BRITISHMEDICALJOURNALVOLUME2869APRIL1983Theclassicalalphablockersphentolamineandphenoxybenzamineaffectbothalphareceptorsandalpha2receptorsPRAZOSINHYPOVASEMINIPRESSPrazosinisaquinazolinederiva ID: 855556
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1 1192BRITISHMEDICALJOURNALVOLUME2869APRIL
1192BRITISHMEDICALJOURNALVOLUME2869APRIL1983whosepotassiumconcentrationsaremoderatelyraisedandinwhomthereisnoelectrocardiographicupset.Weconcludethatalthoughhyperkalaemiaiscommoninpatientsinhospital,itisrarelylifethreatening.Thosewithrapidlyincreasingpotassiumconcentrations,inthepresenceofrenalfailure,aremostatriskofdevelopingpotassiumcardio-toxicity.Patientsinthishighriskgroupshouldundergocon-tinuousbiochemicalandelectrocardiographicmonitoring.Acutecardiactoxicityinducedbyhyperkalaemiashouldbereversedpromptlywithcalciumgluconate,whilesevereab-normalitieswillrespondreadilytoglucoseandinsulintreatment.Cationexchangeresinsshouldbeusedtocorrectmoderatehyperkalaemiaduetoexcesspotassiumloadinganddialysiswhenhyperkalaemiaissevereorduetodiminishedpotassiumexcretion.ReferencesStephenST,DluhyRG.Hyperkalaemiaandhypokalaemia.JAMA1975;6:631-3.2LawsonDH.Adversereactionstopotassiumchloride.QJMed1974;171:433-40.3GreenblattDJ,Koch-WeserJ.Adversereactionstospironolactone.JfAMA1973;1:40-3.4LawsonDH,O'ConnorPC,JickH.Drugattributedalterationsinpotassiumhandlingincongestiveheartfailure.EurJfClinPharmacol1982;23:21-5.5BronsonWR,DeVitaVT,CarbonnePP,CotloveE.Pseudohyper-kalaemiaduetoreleaseofpotassiumfromwhitebloodcellsduringclotting.NEnglJ3Med1966;274:369-75.6HartmannRC,MelinkoffSM.Therelationshipofplateletstotheserumpotassiumconcentration.JClinInvest1955;4:938-40.7HeasmanMA.Scottishhospitalinpatientstatistics-sourcesanduses.HealthBull1968;26:10-3.8LawsonDH,HenryDA,LoweJM,GrayJMB,MorganHG.Severehypokalaemiainhospitalisedpatients.ArchInternMed1979;139:978-80.LevinskyNG.Managementofemergencies:VIhyperkalaemia.NEnglJMed1966;274:1076-7.10ShapiroS,SloneD,LewisGP,JickH.Fataldrugreactionsamongmedicalinpatients.JAMA1971;3:467-72."AlbertiKGMM.Lowdoseinsulininthetreatmentofdiabeticketoacidosis.ArchInternMed1977;137:1367-76.12SurawiczB,ChlebusH,MazzoleniA.Haemodynamicandelectro-cardiographiceffectsofhyperpotassaemia.DifferencesinresponsetoslowandrapidincreasesinconcentrationofplasmaK.AmHeartJ1967;73:647-51.(Accepted9February1983)NezoDrugsAlpha-blockersandconvertingenzymeinhibitorsPCRUBIN,JLREIDAlpha-blockersandconvertingenzymeinhibitorshavebeenintroducedforthetreatmentofhypertensionandmorerecentlyinrefractorycongestivecardiacfailure.Thesedrugscausedilatationofboththearterialandvenoussideofthecirculationbyspecificmechanisms:antagonismofcatecholaminesatalphareceptorsandpreventionofangiotensinIIgenerationrespectively.Theprincipalroleofthesedrugsatpresentisinthemoresevereorresistantgradesofhypertension.Severalnewtreatmentstrategieshaveemerged,however,forthemanagementofcongestivecardiacfailure.Traditionaltherapeuticapproacheshaveincludedtheuseofdiureticsandcardiacglycosides.Inaddition,drugtreatmentisnowusedalsotoproducevaso-dilatation.Onthearterialsideofthecirculationthiswillreducetheloadagainstwhichtheheartmustpump(afterload),whileonthevenoussidetherewillbeareductioninbloodvolumeloaddeliveredtothefailingheart(preload).Alpha-blockersandconvertingenzymeinhibitorsnotonlyhavebeneficialacuteUniversityofGlasgow,DepartmentofMateriaMedica,StobhillGeneralHospital,GlasgowG213UWPCRUBIN,DM,MRCP,WeilcomeseniorresearchfellowinclinicalscienceJLREID,DM,FRcP,regiusprofessorofmateriamedicahaemodynamiceffectsbutmayleadtolongertermimprovementinpatientswhoarerefractorytomoreconventionalmanagement.Alpha-blockersPrazosin,labetalol,andindoraminarealpha-adrenoceptorantagonists,butonlyprazosinshowsthisasitssoleeffectatdosesusedandconcentrationsachievedtherapeutically.Labetalolisprimarilyabeta-adrenoceptorantagonistwithmodestalpha-blockingactivity.Indoraminisanalpha-adrenoceptorantagonistbutalsohasarangeofadditionalpharmacologicaleffects.Alpha-adrenoceptorsexistinatleasttwoforms.Alpha,-receptorsarefoundonpostsynapticmembranessuchasthesmoothmuscleofarteriesandveins.Stimulationofthesereceptorsbycatecholaminesleadstovasoconstriction.Alpha2-receptorsarefoundbothperipherallyandinthecentralnervoussystem.Intheperipherytheyhavebeenidentifiedonpre-synapticnerveterminalsandheretheirstimulationbycate-cholaminesorotheragonistsresultsinadiminishedreleaseofnoradrenaline.Recentreportssuggestthatthesereceptorsmayalsobelocatedpostsynapticallyandrespondparticularlytocirculatingcatecholamines.Inthecentralnervoussystemalpha2-receptorsarefoundprimarilyonpostsynapticnervecellmembranes,andtheirstimulationresultsindiminishedsym-patheticoutflow.Alpha2-receptorsinthebrainarealsointimatelyconcernedinthemechanismscontrollingsleep,andthusaconsequenceofcentralalpha2-receptorstimulationissedation. BRITISHMEDICALJOURNALVOLUME2869APRIL1983Theclassicalalpha-blockersphentolamineandphenoxy-benzamineaffectbothalpha,-receptorsandalpha2-receptors.PRAZOSIN(HYPOVASE,MINIPRESS)Prazosinisaquinazolinederivativethatwasoriginallythoughttoactbydirectvasodilatation,possiblybyphosphodiesteraseinhibition.Itisnowknown,however,thatattheconcentrationsachievedinclinicalpracticeprazosinisaselectiveantagonistofalpha,-adrenoceptors.Thereweresuggestionsthatprazosinlowersbloodpressurewithoutproducingreflexincreasesinheartrateorreninrel
2 ease,buttheseclaimshavenotstoodthetestof
ease,buttheseclaimshavenotstoodthetestofcarefulstudy.Prazosinactsonbotharterialandvenoussidesofthecirculation.PharmacokineticsPrazosinundergoesfirstpasslivermetabolism.About50-70S,ofaswalloweddosereachesthesystemiccirculationunchanged.Thedrugismorethan95')/proteinboundbothtoalbuminandtoacutephaseproteinssuchasalpha,-acidglycoprotein.Patientswithhypoalbuminaemiashowathreefoldtofourfoldincreaseintheconcentrationofunbound,andthereforepharmacologicallyactive,drug.Eliminationfromthebodyisalmostexclusivelybylivermetabolism,andclinicallyimportantchangesineliminationwillprobablyoccurinpatientswithseverecirrhosis,butnodatainthisareaareavailable.Thepharmacokineticsofprazosinarenotappreciablyalteredinelderlypatients.AdversereactionsIngeneral,prazosiniswelltolerated.Duringitsearlierclinicalusetheonlyproblemthatoccurredwithanyfrequencywastheso-calledfirstdosereaction.Thiswasasyncopalattackresultingfromaprecipitousfallinbloodpressureandusuallyoccurredafterthefirstdose,particularlyinpatientsreceivingbeta-blockersordiuretics,butwasalsoseenafterasubstantialandabruptincreaseindose.Theuseofasmallstartingdose(0-5mg)togetherwithcautiousincrementsofthedosewillvirtuallyeliminatethisproblem.Additionaladverseeffectsoccasionallyencounteredarenauseaandheadache.Occasionalcasesofurinaryincontinencehavebeenattributedtoprazosinandprobablyresultfromitsalpha-blockingactivityonsmoothmusclesoftheneckofthebladder.PrazosininhypertensionThestartingdoseofprazosinshouldbe0-5mggivenintheevening,andthepatientshouldbetoldofthepossibilitythatanorthostaticreactionmightoccurandbeaskedtoremainathomeafterthefirstdose.Subsequentlythedoseis0-5mgtwiceaday,increasingbysmallincrementseverytwotothreedaystowhateverdoseisnecessarytocontrolthebloodpressure.Itisusuallyunnecessarytoadministerprazosinmoreoftenthantwiceaday.Inthemoresevereformsofhypertensiondosesof20mgadayormoreareoftennecessary.Themajorclinicalroleofprazosinisasathirdlinedruginmanaginghypertension.Itisrarelyusedasafirstlinedrugbecausethereflexcardiovascularresponsestothefallinbloodpressureproducedbyprazosinmaylimititsantihypertensiveefficacy.Ifabeta-blockeranddiureticalonehavefailedtocontrolthebloodpressureorifoneorotherarecontraindicatedorpoorlytoleratedthenprazosinwouldbeanappropriatedrugtoconsider.Ithasbeenclaimedthatprazosincausesamore1193favourablechangeinplasmalipidsandlipoproteinsthanbeta-blockersordiuretics.Thisobservationanditsrelevanceremaincontroversial.PrazosinincongestivecardiacfailureInacutehaemodynamicstudiesprazosinhasbeenshowntoimproveperformanceinsomepatientswithrefractorycongestivecardiacfailure.Thisactionseemstodependmainlyonareduc-tioninpreloadaftervenodilatation.Longertermtreatmentwithprazosinhasledtosymptomaticimprovement,althoughthereisdoubtastowhetheritinfluencesmortalityinsevereheartfailure.Insomepatientstoleranceappearstodevelopaftertreatmentforweeksormonths.Whetherthishasametabolicordynamicbasisremainsunclear.LABETALOL(TRANDATE)MechanismofactionLabetalolismarketedasamixtureoffourdiastereoisomerswhichcombinealpha-andbeta-adrenoceptorantagonistactivity.Inpracticethebeta-blockingactivitypredominates,andlabetalolhasarangeofclinicalactivitysimilartonon-selectivebeta-blockerssuchaspropranolol.Italsohasamildvasodilatingactionresultingfromitsalpha,-blockingproperties.PharmacokineticsLabetalolundergoesextensivefirstpassmetabolism,andthebioavailabilityofunchangeddrugissubstantiallyincreasedinpatientswithcirrhosis.Clearanceisbylivermetabolism,andreducedeliminationisseeninpatientswithcirrhosis.AdversereactionsAdversereactionsaregenerallysimilartothoseofthenon-selectivebeta-blockers,andlabetalolshouldnotbegiventopatientswithasthma,heartfailure,orcardiacconductionabnormalities.Nauseaandposturalhypotensionmayoccur,particularlyathigherdoses.Atransienttinglingofthescalpiscommonafterintravenousadministration.LabetalolinhypertensionLabetalolhastobegiventwotothreetimesadayandthisclearlyputsthedrugatadisadvantagecomparedwiththosebeta-blockersthatareeffectivewhengivenoncedaily.Inmostpatientsthepossessionofmildalpha-blockingactivityprobablydoesnotoutweighthismajordisadvantage.Thedoseis100mgthreetimesadayinitially,increasingasrequiredtocontrolbloodpressure.Lowerdosesshouldbeusedinpatientswithcirrhosis.Themainindicationforlabetalolisessentialhypertension.Ithasalsobeenusedintravenouslyfortheemergencyreductionofbloodpressurewhen50mgisgivenoveroneminuteandrepeatedifnecessary.Labetalolhasbeenusedtomanagehypertensionduringpregnancybutthereisnoevidencetosuggestthatitissuperiortomethyldopa.INDORAMIN(BARATOL)MechanismofactionIndoraminhasseveralpharmacologicaleffects.Invitroitshowsselectiveantagonismatalpha1-adrenoceptors.Inaddition BRITISHMEDICALJOURNALVOLUME2869APRIL1983ithasmembranestabilisingeffectsandalsoantagonisestheactionsofhistamineandserotonin.PharmacokineticsIndoraminseemstoundergoextensivefirstpassmetabolismandiseliminatedbylivermetabolism.Thereiscurrentlynoevidenceconcerningthebehaviourofthedruginpatientswithliverdisease.Itismorethan90°proteinbound.AdversereactionsSedationisthemostfrequenteffectandm
