DR/AWADELJACKZAYED

PHARMACOLOGY LECTURES/1

I
NTRODUCTI
ON

Pharmacol
ogyisthescienceconcer
nedwit
hstudyof
i
nteract
ionsofchemicalagents(
Drugs)
wit
hli
vi
ngsystems.That
i
ncludesknowledgeof:

a-Phar macoki
neti
cs:-
Defi
nedas(Studyofeff
ectofthebodyont heDrug).
IncludesstudyofAbsorpt
ion,Di
str
ibuti
on,Metaboli
sm
(Biotransf
ormati
on)andexcreti
on(Eli
minat
ion)ofthe
Drug.(ADME) .

b-Phar macody nami cs: -

Isknowl edgeofhowDr ugexer t
sitsef fectsont hebody. ie.
TheModeofAct ionoft heDr ug, it
sTher apent i
cEf fectandAdv erse
Effects.
Dr ugsar echemi cal agent sadmi nister edt oaltert hef uncti
on
ofal i
vi
ngsy stem byaspeci ficmechani sm ( ModeofAct ion).
Accor dingt ot hei rsour sesDr ugsar ediv idedt o:-
a-Natur alDr ugs:usual lyobt ainedfrom Pl ant seg.Qui nine
(CinchonaBar k), At r
opi ne( AtropaBel l
adonna), Cardiac
glycosides(Di gitalisLanat a) ,
Sennosoi ds( Cassi aacut ifolia),
Hy ocine( Henbaneshr ub) …et c.
b-SemiSy nthest icDr ugs:Or i
ginall
yNat ural Drugswhi char e
subj ectedt ochemi cal modi fi
cat i
oneithert oi ncr easet heir
therapeut icef ficacyort omi nimi zetheiradv erseef fectseg.
Amoxy cill
in( modi fiedpeni cil
l
inG) ,Doxy cycl i
ne( modi fied
tetracycline)I pr at r
opium( modi f i
edAt r
opi ne) ,…et c
c-Synthest i
cDr ugs: -Pur elysy nthest
izedf ort heir
Phar macol ogical effecteg.Sul phonanides, Qui nolones, I
soni azi
d
(INH), Imi daz oles…et c
.
ROUTESOFDRUGADMI
NSTRATI
ON

Ther
earemanyrout
esf
ordrugadmi
nist
rati
on.Thechoice
oft
heappropi
ater
out
eisi
ndi
cat
edbythedoctoraccor
dingt
ot he

NOTESONPHARMACOLOGY 1
DR/AWADELJACKZAYED

cl
ini
calcr
it
eri
aconcer
ningt
hepat
ient
.
TheseRoutesi
ncl
ude:
.

A-
TheOr
alRout
e:
Taki ngt hedr ugbyswal lowi ng, thedr ugi nt hisr outei s
absor bedf rom GI T.Or al routei st hemostcommonl yusedone.
Dosagef orm ofdr ugst akenor allyi nclude:
a-
Tabl et s:maybeswal lowedorchewed.Phar maceut icallymay
beuncoat ed, orcoat edt ocompactunaccept abl et ast eor
odour .Ty pesofcoat ingi ncludeSugar, fil
m orent er i
ccoat ingused
toex ertapr olongedact ion.
Or allyadmi nistereddr ugsar eabsor bedei theri nst omachor
smal lintest inesaf terbei ngdi sint egratedanddi ssol uted.Theyar e
subject edt oFi r
stpassMet abol i
sm ( mai nlyint hel i
ver )
.
b-Capsul es:t hedr ugi nt hisdosagef or misi mpact edi nacapsul e
madeofei therhar dorsof tGelat in.Gel atinisapr oteinwhi chi s
digestedt odi schar get hedr ug.Capsul esar eusedt oav oid
unaccept abl eodourort ast eoft hedr ug.
c-Suspensi ons: -Isal i
quiddosagef orm usedf ordr ugswhi char e
i
nsol ublei nt hev ehi cleused.Mai nlyisusedf oradmi nst rationof
drugst oI nfant sandChi ldrenorEl derswhocan’ tswal lowt ablets
andcapsul es.Absor ptionofsuspensi onsi sal way sfast ert han
tabletsandcapsul es.Somedr ugsneededf orl ocal actionar e
formul atedi nsuspensi onf orml ikeAnt acidsandGI Tdi sinfectants
.(eg.Neomy cin)
d-Syrups: -Al iquiddosagei nwhi cht hedr ugi ssol ubl eint he
vehicleusedl ikeCoughSy rups.
Mi
norOr
alRout
es:
i
-Subli
ngualRoute:Thedr ugi sadmi nst
eredbyplaci
ngunderthe
tongue.Usedusual l
ywhenar api
dact i
onisneededbecause
absorpti
onisfastandf i
rstmet aboli
sm isbypassedeg.Gl
yceri
ne
Trini
tr
ateandIsosorbidef ortr
eatmentofAngi na.
i
i-BuccalRout
e:inthisroutethedr ugsisplacedint
hemouthand
absorbedbyoralmucosa. Alocaleffectmaybeneededeg.

