D.1.1Listtheeffectsofmedicinesanddrugsonthefunctioningofthebody.

Drugormedicineisasubstancethatdoesoneormoreofthefollowing:

Altersphysiologicalstateconsciousness,activitylevel,coordination
Altersincomingsensoryexperience
Altersmoodoremotion

Theactiveingredientsindrugsandmedicinescanbeisolatedfromaplantsandanimalsorsynthesized
artificially.
Drugssupposedtoassisthumanbodysnaturalselfhealingcapabilities.
Placebosaredrugscontainingnoactiveingredient,whichfoolthehumanbodyintohealing.
D.1.2Outlinethestagesinvolvedintheresearch,developmentandtestingofnewpharmaceutical
products.
Theresearchanddevelopmentofnewmedicinesisalongandcostlyprocess.Itusuallytakesupto12
yearsandcostsmorethan$200million.
1.
2.
3.
a.
b.
c.
4.
5.

Firstthedrugmustbeisolatedorsynthetized.
Thedrugistestedonanimals.LD50andED50aredetermined.
ThedrugmovestoClinicalTrials
HumanPharmacologytestingonsmallgroupofhealthyvolunteersforsafety
TherapeuticExploratoryevaluatesdrugsefficiencyandsideeffects
ConfirmatoryStagelargescaletestingofdrug
Alocaldrugregulatoryagencyapprovesamedicineanddecideswhetheritwillbe
OTC(overthecounter)oronprescriptiononly.

LD50isalethaldosenecessarytokill50percentofanimalpopulation.ED50isaneffectivedose,one
creatinganoticeableeffectin50%ofanimalpopulation.TheratiobetweenLD50andED50iscalled
theTherapeuticIndex.
TherapeuticIndex=LD50/ED50
Therapeuticdeterminesasafetyofdrug.Ifthetherapeuticindexofadrugis10,apersonwouldhaveto
intaketentimesmoredrugthantheeffectivedosefortheeffectstobelethal.Accordingtothe
therapeuticindex,theresearchersdecidewhetheradosagemustbecontrolled.IfTIislow,thedosage
mustbecloselycontrolled.
Duringtesting,halfofthepatientsreceivearealdrugandtheotherhalfsimilarlookingplacebo.This
determinedwhetherthedrughasarealeffectorthepillonlyfooledbodyintohealing.
NOTE:WemustknowThalidomideasanexampleofwhatcangowrongduringR&Dprocessofa
drug.Thalidomidealleviatesmorningsicknessduringpregnancy.Thedrugsdevelopmentrevealed
severesideeffectsbabies,whosemothersusedthemedicine,gotbornwithdeformedlimbs.
D.1.3Describethedifferentmethodsofadministeringdrugs.
Therearefivewaysofadministeringadrug:
1.
Injection
a.
Intravenousveins

2.
3.
4.
5.

b.
Intramuscularmuscles
c.
Subcutaneousunderskin
Orallymouth
Rectallyanus
Byinhalation
Topicallyontheskin(ointments,creams,)

D.1.4Discussthetermstherapeuticwindow,toleranceandsideeffects.
Therapeuticwindowthedifferencebetweentheeffectivedoseandlethaldose;alsocalledtherapeutic
index
Sideeffectstheundesiredeffectsofdrugs
Ex:aspirinthinstheblood(usedasananticlottingagenttopreventahearthattack)
Morphium,thepainreliever,causesconstipation.
Toleranceapersontakingadrugoftengetsusedtotheactiveingredient,soittakeslargerandlarger
dosestoobtainthedrugsdesiredeffect.Thereisadangerthatabodywouldcreateaphysical
addictiontoadrug.Forinstance,anaddictiontocaffeine:iftheaddictdoesnotgethis/hercoffee,
he/shegetsheadaches.Anotherissueisthatwithincreasingdose,theuseriscomingcloserandcloser
tothelethaldose.
Risktobenefitratiodetermineswhetherthesideeffects(risk)ofthedrugareacceptableinrelation
toitscuringeffects;forexample,adrugcuringbanefuldiseasewouldbeaccepteddespitehighrisks
D2:Antacids
D.2.1Stateandexplainhowexcessacidityinthestomachcanbereducedbytheuseofdifferent
bases.
Humanstomachcontainsgastricjuicessecretedbysomecellsofthestomachwalls.Thegastricjuices
areacidic,withpHbetween1.0and3.0,becausetheycontainhydrochloricacid(HCl).Excessiveacid
productioncausesheartburnanddamageofthemucuscoveringthewallsofthestomach.Moreover,
excessproductionofacidcreatesanidealenvironmentforthebacteriaHelicobacterpylori,causing
pepticulcers.
Hearthburnthesituationwhengastricjuicesoverflowthroughesophagus
Ulcersscarsonthewallsofstomach,indirectlycausedbyanexcessiveacidity.
Antacidsareweakbases,utilizedtoneutralizetheexcessacidityinahumanstomach.Theyrelievethe
painofulcersandpreventulcersandheartburnfromhappening.Antacidsaremetaloxides,hydroxides,
carbonatesorhydrogencarbonates.
Antacid

