21 ST EDITION
`
`Remington
`
`The Science and Practice
`of Pharmacy
`
`,~ LIPPINCOTT WILLIAMS & WILKINS
`A Wolters Kluwer Company
`•
`Philadelphia • Baltimore • New York • London
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`Eton Ex. 1111
`1 of 14
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`r
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`Editor: Dnv:d.H. ~~~~ttheW J. Haube_r
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`885 by Joseph p Remmgton, m
`Printed in the m e
`·n the year 1
`Entered according to Act of Congress, l
`· gton
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`. ht 1889 1894, 1905, 1907, 1917, by Joseph p ernm
`opyng
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`h p R rnington Estate
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`i ht 1926, 1936, by the Josep
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`le e of Pharmacy and Science
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`Copyright 1948, 1951, by the Philadelphia Col g
`Philadelphia College of Pharmacy and Science
`. ht1956 1960 1965,1970, 1975, 1980, 1985, 1990, 1995,bythe
`opyng
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`. ht 2000 2006 by the University of the Sciences m Philadelp ia
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`The use of structural formulas from USAN and the USP Dictionary of Drug Names is by permission of The USP Convention. The
`Convention is not responsible for any inaccuracy contained herein.
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`Notice-This text is not intended to represent, nor shall it be interpreted to be, the equivalent of or a substitute for the official
`United States Pharmacopeia (USP) and I or the National Formulary (NF). In the event of any difference or discrepancy between the
`current official USP or NF standards of strength, quality, purity, packaging and labeling for drugs and representations of them
`herein, the context and effect of the official compendia shall prevail.
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`1 2 3 4 5 6 7 8 9 1°
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`Eton Ex. 1111
`2 of 14
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`

`

`Contents
`
`Port 1 Orientation
`
`1
`2
`3
`4
`5
`6
`7
`8
`
`9
`10
`
`Scope of Ph,1rmacy . .... .. . .. ... . .... .. . .. , ....... 3
`Evolution of Pharmacy
`. ....... . .... ... . . ... .. . . .. . 7
`Ethics and Professionalism .. .. . . ....... .... .... .. . . 20
`The Prac tice of Community Pharmacy ....... .. ...... .30
`Pharmacists in Industry . . .. ..... . ... . . .. . . ...... . . 35
`Pl1nrmacists in Government ... . .. ... ... . ........ . .. 40
`Pharmacists and Public Health ... . . .. . ...... ... . . . . . 51
`Information Resources in Pharmacy and the
`Pharmaceutical Sciences
`...... .... . 64
`Clinical Drug Litera ture . : : : : : : : : : : : : : : : ..... . .... . 74
`Research . .. .. . ........ .. ...... . .... ... .. . .... . 87
`
`Part 2 Pharmaceutics
`
`11
`12
`13
`14
`15
`16
`17
`18
`19
`20
`21
`22
`23
`
`.. . .... ... 99
`Metrology and Pharmaceutical Calculations
`Statistics . ... . . . ........... .. ..... .. . . ... ... . . 127
`Molecular Structure, Properties, and States of Matter .. . 162
`Complex Formation .. . ... . ........... ...... . ... 186
`Thermodynamics ... ...... .. ... . .... . . ......... . 201
`Solutions and Phase Equilibria . .... ... .. ... .... .. .. 211
`Ionic Solutions and Electrolytic Equilibria . ...... . ..... 231
`Tonicity, Osmoticity, Osmolality, and Osmolarity . . ..... 250
`Chemical Kinetics ... ...... .. . .. .. . . .... . . .. .... 266
`.. ... . .................... 280
`lnterfacial Phenomena
`Colloidal Dispersions ... .. .. .. . ... . .... . ... . ... .. 293
`Coarse Dispersions . .. .. . ..... . . ... . ........... .319
`Rheology ... . . ......... . ... .. . . ........... .. .338
`
`Part 3 Pharmaceutical Chemistry
`
`24
`25
`26
`27
`28
`29
`
`Inorganic Pharmaceutical Chemistry ..... . . ...... ... 361
`Organic Pharmaceutical Chemistry . . . . ... . . ....... . 386
`Natural Products . .... .... ... .. ................. 410
`Drug Nomenclature-United States Adopted Names ... .443
`Structure-Activity Relationship and Drug Design ..... . .468
`Fundamentals of Medical Radionuclides . ............ 479
`
`Part 4
`
`Pharmaceutical Testing, Analysis, and Control
`
`30
`31
`32
`33
`34
`35
`
`Analysis of Medicinals .. ... .. . ......... . .. . .... . . 495
`Biological Testing .. . .. .. .. . .. . ..... . . .. ... .. ... 553
`Clinical Analysis .. ..... ..... .. . .. . . .... . . . .. . . . 565
`Chromatography .. . ... . ..... . ... ... .. . ....... . 599
`Instrumental Methods of Analysis ... .. .. ........... 633
`Dissolution ... .... .. . ... ... ...... .. ........... 672
`
`Part 5 Pharmaceutical Manufacturing
`
`36
`37
`38
`39
`40
`41
`42
`43
`44
`45
`46
`47
`48
`
`Separation .. ............. . ..... . . ........ .. .. 691
`Powders .. . ... .. .... .. .... .. . ... .... .. .... .. . 702
`Property-Based Drug Design and Preformulation . ... ... 720
`Solutions, Emulsions, Suspensions, and Extracts ....... 745
`Sterilization . . . . . . .
