Pharmacodynamics Notes
Pharmacodynamics and Interpatient Variability
Pharmacodynamics is how a medicine changes the body. It helps predict if a drug will produce a change and ensures that the drug will provide safe and effective treatment. Safe treatment is guided by a combination of drug guides and intuitive experience.
Frequency Distribution Curve
A frequency distribution curve is a graphical representation of the number of patients responding to a drug action at different doses. The peak of the curve indicates the largest number of patients responding to the drug, but it does not show the magnitude of response.
Median Effective Dose (ED Subscript 50)
The median effective dose (ED Subscript 50) is the dose that produces a therapeutic response in 50% of a group. It is sometimes called the “average” or “standard” dose. Many patients require more or less than this dose. A nurse’s skill is critical in determining if the average dose is effective through patient observation, taking vital signs, and monitoring lab data.
Median Lethal Dose (LD Subscript 50)
The median lethal dose (LD Subscript 50) is used to assess the safety of a drug and is shown on frequency distribution curves. It is determined in preclinical trials and is the lethal dose in 50% of a group of animals. It cannot be experimentally determined in humans.
Median Toxicity Dose (TD Subscript 50)
The median toxicity dose (TD Subscript 50) is the dose that will produce a given toxicity in 50% of a group of patients. Its value may be extrapolated from animal data and adverse effects in patient clinical trials because the median lethal dose cannot be tested in humans.
Therapeutic Index and Drug Safety
The therapeutic index is a measure of a drug’s safety margin. The higher the value, the safer the drug.
Calculating Therapeutic Index
The therapeutic index is calculated as follows:
For example, a therapeutic index of 4 means that an error of four times the dose is needed to be lethal.
Graded Dose—Response Relationship and Therapeutic Response
The graded dose-response relationship graphically visualizes differences in responses to medications in a single patient. It is obtained by observing and measuring a patient's response at different doses of the drug.
Three Phases of Graded Dose—Response Curve
Phase 1 occurs at the lowest dose, where few target cells are affected by the drug.
Phase 2 is the straight-line portion of the curve and the most desirable range, showing a linear relationship between the amount of drug administered and the degree of patient response.
Phase 3 is where a plateau is reached, and increasing the dose has no therapeutic effect and may produce adverse effects.
Two Ways to Compare Medications
Medications can be compared by:
Potency
Efficacy
Potency
A drug with higher potency produces a therapeutic effect at a lower dose compared with another drug in the same class.
Efficacy
Efficacy is the magnitude of maximal response that can be produced from a particular drug. From a pharmacotherapeutic perspective, efficacy is almost always more important than potency.
Receptor Is Macromolecule
A receptor is a molecule to which a medication binds in order to initiate its effects. It binds endogenous molecules such as hormones, neurotransmitters, and growth factors. Most drug receptors are protein agonists and are associated with the plasma membrane or intracellular molecules.
Drug Attaches to Receptor
Drug attachment to a receptor is comparable to how a thumb drive docks to a USB port on a computer. It may trigger second messenger events, such as the activation of specific G proteins and associated enzymes, which initiates drug action.
Receptor Subtypes Still Being Discovered
The discovery of receptor subtypes permits “fine-tuning” of pharmacology. Two basic receptor types are alpha and beta. Drugs affect each subtype differently. Intercellular molecules (DNA or enzymes in the cytoplasm) interact with receptors by inhibiting protein synthesis or regulating cell events.
Nonspecific Cellular Responses
Nonspecific cellular responses are caused by drugs that act independently of receptors. An example is changing the permeability of cellular membranes.
Drugs That Act as Agonists
Drugs that act as agonists bind to a receptor and produce the same response as an endogenous chemical. Sometimes they produce a greater maximal response.
Drugs That Act as Partial Agonists
Drugs that act as partial agonists bind to a receptor and produce a weaker, less effective response than agonists.
Drugs That Act as Antagonists
Drugs that act as antagonists occupy a receptor and prevent an endogenous chemical from acting. They often compete with agonists for the receptor. Functional antagonists inhibit the effects of an agonist not by competing for a receptor but by changing pharmacokinetic factors.
Pharmacology of the Future: Customized Drug Therapy
The future of pharmacology involves the end of single-drug, one-size-fits-all policies and will involve DNA tests before receiving a drug. This will aid in the prevention of idiosyncratic (unpredictable and unexplained) drug reactions. Pharmacogenetics is an area of pharmacology that examines the role of heredity in drug response.