Flashcards in Chapter 5 - (Pharmacodynamics) Deck (20):
Dose- Response Relationship
Dose-response relationship is graded. That is, as the dosage increases, the response becomes progressively larger. Because drug responses are graded, therapeutic
effects can be adjusted to fit the needs of each patient.
Refers to the strength of the attraction between a drug and its receptor. Drugs with high affinity are strongly attracted to their receptors. Conversely, drugs with low affinity are weakly attracted.
Agonists are molecules that activate receptors. Because neurotransmitters, hormones, and all other endogenous regulators of receptor function activate the receptors to which they bind, all of these compounds are considered agonists. When drugs act as agonists, they simply bind to
receptors and mimic the actions of the body's own regulatory molecules
Antagonists produce their effects by preventing receptor
activation by endogenous regulatory molecules and drugs. Antagonists have virtually no effects of their own.
In terms of the modified occupancy theory, an antagonist is a drug with affinity for a receptor but with no intrinsic activity. Affinity allows the antagonist to bind to receptors, but lack of intrinsic activity prevents the bound antagonist from causing receptor activation.
Competitive (surmountable) antagonists
-bind reversibly to receptors. As their name implies, competitive antagonists produce receptor blockade by
competing with agonists for receptor binding. If an agonist and a competitive antagonist have equal affinity for a particular receptor, then the receptor will be occupied by whichever agent—agonist or antagonist—is present in the highest concentration. If there are more
antagonist molecules present than agonist molecules, antagonist molecules will occupy the receptors and receptor activation will be blocked. Conversely, if agonist molecules outnumber the antagonists, receptors will be occupied mainly by the agonist and little inhibition will occur.
Non-competitive (non-surmountable) antagonists
-bind irreversibly to receptors. The effect of
irreversible binding is equivalent to reducing the total number of receptors available for activation by an agonist. Because the intensity of the response to an agonist is proportional to the total number of receptors occupied, and because noncompetitive antagonists decrease the number of receptors available for activation, noncompetitive antagonists reduce the maximal response that an agonist can elicit. If sufficient antagonist is present, agonist effects will be blocked completely.
-Is the dose that is required to produce a defined therapeutic response in 50% of the population.
-The ED50 can be considered a standard dose and, as such, is frequently the dose selected for initial treatment. After evaluating a patient's response to this standard dose, we can then adjust subsequent doses up or down to meet the patient's needs.
-(ED50 is an abbreviation for average effective dose.)
-Is the ability of a drug to activate a receptor
-Drugs with high intrinsic activity cause intense receptor activation. Conversely, drugs with low intrinsic activity cause only slight activation.
The average lethal dose, is the dose that is lethal to 50% of the animals treated.
-is the largest effect that a drug can produce. Maximal
efficacy is indicated by the height of the dose-response curve.
-Is an agonist that has only moderate intrinsic activity.
As a result, the maximal effect that a partial agonist can produce is lower than that of a full agonist.
-is any functional macromolecule in a cell to which a drug binds to produce its effects.
-a small (or low) therapeutic index indicates that a drug is
-a highly desirable characteristic of a drug, in that
the more selective a drug is, the fewer side effects it will produce.
-Selective drug action is possible, in large part, because drugs act through specific receptors.
-The therapeutic index is a measure of a drug's safety. The therapeutic index, determined using laboratory animals, is defined as the ratio of a drug's LD50 to its ED50.
-Refers to the amount of drug we must give to elicit an effect. Potency is indicated by the relative position of the dose response curve along the x (dose) axis.
Potency is rarely an important characteristic of a drug. It is important to note that the potency of a drug implies nothing about its maximal efficacy!
4 main receptor families
1. cell membrane–embedded enzymes
2. ligand-gated ion channels
3. G protein–coupled receptor systems
4. transcription factors.
Simple Vs. Modified Occupancy
-The simple occupancy theory of drug receptor interaction states that: (1) the intensity of the response to a drug is proportional to the number of receptors occupied by that drug and that (2) a maximal response will occur when all available receptors have been occupied.
-The modified occupancy theory of drug-receptor interaction explains certain observations that cannot be accounted for with the simple occupancy theory.
-The simple occupancy theory assumes that all drugs acting at a particular receptor are identical with respect to (1) the ability to bind to the receptor and (2) the ability to influence receptor function once binding has taken
place. The modified occupancy theory is based on different assumptions.
-The modified theory ascribes two qualities to drugs: affinity and intrinsic activity. The term affinity refers to the
strength of the attraction between a drug and its receptor. Intrinsic activity refers to the ability of a drug to activate the receptor following binding. Affinity and intrinsic activity are independent properties.
-act through simple physical or chemical
interactions with other small molecules.