NOTESONPHARMACOLOGY 2
DR/AWADELJACKZAYED

Nystat
inor alsuspensionandMi conazoleoralGel
.
AdvantagesofOr aladmi nster
ationofDrugs:
-
-Easysel fmedicat i
on
-
-Noski l
ledper soni sneeded
-
-Ov er
dosecanbemanaged
Di
sadvant agesinclude:
-
-Delayedonsetofact i
on
-
-CausesGI Tadv ersereactionseg:nausea,vomit
ti
ng,anorexi
a….
-
-Drugst akenor all
yar eaffectedbyFir
stPassMet abol
ism

B)Par
ent
ral
Rout
es:
-
IntheseRoutesthedr ugi
sadmi nst
eredi ninj
ectabl
eform
.All parent
ralrout
esbypassFi rstPassMet aboli
sm .Usuall
ythese
routesar eusedwhen:
a-Rapidactionisneeded.
b-Thepat i
entiscomatizedorunco-operated.
c-Nausea&Vomi tt
ingexist.
d-Highconcent r
ati
onofdr ugi
sneededt oexerttheTherapeuti
c
effecteg.I ncaseofSept i
cemias,Cardi
corRespi rat
oryFail
lur
e.

Par
ent
ral
Routesi
nclude:
I
a-nt
ravenous(
I.V.)Rout
e):
Usedf or**DrugswhicharenotabsorbedbytheGIT
eg.I
nsuli
n,Ami nogl
ycosidesor**Drugshighl
yaff
ectedbyfi
rst
passmet aboli
sm eg:Quindi
ne,.
Bioavai
labi
lyisAbsolute(100%)byi
ntrav
enousinj
ecti
on.All
i
nfusionsareadmi nster
edI.V.

b-Intr
amuscul ar(I.
M. )Rout e:-
Isusedf orbypassi ngfirstpassmet abolism &whenonsetof
act i
oni stober api
d&dr ugisnotabsor bedwel lbyoralroute.eg.
Pr ocainepeni cil
li
n,Ami nogl ycosides. Alsousedf ordepotdrugseg:
InjectableCont r
acept i
ves( Methy lProgestrone),someMaj or
Tr anquill
izers(Trif
luper azine)andl ongact ing
St eroi
ds(Tr iamcinoline).
c-Sub-Cut aneous( sub. cut)Rout e:
-
TheDr ugisinjecteddi r
ectlyundert heski n,usedforirri
tati
ng
dr ugs,orunst abledrugseg.I nsulin,
Adr enaline.
d-Intr
aThei calRout e:
-
Injecti
onoft het heDr ugdirectlyinCSFbet weenVer t
ebra
(lumbarpuct ure).Usual lyusedf oradmi nstrat
ionofAnaet hestics

NOTESONPHARMACOLOGY 3
DR/AWADELJACKZAYED

,
andAnt
i-
inf
ect
iveDr
ugsusedt
reat
mentofsev
eremeni
ngi
ti
s.

e-
Intr
aDer mal Route:
-
Injecti
onoft heDrugisintheDermi
s,mainl
yusedf orl
ocal
anaethesticseg,Xy l
ocai
neforminoroper
ati
ons.
f-
Int
raAr ter
ialRoute:-
TheDr ugisinjecteddir
ect
lyinanart
ery.I
sanemer gencyrout
e
forobtainingapr omptonsetofacti
on.

