficacy) of the two.
How is potency used in clinical settings?
The prescriber considers the relative efficacies of different drugs, rather than the potency. Potency itself is expressed in the dosage units needed for a clinical end point (ie, 20mg of lisinopril vs 50mg of captopril), and is not particularly important unless a drug requires very large volumes.
How is efficacy used in a clinical setting?
Therapeutically, efficacy refers to the extent a clinical effect can be acheived in a patient rather than an action at a specific target. Therefor, efficacies of different drugs can be compared even if they work on very different targets, such as morphine (mu opioid agonist) being considered a more efficacious analgesic than aspirin (COX inhibitor).
What are the possible pathways in which an antagonist functions?
Antagonists may be receptor or non-receptor antagonists. Receptor antagonists further divide into reversible or non-reversible and active site or allosteric binding. The vast majority of antagonists bind reversibly to the active site, and are thus competitive inhibitors (95%)
What is a pharmacologic antagonist?
A pharmacologic antagonist binds reverisbly to the same receptor as an agonist. Binding prevents activation of the receptor by the agonist, but can be overcome by increasing agonist concentration. Example: norepinephrine produces tachycardia leading to increased BP via overstimulation of cardiac B1 receptors. Metoprolol treats hypertension by blocking B1 receptors. Thus, metoprolol is a pharmacologic antagonist of norepinephrine. Essentially, EC50 of norepinephrine increases, Emax is unchanged.
What is the difference in effect of a non-competitive antagonist vs a competitive antagonist?
A non-competitive antagonist will decrease the Emax of the agonist (ligand) regardless of concentration (inhibition is "insurmountable") but not change the EC50. A competitive antagonist (reversible, pharmacologic) will only increase the EC50 of the agonist, but the Emax will be unchanged; inhibition will be "surmountable".
What are spare receptors and what likely causes them?
Spare receptors are shown to exist if Emax occurs with less than maximal occupation of receptors (EC50
What are physiologic non-receptor antagonists and how do they function?
Non-receptor, physiological antagonists act on different receptors from the agonist to oppose the agonist action. In anaphalaxis, histamine activates H1 receptors to produce broncorestrction and epinephrine activates B2 receptors to cause broncodilation.
What is an example of a chemical non-receptor antagonist?