IngredientName

ChemicalFormula

Tums

Calciumcarbonate

CaCO3

Gaviscon

Aluminumhydroxide

Al(OH)3

MilkofMagnesia

Magnesiumhydroxide/oxide

Mg(OH)2,MgO

Commoningredientsofantacidsarealginatesandantifoamingagents.

Alginatescreatealayerofmucusonthewallsofstomachandinesophagus,whichpreventsthe
heartburn.
Antifoamingagentspreventflatulence(farting)andburping.Acommonantifoamingagent
isdimethicone.

D3Anelgesics
D.3.1Describeandexplainthedifferentwaysthatanalgesicspreventpain.
Analgesicsaredrugsthatrelievepain.Theycanbemildorstrong.
Mildanalgesicsinterceptthepainstimulusatitssource.Modesofoperation:(1)interferewiththe
productionifprostaglandins,chemicalsthatcausepain;(2)reducefever;(3)reduceswelling.
Stronganalgesics(narcotics)relievepainbytemporarilybondingtothepainreceptorsininthebrain.
Theypreventthetransmissionofpainimpulsesintothebrain.
*Mildanalgesicsfunctionbyinterceptingthepainstimulusatthesource,oftenbyinterferingwiththe
productionofsubstances(forexample,prostaglandins)thatcausepain,swellingorfever.Strong
analgesicsworkbytemporarilybondingtoreceptorsitesinthebrain,preventingthetransmissionof
painimpulseswithoutdepressingthecentralnervoussystem
D.3.2Describetheuseofderivativesofsalicylicacidasmildanalgesicsandcomparethe
advantagesanddisadvantagesofusingaspirinandparacetamol(acetaminophen).
Salicylicacidwasananalgesicobtainedfromthebarkofwillowtrees.However,salicylicacidhad
severesideeffects.Therefore,researchersmodifiedthestructureofsalicylicacid,creatingderivatives.
Derivativemoleculesmeantheyhavedifferentactivegroupsattachedtothem.
Derivativesofsalicylicareusedasmildanalgesics.Theycontrolthereleaseofprostaglandinsandthus
reducepain.Twoexamplesofderivativesofsalicylicacidareaspirinandparacetamol.Both
medicinesarepainkillersandreducefever(antipyretic).However,onlyaspirinreducesinflammation.
Aspirin
Paracetamol
Advantages
Disadvantages
Advantages
Disadvantages
Preventsbloodclotting, Irritatesstomachwalls,so Safeinthecorrectdose
Blooddisorders
sopreventsheartattacks
mayinducepepticulcers Safeforchildren
Kidneydamage
Reducesinflammation
andstomachbleeding
Overdoseliverdamage,
Allergicreactions
braindamageanddeath
Reyessyndromein
children,apotentially
fatalliverandbrain
disorder
*Aspirinhasbeenfoundtobeusefulinpreventingtherecurrenceofheartattacksandstrokes.The
disadvantagesofaspirinincludeulcerationandstomachbleeding,allergicreactionsandReyes
syndromeinchildren(apotentiallyfatalliverandbraindisorder).Paracetamolisverysafeinthe
correctdosebutcan,inrarecases,causeblooddisordersandkidneydamage.Overdosagecanleadto
seriousliverdamage,braindamageandevendeath.

D.3.3Comparethestructuresofmorphine,codeineanddiamorphine(heroin,asemisynthetic
opiate).
Morphine,codeineanddiamorphine(heroin)arepowerfulstronganalgesics,whichblockthe
perceptionofpaininthebrain.