C)
Topi
cal
Rout
e:-
Int hisrouteal ocal effectisneededsot hedr ugisappl iedon
theout erbodysur faces( Ski
n, eyelid,nost
ri
ls,ears, vagina)inf or
m
ofointment s,cr
eams, gels,drops, dusti
ngpowder ,supposi tories
andPessar i
es.I
nt hisr outetheDr ugdoesnotr eacht hesy stemi c
cir
culation.
N.B: Admi nstrati
onofdr ugsbyi nhl
ationisalsocl assified
withtopi calrouteswher etheact ionisconfiedtotheAl veoli(eg.
SalbutamolBecl omet hazonei nhalersforBronchial asthma) .

D)
Rect
alRout
e:-
Thedrugisadmi nsteredi
nf orm ofSuppositor
iesi nsertedin
Rectum .Thi
sroutepar t
iall
ybypassesf irstpassmet abolism .Is
commonl yusedininfants.InAdultsisalsousedt oobt ai
nf ast
acti
onorinpati
entsofPept i
culcereg.Anal egsi
cdrugs
(Par
acetamol,
Glyer
ine,Indomethaci n)
.Alsousedf oritslocal ef
fect
eg.AntiHaemorroi
dal Drugs.

,
,
,,
,,
,
,,
,,
,
,,
,,
,
,

PHARMACOKI
NETI
CS

Studyofactionofbodyont hedr ug,i

nvol
vesstudyof
Absor
ption,Dist
ri
buti
on,Met abol
ism andExcreti
on.
DrugAbsorpti
on:--
1
*I
mportantincaseofOraladmi ni
str
ation.Theconcentr
ati
onin
pl
asma( Bi
oavail
obil
it
y)i
spr oport
ionaltorapi
dit
yofAbsorpti
on.

NOTESONPHARMACOLOGY 4
DR/AWADELJACKZAYED

Theconcen-
trationi ncreasesgradual
lyuntil
lreachingapeak.
-:
* Bioav ail
abil
ty
Ist hef racti
onoft heunchangedDr ugt hatreachessyst
emic
circul ati
on
fol lowingadmi nstr
ati
on.
*Mi nimum Ef fect
iveConcentr
ation(MEC): Istheconcent
rat
ionof
thedr ugbel owwhi chnotherapeuticeffectispossi
ble.
*Dr ugHal fli
fe(T½) :
ist
hetimer equir
edt oexcrete
50%oft heamountoft headmi nister
eddr ug.Some

Dr
ugshav
eshortT½t
(Benzylpencil
l
in) Pl
asma MEC
Ot
her
shavel
ongT½ (Doxycy
cline). cone

T½

Ti
me

Pharmaceut i
all
yslowr el
easedformscani ncreasetheT½oft he
Drug.ie:I
nter
valsbetweenDosesi si
ncreased.
Toobt ainconstantBioav
ailobi
lyforagiventi
me,mul t
ipl
e
dosesy st
em isappli
ed. Ahighinti
alloadi
ngDosei sadminster
ed
fi
rst
ly,main-
tai
nancedosesar egivenatcalculat
edinter
valstoproducelong
l
astingBioanail
abil
it
y.

Pl
asmaconc
Loadi
ng
dose

t
ime

Factorsaffecti
ngDr ugOralAbsorption: -
1-Fact
orsconcer ningtheDrug:*Druglipophobi ci
ty.
Themor ethe
Drugisli
pophi ll
i
c,t
hebet t
eri
tisabsor bed. **
Thepar ti
clesi
zeof
theDrug:thesmal leri
tspart
icl
e, thebet teri
tisabsorbed.
2-Fact
orsconcer ningpati
ent:*
*pHoft hegutandst omachaf f
ects
absorpti
onofsomeDr ugs.**i
ntest i
nemot i
li
tywheni ncr
eases
l
eadst odecr easeinDrugabsorption* *inter
actionwithfood
usuall
ydecr easesofDr ugs**Interacti
onwi thconcurrentl
y

NOTESONPHARMACOLOGY 5
 DR/AWADELJACKZAYED

adminstreddr ugsaf
fect
sleadi
ngtoincreaseordecreasei
nthei
r
Halfl
ives.
3-Factorsconcerni
ngtheDrugDosagef orm:
Dif
ferentDosagefor
mshav edi
fferentr
atesof
Absorpti
on.TheSequenceofAbsorpt
ionf r
om oral
dosagef or
msi:
syr
ups>susp>capsul es>tabl
ets>enteri
ccoatedtabets.