`. ................ . . .... ... . 776
`Parenteral Preparations .. . .... . .... . ..... . ..... .. 802
`Intravenous Admixtures ....... . . . . . ... . .. .... . . . 837
`Ophthalmic Preparations .. . . ... .. ............ . . . . 850
`Medicated Topicals . . .. .. .... ... .. ... . . . ..... . . . 871
`Oral Solid Dosage Forms ... .. . . ... .... .. .... . . ... 889
`Coating of Pharmaceutical Dosage Forms
`. ... . . ..... 929
`Extended-Release and Targeted Drug Delivery Systems .. 939
`The New Drug Approval Process and
`Clinical Trial Design ...... .. .... . . .. . ... . .. . . .... 965
`
`49
`50
`51
`52
`53
`54
`55
`
`Biotechnology and Drugs ... . .. ... .. . ... .. . .. .. . . 976
`Aerosols . . . .
`. ... .. . . . .... ... . . . 1000
`Quality Assurance and Control . .. ... . . . . ... . .. . . . 1018
`Stability of Pharmaceutical Products .. . .. . .. ...... . 102 5
`Bioavailability and Bioequivalency Testing ..... .. . .. . 1037
`Plastic Packaging Materials ...... .. . . ... . ... . .... 104 7
`Pharmaceutical Necessities . . .. . ...... . . . . . . ... . . 1058
`
`Part 6 Pharmacokinetics and Pharmacodynamics
`
`56
`57
`58
`59
`60
`61
`62
`63
`
`Diseases: Manifestations and Pathophysiology .. .. .. . 1095
`Drug Absorption, Action, and Disposition ... . ... .... 1142
`Basic Pharmacokinetics and Pharmacodynamics
`. . . ... 1171
`Clinical Pharmacokinetics and Pharmacodynamics . .. .. 1191
`Priniciples of Immunology .... .. .. .... . ... . . .... . 1206
`Adverse Drug Reactions and Clinical Toxicology .. . ... 1221
`Pharmacogenomics . ... ... ... .. . . ..... . . ... .... 1230
`Pharmacokinetics/Pharmacodynamics in
`Drug Development . .. . ..... ..... .... .......... 1249
`
`Part 7 Pharmaceutical and Medicinal Agents
`
`64
`65
`66
`67
`68
`69
`70
`71
`72
`
`73
`74
`75
`76
`77
`78
`79
`80
`81
`82
`83
`84
`85
`86
`87
`88
`89
`90
`91
`92
`93
`
`Diagnostic Drugs and Reagents . .. . . ..... . . .... ... 1261
`Topical Drugs ... . . ... . .. .. . .......... . . . . . .. . 1277
`Gastrointestinal and Liver Drugs .. .. . .. .. ....... .. 1294
`Blood, Fluids, Electrolytes, and Hematological Drugs ... 1318
`. . . . . .... .. .. ........... .. 1350
`Cardiovascular Drugs
`Respiratory Drugs ...... .. . . . ....... ... .. . . .. .. 1371
`Sympathomimetic Drugs ...... . ......... .. . . .... 1379
`Cholinomimetic Drugs .. . . . ... .. . ...... .... . . . . 1389
`Adrenergic Antagonists and Adrenergic
`Neuron Blocking Drugs ..... . .......... .... . .... 1399
`Antimuscarinic and Antispasmodic Drugs . ... . . .. ... 1405
`Skeletal Muscle Relaxants . . ....... .. ... ..... . . . . 1411
`Diuretic Drugs . ...... . .... . . ...... . . . ....... .. 1422
`Uterine and Antimigraine Drugs . . .. ..... .. ... . .. . 1432
`Hormones and Hormone Antagonists . .. .. . ........ 1437
`General Anesthetics
`. . .... . . . ... .. . . . ... . . . .. .. 1474
