Clinical Pharmacology & Therapeutics: Proceedings of Plenary Lectures Symposia and Therapeutic Sessions of the First World Conference on Clinical Pharmacology & Therapeutics London, UK, 3–9 August 1980

568 Pages·1980·61.886 MB·English

by  P. Turner, C. Padgham, A. Hedges (eds.)

Clinical Pharmacology &Therapeutics
WORLDCONFERENCEON CLINICAL
PHARMACOLOGY&THERAPEUTICS
Sponsoredby theInternationalUnion 0/
PharmacologyandtheBritish PharmacologicalSociety
Patron: HerMajesty TheQueen
President: SirArnold BurgenFRS
Chairman: ProfessorColinDollery
OrganisingCommittee
ProfessorA. M. Barrett
Dr T. B.Binns
MissD.Boland
ProfessorA.M. Breckenridge
ProfessorJ. Crooks
DrC.C.Downie
ProfessorD. G.Grahame-Smith
ProfessorD. R. Laurence
DrP.J.Lewis
ProfessorD.G.McDevitt
ProfessorM.D. Rawlins
ProfessorP. Turner
ii
Clinical Pharmacology
&Therapeutics
Proceedings ofPlenaryLectures
Symposia and Therapeutic Sessions
oftheFirst World Conference on
ClinicalPharmacology& Therapeutics
London, UK,3-9August1980
Editedby
P. TURNER
Executiveeditors
c.
PADGHAM
A. HEDGES
M
MACMILLAN PUBLISHERS
©Thecontributors1980
Softcoverreprintofthehardcover1stedition 1980978-0-333-31229-2
Allrightsreserved.No part ofthispublicationmaybereproducedortransmitted,
inany formorbyanymeans, withoutpermission
Firstpublished1980by
Scientific&MedicalDivision
MACMILLANPUBLISHERSLTD
LondonandBasingstoke
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Typeset in GreatBritain by
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ISBN978-1-349-05954-6 ISBN978-1-349-05952-2(eBook)
DOI 10.1007/978-1-349-05952-2
This book issoldsubjecttothestandardconditionsoftheNetBookAgreement
IV
CONTENTS
PLENARYLECTURES
TheEthicaland ScientiücBasis ofRegulation Prof.L. Lasagna,USA 3
PredictiveValueofPre-Clinical Drug Prof.G. Zbinden,
SafetyEvaluation Switzerland 9
ThePharmacologyandC1inicalPotential Dr. S.Moncada&
ofProstacyclin Dr.J.R. Vane,UK 15
PossiblePhysiologicalRoles ofthe Prof. H. W. Kosterlitz,
Enkephalinsand Endorphins UK 33
ENVIRONMENTALANDGENETIC
FACTORSIN DRUGMETABOLISM
Chairmen:A. H. Conney,USA,
R. Kato, Japan
DedicationoftheSymposiumto
Dr. BernardB. Brodie
VariabilityinHumanDrugMetabolism A.H.Conney,
E.J. Pantuck,
C.B.Pantuck,
J.G.Fortner,
A. P.Alvares,
K. E.Anderson&
A. Kappas 51
Gene-EnvironmentInteractionsin
DrugMetabolism E.S.Vesell 63
ImportanceofPurifrcationofHepatic
CytochromeP-450forStudyingDrug R. Kato&
MetabolisminMan T. Kamataki 80
v
vi CONTENTS
THERAPEUTICSAT THEEXTREMES
OFAGE
Chairmen: A. Rane,Sweden,
K.O'Malley,Eire
BiologicalAgeing R. D. T.Cape 89
DrugMetabolismat VariousAges- Young A.Rane 98
MethodologicalProblemsAssociatedwith
StudiesofDrugMetabolisminthe Elderly R. E. Vestal 108
Renal EliminationofDrugsat Various Ages A. H. Neims 117
Responsivenessto Drugsat ExtremesofAge K. O'Malley&
J. G. Kelly 124
ALTERATIONSINRECEPTORSDURING
CHRONICDRUGTHERAPY
Chairmen: D. Grahame-Smith,UK
J.Oates,USA
TheEffectsofDigoxinon Red Cell Digitalis
Receptor Functionin Man J.K. Aronson 135
Mechanismsfor Regulationofß-Adrenergic
Receptor Functionin Desensitization R.J. Lefkowitz 145
ReversalofPharmacologicaland Biochemical
EffectsofNeurolepticDrugson C. D. Marsden&
ChronicAdministration P.Jenner 154
a-Adrenoceptorsand the Clinical S.Z.Langer&
PharmacologyofClonidine R. Massingham 158
TheEffectofOralContraceptiveson Platelet J. R. Peters,
Noradrenalineand 5-Hydroxytryptamine J.M.Elliott&
Receptorsand Aggregation D. G. Grahame-Smith 165
Assessmentofß-Adrenoceptor
Down-Regulationin Man A. J.J.Wood 175
INOTROPICAGENTS AND
VASODILATORS
Chairmen: L. I. Goldberg, USA
J. N. Cohn, USA
