Kee: Pharmacology, 8th Edition

Chapter 1: Drug Action: Pharmaceutic, Pharmacokinetic, and Pharmacodynamic Phases

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The nurse must have adequate understanding of the three phases of drug action:
pharmaceutic, pharmacokinetic, and pharmacodynamic.

PHARMACEUTIC PHASE

The pharmaceutic phase (dissolution) is the first phase of drug action.

In the gastrointestinal (GI) tract, drugs need to be in solution so they can be absorbed. A
drug in solid form (tablet or capsule) must disintegrate into small particles to dissolve
into a liquid, a process known as dissolution, so that it can cross the biologic membrane.
When the drug is administered parenterally by subcutaneous (subQ), intramuscular (IM),
or intravenous (IV) routes, there is no pharmaceutic phase.
Disintegration is the breakdown of a tablet into smaller particles.
Dissolution is the dissolving of the smaller particles in the GI fluid before absorption.

PHARMACOKINETIC PHASE

Pharmacokinetics is the process of drug movement to achieve drug action.

The four processes of pharmacokinetics are absorption, distribution, metabolism, and
excretion.
Absorption is the movement of drug particles from the GI tract to body fluids by passive
absorption, active absorption, or pinocytosis.
o Passive absorption occurs mostly by diffusion.
o Active absorption requires a carrier such as an enzyme or protein to move the
drug against a concentration gradient.
o Pinocytosis is a process by which cells carry a drug across their membrane by
engulfing the drug particles.
Drug absorption can be altered by blood flow, pain, stress, hunger, fasting, food, pH, and
method of administration.
The process in which the drug passes to the liver first, where it is either metabolized to an
inactive form or a drug metabolite, is called the first-pass effect.
Bioavailability is the percentage of the administered drug dose that reaches the systemic
circulation. Factors that alter bioavailability include (1) the drug form, (2) route of
administration, (3) GI mucosa and motility, (4) food and other drugs, and (5) changes in
liver metabolism.
Distribution is the process by which the drug becomes available to body fluids and body
tissues.
Drug distribution is influenced by blood flow, the drugs affinity to the tissue, and the
protein-binding effect.
Copyright 2015, 2012, 2009, 2006, 2003, 2000, 1997, 1993 by Saunders, an imprint of Elsevier Inc.

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As drugs are distributed in the plasma, many are bound to varying degrees (percentages)
with protein (primarily albumin). The portion of the drug that is bound is inactive
because it is not available to receptors, and the portion that remains unbound is free,
active drug.
Metabolism is the process by which the body inactivates or biotransforms drugs. Drugs
can be metabolized in several organs; however, the liver is the primary site of
metabolism.
The half-life (t) of a drug is the time it takes for one-half of the drug concentration to be
eliminated. Metabolism and elimination affect the half-life of a drug.
The main route of drug elimination is through the kidneys (urine). Other routes include
bile, feces, lungs, saliva, sweat, and breast milk. With a kidney disease that results in
decreased glomerular filtration rate (GFR) or decreased renal tubular secretion, drug
excretion is slowed or impaired. Common tests used to determine renal function are
creatinine clearance (CLcr) and blood urea nitrogen (BUN).

PHARMACODYNAMICS

Pharmacodynamics is the study of the way drugs affect the body.

Dose response is the relationship between the minimal versus the maximal amount of
drug dose needed to produce the desired drug response.
All drugs have a maximum drug effect (maximal efficacy).
Onset of action is the time it takes to reach the minimum effective concentration (MEC)
after a drug is administered. Peak action occurs when the drug reaches its highest blood
or plasma concentration.
Duration of action is the length of time the drug has a pharmacologic effect. If drug
serum level decreases below threshold or MEC, adequate drug dosing is not achieved; too
high a drug level above the minimum toxic concentration (MTC) can result in toxicity.
Drugs act through receptors by binding to the receptor to produce a response or to block a
response.
Most receptors, which are protein in nature, are found in cell membranes. There are four
receptor families: (1) kinase-linked receptors, (2) ligand-gated ion channels, (3) G
protein-coupled receptor systems, and (4) nuclear receptors.
Drugs that produce a response are called agonists. Drugs that block responses are called
antagonists.
Drugs that affect various sites are nonspecific drugs; drugs that evoke a variety of
responses throughout the body have a nonspecific response. Drugs that affect various
receptors are nonselective drugs or have properties of nonselectivity.
The four categories of drug action include (1) stimulation or depression, (2) replacement,
(3) inhibition or killing of organisms, and (4) irritation.
o In drug action that stimulates, the rate of cell activity or the secretion from a gland
increases.
o In drug action that depresses, cell activity and function of a specific organ are
reduced.
o Replacement drugs replace essential body compounds.