`Local Anesthetics ....... . . .. . . ..... . .......... 1479
`Antianxiety Agents and Hypnotic Drugs .. . ... . . ... . 1486
`Antiepileptic Drugs . ...... .... ... .......... .. .. 1501
`Psychopharmacologic Agents . . ....... ... ........ 1509
`Analgesic, Antipyretic, and Anti-Inflammatory Drugs ... 1524
`Histamine and Antihistaminic Drugs ... .......... .. 1543
`Central Nervous System Stimulants ........ . ... .... 1551
`Antineoplastic Drugs ....................... .. .. 1556
`lmmunoactive Drugs ........ .. . .... . .. ....... .. 1588
`Parasiticides ...... .... . .. . .. . ......... . ...... 1595
`Immunizing Agents and Allergenic Extracts .. . . .. . ... 1600
`Anti-lnfectives ..... ..... . .................... . 1626
`Enzymes ........ .... ..... . . ... .. .. .. .. ...... 1685
`Nutrients and Associated Substances ... ......... .. 1688
`. . ...... . .. .... .. ...... . .. .. . ...... 1719
`Pesticides
`
`Part 8 Pharmacy Practice
`
`A Fundamentals of Pharmacy Practice
`Application of Ethical Principles to Practice Dilemmas .. 1745
`Technology and Automation . ... .. . .. . ... .. .. . .. . 1753
`The Patient: Behavioral Determinants ....... ... . . .. 1762
`. . ........ . .... ... .... .. 1770
`Patient Communication
`Patient Compliance .... .. ....... . .... .... . .... . 1782
`Drug Education .. . . ......... .. ............ ... . 1796
`
`94
`95
`96
`97
`98
`99
`
`xxi
`
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`
`

`

`xxii
`
`CONTENTS
`
`100
`101
`102
`
`103
`104
`105
`106
`107
`108
`109
`110
`
`111
`112
`113
`114
`115
`116
`
`.. . ...... 1808
`. . . .... _ 1823
`Professional Communications . • • • · · · ·
`The Prescription . .... . . . .. .. . • • • • • · · · ·
`Providing a Framework for Ensuring
`Medication Use Safety ... • • • • · • · · · · · · · · · · · · · · · · 1840
`Poison Control . . .. . . . . . .. . . . ... .. . .. . . . • . • · · .188l
`Drug Interactions . . . . .... . . .. . . ....... .. ...... 1889
`Extemporaneous Prescription Compounding .. . .. . ... 1903
`Nuclear Pharmacy Practice
`.. .. .. . . . . . .. . .. . . . ... 1913
`Nutrition in Pharmacy Practice .... . .. . ..... . . . . . .. 1925
`Pharmacoepidemiology . . . .. . . . . . . ..... . .... .... 1958
`Surgical Supplies . . .. . .... . . . .. . ...... . . . .. . .. . 1968
`Health Accessories . .. . .. . .. . . . .... . . .. . . .... . . 1979
`B Social, Behavioral, Economic, and
`Administrative Sciences
`Laws Governing Pharmacy ... .. ...... ... . . . . .. . . 2015
`Re-engineering Pharmacy Practice .. ... . . .. .. .. . . .. 2055
`Pharmacoeconomics ... .... .. .. . .... .. . ... ... .. 2070
`Community Pharmacy Economics and Management ... 2082
`Product Recalls and Withdrawals .... . .. . . . . . .. . ... 2098
`Marketing Pharmaceutical Care Services .. . . . .. . . .. . 2107
`
`117
`
`118
`119
`
`120
`121
`122
`
`123
`124
`125
`126
`127
`128
`129
`130
`131
`132
`133
`
`t.
