Basic Principles of Pharmacology I & II Flashcards
Difference between drug action vs. drug effect
Drug action: molecular effect. INVISIBLE.
Drug effect: pharmacologic effect. VISIBLE response.
What is selectivity?
A property of a drug to cause a specific effect. Few drugs produce a single effect.
Primary effect –> desired
Secondary effect –> “side effects”, may or may not be desirable
What are pharmacokinetics?
The time course of drug absorption, actions, and elimination
What are pharmacodynamics?
The types of drug actions. Can be physiochemical (simple chemical interactions that are nonspecific like antacids, antiseptics) or receptor interactions (drug interacts with physiologic receptors)
Which drug-receptor bonds are reversible, irreversible?
Reversible – ionic, van der waals, hydrogen
Irreversible – covalent
What do second messengers do?
Produce amplification of the drug-receptor interaction
- Converts an event that happens outside the cell into a change that happens inside the cell
Relationship between structure and activity
The better the drug fits in the receptor, the better the stimulation
Michaelis-Menten equation
Effect = (Emax *[D])/(Kd+[D]) where Kd = dissociation constant = EC 50
- it’s a little different than enzyme kinetics. The drug is not consumed as a substrate, and the macromolecule is one of the reactants, not simply a catalyst.
threshold (log dose response curve characteristic)
the beginning of the curve. The dose of agonist at which a response begins. May relate to the affinity of the agonist for the receptor.
slope (log dose response curve characteristic)
rate of rise of the response on the steep portion of the curve, also relates to affinity
maximal asymptote (log dose response curve characteristic)
the top of the curve, represents Emax for that particular agonist
Receptor occupancy
Intensity of response is proportional to the fraction of the receptors occupied
Intrinsic activity ***
ability to stimulate the receptor once bound. Relates to structure and influences efficacy and potency.
Greater intrinsic activity = greater efficacy
Spare receptors
Not all receptors need to be occupied to achieve Emax. Less efficacious agonists may need to occupy more receptors than highly efficacious agonists.
Secondary receptors
Receptors outside of the target tissue. May mediate other effects of the drug, aka “side effects”.
How does the cell regulate receptors?
The cell can up or down-regulate a population of receptors by changing the total number of receptors or their sensitivity.
Ex: desensitization: can occur with down-regulation of the receptor, or fatigue or depletion of the intracellular or tissue mechanisms
Agonist drugs
These drugs bind to the receptor and produce a pharmacologic effect. There are 2 important events:
- Binding to the receptor
- Activating the receptor after binding
- a better fit to the receptor from a more specific structure of the molecule results in more drug-receptor interaction and effect at lower doses
Relationship between structure and activity
There is a difference between the binding site of the receptor and the effector portion of the receptor. The better a drug fits both of these, the greater the response. A drug that only fits the binding site and not the effector site will have no effect.
Agonists with the same intrinsic activity
Agonists will differ by binding but not in activating the receptor (all can achieve Emax, therefore have the same intrinsic activity)
Agonists with different intrinsic activity
Agonists will bind to the receptor in the same way but will differ in activating the receptor
Agonists with different intrinsic activity AND different affinity
Agonists will have different affinities to the receptors AND also different intrinsic activities
Efficacy
The ability of the drug to activate the effector portion of the receptor once the drug is bound to the receptor. Depends upon the STRUCTURE of the drug. VERTICAL relationship.
Potency
Relates to the AMOUNT of drug needed for effect. Depends on the biologic system (receptor density, efficiency of stimulus-response mechanism of tissue) as well as interaction of the drug with the receptor (affinity, efficacy). HORIZONTAL effect.
Competitive antagonists
Antagonist effect can be overcome by increasing dose of agonist.
Simple competitive antagonism: a simultaneous equilibrium exists for agonist and antagonist. Binding of antagonist to the receptor is weak and easily reversed.
Noncompetitive antagonists
Can’t be overcome by increasing doses of agonist. Receptors remain occupied by antagonist because binding of the antagonist to receptor is strong (like covalent) and not easily reversed. The inhibitor can change the effector OR the binding site.
