Adams ch04 lecture

PHARMACOLOGY FOR NURSESPHARMACOLOGY FOR NURSES
A Pathophysiological ApproachA Pathophysiological Approach
FOURTH EDITIONFOURTH EDITION
Copyright © 2014, © 2011, © 2008 by Pearson Education, Inc.
All Rights Reserved
CHAPTER
Pharmacokinetics
4

Pharmacology for Nursing: A Pathophysiology Approach, Fourth Edition
Michael Patrick Adams | Leland N. Holland | Carol Urban
Application of Pharmacokinetics toApplication of Pharmacokinetics to
Clinical PracticeClinical Practice
• Pharmacokinetics: the study of drug
movement throughout the body
• Know how the body handles medication
• Understand actions and side effects of
drugs
• Understand obstacles that a drug faces
to reach target cells

Drugs in the BodyDrugs in the Body
• Greatest barrier for many drugs is
crossing many membranes.
• Enteral route drugs are broken down by
stomach acids and enzymes.
• Organs attempt to excrete medicines.
• Phagocytes may attempt to remove
medicines seen as foreign.

Four Components ofFour Components of
PharmacokineticsPharmacokinetics
• Absorption
• Distribution
• Metabolism
• Excretion

Figure 4.1 The four processes of pharmacokinetics: absorption, distribution, metabolism, and excretion

Drugs Cross Plasma MembranesDrugs Cross Plasma Membranes
to Produce Effectsto Produce Effects
• Diffusion or passive transport
• Active transport

Diffusion or Passive TransportDiffusion or Passive Transport
• Molecules move from higher to lower
concentration.
• Usually small, nonionized, or lipid-
soluble molecules

Active TransportActive 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.

AbsorptionAbsorption
• Movement from site of administration,
across body membranes, to circulating
fluids
• Primary factor determining length of
time for effect of drug to occur

Factors Affecting Drug AbsorptionFactors Affecting Drug Absorption
• Route of administration
• Drug formulation
• Drug dosage
• Digestive motility
• Digestive tract enzymes
• Blood flow at administration site

Factors Affecting Drug AbsorptionFactors Affecting Drug Absorption
• Degree of ionization of drug
– In acid of stomach, aspirin is nonionized
and easily absorbed by bloodstream.
– In alkaline of small intestine, aspirin is
ionized and less likely to be absorbed.
• pH of surrounding environment
• Drug-drug/drug-food interactions
• Dietary supplement/herbal product–
drug interactions

Figure 4.2 Effect of pH on drug absorption: (a) a weak acid such as aspirin (ASA) is in a nonionized form in an
acidic environment and absorption occurs; (b) in a basic environment, aspirin is mostly in an ionized form and
absorption is prevented

Metabolism of MedicationsMetabolism of Medications
• Also known as biotransformation
• Changes drug so it can be excreted
• Involves 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 LiverMetabolism 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 InductionEnzyme 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-PortalOral Drugs Enter Hepatic-Portal
Circulation (First-Pass Effect)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.

Figure 4.4 First-pass effect: (a) drugs are absorbed; (b) drugs enter hepatic portal circulation and go directly
to liver; (c) hepatic microsomal enzymes metabolize drugs to inactive forms; (d) drug conjugates, leaving liver;
(e) drug is distributed to general circulation

Metabolism and PharmacotherapyMetabolism and Pharmacotherapy
• Can be decreased metabolic activity in
some patients:
– Infants and elderly
– Patients with severe liver disease
– Patients with certain genetic disorders
– Dosages need to be adjusted in these
patients.

Distribution of MedicationsDistribution of Medications
• Distribution involves the transport of
pharmacologic agents throughout the
body.
– Simplest factor determining distribution
is the amount of blood flow to body
tissues.

• Physical properties of drug have big
influence.
• Certain tissues, such as bone marrow,
have a high affinity, or attraction, for
certain medications.

Drugs Bind with Plasma ProteinsDrugs 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.

Primary Site of Excretion of DrugsPrimary Site of Excretion of Drugs
Is KidneysIs Kidneys
• Free drugs, water-soluble agents,
electrolytes, and small molecules are
filtered.
• Drug-protein complexes are secreted
into distal tubule.
• Secretion mechanism is less active in
infants and older adults.
• pH of filtrate can increase excretion.

Renal Failure DiminishesRenal Failure Diminishes
Excretion of MedicationsExcretion of Medications
• Drugs are retained for extended times.
• Dosages must be reduced.

Other Organs Can Be Sites ofOther Organs Can Be Sites of
ExcretionExcretion
• Respiratory system
• Glands
• Biliary system

Enterohepatic RecirculationEnterohepatic Recirculation
of Drugsof Drugs
• Drugs are excreted in bile.
• Bile recirculates to liver.
• Percentage of drug recirculated
numerous times
• Prolongs activity of drug
– Activity of drug may last after
discontinuation.

Figure 4.5 Enterohepatic recirculation

Drug Plasma Concentration andDrug Plasma Concentration and
Therapeutic ResponseTherapeutic Response
• Concentration of medication in 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

Drug Plasma Concentration andDrug Plasma Concentration and
Therapeutic ResponseTherapeutic Response
• Concentration of medication in target
tissue is often impossible to measure,
so it must be measured in plasma.
– Therapeutic range—plasma drug
concentration between the minimum
effective concentration and the toxic
concentration

Plasma Half-Life (t½) of DrugsPlasma Half-Life (t½) of Drugs
• 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 dosages

How Drug Reaches and MaintainsHow Drug Reaches and Maintains
Therapeutic RangeTherapeutic Range
• Repeated doses of drug are given
• Drug accumulates in bloodstream.
• Plateau is reached.
• Amount administered equals amount
eliminated.

Figure 4.6 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 4.7 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 DoseLoading Dose
• Higher amount of drug given
• Plateau reached faster
• Quickly produces therapeutic response

Maintenance DoseMaintenance Dose
• Keeps plasma-drug concentration in
therapeutic range

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