L.V.B.

PHARMACOLOGY LEVEL 2 BLOCK E

Pharmacodynamics
Pharmaco- refers to medicines,
Dynamics- “change.”
- refers to how a drug changes the body.
-branch of pharmacology concerned with the mechanisms of drug action and the relationships between drug
concentration and responses in the body.

Interpatient Variability- Patients have widely different responses to drugs

Frequency distribution curve- is a graphic representation of the actual number of patients responding with a
particular drug action at different doses.

Median Effective Dose (ED 50 ) . The dose in the middle of the frequency distribution curve.
- dose required to produce a specific therapeutic response in 50% of a group of patients.
- “average” or standard dose for a drug.

CLININICAL IMPLICATIONS: the standard or average dose predicts a satisfactory therapeutic response for only
half the population.

Nursing Responsibility: It is not enough to simply memorize an average dose for a drug; the nurse must have the
skills to know when and how to adjust this dose to obtain the optimum therapeutic response.

Therapeutic Index- describes a drug’s margin of safety.

Frequency distribution curves can also be used to illustrate the safety of a drug.

Median Lethal Dose (LD 50 )- a value often determined in laboratory animals in preclinical experiments during
the drug development process.
The LD 50 is the dose of drug that will kill 50% of a group of animals.

The ED 50 and LD 50 are used to calculate a drug’s therapeutic index.

The therapeutic index (TI) is defined as the ratio of a drug’s LD 50 to its ED 50 .

Interpretation: The larger the difference between the two doses, the greater the TI.
Essentially, this means that it would take an error in magnitude of approx. 4x the average dose to be lethal to a
patient.
**the higher the value, the safer the medication.

**narrow safety margin- Small medication errors or changes in the drug’s metabolism or excretion could have
lethal consequences.
- require careful assessment of hepatic and renal function prior to the initiation of therapy.

*With drugs exhibiting a low TI, it is prudent to begin with the lowest dose possible, then increase the amount
of drug with careful monitoring.
L.V.B. PHARMACOLOGY LEVEL 2 BLOCK E

*Median Toxicity Dose (TD 50 ) is the dose that will produce a given toxicity in 50% of a group of patients.
- value may be extrapolated from animal data or based on adverse effects recorded in patient clinical trials.

*Margin of Safety (MOS)- another index of a drug’s effectiveness and safety. The MOS is calculated as the
amount of drug that is lethal to 1% of animals (LD 1 ) divided by the amount of drug that produces a therapeutic
effect in 99% of the animals (ED 99 ).
**In general, the higher the MOS value, the safer the medication.

Dose–Response Relationship- describes how the actions of a drug change with increasing dose.
In the preceding section, frequency distribution curves were used to graphically visualize interpatient
differences in responses to medications in a population . Pharmacodynamics is also used to study the variability
in responses in a single patient .

Dose–Response curve- plots the drug dose administered to the patient versus the intensity or degree of
response obtained.

3 Phases:
*Phase 1- occurs at the lowest doses. The flatness of this portion of the curve indicates that few target cells
have been affected by the drug; doses that are too small will not produce a therapeutic effect.
*Phase 2 - the rising, straight line portion of the curve.
- there is a linear relationship between the amount of drug administered and the degree of response obtained
from the patient.
For example, if the dose is doubled, twice as much response may be obtained.
*Phase 3 increasing the drug dose produces no additional therapeutic response—a plateau has been reached.
Possible Causes:
a. all the target receptors for the drug are occupied.
b. drug has brought 100% relief.
*giving higher doses produces no additional relief.
**Note- nurse should be mindful that increasing the dose = more adverse effects

Potency and Efficacy

*not all drugs are equally effective at treating a disorder.
Ex: antineoplastic, antihypertensive, analgesics, antibiotics

A. Potency- the strength of a drug at a specified concentration or dose.

* more potent= produce its therapeutic effect at a lower dose.
Give image:

Thus, potency is a way to compare the doses of two independently administered drugs in terms of how much is
needed to produce a particular response.

B. Efficacy the greatest maximal response that can be produced from a particular drug

From a pharmacotherapeutic perspective, efficacy is almost always more important than potency.

As another comparison, the patient with cancer is much more concerned with how many cancer cells have
been killed (efficacy) than with the dose the nurse administered (potency).
L.V.B. PHARMACOLOGY LEVEL 2 BLOCK E

Caution: higher doses produce more intense adverse effects.

*true only when comparing doses of the same drug.

Receptor Theory
- explains the mechanisms by which most drugs produce their effects

Receptor- a cellular molecule to which a medication binds to produce its effects

-a drug’s specific target.
*Drug receptors- mostly protein in nature
- can be found in cell membranes or within the cell

*Note: Receptors do not exist in the body solely to bind drugs

Normal function: is to bind endogenous molecules, sometimes called ligand (e.g. hormones, neurotransmitters,
and growth factors)
Endogenous molecules- those that originate from within a system (e.g. organism, tissue, cell)

*Intrinsic Activity- the ability of a drug to bind to a receptor and produces a strong activity.
I.A. = Efficacy; high I.A. = high Efficacy
4 RECEPTOR FAMILIES
1. Cell membrane–embedded enzymes. The ligand-binding domain for drug binding is on the cell surface. The
drug activates the enzyme inside the cell, and a response is initiated.
2. Ligand-gated ion channels. The channel crosses the cell membrane. When the channel opens, ions flow into
and out of the cells. This primarily affects sodium and calcium ions.
3. G protein–coupled receptor systems. The three components to this receptor response are (1) the receptor, (2)
the G protein that binds with guanosine triphosphate (GTP), and (3) the effector, which is either an enzyme or
an ion channel. The system works as follows:

4. Transcription factors. Found in the cell nucleus on DNA, not on the surface. Activation of receptors through
transcription factors regulates protein synthesis and is prolonged.
L.V.B. PHARMACOLOGY LEVEL 2 BLOCK E

Agonists and Antagonists

*Agonist- A drug that activates a receptor and produces the same type of response as the endogenous
substance
- it sometimes produces a greater maximal response than the endogenous chemical

*Partial Agonist- used to describe a medication that produces a weaker, or less efficacious, response than an
agonist.

*Antagonist- a drug that will occupy a receptor and prevent the endogenous chemical from binding to produce
its action
-often competes with agonists for receptor binding sites
Functional antagonist
- used in drug overdose – reverse adverse effects

Pharmacogenetics

- branch of pharmacology that examines the role of

genetics in drug response.
- specifically, it is the study genetic factors that
influence an individual’s response to a specific drug

*Idiosyncratic response- any unpredictable and

unexplained drug reaction

Human Genome Project (HGP)- an international

collaborative research program
- performed DNA testing on populations all over the
world.
Findings: human beings are 99.9% genetically
identical; this implies that there are not multiple races
but multiple genotypes (an individual’s genetic
identity).

Nursing Challenge- integrate knowledge of

pharmacogenetics into their practice in order to
identify patients at increased risk for adverse drug
reactions, and they must effectively monitor patients
for therapeutic drug responses and prevent
complications to drug therapy.