`s,·IIing and Reimbursement for
`21
`'
`Documen ,ng,
`Pharmaceutical Care Services
`. . . . . . . . . . . . . . . . . . . . 14
`·
`I R. k Management . . - • - - • · · · · · • • • , .2124
`PharmaceutIca
`,s
`2 ~
`Ith care Delivery Systems .. - - • • • - • . . . 1 JO
`d H
`Integrate
`ea
`c Patient Care
`· Pharmacy Practice . .. . • - - • • • - • - • • .2155
`· 1· 1·
`Speoa ,za ,on in
`Pharmacists and Disease State Management . ... .. . .. 2163
`Development of a Pharmacy Care Plan and
`Patient Problem-Solving
`. . . . - - • • • · · · · · · · · · · · · · · .2170
`Ambulatory Patient Care . . .. . .. . . • • • · · - · · · · · · · · .2 179
`Self-Care .. . .. ...... . ... .. - . . • • • - • • • • · · - - · - · .2197
`Diagnostic Self-Care ..... .. . .. . . . . - . . - .. • - . . • • .2206
`Preventive Care .. . .. . . . ... . .. . . ..... . . - • - - . - . . 2223
`Hospital Pharmacy Practice ........ .... ..... . . ... 224 7
`Emergency Medicine Pharmacy Practice .. . . . .. . .. .. 2265
`Long-Term Care . . ... ... ... .. ........ . . ... .... 2272
`Aseptic Processing for Home Infusion Pharmaceuticals .2290
`The Pharmacist's Role in Substance Use Disorders .. . .. 2303
`Complementary and Alternative Medical Health Care .. 23 18
`Chronic Wound Care . . . . .. .. .. .. ..... . . . ... ... 2342
`
`Eton Ex. 1111
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`
`

`

`Intravenous Admixtures
`
`Salvatore J Turco, PharmD, FASHP
`
`C HAPTER 42
`
`It has been estimated that 40% of all drugs administered in
`hospitals are given in the form of injections, and their use is in(cid:173)
`creasing. Part of this increase in parenteral therapy is due to
`the wider use of intravenous fluids (IV fluids). In the last
`decade the use of IV fluids has doubled, increasing from 150
`million units to 320 million units annually. Not only do IV flu(cid:173)
`ids continue to serve as the means for fluid replacement, elec(cid:173)
`trolyte-balance restoration, and supplementary nutrition, they
`also are playing major roles as vehicles for administration of
`other drug substances and in total parenteral nutrition (PN).
`Intravenous fluids are finding greater use as the means of ad(cid:173)
`ministering other drugs because of convenience, the means of
`reducing the irritation potential of the drugs, and the desir(cid:173)
`ability for continuous and intermittent drug therapy.
`The techniques for providing PN parenterally have im(cid:173)
`proved steadily in the last decade, and such use is increasing.
`The use of IV fluids for these purposes requires the compound(cid:173)
`ing of specific intravenous admixtures (parenteral prescrip(cid:173)
`tions) to meet the clinical needs of a given patient. However, the
`combination of drug substances in an IV fluid can promote par(cid:173)
`enteral incompatibilities and give rise to conditions not favor(cid:173)
`able for drug stability. A new area of specialization has been
`created for hospital pharmacists who can develop the expertise
`to prepare these solutions-recognizing their compatibility and
`stability problems and the potential for contamination-and
`participate in the administration of the solutions. The complex
`compounding of an order for PN requires knowledgeable per(cid:173)
`sonnel capable of making accurate calculations, compounding,
`and having aseptic technique. The parenteral prescription is
`becoming increasingly important in hospitals. Centralized
`admixture programs are now found in 90% of the nation's hos(cid:173)
`pitals with 300 beds or more. Equipment available for adminis(cid:173)
`tering IV fluids has become more sophisticated and has made
`possible increased accuracy of dosage and led to the develop(cid:173)
`ment of new concepts and methods of nutrition and drug
`therapy.
`E!ectronic mechanical equipment is now commonplace _in
`hospitals. Its use, as well as its sophistication, continues to m(cid:173)
`crease. Newly designed electronic pumps have been developed
`for ~ospital ambulatory use. Multichannel pumps have become
`~vailable for multiple-drug infusion. Over 500,000 implantable
`inf~sion ports have been inserted into patients and 100,000 new
`~abents receive these implantable ports each year to accomplish
`b rug ~herapy. New methods of IV drug delivery systems have
`;en i_ntroduced and are constantly evolving. The intr?ductio?(cid:173)
`0
`t rtie~t-controlled analgesia (PCA) is commonplace m hosp1-
`
`t s. This technology allows the patient with pain to control the
`
`e~~e of analgesia.
`PN e growth of PN in hospitals has been paralleled by home
`nut ~~ograms. Large numbers of patients conduct parenteral
`l'ltion in the home environment, including those with infec-
`
`tious and neoplastic diseases. More-stringent and more(cid:173)
`complete guidelines for the preparation of parenterals in hospi(cid:173)
`tals by pharm acists have been published. These guid elines,
`promoting sophisticated methods of preparation by the phar(cid:173)
`macist, have become recommendations. They are a testament
`to the importance of parenteral preparation in the institutional
`setting. Packaging of parenterals in the past 5 years al so has
`undergone dramatic changes. Prefilled, premixed, prefrozen
`parenterals are now supplied by the manufacturers. Plastic
`minibags (ADD-Vantage, Abbott ) have been introduced. Pre(cid:173)
`mixed liquids (eg, antibiotics, theophylline, heparin, lidocaine,
`dopamine) are available from parenteral manufacturers. Mul(cid:173)
`tiple-dose containers have been developed to accommodate new
`methods of preparation of parenterals by the pharmacist. The
`pharmaceutical industry has responded to the needs of phar(cid:173)
`macists by addressing the packaging, labeling, and design re(cid:173)
`quirements necessary to facilitate patient care. The parenteral
`drug industry continues its efforts to meet higher standards of
`quality and to ensure the availability of sterile and particulate(cid:173)
`free products.