InotropicAgents: An Overview L. I.Goldberg&
S.I. Rajfer 181
InotropicDrugsinClinical Practice J.Coltart&
P.Willicombe 188
CONTENTS vii
ANTIPLATELET DRUGSAND
ANTITHROMBOTICCHEMOTHERAPY
Chairmen:J. F. Mustard,Canada
M. Verstraete, Belgium
TheMechanismofAction ofDrugsthat Modify M. A. Packham&
Plateletand Vessel Wall Function 1.F.Mustard 197
TheEffectsofPlateletRegulatory Drugsin
ExperimentalModelsofThrombosis A.M.White&
Atherosclerosisand Myocardial Infarction K. D.Butler 213
TheEffectivenessofDrugsthatModify Platelet
Functionin Peripheral VenousThrombosis
and PulmonaryEmbolism A. G. G. Turpie 224
BasicCurrentEvidenceforthe UseofDrugs
to Both Preventand TreatPatientswith
VenousThrombosisand Pulmonary
c.
Embolism V. Ruckley 234
TheValueofDrugsthatModify Platelet
and Vessel Wall Functionfor the
ClinicalComplicationsofAtherosclerosis G. P. McNicol 242
THERAPYOFHYPERTENSION
Chairmen:J. Koch-Weser,France
A. Zanchetti,Italy
IndividualizationofAntihypertensiveTreatment 1. Koch-Weser 251
Doesthe AssayofCatecholamineLevels
Contributetothe Tailoringof W. H. Birkenhäger&
AntihypertensiveTreatment? P.W.de Leeuw 256
ß-AdrenoceptorBlockingDrugsand the 1.Menard,
Renin-AngiotensionSystem P. Bautier,
P.F. Plouin,
M.Thibonnier&
P.Corvol 264
Rational ApproachestoClinicalTherapy A.Zanchetti 270
viii CONTENTS
PHARMACOLOGYANDTHERAPEUTICS
OFANTIRHEUMATICDRUGS
Chairmen:W. Buchanan,Canada
H. Paulus,USA
TheTherapeuticandToxicEffects of
Anti-InflammatoryDrugsWhichInterfere G.A.Higgs&
withArachidonicAcidMetabolism B.J.R.Whittle 277
ClinicalEffects and Interactionsofthe
Non-SteroidAnti-InflammatoryDrugs P. M.Brooks 288
SpecificTherapyfor RheumatoidArthritis E.C. Huskisson 298
ImmunologicalModificatlontoTreat
RheumatoidArthritis P.H.Plotz 304
PAIN
Chairmen:J. D. Loeser,USA
D. G. Albe-Fessard,France
Perspectiveson Pain J. D.Loeser 313
NociceptivePathwaysandTransmitters H. O. Handwerker 317
AnalgesiaProducedbyStimulationofthe R.L. Nahin&
NervousSystem J.C.Liebeskind 328
EndorphinsandCentralNeurotransmitters
inClinicalPain L. Terenius 338
PsychologicalAspectsofPain M.Bond 345
DRUGDEPENDENCE
Chairmen:L.Lemberger,USA
E.Änggärd,Sweden
Clinical PharmacologicalActions and
PotentialTherapeuticEffects ofMarihuana
and RelatedDrugs L. Lemberger 353
Alcohol: TheOld Rascal inNewClothes J.ldänpään-Heikkilä 360
ClinicalPharmacologyofBenzodiazepine
Dependence P.Tyrer 368
Relationshipof p-EndorphininPhysical
Dependence E.L. Way 373
MethadoneMaintenanceTreatmentof E. Änggärd,
HeroinAddictioninSweden I-M.Nilsson,
L. Grönbladh&
L-M.Gunne 382
CONTENTS ix
CLINICALPHARMACOLOGYOF SKIN
Chairmen:S. Shuster,UK
H. Schaefer, France
PrinciplesofPercutaneousAbsorption H.Schaefer,
G.Stullegen,
W.Schalla,
J.Gazilla&
E.Bauer 395
Biochemical Pharmacologyofthe Epidermis E.A.Duell 404
Drug MetabolisminSkin D.Rawlins,
S.Shuster,
P. H.Chapman,
V.Shaw&
V.A.ü'Neill 410
UV Inflammationand Anti-Inflammatory
Drugs M.W.Greaves 415
Objective ComparisonoftheResponseof S.Shuster,
PsoriasistoTreatmentwithPUVAand M. Rawlins,
Dithranol S.Rogers,
B.Chadkirk,
J. Marks &
J.S.Comaish 421
PHARMACOLOGICALASPECTSOF
ANTICANCERCHEMOTHERAPY
Chairmen:J. Bertino, USA
D. Crowther,UK
Recent StudiesonBleomycin H.Umezawa 427
RegressionAnalysisof4'-(9-Acridinylamino)
Methanesulphon-m-Anisidine(m-AMSA) B.F.Cain,
Analogue Properties ProvidingHigh Dose B.C.Baguley
PotencyinLeukaemiaL1210Assays W.A.Denny&
G. J.Atwell 436
THERAPYOFTROPICALDISEASES
Chairmen: A.O. Lucas,Switzerland,
N. D. W. Lionel,SriLanka
TherapyofTropicalDiseases- Schistosomiasis J.M.KoflEkue 445
TherapyofTropical Diseases- Filariasis K.Awadzi 449