Pharmacology For Nurses: A Pathophysiologic Approach: Fifth Edition

Pharmacology for Nurses: A Pathophysiologic
Approach
Fifth Edition
Chapter 4
Pharmacokinetics
Copyright © 2017, 2014, 2011 Pearson Education, Inc. All Rights Reserved
Application of Pharmacokinetics to
Clinical Practice
• Pharmacokinetics: the study of drug movement
throughout the body
• Know how the body deals with medication
• Understand and predict actions and side effects of
medications
• Understand obstacles that a drug faces to reach target
cells
Drugs in the Body
• Greatest barrier for many drugs is crossing many

membranes
• Enteral route drugs are broken down by stomach acids
and digestive enzymes
• Organs attempt to excrete medicines
• Phagocytes may attempt to remove medicines seen as
foreign
Four Categories of Pharmacokinetic
Processes
• Absorption
• Distribution
• Metabolism
• Excretion
Figure 4.1 The Four Processes of Pharmacokinetics:
Absorption, Distribution, Metabolism, and Excretion
Drugs Cross Plasma Membranes to
Produce Effects
• Active transport
• Diffusion or passive transport
Active Transport
• Chemicals move against concentration or

electrochemical gradient
• Usually large, ionized, or water-soluble molecules
• Cotransport involves the movement of two or more
chemicals across the membrane
Diffusion or Passive Transport
• Molecules move from higher to lower concentration

• Usually small, nonionized, or lipid-soluble molecules
Absorption
• Movement from site of administration, across body

membranes, to circulating fluids
• Primary pharmacokinetic factor determining length of
time for drug to produce effect
Factors Affecting Drug Absorption (1 of 2)
• Drug formulation and dose

• Dose
• Route of administration
• Size of drug molecule
• Surface area of absorptive site
• Digestive motility
• Blood flow
• Lipid solubility of drug
Factors Affecting Drug Absorption (2 of 2)
• Degree of ionization of drug

– In stomach acid, aspirin nonionized and easily
absorbed by bloodstream
– In small intestine alkaline, aspirin ionized and less
likely to be absorbed
• pH of local environment
• Drug-drug/food-drug interactions
• Dietary supplement/herbal product–drug interactions
Figure 4.2 Effect of pH on Drug
Absorption (1 of 2)
(a) a weak acid such as aspirin (ASA) is in a nonionized
form in an acidic environment and absorption occurs
Figure 4.2 Effect of pH on Drug
Absorption (2 of 2)
(b) in a basic environment, aspirin is mostly in an ionized
form and absorption is prevented
Distribution of Medications (1 of 4)
• Distribution—transport of drugs throughout the body

– Simplest factor determining distribution is the amount
of blood flow to body tissues
• Physical properties of drug have great influence

• Certain tissues (bone marrow, teeth, eyes, adipose
tissue) have a high affinity, or attraction, for certain
medications
Drugs Bind with Plasma Proteins
• Many drug molecules form drug–protein complexes—

binding reversibly to plasma proteins—and thus never
reach target cells
• Cannot cross capillary membranes
• Drug not distributed to body tissues
Figure 4.3 Plasma Protein Binding and
Drug Availability
(a) drug exists in a free state or bound to plasma protein;
(b) drug–protein complexes are too large to cross
membranes
• Drugs and other chemicals compete for plasma protein–

binding sites
– Drug–drug and drug–food interactions may occur
when one drug displaces another from plasma
proteins
• Some have greater affinity
• Displaced drug can reach high levels
– Can produce adverse effects
• Blood-brain barrier and fetal-placenta barrier: special

anatomic barriers that prevent many chemicals and
medications from entering
– Makes brain tumors difficult to treat
– Fetal-placenta barrier protects fetus; no pregnant
woman should be given medication without strong
consideration of condition
Metabolism of Medications
• Also known as biotransformation

• Chemically converts drug so it can be easily removed
from body
• Involves complex biochemical reactions
• Liver—primary site
• Addition of side chains, known as conjugates, makes
drugs more water soluble and more easily excreted by
the kidneys
Metabolism in the Liver
• Hepatic microsomal enzyme system (P-450 system)