`
`INTRAVENOUS FLUIDS
`Large-volume injections intended to be administered by intra(cid:173)
`venous infusion commonly are called IV fluids and are included
`in the group of sterile products referred to as large-volume par(cid:173)
`enterals. These consist of single-dose injections having a vol(cid:173)
`ume of 100 mL or more and containing no added substances.
`Intravenous fluids are packaged in containers having a capac(cid:173)
`ity of 100 to 1000 mL. Minitype infusion containers of 250-mL
`capacity are available with 50- and 100-mL partial fills for
`solution of drugs used in the piggyback technique (ie, the ad(cid:173)
`ministration of a second solution through a Y-tube in the ad(cid:173)
`ministration set of the first intravenous fluid, thus avoiding the
`need for another injection site). In addition to the IV fluids, this
`group also includes irrigation solutions and solutions for dialy(cid:173)
`sis.
`Intravenous fluids are sterile solutions of simple chemicals
`such as sugars, amino acids, or electrolytes-materials that
`easily can be carried by the circulatory system and assimilated.
`Prepared with Water for Injection USP, the solutions are
`pyrogen-free. Because of the large volumes administered intra(cid:173)
`venously, the absence of particulate matter assumes a signifi(cid:173)
`cant role in view of possible biological hazards resulting from
`insoluble particles. Absence of particulate matter or clarity of
`IV fluids is as important at the time of administration following
`their manipulation in the hospital as it is at the time of manu(cid:173)
`facture of the injection.
`Limits for particulate matter occurring in IV fluids or large(cid:173)
`volume injections used for single-dose infusion are defined in
`
`837
`
`Eton Ex. 1111
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`
`

`

`838
`
`PART 5: PHARMACEUTICAL MANUFACTURING
`
`the USP. This represents the first regulatory attempt to define
`limits for particulate matter in parenterals. Limits also ~pply
`to multiple-dose injections, small-volume injections, or mJeC(cid:173)
`tions prepared by reconstitution from sterile solids. The USP
`defines particulate matter as extraneous, mobile, undissolv:d
`substa nces, other than gas bubbles, unintentionally present m
`parenteral solutions. The total numbers of particles having ef(cid:173)
`fective linear dimensions equal to or larger than 10 µm and
`larger than 25 1.1.m are counted. The IV fluid meets the require(cid:173)
`ment of the test ifit contains not more than 50 particles per mL
`that are equal to or larger than 10 1.1.m and not more than 5 par(cid:173)
`ticles per mL that are equal to or larger than 25 µm in linear
`dimension.
`Intravenous fluids commonly are used for a number of clini(cid:173)
`cal conditions. These include:
`
`Correction of disturbances in electrolyte balance.
`Correction of disturbances in body fluids (fluid replacement).
`The means of providing basic nutrition.
`The basis for the practice of providing PN.
`Vehicles for other drug substances.
`
`In both of the latter two cases it has become common practice to
`add other drugs to certain IV fluids to meet the clinical needs of
`the patient. Using IV fluids as vehicles offers the advantages
`of convenience, the means ofreducing the irritation potential of
`the drug, and a method for continuous drug therapy. However,
`the practice requires that careful consideration be given to the
`stability and compatibility of additives present in the IV fluids
`serving as the vehicle. This approach also demands strict ad-
`
`herence to aseptic techniques in _adding the drugs us
`the administration of the IV flmds. Th:se procedur/'eli asi
`cussed later in the chapter. The IV flmds common] s are din
`Y llst'{j ri·
`arenterals are shown m Tabl~ 42-1.
`.
`P Many disease states result !n electrolyte depletio
`t
`Proper electrolyte concentrat10n and ?alance in p]:~ndlo,
`tissues are critical for pro~er body functJ~n . Electrolyte~rn.a and
`tion and balance are ach1_eved most rap1dl!' through restora.
`tration of IV fluids. _Reqmred ele~trolytes Include Sod~dtnini,.