2)Dr ugDi stri

but i
on: -
Aft
erabsor ptionthedrugi sdi stri
but edindifferentbody
ti
ssueswi thci rculat i
ontoreacht hesi teofact i
on.Mostdr ugs
bindswi t
hpl asmapr otei
ns(car r
iedbypl asmapr oteins).
DrugPl asmapr ot einsBindi
ngi nt hispat tern:-
Pl
asmapr oteinsbindwi thDr ugsas:
1-Albumin: BindsAci di
cdrugs( Atropi ne,Indomet hacin,Acetyl
sali
cy l
icacid) .
2-Glycoprotei ns: bindBasicdr ugs( Pr opranolol,Imipramine).
3)Glubuli
ns: bi ndSt eroi
daldrugs, Thy roxi
ne, Vi
tami nB12,melat
s
l
ikeI r
on( Transf erri
n)andCopper( Caer oplasmi n).

4)Li
poprotei
ns:-bi
ndhighhi
popli
l
ici
tydr
ugs(quini
ne&qui
nidi
ne.
)
N.B.
:
Somedr ugsarenotboundtoprot
ein&aredi
str
ibut
edfr
eel
yeg.
Hepari
n, I
NH, Al
lopur
inol
.

Absor
pti
on
Theacti
ondrugi
sonl
y
theunboundfor
m
Pl
asma
B-dr
ug
met
abol
i
sm
Unbound
excr
eti
on excr
eti
on

Siteof
acti
on
B-dr
ug Ti
ssue

U-dr
ug
B=bound
U=unbound

Bi
oav
ailabi
l
ity:
I
sdefi
nedas( Thef
ract
ionoft
heunchangedDr
ugt
hatr
eachest
he

NOTESONPHARMACOLOGY 6
DR/AWADELJACKZAYED

systemiccirculat
ionfol
lowingadminsterat
ion).Intra-
venousadmi
-
nstrati
onpr oducesAbsolute(100%)Bioavail
abili
ty.Theleast
Bioavail
a-
bi
lityisproducedbyOr aladminstr
ati
onduet oi ncompl et
e
absorptionand
effectofFirstPassmet abol
ism.
Fi
rstpassmet aboli
sm :-
I
sshownbydr ugstakenoral
l
y,occur
sinthel
iverwheretheDr
ugispart
ial
l
y
metaboli
zedbef
orereachi
ngthesyst
emiccir
culat
ion.Dr
ugsaff
ectedar
e
t
hose
Deacti
vedbymetaboli
sm.
3-
Met
abol
i
sm :
-

Takespl
acei
n3si
tes:

a-
Gutmucosal Met abolism :
occursbyact i
onofgastri
c&
pancreati
cjuice(Aci dit
y&basi cit
y )ontheDrug.Notsi gni
ficant
.Usefullf
orgener ati
onofsomedr ugsf r
om theirpr
odrugs.eg.
Choroquinephosphat e →chl oroquinebase.
Eryt
hromy ci
nst earat
e Erythromy ci
n+St eari
cacid.
b-I
ntesti
nalFloraMet aboli
sm :
Bacter
iaofintestinalFl
oracanbr eakdownsomeconj ugat es
ofDr ugswhi chunder goEntero-hepaticcir
culat
ion.

c-Hepat i
cMet abol i
sm ofDr ugs: -
Liverismai nsi t
eofmet abolism .Hepat icmet abolism hast wo
phases:
a)Phase1: involv esinduct i
onofachemi cal change( s)i
nt he
Drugmol -
ecule.Thesechangesar ecat ali
zedbyagr oupofEnzy mesknown
as Cy t
ochromesP450. Changesmayi nvolve: intr
oduct i
onor
remov alofachemi cal groupeg: Hy droxylation- Demet hyl
ation
.Thechemi cal changemayl eadt o•lossofphar macological
effect(inactivation)oft heDr ugegPeni cil
li
ns, Sulphonami des
•SomeDr ugspr oducephamacol ogicall
yactive
met abolit
esegTheβadr ener gicbl ockerPr opr anolol..
•phar macol ogical acti
v i
tyofsomeDr ugsi snot
affectedegBenz odiazepines
.
b)Phase11: i
nv olvesconj ugat i
onofmet abol it
espr oducedi n
Phase1wi t
hsomesubst ancesi ncluding:Gl ucour onicAcid,
Glycine, Sul
phat esorGl utathione.Conj ugationi ncreaseswat er
solubili
tyofthepr oductandconsequent l
yf acili
tatestheirRenal

NOTESONPHARMACOLOGY 7
DR/AWADELJACKZAYED

ex
creat
ion.