Morphine

Benzenering
Ether
Alkene
Alcohol(x2)
Tertiaryamine

Codeine

Benzenering
Ether(x2)
Alkene
Alcohol
Tertiaryamine

Diamorphine(heroin)

Benzenering
Ether
Alkene
Ethanoate(x2)
Tertiaryamine

Morphineandcodeineareobtainedfromtheopium(foundinthepuppyplants).Lowconcentrationsof
heroincanbefoundinopium;however,thisdrugisusuallypreparedsynthetically.
Morphine+ethanoicacidheroin+water
Thereactionbetweenmorphineandethanoicacidisacondensationreaction.Theacidreactswith
alcoholgroupsinmorphine(alsoreferredtoashydroxyorOHgroups).Theproductofthereactionis
waterandheroin.
*Stressthefunctionalgroupmodificationtothestructureofmorphinethatresultsinthesemisynthetic
drugdiamorphine(heroin).
D.3.4Discusstheadvantagesanddisadvantagesofusingmorphineanditsderivativesasstrong
analgesics.
Morphine
Codeine
Diamorphine(heroin)
Adv.
Dis.
Adv.
Dis.
Adv.
Dis.
Managementof Majorside
Secondstage
Maynot
Reliefofvery Strongaddiction
severepainsuch effect
paintreatment
completelytreat severepain
withrapidly
asadvanced
constipation
with
thepain
Euphoriceffects increasing
cancer
Canleadto
paracetamoland
tolerance
Treatmentof
dependence
aspirin
Dependence
diarrhea
Coughtreatment
leadsto
Fewerside
withdrawal
effectsthan
symptoms
morphineand
Death
heroine
Productivitycost
duetomoney
spendondrugs

D4Depressants
D.4.1Describetheeffectofdepressants.
Depressantsaredrugsthatdepress(calmandrelax)thecentralnervoussystembyinterferingwiththe
transmissionofnerveimpulsesintheneurons.
Effectbydose:

Lowdosesincreasefeelingofcalm,drowsiness,increasedspontaneity,slowermentalactivity
Moderatedosessoothing,reductionofanxiety,alteredperception
Highdosesslurredspeech,falteringmovement,alteredperception,sleep
Extremelyhighdoseslowbreathingandheartrates,sleep,coma,death
Effectbytype:
Tranquilizers(alcohol,valium)reducenervoustensionwithoutinducingsleepinmoderatedoses.
Sedatives(barbiturates)soothdistresswithoutinducingsleepinmoderatedoses.
Hypnotics(chloralhydrate)inducesleep.
NOTE:Depressantsareoftendescribedasantidepressantsbecausetheyrelievedepression.
*Atlowdosesadepressantmayexertlittleornoeffect.Atmoderatedosesthecompoundmayinduce
sedation(soothing,reductionofanxiety).Athigherdosesitmayinducesleep.Atextremelyhighdoses
itmaycausedeath.Depressantsareoftendescribedasantidepressantsbecausetheyrelieve
depression.
D.4.2Discussthesocialandphysiologicaleffectsoftheuseandabuseofethanol.
Shortterm:
Lossofselfrestraint
Impairmentofmemoryandconcentration
Lossofbalance
hangoverdehydrationandheadacheduetoincreasedurineoutput
Vomiting,lossofconsciousness,comaanddeath
Violentbehaviorathomedomesticabuse
Drivingunderinfluencecaraccidents
Longterm:
Dependencealcoholism
Liverdiseasecirrhosisorcancer
Fetalalcoholsyndrome
Coronaryheartdisease
Permanentbraindamage
Deteriorationofrelationships,andageneraldecreaseinperformanceindailyactivities
D.4.3Describeandexplainthetechniquesusedforthedetectionofethanolinthebreath,the
bloodandurine.
Breathanalyzercontainsacidifiedpotassiumdichromate(VI)crystals,whichturnfromorangetogreen
astheyarereducedbyethanolinbreath.Worksbecauseethanolpassesfromstomachtothebloodand
tothelungs,wherebloodairequilibriumisestablished.
Fuelcellmayalsocontainacidifiedchromium(VI)crystals.Inthisdevice,theethanolisoxidized
usinganoxidizingagent,whichgenerateselectricity.Thepotentialdifference,generatedbytheredox
reaction,isproportionaltothealcoholcontainedintheblood.
Infraredabsorptionintoximetersuseinfraredspectroscopytodeterminethealcoholcontent.TheCH
bondinethanolabsorbsparticularinfraredwavelengthandtheapparatusmeasureshowmuchatthis
wavelengthisabsorbed.Dependingonhowmuchlightthesampleabsorbs,theamountofethanolin
breathcanbedetermined.Maynotworkwithdiabetics,whobreatheoutalotofketones,whichshows
afalsepositive.
GasLiquidChromatography(bloodandurine)Canonlybedoneinalaboratory.Givesveryaccurate
results.Bloodorurineisvaporizedandinjectedintoastreamofaninertgasoverthesurfaceofanon
volatileliquid.Duetotheirdifferentsolubilitiesandboilingpointsthemoleculesinthebloodorurine

