Physiological Pharmaceutics

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Chapter TenPulmonary Drug DeliverySTRUCTURE AND FUNCTION OF THE PULMONARY SYSTEMThe lungUpper airwayStructure of the tracheo-bronchial treeEpitheliumUpper airwaysBronchi and bronchiolesAlveoliAlveolar-capillary membraneLung permeabilityLung mucusLung defensesLung surfactantBlood supplyLymphatic systemNervous controlCough reflexBiochemical processes which occur in the lungBreathingRespiratory diseaseAsthmaAcute bronchitisChronic bronchitisPulmonary emphysemaBronchiectasisDOSAGE FORMS FOR PULMONARY DRUG DELIVERYPressurized inhalation aerosolsDry powder inhalersNebulizersSpacer devices and ancillary equipmentASSESSMENT OF DEPOSITION BY GAMMA SCINTIGRAPHYChoice of radiolabelLabeling inhalation formulationsLabeling dry powder inhalersValidationFACTORS AFFECTING PARTICLE DEPOSITION IN THE LUNGPhysicochemical propertiesDeposition patterns from different dose formsPhysiological variablesInhaler techniqueEffects of diseaseDRUG ABSORPTIONPHARMACOKINETICS221
222 Physiological PharmaceuticsDRUGS ADMINISTERED VIA THE PULMONARY ROUTEAnti-allergy agentsBeta receptor agonistsAdrenocorticosteroidsLeukotriene inhibitorsOther bronchodilating agentsMucolyticsSystemically-absorbed drugsREFERENCESSTRUCTURE AND FUNCTION OF THE PULMONARY SYSTEMThe major function of the pulmonary system is the oxygenation of blood and the removalof carbon dioxide from the body. Breathing ventilates the respiratory tissue leading togaseous exchange in the lungs. The tissue is therefore specialized to present the largestavailable surface area within the protection of the thoracic cavity. The large oxygenrequirement is necessary to support the high metabolic rate of mammals.The respiratory system in man is divided into the upper and lower respiratory tracts.The upper respiratory tract consists of the nose, nasal passages, paranasal passages, mouth,Eustachian tubes, the pharynx, the oesophagus and the larynx. The trachea and bronchi aresometimes included as part of the upper respiratory tract. The lower respiratory tractconsists of the true respiratory tissue, i.e. the air passages and alveoli.The lungThe organ lung comprises of a left and right lung, divided in slightly unequal proportionsthat occupy most of the intrathoracic space. The right lung represents 56 percent of the totallung volume and is composed of three lobes, a superior, middle, and inferior lobe, separatedfrom each other by a deep horizontal and an oblique fissure. The left lung, smaller in volumebecause of the asymmetrical position of the heart, has only two lobes separated by anoblique fissure. The space between the lungs is filled by a connective tissue space containingthe heart, major blood vessels, trachea with the stem bronchi, oesophagus and thymusgland. In the thorax, the two lungs rest with their bases on the diaphragm, while their apicesextend above the first rib.Upper airwayAs discussed in Chapter 9, the function of the nose is to provide humidification, filtrationand warming of the inspired air. Although the nose is designed as the primary route of entryfor gases, most people also breathe through the mouth, particularly during stress. In thiscase many of the nasal defensive pathways are lost. Hence the lung also has to havemechanisms to condition the air and remove foreign particles.The nasopharynx is primarily a passageway from the nose to the oral pharynx for airand secretions. It is also connected to the tympanic cavity of the middle ear through theauditory tubes that open on both lateral walls. The act of swallowing briefly opens thenormally collapsed auditory tubes and allows the middle ears to be aerated and pressuredifferences to be equalized. In the posterior wall of the nasopharynx is located a lymphaticorgan, the pharyngeal tonsil.The larynx is an organ of complex structure that serves a dual function: as acontrolling air canal to the lungs and as the organ of phonation. Below the larynx lies thetrachea, a tube about 10 to 12 centimetres long and two centimetres wide. Its wall isstiffened by 16 to 20 characteristic horseshoe-shaped, incomplete cartilage rings that open
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For Alexander and SarinaWith all ou
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First edition 1989Second edition fi
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viPrefacepublishers, who I am sure,
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viiiAcknowledgementsFig 6.5 is repr
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Table of Contents1. Cell Membranes,
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xiiContentsGASTRIC pH .............