Copyright 2015, 2012, 2009, 2006, 2003, 2000, 1997, 1993 by Saunders, an imprint of Elsevier Inc.

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o Drugs that inhibit or kill organisms interfere with bacterial cell growth.
o Drugs also can act by the mechanism of irritation.
The therapeutic index (TI) estimates the margin of safety of a drug through the use of a
ratio that measures the effective (therapeutic) dose (ED) in 50% of people (ED50) and the
lethal dose (LD) in 50% of people (LD50). Drugs with a low therapeutic index have a
narrow margin of safety. Drugs with a high therapeutic index have a wide margin of
safety and less danger of producing toxic effects.
The therapeutic range (therapeutic window) of a drug concentration in plasma is the level
of drug between the minimum effective concentration in the plasma for obtaining desired
drug action and the minimum toxic concentration (the toxic effect). Peak drug levels
indicate the rate of absorption of the drug, and trough drug levels indicate the rate of
elimination of the drug. Peak and trough levels are requested for drugs that have a narrow
therapeutic index and are considered toxic.
When immediate drug response is desired, a large initial dose, known as the loading dose,
of drug is given to achieve a rapid minimum effective concentration in the plasma.
Side effects are physiologic effects not related to desired drug effects. All drugs have
desirable or undesirable side effects. Adverse reactions are more severe than side effects.
They are a range of untoward effects of drugs that cause mild to severe side effects.
Toxic effects, or toxicity, of a drug can be identified by monitoring the plasma (serum)
therapeutic range of the drug. When the drug level exceeds the therapeutic range, toxic
effects are likely to occur from overdosing or drug accumulation.
Pharmacogenetics is the scientific discipline studying how the effect of a drug action
varies from a predicted drug response because of genetic factors or hereditary influence.
Tolerance refers to a decreased responsiveness over the course of therapy.
Tachyphylaxis refers to a rapid decrease in response to the drug.
A placebo effect is a psychological benefit from a compound that may not have the
chemical structure of a drug effect.
To avoid toxic effects, the nurse must know the half-life, protein-binding percentage,
normal side effects, and therapeutic ranges of the drug.

NURSING PROCESS

Take a history to identify factors that may affect drug pharmacokinetics (e.g. gastric
surgery will affect absorption; low serum albumin will affect protein-binding; peripheral
vascular disease may affect drug distribution to extremities).
Examine the patients history to identify factors that may affect pharmacodynamics (e.g.,
a G6PD deficiency may cause hemolytic anemia if some common drugs are given).
Perform a physical exam to identify problems that may affect pharmacodynamics,
(elevated BP, dysrhythmias, or other abnormal findings may be an indication for drug
therapy).
Identify side effects of drugs that are nonspecific (same receptor at different tissue and
organ sites). If nonspecific drugs are given in large doses or at frequent intervals, many
side effects are likely to occur.

Copyright 2015, 2012, 2009, 2006, 2003, 2000, 1997, 1993 by Saunders, an imprint of Elsevier Inc.

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Check peak levels and trough levels of drugs such as aminoglycosides that have a narrow
therapeutic range. If the trough level is high, toxic effects can result.
Monitor the therapeutic range of drugs that are more toxic or have a narrow therapeutic
range (e.g., digoxin).
Be aware that individuals of some ethnic or racial heritage metabolize drugs differently
than the general population. Assess for adverse effects that may result from this variation
in metabolism.
Assess for signs and symptoms of drug toxicity when giving two drugs that are highly
protein-bound. The drugs compete for protein-binding sites, and displacement of drugs
occurs. More free drug is in circulation because there are not enough protein-binding
sites. Too much of a free drug can result in drug toxicity.

Copyright 2015, 2012, 2009, 2006, 2003, 2000, 1997, 1993 by Saunders, an imprint of Elsevier Inc.