`chloride ions, which m normal salme m?re closely ap r u~ and
`the composition of the e~tracellular_flu_1d t~an soluti~n~X1rna~
`other single sa!t; potassmm, the prmc1pal intracellular ~f ~1y
`of most body tissues and essential for the functionin cation
`nervous and muscular systems as well ~s the heart• g of tfit
`sium, as a nutritional supple~ent es~ec1ally in PN ;0~a_gn,_
`and phosphate ion, important ma variety ofbiochemica]horl.l;
`tions. In addition to the number of standard electrolyte reat.
`shown in Table_ 42-1, a large ~umber of c?mbinations 0fu1i],
`trolytes in varymg concentrat10ns are available com
`_~let.
`Some of these electrolyte fluids als_o contain dextrosterciaUy,
`IV fluid, either _for nutntI~n. or for _flmd replacemen{ r~
`Dextrose Injection 5%_ (_D5/W) 1s the ?1ost frequent! ,
`slightly hypotomc and admm1s te:ed mtravenously into a I
`ripheral vein; 1 g of dextrose provides 3.4 cal, and 1 L ofD5~:
`supplies 170 Kcal. _The body uses dextrose ~t a rate of O 5 ~
`per kg of body weight per hour. More-rapid administ ·. g
`can result in glycosuria. Therefore, 1 L of D5/W require:~t:
`hr for assimi~ation. The pH. rang~ of D5/W can vary from 3 5
`to 6.5. The wide range permitted 1s due to the free sugar acids
`
`IS
`
`Table 42-1. Fluids Used Commonly for IV Use
`
`INJECTION
`Alcohol
`with D5/Wa
`with D5/W in NSSb
`Amino acid (synthetic)
`Aminosyn II (Abbott)
`FreAmine Ill (B.Braun)
`Travasol (Baxter)
`Ammonium chloride
`Dextran 40
`in NSS
`in D5/W
`Dextran 70
`in NSS
`in D5/W
`Dextrose (glucose, D5/W)
`Dextrose and sodium
`chloride
`
`Lactated Ringer's (Hartmann's)
`NaCl
`KCI
`CaCl2
`Lactate
`Mannitol, also in combination
`with dextrose or sodium chloride
`
`Multiple electrolyte solutions,
`varying combinations of
`electrolytes, dextrose,
`Ringer's
`NaCl
`KCI
`CaCl2
`Sodium bicarbonate
`Sodium chloride
`Sodium lactate
`Sterile water for injection
`
`~ 5% Dextrose in water.
`b Normal saline solution.
`
`CONCENTRATION(%)
`
`5
`5
`
`3.5, 7, 8.5, 10, 15
`8.5, 10
`3.5, 5.5, 8.5. 10
`2.14
`
`10
`10
`
`6
`6
`2.5-50
`Varying concn of dextrose, 5-20
`with varying concn of sodium'
`chloride 0.22-0.9
`
`0.6
`0.03
`0.02
`0.3
`5
`15
`20
`
`0.86
`0.03
`0.033
`5
`0.45, 0.9, 3, 5
`1/6 M
`
`PH
`
`4.5
`
`5.25
`6.6
`6.0
`4.5-6.0
`
`5
`4
`
`5
`4
`3.5-6.5
`3.5-6.5
`
`6.0-7.5
`
`THERAPEUTIC USE
`
`Sedative, analgesic, calories
`Sedative, analgesic, calories
`Fluid and nutrient replenisher
`
`Metabolic alkalosis
`
`Priming fluid for plasma volume expander
`Priming fluid for plasma volume expande1
`
`Plasma volume expander
`Plasma volume expander
`Fluid and nutrient replenisher
`.
`Fluid, nutrient, and electrolyte replenisher
`
`Systemic alkalizer; fluid and electrolyte
`replenisher
`
`5.0-7.0
`
`Osmotic diuresis
`
`5.5
`
`5.0-7.5
`
`8
`4.5-7.0
`6.3-7,3
`s.s
`
`Fluid and electrolyte replacement
`
`Fluid and electrolyte replenisher
`
`Metabolic acidosis
`Fluid and electrolyte replen!sh:~
`Fluid and electrolyte replenish
`Diluent ~
`
`Eton Ex. 1111
`6 of 14
`
`

`

`rable 42.2. IV Fluid Systems
`- - -
`CONTAINER
`~
`Glass
`aaxter
`
`eaxter (Via flex)
`
`a.Braun
`
`a.Braun (Excel)
`Abbott
`
`Abbott (Lifecare)
`
`Plastic
`
`Glass
`
`Plastic
`Glass
`
`Plastic
`
`• Part of administration set.