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xivContents9. Nasal Drug Delivery .
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Chapter OneCell Membranes, Epitheli
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Membranes and barriers 3Figure 1.1
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Membranes and barriers 5Modulation
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Membranes and barriers 7Membrane pr
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Chapter TwoParenteral Drug Delivery
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Parenteral drug delivery 21Figure 2
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Parenteral drug delivery 23catheter
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Parenteral drug delivery 29fluid is
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Parenteral drug delivery 33Receptor
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Parenteral drug delivery 3526. Tsuj
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38 Physiological PharmaceuticsANATO
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40 Physiological PharmaceuticsFigur
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42 Physiological Pharmaceuticsgland
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44 Physiological PharmaceuticsABSOR
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48 Physiological Pharmaceuticsa) in
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52 Physiological Pharmaceuticsin de
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56 Physiological Pharmaceutics8. We
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58 Physiological Pharmaceutics59. A
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60 Physiological PharmaceuticsINTRO
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64 Physiological PharmaceuticsTable
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66 Physiological Pharmaceuticsliqui
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70 Physiological PharmaceuticsTable
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72 Physiological Pharmaceutics12. W
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Chapter FiveThe StomachANATOMY AND
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The stomach 77Figure 5.2 Structure
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The stomach 79Gastric glandsThe gas
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The stomach 81Figure 5.7 Mechanism
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The stomach 83absorbed from the sto
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The stomach 85Night-time transient
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The stomach 87particle size indiges
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The stomach 89Figure 5.13 MRI cross
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The stomach 91species and man is po
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The stomach 93Figure 5.15 The effec
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The stomach 95emerged from the shel
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The stomach 97Figure 5.17 The gastr
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The stomach 99In order to improve b
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The stomach 101Figure 5.21—Gastri
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The stomach 103The anatomy and dime
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The stomach 10533:1283-1290.35. Cun
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The stomach 10782. Ingani HM, Timme
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Chapter SixDrug Absorption from the
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Small intestine 111Figure 6.1 Secti
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Small intestine 113are uncommon and
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Small intestine 115underlying tissu
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Small intestine 117Brief periodic b
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Small intestine 119is extremely rap
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Small intestine 121Figure 6.5 Segme
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Small intestine 123Measurements of
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Small intestine 125Figure 6.8 Small
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Small intestine 127Scintigraphy oft
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Small intestine 129It is known that
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Small intestine 131It was soon real
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Small intestine 133colonic absorpti
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Small intestine 135also transform d
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Small intestine 137REFERENCES1. Bry
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Small intestine 13949. Hidalgo IJ,
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Small intestine 14193. Bogentoft C,
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144 Physiological PharmaceuticsAnti
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146 Physiological PharmaceuticsFigu
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148 Physiological Pharmaceuticsto t
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150 Physiological Pharmaceuticssodi
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Page 266 and 267: Chapter ElevenOcular Drug DeliveryI
Page 268 and 269: Ocular drug delivery 251STRUCTURE O
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Page 272 and 273: Ocular drug delivery 255The superfi
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Page 276 and 277: Ocular drug delivery 259Figure 11.9
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Chapter TwelveVaginal and Intrauter
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Vaginal and intrauterine drug deliv
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284 GlossaryAntipyrine An analgesic
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286 GlossaryClonazepam An anticonvu
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288 GlossaryEsterase An enzyme whic
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290 Glossaryfound in the synovial f
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294 GlossaryPectoral muscle Chest m
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296 Glossarysize exclusion (gel fil
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298 GlossaryTributyrase An enzyme w
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300 Indexß-glucuronidase 276B cell
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302 IndexDiazoxide 262Dichlorodiphe
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304 IndexGelling polymers 264Gels 1
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306 IndexEpithelium 225Factors affe
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308 IndexOros ® 158Osmotic deliver
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310 IndexAbsorption 186Age 188Disea
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312 IndexDrug absorption 277Fluid 2
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