travelasdifferentspeedsalongtheliquid.Thetimetakentomovealongtheliquidiscalledthe
retentiontime.
D.4.4Describethesynergisticeffectsofethanolwithotherdrugs.
Ethanolmayincreasetheeffectofadrug:alcoholincreasestheriskofstomachbleedingwithaspirin
andbooststhepotencyofsedatives.Also,ethanolincreasestoxiceffectsofparacetamol.Alternatively,
ethanolmayreduce/negateeffectsofsomedrugs.
D.4.5Identifyothercommonlyuseddepressantsanddescribetheirstructure.
OthercommonlyuseddepressantsincludeValium,MogadonandProzac.Theycanbeallfoundinthe
databooklet.ValiumandMogadonhaveasimilarstructure,butValiumcontainsClonitsbenzene
ring,whileMogadoncontainsNO2onitsbenzenering.
Uses:
Valiumtreatsanxietyandtension
Mogadonsleepingpill,containsseizuresandinfantspasms
Prozacimprovesmoodbymakingserotoninmoreavailable
D5Stimulants
D.5.1Listthephysiologicaleffectsofstimulants
Stimulantsaredrugswhichincreaseapersonsstateofmentalalertness.Allstimulantstendtoincrease
concentration,butotherpsychologicaleffectsvaryaccordingtothegivenstimulant.Stimulants
decreaseappetite.
Generallyspeaking,thephysiologicaleffectsofstimulantsare:
1) Increasedbloodpressureandheartrate
2) Constrictionofarteries
3) Dilationofpupils
4) Sweating
5) Reducedappetite
D.5.2Compareamphetaminesandepinephrine(adrenaline).
*Amphetaminesandepinephrine(adrenaline)arechemicallysimilarinthatbothderivefromthe
phenylethylaminestructure.Amphetaminesmimictheeffectsofepinephrine(adrenaline)andare
knownassympathomimeticdrugs.
Amphetaminesmimictheeffectsofadrenaline(epinephrine),theflightorfighthormone.
Amphetamineisasympathomimeticdrug:itmimicsthestimulationofthesympatheticsystem,a
structureresponsibleforsubconsciousreflexes,byadrenaline.

Structuralsimilarities:Bothadrenalineandamphetaminehave(1)abenzineringand(2)anamine.
Struturaldifferences:Inadrenalinetheamineisprimary,whileinamphetamineitissecondary.Also,
adrenalinecontainsthreealcoholgroups,whileamphetaminedoesnot.

Bothamphetamineandadrenalinespeeduptheheartrateandbloodpressure.Thus,theyworktoavoid
sleeping(narcolepsy=uncontollabledesiretosleep).Intheshortterm,amphetainesincreasemental
energy,reduceapetiteandinduceasenseofeuphoria.Inthelongterm,amphetaminescanleadto
severeaddicitionanddepression.
D.5.3Discusstheshortandlongtermeffectsofnicotineconsumption.
Nicotineisasympathomimicdrug,containedintobaccoleaves.
Shorttermeffects:
1) Increasedheartrateandbloodpressure
2) Reductioninurineoutpute
3) Increasedmentalalertnessandphysicalenergy
4) Constrictsbloodvesselswhichputsstressontheheart
Longtermeffects:
1) Riskofheartdiseaseandcoronarythrombosisduetothestrainitputsontheheart
2) Riskofpepticulcersduetoexcessproductionofgastricjuices
3) Toleranceandaddiction
4) Costtosocietyandfamilysmokersspendlargeamountofmoneyoncigarettes
D.5.4Describetheeffectsfcaffeineandcompareitsstructurewiththatofnicotine.
*Caffeineisarespiratorystimulant.Whenconsumedinlargeamountsitcancauseanxiety,irritability
andsleeplessness.Itisaweakdiuretic.Bothcaffeineandnicotinecontainatertiaryaminegroup.
Effectsofcaffeineinclude,
(a) Insmallamounts
1) Frequentunrination
2) Increasedconcentrationandalertness
3) Increasedbreathingrate
(b) Inlargeamounts
1) Anxiety
2) Irritability
3) Sleeplessness(insomnia)
4) Addictionandwithdrawalsymptomssuchasnausea

Caffeine

Nicotine

Pentagonring
Hexagonring
Tertiaryamine(1)
Alkene
Secondaryamide(2)