`
`CHARACTERISTICS
`Vacuum
`Air tube
`Polyvinyl chloride
`Flexible
`Nonvented
`Vacuum
`Air tube
`Flexible
`Vacuum
`Air filtera
`Polyvinyl chloride
`Flexible
`Nonvented
`
`present and form~d ~uring th~ s_t~r_ilization and storage of the
`injection. To avmd mcompatib1h~ies_ when other drug sub(cid:173)
`stances are ad~ed to J?extr~se I_nJect10n, the possible low pH
`should be considered m usmg it as a vehicle. More-concen(cid:173)
`trated solutions of dextrose are available and provide
`increased caloric intake with less fluid volume. Being hyper(cid:173)
`tonic, the more concentrated solutions may be irritating to
`peripheral veins. Highly co_ncentrated solutions are adminis(cid:173)
`tered in a larger central vem.
`Intravenous fluids containing crystalline amino acids can
`provide biologically usable amino acids for protein synthesis
`(Chapter 106). Protein contributes to tissue growth, wound re(cid:173)
`pair, and resistance to infection. The protein requirement for
`the normal adult is 1 g per kg per day; children and patients
`under stress require greater amounts. Attempts are made to
`maintain a positive nitrogen balance, indicating that the pro(cid:173)
`tein administered is being used properly and not broken down
`and eliminated through the urine as creatinine and urea,
`which are normal waste products. In a positive nitrogen bal(cid:173)
`ance patients are taking in more nitrogen than they are elim(cid:173)
`inating. In a negative nitrogen balance there is more nitrogen
`being eliminated through the urine regularly than is being ad(cid:173)
`ministered intravenously. This means that tissues are contin(cid:173)
`uing to be torn down, and repair is not necessarily taking
`place. Amino Acid Injection can afford the total body require(cid:173)
`ments for proteins by the procedure known as PN (discussed
`below) or be used for supplemental nutrition by peripheral ad(cid:173)
`ministration. In addition to the amino acids, these nutritional
`injections also may contain dextrose, electrolytes, vitamins,
`and insulin. Fat emulsion (Intralipid, Baxter; Liposyn II, Ab(cid:173)
`bott) sometimes is used concurrently but usually administered
`at Y-site. However, new systems such as three-in-one packag(cid:173)
`ing permit mixing of amino acids, carbohydrates, and fat in
`one container for PN.
`
`Packaging Systems
`Containers for intravenous fluids must be designed to maintain
`solution sterility, clarity (freedom from particulate matter), and
`nonpyrogenicity from the time of preparation, through storage,
`and during clinical administration. Container closures must be
`designed to facilitate insertion of administration sets through
`~vhich the injections are administered at a regulated flow-rate
`into suitable veins. IV fluids are available in glass and plastic
`~ontainers; the latter are made from a flexible plastic material.
`V fluids are supplied in 1000-mL 500-mL and 250-mL sizes in
`add' ·
`'
`·
`L ihon to 250-mL capacity containers packaged with 50 or 100
`: a of~?IW or sodium chloride injection 0.9% for piggybac~ ~se
`t.. ddihon to 0.45% sodium chloride and 2.5% dextrose mJec-
`10118 IV fl ·a ·
`·
`wh· h ui s m glass con tamers are pac age un er vacuum,
`k
`d d
`gl ic mus~ be dissipated prior to use. For fluid to leave the IV
`rn ~s~ co?tamer and flow through the administration set, some
`ec anism is necessary to permit air to enter the container.
`
`CHAPTER 42: INTRAVENOUS ADM IXTURES
`
`839
`
`Current flexible plastic systems do not require air introduction
`to function. Atmospheric pressure pressing on the container
`forces the fluid to flow.
`All glass and plastic containers are single-dose and should
`be discarded after opening even if not used. Intravenous fluids
`are packaged with approximately 3% excess fill to allow for re(cid:173)
`moval of air from the administration set and permit the labeled
`volume to be delivered from the container. The containers are
`graduated at 20-mL increments on scales that permit the vol(cid:173)
`ume in a container to be determined from either an upright or
`inverted position. Glass containers have aluminum and plastic
`bands for hanging, while plastic containers have eyelet open(cid:173)
`ings or plastic straps for attachment to IV poles.
`Fluids for IV use are available from three sources (Abbott,
`Baxter, and B.Braun ); all provide both glass and plastic con(cid:173)
`tainers. The glass-container systems of Baxter and B.Braun are
`similar. The characteristics of current packaging systems are
`summarized in Table 42-2.