– Inactivates drug
– Accelerates drug excretion
– Some agents, known as prodrugs, have no
pharmacologic activity unless first metabolized to
active form by body
Enzyme Induction
• A drug increases metabolic activity in the liver

• Changes in the function of the hepatic microsomal
enzymes can significantly affect drug metabolism
Oral Drugs Enter Hepatic Portal
Circulation (First-Pass Effect)
• Drug is absorbed
• Drug enters hepatic circulation, goes to liver
• Drug is metabolized to inactive form
• Drug conjugates and leaves liver
• Drug is distributed to general circulation
• Many drugs are rendered inactive by first-pass effect
Pharmacotherapy Illustrated 4.1 First-Pass Effect:
Oral Drug Is Metabolized to an Inactive Form Before
It Has an Opportunity to Reach Target Cells
Metabolism and Pharmacotherapy
• Metabolic activity may be decreased in some patients:

– Infants and elderly
– Patients with severe liver disease
– Patients with certain genetic disorders
• Dosages in patients with decreased metabolic activity
must be reduced to prevent toxicity
Primary Site of Excretion of Drugs Is
Kidneys
• Free drugs, water-soluble agents, electrolytes, and small
molecules are easily filtered
• Drug-protein complexes and large substances are
secreted into distal tubule of nephron
• Secretion mechanism is less active in infants and older
adults
• pH of filtrate can increase excretion
Renal Failure Diminishes Excretion of
Medications
• Drugs are retained for extended times
• Dosages must be reduced
Other Organs Can Be Sites of Excretion
• Respiratory system
• Glands
• Biliary system
Enterohepatic Recirculation of Drugs
• Drugs are excreted in bile

• Bile recirculates to liver
• Percentage of drug may be recirculated numerous times
• Prolongs activity of drug
– Activity of drug may last after discontinuation
Figure 4.4 Enterohepatic Recirculation
Drug Plasma Concentration and
Therapeutic Response
• Concentration of medication at target tissue is often
impossible to measure, so it must be measured in plasma
– Minimum effective concentration—amount of drug
required to produce a therapeutic effect
– Toxic concentration—level of drug that will result in
serious adverse effects
– Therapeutic range—plasma drug concentration
between the minimum effective concentration and the
toxic concentration
Plasma Half-Life  t ½  of Drugs
1 sub one half
• Length of time needed to decrease drug plasma

concentration by one half
• The greater the half-life, the longer it takes to excrete
• Determines frequency and dosage
How Drug Reaches and Maintains
Therapeutic Range
• Repeated doses of drug are given
• Drug accumulates in bloodstream
• Plateau is reached
• Amount administered equals amount eliminated
Figure 4.5 Single-Dose Drug Administration
pharmacokinetic values for this drug are as follows: onset of action = 2 hours;
duration of action = 6 hours; termination of action = 8 hours after
administration; peak plasma concentration = 10 mcg/mL; time to peak drug
effect = 5 hours; t½ = 4 hours
Figure 4.6 Multiple-Dose Drug
Administration
drug A and drug B are administered every 12 hours; drug B
reaches the therapeutic range faster, because the first
dose is a loading dose
Loading Dose
• Higher amount of drug given

• Plateau reached faster
• Quickly produces therapeutic response
Maintenance Dose
• Keeps plasma-drug concentration in therapeutic range
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Pharmacology for Nurses: A Pathophysiologic

• Greatest barrier for many drugs is crossing many

• Chemicals move against concentration or

• Molecules move from higher to lower concentration

• Movement from site of administration, across body

• Drug formulation and dose

• Degree of ionization of drug

• Distribution—transport of drugs throughout the body

• Physical properties of drug have great influence

• Many drug molecules form drug–protein complexes—

• Drugs and other chemicals compete for plasma protein–

• Blood-brain barrier and fetal-placenta barrier: special

• Also known as biotransformation

• Hepatic microsomal enzyme system (P-450 system)

• A drug increases metabolic activity in the liver

• Metabolic activity may be decreased in some patients:

• Drugs are excreted in bile

• Length of time needed to decrease drug plasma

• Higher amount of drug given

• Keeps plasma-drug concentration in therapeutic range

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