Adams ch04 lecture

PHARMACOLOGY FOR NURSESPHARMACOLOGY FOR NURSESA 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 EditionMichael Patrick Adams | Leland N. Holland | Carol Urban

Application of Pharmacokinetics to Application 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 of Four Components of PharmacokineticsPharmacokinetics

• Absorption• Distribution• Metabolism• Excretion


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


Drugs Cross Plasma Membranes Drugs 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-Portal Oral 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 Drugs Primary 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 Diminishes Renal Failure Diminishes Excretion of MedicationsExcretion of Medications

• Drugs are retained for extended times.• Dosages must be reduced.


Other Organs Can Be Sites of Other Organs Can Be Sites of ExcretionExcretion

• Respiratory system• Glands• Biliary system


Enterohepatic Recirculation Enterohepatic 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 and Drug 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 and Drug 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 Maintains How 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