`
`Administration Sets
`Administration sets used to deliver fluids intravenously are
`sterile, pyrogen-free, and disposable. Although these sets are
`supplied by different manufacturers, each for its own system,
`they have certain basic components. These usually include a
`plastic spike to pierce the rubber closure or plastic seal on the
`IV container, a drip (sight) chamber to trap air and permit ad(cid:173)
`justment of flow rate, and a length (150 to 450 cm) of polyvinyl
`chloride (PVC) tubing terminating in a gum-rubber injection
`port. Non-PVC sets are available for special uses. At the tip of
`the port is a rigid needle or catheter adapter. An adjustable
`clamp (screw or roller type) on the tubing pinches the tubing to
`regulate flow . Since the Y-site port is self-sealing, additional
`medication can be added to the IV system at these ports of en(cid:173)
`try. Glass containers that have no air tubes require air-inlet fil(cid:173)
`ters designed as part of the administration set (Abbott ). See
`Figures 42-1 to 42-6.
`
`Administration Procedures
`In the administration of IV fluids, the primary IV container
`provides for fluid replacement, electrolyte replenishment, drug
`therapy, or nutrition; the fluid can be infused usually over a 4-
`to 12-hr period. In some cases an IV fluid is infused slowly for
`the purpose of keeping the vein open (KVO). This will allow ad(cid:173)
`ditional drugs to be administered when required. The primary
`IV fluid also can serve as a vehicle for other drugs to be admin(cid:173)
`istered, thus becoming an intravenous admixture (IV drip), and
`
`I
`Air
`vent
`
`-Drip
`chamber
`
`- Clomp
`
`-
`
`Tubing
`
`Figure 42-1. Parts of basic administration sets.
`
`Eton Ex. 1111
`7 of 14
`
`

`

`t•J\111
`
`I'll ttM LLU II
`
`A 1u111NG
`l Mi\Nl) I
`
`Tor(IOI 01 0 1,1
`(for IV 11plko)
`
`olld rubbOf
`Stopporb ponotrotod
`(connot o
`oy noodlo)
`
`A
`
`)
`
`1000 llil.
`
`GOO rnl.
`
`250 ml copaolly
`(Plggybnck)
`
`l il t• ,111 vcntin\J is provid •tl
`,t IIH'r
`riu11u ,U-2 .. ,\bl) II IV \!1.1,~ ,~'. :,11ke ·of tl ;e ,1d111i11I tration ct. Sec
`lhn uoh till' ,11r l1II L•r lo o1 l t 111 11.
`l 11 )l lll' •' · I.
`
`f
`
`11 , I di·uJ.!~ 011cu tho
`111 1 u
`'
`. I
`
`I
`I
`t't•::1tll :-1 in 1·1111ti1111011:-1 hloorl
`tJ \'P s 11
`lt1~hwrntcd PVC pro(htr ts Jll'O(hl C( hydro~c\chlol'J( O uns ns
`~11•i1<lv 1~1111
`Im~ h1•1•11 renchl'd,
`'
`11 toxic pol111t1111t llieth ylh1•xvlphthnl11tu (Dblll ), n component
`f P\I ~ c1111tni11c;·:-1
`11111v h•m·i1 into the :-ioil in lnndfills. A nu~n-
`1:"r of tlrntii. nd::;o,:b 01{ P\I ' 1·011tni11 rs, 1_wt11l>ly ni troglycerm.
`Some d,·11,zs (f:\t e11u11flio11 s, bloorl, Pnclttnxul) nre known to
`h•nrh J>l-:111'.
`.
`.
`. .
`.
`'l'he 1':xt:l'I cont,1i11cr i::i clnimctl to ul1111111nt~ ~)I' 1111mm1ze
`tlu•:-1L' pl'tlble11\l:l, The plnstic film c~nt11ins 110 plnst1c1zo~·s nnd ex(cid:173)
`hibit ~ 1w knchnbilit y. Th<' soluturn-contnct lny~r o! the con~
`tniner i1: rompo:-11'1! of n rubberized copolymor o! othylon_e an~l
`propylene, which i1: dainwd to be clear, nontoxic, nnd b10log1-
`rnlly i,wrt. Tlw co11t:1inor is nvnilnblo in 260-mL, 500-mL, and
`J.t,' :-izt•~. 8111:1lll1r ~i zcs :iro av:1il11blo in 26, GO, and 100 mL
`known 111: PAU contain •rs.
`111 prqmring nn IV fluid for ndministrntion, the following
`}ll'lll'clhn·l• is \l f;t'd.
`
`Th,i spike :11lnpll'l' of the ndmini