Pentagonring
Hexagonring
Tertiaryamine(1)
Alkene

D.6Antibacterials

D.6.1Outlinethehistoricaldevelopmentofpenicillins
DiscoveryofpenicillinisusuallyattributedtotheScotAlexanderFleming.Flemingleftanopendish
withStaphylococcusaureus,inhislaboratoryandwhenhereturnedfromaholiday,amoldgrewinside
thepetridish.Thismoldinhibitedthegrowthofbacteria.Flemingpublisheshisresultsin1929,buthe
didnotpursuethediscovery.
PenicillinwaspursuedbyHowardFlorey

andErnstChain,whoisolatedandpurifiedpenicillin.They
alsoshowedthepenicillinwasharmlessonmiceandasthefirstusedthedrugonhumans.Thetwo
menreceivedaNobelPrizeforChemistry.IntheUS,companiesstartedmassproductionofpenicillin.
First,bygrowingthefungiinlargetanksandthenbysynthetizingthedrug.
D.6.2Explainhowpenicillinsworkanddiscusstheeffectsofmodifyingthesidechain.
*Penicillinsworkbyinterferingwiththechemicalsthatbacterianeedtoformnormalcellwalls.
Modifyingthesidechainresultsinpenicillinsthataremoreresistanttothepenicillinaseenzyme.
Penicillinisbactericidal,whichmeansitkillsbacteria.
1.
2.
3.

Penicillininterfereswiththeenzymesthatbacterianeedtoformnormalcellwalls.
Attemptingcelldivision,bacteriaswellandosmoticpressureputsstressontheircellwall
Thecellwallsburstandbacteriadisintegrate

Allpenicillinshavecommonstructure,includingthebetalactamring.Thebetalactamringisasquare
arrangementofcarbonandnitrogenatomswithotheratomsattached.TheRisafunctionalgroup
attachedtothepenicillin.

Differentfunctionalgroupsprovidepenicillindifferentproperties.Somebacteriadevelopedresistance
againstpenicillinandproducetheenzymepenicillinase,whichbreaksbreakdownthebetalactamring.
Attachingdifferentfunctionalgroupscanmakepenicillinsmoreresistanttopenicillinase.Also,some
penicillins,suchasPenicillinG,hadtobeinjectedastheygotbrokendownbythestomachacid
nowadays,thefunctionalgroupsweremodified,sothatpenicillincanbetakenorally
D.6.3Discussandexplaintheimportanceofpatientcomplianceandtheeffectofpenicillin
overprescription.
1.
2.
3.

Duetotheuseofantibioticstocureminorailments,somebacteriabecameresistanttocertain
kindsofpenicillins.
Harmlessandhelpfulbacteriainthedigestivesystemcanbewipedout.
Bacteriamutate,whichresultsinsuperbugsresistanttoantibiotics.Thisrequirescostly
developmentofnewantibiotics.

Patientcomplianceisimportanttoavoidmutationofbacteria,butalsotoensurenoallergicreaction
willoccur(manypeopleareallergictopenicillin).
Farmersoftenaddantibioticsintofeedstocktopreventillnessesandtobolsterthegrowthofanimals.
Thismayresultinamutationofharmlessbacteria.Humansconsumethemeat,takingintheantibiotics
aswellastheresistantbacteriain.
*StrictadherencetoarecommendedtreatmentregimeisnecessaryfortheeffectivenessofantiTB
drugs(frequentlyseveraldrugsareusedincombination).Theuseofpenicillinsinanimalfeedstock
alsocontributestotheresistanceproblem.
D.7.1Statehowvirusesdifferfrombacteria.
Relevantpoints:

1)
2)
3)
4)
5)

virusesare20xsmallerthanbacteria;
unlikebacteriavirusesarenotcellularbacteriahavecellwallandnucleus
virusesdonothavecytoplasm,whilebacteriado
virusesdonotfeed,excreteandgrow,whilebacteriadoes
virusesusecellmaterialoftheinvadedcelltoreproducethemselves,whilebacteria
usecelldivision

VirusesinjecttheirRNAorDNAintotheirhostcellscytoplasmandusethecelltoreplicate.Thenew
celleitherreleasesthevirusorreleasesotherinfectedcell.Thischangeincellstructurecause
symptomsofviralinfection.
D.7.2Describethedifferentwaysinwhichantiviraldrugswork.
1)Preventvirusesfromleavingthehostcell.
2)Blockthereversetranscriptaseenzymeactivitytoavoidaconversionofthevirusintoaformthat
canenterthehostcell.
3)Alterthehostcellsgeneticmaterial,sothatvirusescannotuseittomultiply.
4)Blocktheenzymeactivitywithinthehostcell,sovirusescannotmultiply.
*Antiviraldrugsmayworkbyalteringthecellsgeneticmaterialsothattheviruscannotuseitto
multiply.Alternatively,theymaypreventthevirusesfrommultiplyingbyblockingenzymeactivity
withinthehostcell.
D.7.3DiscussthedifficultiesassociatedwithsolvingtheAIDSproblem
Theantiviralagentsareveryexpensive,whichmakestreatmentofHIVdifficultindeveloping
countries.Peoplecannotaffordthedrugs.
TherearesocioculturalissuesfosteringthespreadofHIV,too:
Socioculturalissue
Condomuse
Culturalfactors
Illegalactivities