3 aybeencounteredinuptohalfthepatientsrece
aybeencounteredinuptohalfthepatientsreceivingindoramin.Itappearstobedoserelated.Thiseffectmayinterferewiththepatient'sabilitytodriveoroperatemachinery.Failureofejaculationisalsoarelativelycommonproblem,thoughitissaidtoresolvewithcontinuedtreatment.Thenegativeinotropiceffectmayexacer-bateheartfailureinpatientswithcardiacdisease.Severalotherunwantedeffectsincludedrynessofthemouth,depression,weightgain,andfluidretention.Fluidretentioniscommonwithalpha-blockersandisminimisedbytheconcomitantuseofadiuretic.IndoramininhypertensionUnlikeprazosinindoramindoesnothaveafirstdoseeffectanddoesnotcauseareflexbradycardia.Likeprazosinitdoesnotcarrytheriskofexacerbatingperipheralischaemiaorbroncho-spasmassociatedwithtreatmentwithbeta-blockers.Thestartingdoseis25mgtwicedailyandmaybeincreasedeverytwoweekstoamaximumof100mgtwicedaily.Thedrugseemstobeaseffective(butmoreexpensive)asmethyldopaorprazosininloweringbloodpressurebutitsrangeofunwantedeffectswilllimititsuse.ConvertingenzymeinhibitorsInhibitionofangiotensinconvertingenzymeisanovelapproachtothetreatmentofseveralcardiovasculardiseases,includinghypertensionandcongestivecardiacfailure.Convertingenzymeisfoundinmanysitesincludingplasma,lung,andbloodvessels.ItformsactiveangiotensinIIfromtheinactivedecapeptideangiotensinI.AngiotensinIIraisesbloodpressuredirectlybyvasoconstrictionandindirectlybyincreasingaldosteronerelease.Convertingenzymeinhibitionreducestheseeffects.TheearliestconvertingenzymeinhibitorswerederivedfromthevenomoftheBrazilianpitviper.Latersyntheticpeptideanalogues(TeprotideorSQ20881)loweredbloodpressureinanimalsandmanbutwereonlyactivewhengivenintravenously.Theseresultsencouragedthesearchfororallyactiveconvertingenzymeinhibitors.Atpresentoneofthese,captopril(SQ14225),isavailableforclinicaluse,andseveralothersareatadvancedstagesofdevelopmentinclinicaltrials.CAPTOPRIL(CAPOTEN)MechatnismofactionCaptoprilisaprolinederivativecontainingasulphydrylgroupandisacompetitiveantagonistofangiotensinconvertingenzyme.Inaddition,byblockadeofkininaseIIitpreventsbradykininbreakdownandmayalsointerferewithdegradationofenkephalins.Captoprillowersbloodpressureinhypertensivepatientsandnormotensivesubjectswithoutanypronouncedposturaleffect.Thefallinbloodpressurelastsforsixtoeighthoursandisnotusuallyaccompaniedbyatachycardiaorotherreflexconsequencesofperipheralvasodilatation.Theintensityofcardiovasculareffectsdependsonthesodiumbalanceofthesubjectandtheactivityoftherenin-angiotensinsystem.In-creasedplasmareninactivity,resultingfromsodiumrestriction,diuretictreatment,orrenovasculardisease,leadstogreaterfallsinbloodpressurethaninthosewithanormalorhighintakeofsalt.Haemodynamicstudiesinpatientswithhypertensionorcardiacfailuresuggestanactiononvenouscapacitancevesselsinadditiontoarteriolarresistance.PharmacokineticsCaptopriliswellabsorbedafteroraladministrationbutdataondrugdispositionandpharmacokineticsarelimitedasreliablemeasurementofthedruginbodyfluidsisdifficult.Althoughhepaticmetabolismdoesoccur,theprolongeddurationofdrugactioninpatientswithrenalfailuresuggeststhatrenalexcretionofthedrugoractivemetabolitesisalsoimportant.Thepaucityofinformationondrugdispositionhasledtoproblemsinoptimisationofdoseandfrequencyofadministration.Thehighdosesusedinearlystudiesmayhaveinfluencedthepatternofadversereactionsnotedinclinicaltrials.AdversereactionsAdverseeffectsofcaptoprilincluderelativelyfrequent(500ormore)reportsofrashes,lossoftaste,andgastrointestinalsymptoms.Dermatologicalreactionshavetakenawidevarietyofformsandwhileusuallyseenathigherdoselevelshavenotalwaysbeencloselydoserelated.Depression,sedation,ordrowsinesshavenot,however,beenafeatureoftreatmentwithcaptopril.Seriousadverseeffectsarefortunatelyrare(lessthan1',,)andincludeproteinuriaandbonemarrowdepression.Theseeffectshaveusuallybeenseeninpatientsreceivinghighdoses(greaterthan450mg/day),whoeitherhavepre-existingrenaldiseaseorproteinuria,orboth,orhaveunderlyingimmunologicaldisturbances(systemiclupuserythematosus).Theymayalsooccurinseverelyillpatientstakingotherdrugswithknownrenalandmarrowtoxicity.Themechanismoftoxicityisnotknown,buttherangeofeffects,includingprotein-uria,marrowdepression,rash,andtastedisturbance,issimilartothatseenwithD-penicillamine,anotherdrugcontainingsulphydryl.Thefrequencyoflifethreateningsideeffectsremainstobeestablishedinwiderclinicalpractice.Atpresent,however,itisreasonabletolimittheuseofcaptopriltoseverehypertensionresistanttoconventionaltreatment.CaptoprilinhypertensionCaptoprilhasbeenatleastaseffectiveastripletreatmentwithbeta-blocker,diuretic,andvasodilatordrugsandisparticu-larlyusefulinhypertensionassociatedwithrenalarterystenosis,characterisedbyhighplasmareninactivityandsecondaryhyperaldosteronism.Inessentialhypertensionaproportionofpatientswillrespondtocaptoprilaloneandupto80,,tocaptoprilwithathiazidediuretic.Inthesepatientslowerdoses(75mgdailyorless)areatleastaseffectiveashigherdoses.Captoprilisusuallygiveninthreedivideddailydoses,althoughpatientswithrenalimpairmentmayrequirelowerdosesgivenlessfrequently.Thestartingdoseof25mg
4 threetimesdailymaybeincreasedto150mgthri
threetimesdailymaybeincreasedto150mgthricedailyovertwotosixweeksdependingonresponse.Patientswhoaresodiumdepletedorarealreadyreceivingdiureticsshouldbegivenalowerstartingdose(625mg)astheymayshowanexaggeratedresponsetothefirstfewdoses.1194 BRITISHMEDICALJOURNALVOLUME2869APRIL19831195Furtherexperienceinessentialhypertensionwithlowdosesofcaptoprilwillberequiredtodeterminewhetherconvertingenzymeinhibitioncanbeextendedtothemuchlargergroupofmildtomoderatehypertensivepatients.CaptoprilincongestivecardiacfailureCaptoprilcanproduceconsiderableshorttermhaemodynamicimprovementinpatientswithrefractoryheartfailure,andthereisevidenceoflongtermsymptomaticrelief.Itsbeneficialeffectsappeartoresultfromactionsonbotharterialandvenoussidesofthecirculation.Aswithotherrecentdevelopmentsinmanagingheartfailurebyreductionofpreloadorafterload,orboth,captoprilshouldatpresentbereservedforpatientswithpersistentsymptomsandsignsnotrespondingtoconventionaltreatmentwithdiureticsordigoxinorboth.Patientstakingdiureticsshouldstartwithalowdoseofcaptopril,whichmaythenbeincreasedunderclosesupervision.ConclusionSincemostpatientswithhypertensioncanbeadequatelycontrolledbyoncedailytreatmentwithabeta-blockerorathiazidediureticandwithfewadversereactionsthedrugsdescribedabovewillhavelimitedappealforfirstlinetreatmentatpresent.Prazosinandcaptoprilhaveaplaceintreatingthemoreresistantformsofhypertensionandprazosinmightalsobeusedinlowdoses,combinedwithadiuretic,forthosepatientswhoareunabletotakeabeta-blocker.Labetalolhasthedis-advantageofitsdosingfrequencywhileindoraminhasthedisadvantageofitsunwantedeffects.Bothprazosinandcaptoprilmayimprovesymptomsinpatientswithrefractorycongestivecardiacfailure.Thereisnoevidence,however,thattheseagentsaltertheclinicalcourseofthedisease.Forthepresenttheiruseshouldberestrictedtothosepatientswhoremainsymptomaticdespiteconventionaltreatmentwithdiureticsordigitalispreparations,orboth.BibliographyAtkinsonAB,RobertsonJIS.Captoprilinthetreatmentofclinicalhyper-tensionandcardiacfailure.Lancet1979;ii:836-9.Reviewofclinicalexperienceofcaptoprilinsevere,resistanthyper-tensionandrenalarterystenosisindicatingthatthedrugisofsimilarefficacytotripletreatment.Alsoincludesassessmentofcaptoprilinheartfailure.SharpeDN,CoxonRJ,DouglasJE,LongB.Lowdosecaptoprilinchronicheartfailure:acutehaemodynamiceffectsandlongtermtreatment.Lancet1980;ii:1154-7.Studyoflowdosecaptoprilin18patientswithheartfailureshowingbeneficialeffects.CampbellBC,ShepherdAN,ReidJL.Effectsoftheangiotensinconvertingenzymeinhibitorcaptoprilinessentialhypertension.BrJrClinPharmacol1972;13:213-7.Patientswhowerenotcontrolledon150mgadaywerenotcontrolledonhigherdoseswithouttheadditionofadiuretic.RubinPC,BraschkeTF.Clinicalpharmacologyofprazosin.BrJClinPharmacol1980;10:23-32.Anaccountoftheclinicalpharmacologyofprazosintogetherwithadetailedreviewofearlierpapers.Documentsreflextachycardiaandincreasedplasmareninconcentration.Anonymous.Labetalolforhypertension.DrugTherBull1978;16:89-90.Anobjectiveassessmentoftheclinicalpharmacologyandclinicaluseoflabetalol.Anonymous.Indoraminforhypertension.DrugTherBull1982;20:33-5.Anobjectiveassessmentofcurrentpublications.RobertsonJIS.Labetalol:thenineteen-eighties.BrJPharmacol1982;13,suppl1:137S-141S.Asummaryoftheclinicalexperience,includingessentialhypertension,phaeochromocytoma,ischaemicheartdisease,andpregnancybasedonconferenceproceedings.Indoramin.BrJ7ClinPharmacol1981;12,suppl1.Conferenceproceedingscontaininganuptodatereviewofclinicalusewithasummary(TurnerP,139s-140s)andageneraldiscussion(HamerJ,23s-26s)oftheuseofvasodilatorsintreatingcongestiveheartfailure.NezwDevicesDrugconvertaruleMJBRODIE,AROBSON,TMURRAYAbstractAconvenientpocketrulerhasbeendevelopedthatallowsconversionbetweenmetricandmolarmeasure-mentsofmanyofthedrugsforwhichtherapeuticmonitoringinthecirculationiscommonlyused.Theruleralsogivesinformationtotheclinicianonsug-gestedtherapeuticrangesfortheincorporateddrugs.DepartmentsofMedicine,MedicalIllustration,andPharmacy,WesternInfirmary,GlasgowGll6NTMJBRODIE,MD,MRCP,consultantphysicianandclinicalpharmacologistAROBSON,DA,medicalartistTMURRAY,BSC,MSC,principalradiopharmacistCorrespondenceto:DrMJBrodie,DepartmentofMedicine,GardinerInstitute,WesternInfirmary,GlasgowGIl6NT.IntroductionThefinetuningofplasmadrugconcentrationtooptimisepharmacologicalresponseandavoidtoxicityisanattractiveconceptthatisfindingincreasingfavourwithclinicians.Inmosthospitalsdepartmentsofbiochemistryprovideestimationsofdrugconcentrations.Clinicalpharmacistsandclinicalpharmacologistsmayhelptointerpretthefiguresandprovideadviceonadjustmentofthedosagetohelpattainatherapeuticconcentration.Drugconcentrationsareincreasinglybeingprovidedinthemolarunitsfavouredbyscientists,despitethefactthatdrugsarestillprescribedinmetricamounts.Severalconversionscaleshavebeenproduced.'Toavoidpossibleerrorsofinterpretation,wehavedevelopedaconvenientpocketrulerthatnotonlyconvertsmolarunitstometricunitsbutalsoprovidesinformationonthetherapeuticrangesofseveraldrugsforwhichroutineplasmamonitoringiscommonlyuse