INTRODUCTION TO PHARMACOLOGY,

HISTORY, AND DRUG DEVELOPMENT

INSTRUCTOR: Thomas C. Westfall

INTRODUCTION TO PHARMACOLOGY, HISTORY,

AND DRUG DEVELOPMENT
INSTRUCTOR: ThomasC.Westfall
Objectives: Afterstudyingthismaterialyoushouldbeableto:
1. Definethefollowingterms:pharmacology;drug;pharmacodynamics;
pharmacokinetics;pharmacotherapeutics;toxicology;pharmacy
2. Describethetwomaingroupsofdrugsandtwomajortypesofdrugnames
3. DiscusstheimportanceoftheDrugActsof1906,1938and1962
4. Describethefourphasesofclinicaltrials;theINDandNDA
5. Discussthemajordevelopmentsthatoccurredduringthefollowingperiods:
TheEgyptianandBabylonianPeriod
ThePeriodofGreeceandIndia
TheRomanEra
TheMiddleAges
TheModernEra
6. Relatetheimportanceofadvancesinbotany,chemistryandphysiologytothe
developmentanduseofdrugs
7. Describethecontributionofeachofthefollowing:
Hippocrates
ClaudeBernard
Galin
PaulEhrlich
Theophrastus
RudolphBuchheim
Paracelsus
OswaldSchmiedeberg
WilliamHarvey
JohnJacobAbel
W.A.Serturner

Origin Greek
Pharmakon A poison; drug or medicine

Logia To study
A study of

PHARMACOLOGY

-A study of the interactions of chemicals on

the biological system.

- In the present context are those chemicals

(DRUGS) which are useful in the diagnosis,
treatment, prevention or cure of disease.

Druganychemicalagentother
thanfoodthateffectsliving
organisms,inthemedicalsense,a
drugisanychemicalagentusedin
thetreatment,cure,preventionor
diagnosisofdisease.

PHARMACOKINETICSDeals
withtheabsorption,distribution,
biotransformationandexcretionof
drugs.Thesefactors,coupledwith
dosage,determinetheconcentrationof
thedrugatitssiteofactionandhence,
theintensityofitseffectsasafunction
oftime.

PHARMACODYNAMICS
Thestudyofthebiochemicaland
physiologicaleffectsofdrugsand
theirmechanismofaction,and
structureactivityrelationships.

PHARMACOTHERAPEUTICSThe
useofdrugsintheprevention,treatment
anddiagnosisofdisease.

IMPORTANT QUESTION:

ARE DRUGS GOOD GUYS OR BAD GUYS?

TOXICOLOGYThataspectof
pharmacologythatdealswiththeadverse
effectsofdrugs.

IMPORTANT QUESTION:
ARE DRUGS GOOD GUYS OR BAD GUYS?

Drugs are generally divided into two main groups:

1)Non-prescriptiondrugs-Theseareagentsthatmaybesold
overthecounter(OTC)sincetheyarejudgedsafeforuse
withoutmedicalsupervision

2)Prescriptiondrugs-Theseareagentsconsideredtobeunsafe
foruseexceptundersupervisionandwhicharetherefore
dispensedonlybytheorderofpractitionerslicensedbylawto
administerthem,e.g.,physicians,dentists,veterinariansetc.

Proprietary name=tradename(trademarkname).This
nameisassignedbythemanufacturerandisownedbythem.
Whileunderpatentprotectionthedrugcannotbeproducedby
anyoneelse.Onceitgoesoffpatent,othercompaniesmay
manufactureitandthenewcompanymaygiveittheirtradename.
Thereforethesamedrugmayhavemorethanonetradename.
Nonproprietary name=genericname.Ifadrugispromisingand
amanufacturerwantstoputitonthemarket,aUnitedStates
AdoptedName(USAN)isselectedbytheUSANCouncilwhichis
jointlysponsoredbytheAmericanMedicalAssociation,the
AmericanPharmaceuticalAssociationandtheUnitedStates
PharmacopoeiaConvention.Ifthedrugiseventuallyadmittedto
theUnitedStatesPharmacopoeia,theUSANnamebecomesthe
officialname.

Kefauver-HarrisAmendments(1962)totheFood,Drug, Requiredproofofefficacyaswellassafetyfornew
andCosmeticAct
drugsandfordrugsreleasedsince1938;established
guidelinesforreportingofinformationaboutadverse
reactions,clinicaltesting,andadvertisingofnewdrugs
ComprehensiveDrugAbusePreventionandControlAct Outlinedstrictcontrolsinthemanufacture,distribution,
(1970)
andprescribingofhabit-formingdrugs;established
programstopreventandtreatdrugaddiction
OrphanDrugAmendmentsof1983

AmendsFood,Drug,andCosmeticActof1938,
providingincentivesfordevelopmentofdrugsthattreat
diseaseswithlessthan200,000patientsinUSA

DrugPriceCompetitionandPatentRestorationActof
1984

Abbreviatednewdrugapplicationsforgenericdrugs.
Requiredbioequivalencedata.Patentlifeextendedby
amountoftimedrugdelayedbyFDAreviewprocess.
Cannotexceed5extrayearsorextendtomorethan14
yearspost-NDSapproval.

ExpeditedDrugApprovalAct(1992)

AllowedacceleratedFDAapprovalfordrugsofhigh
medicalneed.Requireddetailedpostmarketingpatient
surveillance.

PrescriptionDrugUserFeeAct(1992)

Manufacturerspayuserfeesforcertainnewdrug
applications.FDAclaimsreviewtimefornewchemical
entitiesdroppedfrom30monthsin1992to20months
in1994.

Stagesofnewdrugdevelopment

Timeandcostprofileforthediscoveryanddevelopmentofa
drugcandidate

Howdrugdevelopabilityexperimentsfitintothedrugdiscoveryand
developmentprocess.

Scientificdisciplinesnecessaryfordrugdevelopabilityassessment.

Traditional Process

Reverse Pharmacology

DiseaseState
EndogenousLigand
ReceptorandBiological
Response
DrugCandidate

OrphanReceptor
EndogenousActiveProducts
BiologicalResponses
DiseaseState
DrugCandidate

ASanFranciscoopiumden

Instantaneouscurewithcocainetoothache
drops

IF WE WANT TO SEE AHEAD

WE MUST LOOK BACK

-AlbertSzentGyorgyi

Theoriginsofpharmacology:religion,animals,andplantsFriezefromthepalaceofKingSargonII,inKharasabad.
MuseeduLouvre,Paris,AntiquitesOrientales.(CourtesyofServicedeDocumentationPhotographiquedelaMusees
Nationaux,ChateaudeVersailles)

Foxgloveanddeadlynightshade.Thesearetheplantsourcesofdigoxinand
atropine,respectively,(ReproducedwithpermissionfromGeorgeGraves,
MedicinalPlants,NewYork:CrescentBooks.Copyright1990BrackenBooks.)

Thearabicwordal-kuhloralcohol.Itoriginallyreferredtooneof
thefirstwaysofpreparingdrugsforexternaluse.

The three important figures in the early history of pharmacology are Rudolf
Bucheim, Oswald Schmiedeberg, and John Jacob Abel (left to right). They
not only created new laboratories devoted to the laboratory investigation of
drugs, but also firmly established the new discipline through the training of
future faculty, the writing of textbooks, and the founding of scientific
journals and societies.