Whyisthisavalidissue?
Culturalresistanceandhighcost
Misinformation,ignoranceandwishfulthinking
Druguseandprostitution

*SpecificproteinsontheHIVvirusbindtoareceptorproteinoncertainwhitebloodcells(Tcells).
BecauseoftheabilityoftheHIVvirusestomutate,andbecausetheirmetabolismislinkedcloselywith
thatofthecell,effectivetreatmentwithantiviraldrugsisverydifficult,asisvaccinedevelopment.
ThecontrolandtreatmentofHIVisexacerbatedbythehighpriceofantiretroviralagentsand
socioculturalissues.
D.8.1Describetheimportanceofgeometricalisomerismindrugaction.
Stereoisomersarecompoundswiththesamemolecularandstructuralformula,butadifferent
arrangementofatomsinspace.Geometricisomersareatypeofstereoisomers.Ingeneral,geometric
isomersoccurinspecieswithabondwithrestrictedrotation.However,insomegeometricisomers,
whentherearedifferentatomsbondedtothesamemolecule,likeincisplatin,thephenomenonmay
occur.
Thetransandthecisformofadrugcanexhibitdifferentproperties.Onegeometricisomermayhave
thedesiredpharmacologicaleffect,whiletheothermaybelesseffectiveorhaveadversesideeffects.
Example:Cisplatinisadrugusedtotreattesticularandovariancancer.Themedicineexhibits
geometricisomerism.However,onlythecisformofthedrugiseffectivethetransformhasno
effectswhatsoever.OnlycisplatincanreactwithtwoguaninemoleculesintheDNA.Rememberthat
cisplatinissquareplanar!

CisplatinTransplatin

D.8.2Discusstheimportanceofchiralityindrugaction.
Opticalisomersarestereoisomerschiral,orasymmetric,aroundoneoftheatoms.Bodyisavery
precisemachine,sothechemicalsinsideoftenexistasoneoftheenantiomers.
*Thetwoenantiomersinaracemicmixtureofadrugmayhaveverydifferenteffects,forexample,
Thalidomide.OneenantiomerofThalidomidealleviatesmorningsicknessinpregnantwomen,while
theotherenantiomercausesdeformitiesinthelimbsofthefetus.
Onlyoneenantiomerofdrugsexhibitingopticalisomerismsometimeshasthedesiredpharmacologic
effect.Theotherenantiomermayhaveweakereffectorsevereadversesideeffects.The
pharmaceuticalcompaniesarelikelytomanufactureonlythedesiredenantiomerbecauseproducingthe
ineffectiveenantiomerisfinanciallyinefficient,ortoavoidtheadverseeffectsoftheharmful
enantiomer.
Theatomaroundwhichamoleculeischiralhasfourdifferentatomsattachedtoit!Donotconfuse
opticalisomerismwithgeoisomerism!
Example:Thalidomideoneenantiomeralleviatessymptomsofthepregnancymorningsickness,the
otherenantiomercausesdeformitiesinthelimbsoffetus

Ibuprofenoneenantiomeriseffective,whiletheotherisnot

Naproxenoneenantiomerisapainreliever,theotheroneisalivertoxin

Otherexamplesincludeamphetamineandtaxol.Weuseasterisk(*)todenotethechiralatom.
D.8.3Explaintheimportanceofthebetalactamringactionofpenicillin.
Thebetalactamringhasanunusualsquarestructure,whereeachbondis900
.Duetoitsirregularity,the
betalactamringisveryreactive.Theringopensandcovalentlybondstotheenzymetranspeptidase,
responsiblefortheformingofbacterialcellwalls.Ifbacteriumisunabletobuilditscellwall,itbursts,
disintegratesanddies.

*Thehighreactivityoftheamidegroupwithinthefourmemberedringstructureisaresultofstrain.
Theringopenssothatthepenicillinbecomescovalentlybondedtotheenzymethatsynthesizes
bacterialcellwalls,thusblockingitsaction.
D.8.4Explaintheincreasedpotencyofdiamorphine(heroin)comparedtomorphine.
Diamorphine(heroin)andmorphinehavethesamefunctionalgroups,exceptfortwo.Whilemorphine
containstwoalcoholgroups,diamorphineissyntheticallymodified,sothatthetwoalcoholgroupsare
replacedbyesters.
Duetothedifferenceinfunctionalgroups,diamorphineismuchlesspolarthanmorphine.Asaresult
ofthis,heroincanpassthebloodbrainbarriermuchquickerinamuchlargerconcentration.Thelower
polarityofheroinfacilitatesthedrugstransportationinthenonpolarenvironmentofthecentral
nervoussystem(CNS)remember,likesdissolvelikes!
Becauseheroinrequiresasecondaryreactioninbrain,whichhydrolyzestheesterlinks,another
derivativeofmorphine,6monoacetylmorphine,isevenmoreeffectivethanheroin.6
monoacetylmorphinehasonealcoholandoneestergroup.
*Thepolarhydroxylgroupsinmorphinearereplacedbynonpolarestergroups,facilitatingtransport
intothenonpolarenvironmentofthecentralnervoussystem
D9DrugDesign
D.9.1Discusstheuseofacompoundlibraryindrugdesign.
Compoundlibraryisacollectionofaverylargenumberofrelatedcompoundsproducedby
combinatorialsynthesistechniques.Eachchemicalinthelibraryhasassociatedinformationaboutits
biologicalactivity,suchastheeffectonenzymesandabilitytobindtocertainreceptorsites.
Researcherscanusethisinformationtofindacompound,whichfitswellthepropertiesofthe
researcheddisease(e.g.polarity,stereoisomerism).Theprocessofcreatingcompoundlibrariesis
lengthyandexpensive,sofirmsmustpayroyaltiestoaccessthelibraries.Asopposedtosynthesizing
andindividuallyevaluatingdifferentcompoundsforbiologicalproperties,thisapproachallowsmoney
andtimetobesaved.
*Traditionally,alargecollectionofrelatedcompoundsaresynthesizedindividuallyandevaluatedfor
biologicalproperties.Thisapproachistimeconsumingandexpensive.
D.9.2Explaintheuseofcombinatorialandparallelchemistrytosynthesizenewdrugs.
Combinatorialchemistryusesalargenumberofstartingreactantstocreateavarietyofdifferent
compounds.Thesecompoundsarethentestedforbiologicalactivity,suchastheeffectonenzymesand
theabilitytobondtoreceptorsites.Thisinformationisthenstoredincombinatoriallibraries.
Combinatorialchemistryisveryrepetitiveandlengthy,soitusesalotofcomputermechanics.
Combinatorialsynthesisutilizessolidphasechemistry.Solidphasechemistryisthefollowingprocess:
1) Verysmallresinbeadsaremadetheseprovideasurfacefortheattachmentandreactionofother
molecules.
2) Differentmoleculesareattachedtothesolidbeads.Thisiscalledthemixandsplitmethod.
3) Theproductsarecleavedfromthebeadsbyfiltrationandwashingthebeads.Solidphase
chemistrycanbefullyautomatedanduserobotics,whichsavestimeandmoney.
Combinatorialchemistryalsousesthemixandsplitmethod.Theadvantagesofthecombinatorial
chemistryare:
1) Masstestingandscreeningforbiologicalactivity
2) Highefficiency

Parallelsynthesiscarriesoutthechemistrytocreateasingleproduct.Parallelchemistrycanproduce
muchsmallerandmorefocusedlibraries.
*Combinatorialchemistryisusedtosynthesizealargenumberofdifferentcompoundsandscreen
themforbiologicalactivity,resultinginacombinatoriallibrary.Alternatively,parallelsynthesis
canproducesmaller,morefocusedlibraries.Studentsshouldbeawareoftheimportanceofsolid
phasechemistry.
D.9.3Describehowcomputersareusedindrugdesign.
Threedimensionalmoleculescanbecreatedinsilico,bycomputersoftware.Anactiveingredientcan
bemadesothatthechemicalstructureofthedrugmatchestheshapeofthecompound,whichthedrug
issupposedtoaffect.Forexample,analterationinthiscompoundmaystopthespreadofdiseasethis
isthecaseofthebetalactamringinpenicillin.Computermodelscanalsoassessthebiologicaland
othereffectsofcompoundswithouttheneedtosynthesizethechemicalsinreality.
*Threedimensionalmodelsofdrugscanbecreatedinsilicoandmolecularmodellingsoftwarecanbe
usedforthevirtualdevelopmentandevaluationofnewdrugs.
D.9.4Discusshowthepolarityofamoleculecanbemodifiedtoincreaseitsaqueoussolubility
andhowthisfacilitatesitsdistributionaroundthebody.
Thepolarityofmoleculescanbeincreasedtomakethemmorewatersoluble.Becauseionsarethe
mostwatersoluble,manufacturerstrytomakedrugsionic.Manydrugsthatcontainaminegroupare
reactedwithhydrochloricacidandareadministeredashydrochloridesalt.Manydrugsthatcontain
carboxylicacidgrouparereactedwithabase(e.g.NaOH)andareadministeredastheirsodiumor
calciumsalt.
SolubleaspirinmakesanionwithNaOH;losesH+,soNa+isattractedtothenegativesitewhere
H+waslost
Prozac(fluoxetinehydrochloride)makescationwithHCl;H+fromHClbondstonitrogeninProzac

Mostdrugsaredistributedaroundthebodythroughbloodtheydissolveinthebloodplasma.Blood
plasmaismostlywater,apolarsolvent.Makingamoleculemorepolar,i.e.transformingitintoits
ionicformmakesthechemicalmoresoluble.Thisfacilitatesthedistributionofthedrugaroundthe
humanbody,i.e.increasesthedrugsbioavailability.
D.9.5Describetheuseofchiralauxiliariestoformthedesiredenantiomer.
*Achiralauxiliaryisusedtoconvertanonchiralmoleculeintojustthedesiredenantiomer,thus
avoidingtheneedtoseparateenantiomersfromaracemicmixture.Itworksbyattachingitselftothe
nonchiralmoleculetocreatethestereochemicalconditionsnecessarytoforcethereactiontofollowa
certainpath.Oncethenewmoleculehasbeenformed,theauxiliarycanbetakenoff(recycled)toleave
thedesiredenantiomer.AnexampleisthesynthesisofTaxol,ananticancerdrug.

Achiralauxiliaryisacompound,muchlikeacatalyst,whichisusedtoconvertnonchiralmolecule
intojustthedesiredenantiomer.Thisisimportantbecausesometimesonlyoneenantiomerhasthe
desiredpharmacologicaleffect.Theworkingofchiralauxiliariesisdescribedbelow:
1) Chiralauxiliaryattachestoanonchiralreactant.
2) Thiscreatesthestereochemicalconditionsnecessarytoforcethereactiontofollowacertainpath.
3) Inthispath,onlyoneenantiomerisformed.
4) Chiralauxiliaryistakenofftheproductandrecycled.
5) Theenantiomerisreadyandchiralauxiliarycanbeusedagain.
ChiralauxiliariesareusedtosynthesizeTaxol(paclitaxel),ananticancerdrug,whichisnormally
foundinthebarkofaPacificyewtree.Withoutchiralauxiliaries,enormousquantitiesoftreeswould
havetobecutdowntomeetthedemandforTaxol.
D.10.1Describetheeffectsoflysergicaciddiethylamide(LSD),mescaline,psilocybinand
tetrahydrocannabinol.
Drug
Effects
Lysergicaciddiethylamide
Flashbacks
Changesinvisualandsoundperception
hallucinations;goodorbadtrips
Desiretolaugh
Hypertension,dilatedpupils,changeinbody
temperature&hearthrate
Psychologicaldependence
Mescaline
Subjectivehallucinations
Anxiety,statictremors,psychicdisturbances
Abdominalpainmuscleache
Psilocybin
Subjectivehallucinationsmilderthanwith
mescaline
Changeinmoodpleasantorapprehensive
Inappropriatelaughter,dizziness
Muscleweaknessiscommon
Tetrahydrocannabinol
Appetitestimulation
Lethargy,sluggishness
Anxietyandirritability
Psychologicaldependence
D.10.1DiscussthestructuralsimilaritiesanddifferencesbetweenLSD,mescalineandpsilocybin.
Shouldcompareallthreetotheindolering.
Drug
Lysergicaciddiethylamide

Mescaline

Psilocybin

FunctionalGroups
Benzenering
Alkene(2)
Secondaryamine
Tertiaryamine
Tertiaryamide
Benzenering
Primaryamine
Ether(3)
Benzenering
Secondaryamine
Tertiaryamineion
Phosphate

Allthreedrugscontainbenzenering,LSDandpsolocybinalsocontaincyclopentenering(?)with
secondaryamine,sotheyhavetheindolepart.Mescalinemissesthesecondaryamine.

D.10.3Discusstheargumentsforandagainstthelegalizationofcannabis.
*Argumentsforlegalizationincludetheabilityofcannabistoofferrelieffromcertaindiseases.
Argumentsagainstlegalizationincludethepossibleharmfuleffectsandthepossibilityofcannabis
usersmovingontoharderdrugs.
Argumentsfor:
RelievessymptomsofParkinsonsdisease
Sourceofadditionaltaxrevenue
Nomoreorlessharmingthantobaccooralcohol.

Argumentsagainst:
Steppingstonedrugcanleadtotheuseofharder
drugs
Increasedriskoflungcancer
Riskofdrivingormanipulationwithmachinery
underinfluence,whichincreasesthechanceofan
injury.