Excret
ion:-
Takesplacebymanyor gans:
1-Ki
dneys( RenalExcr
ecti
on): Onl
yunbounddr ugsareexcr
etedby
Glumerularfi
lt
erati
on,mostcommon&i mportant.MostDr
ugsare
excret
edr enal
lyeg:β-
Lactam Anti
biot
ics,Sul
phonamides,
Thi
azide
diur
eti
cs.

2-Bi
l
iar
yEx cr
eti
on:drugsareexcr
etedwit
hbil
eafterconj
ugat
ion,
conj
ugatesarepassedwit
hstools.eg(Ri
fampi
cin)

Ent
erohepat
iccycl
eoft
hedr
ug
oraldr
ug

i
ntest
ine
bi
l
e
por
tal
syst
em

l
i
ver dr
ugconj
ugat
e

sy
stemi
cci
rcul
ati
on

I
.V.dr
ug

NOTESONPHARMACOLOGY 8
DR/AWADELJACKZAYED

PHARMACODYNAMI
CS:

Ist hestudyofeffectoft hedr ugont hebody.

Si
xmechani smsofdr ugact i
onar eknown, whil
emodeofact ion
ofmanydr ugsisunspecifi
ed.
Mechani smsknownar e:-
1-I
nhibit
ionofspecifi
cr eceptorsbyt hedr ug.Examples:
a-
Inhi
bi t
ionofβ-Recept orsfort r
eat mentofar ry
thmiasand
hypertensionbypropranolol,
At enolol,Acebutal
ol ….
etc.
b-I
nhibit
ionofH1andH2r ecept orsbyAnt i-
Histamini
cDrugsfor
tr
eatmentofAl ler
gyandhy peracidityandgast r
icandduodenal
ul
cers.

2-Inhi biti
onofspeci f
icenzy mes: -
Int hismechani sm act i
vityofaspeci ficenzy mei si nhibited
byt hedr ugt opr eventf ormat ionofaspeci ficmet abolit
ewhi ch
elev at i
oncausest hedi sease.
eg.Monoami neoxi dasei nhibtor s(MAOI )whi chpr event
degr edat i
onofadr enal i
ne, noradr enaline,Dopami neand5
Hy dr ox ytr
y ptami ne( 5HT) .UsedasAnt i
-Depressant s(Phenel zine,
Isocar box azid, Par gyli
ne) .
3-Inhi biti
onofamet abolicpr ocessi nt heinf ecti
ngMi cro-
organi sm : -
Penci ll
insactbyi nhibiti
onofbi osy nthesisofbact erialcel l
wal l
,andSul phonami desi nhibitbiosy nthesisofFol i
caci di nbact eri
a.
4-Compet et i
onwi tht hesubst ancecausi ngt hedi sease:
Asi ncaseofant i
histami neswhi char est ructurallysimilarto
Hist i
di ne, socancompet ewi thi tfortheenzy meHi sti
dine
decaboxy laser esul ti
ngi nr educt ionofhi stami nepr oduced–( eg
Chl or pherni r
ami ne, Clamest i
ne) .
5-Di rectchemi cal i
nteract i
on:
Asi ncaseofant acidswhi char echemi callyweakal kali
s,
theycanneut r
alizet heaci dityint heSt omach&Duodenum (eg.
Mg( OH) 2,AL( OH) 3,Ca( OH) 2).
6-Cent rall
yact i
ngDr ugs:
Somedr ugsar ef oundt oaf f
ectcer t
ainBr aincent erswhi char e
cont rol l
ingact i
vityofcer t
ainsy stems.eg.Di phenoxy lateact s

NOTESONPHARMACOLOGY 9
 DR/AWADELJACKZAYED

cent
ral
l
ytost
opdi
arr
hoea.

PHARMACOLOGYLECTURES/
2

ANTI–INEFCTIVECHEMOTHERAPY
(Antii
nfect
iv ugs)
eDr
Chemot
her
apyofMi
crobi
alDi
seases

Cl
assi
fi
cat
ion
Many schemes ofcl assificati
on ar e used .The most
common i scl assi f
icati
on accor di ng to chemi calst ructure and
proposedmodeofact i
on:-
1. Agent st hati nhibitBact er
ial cellwal l
sy nthesis:-
I
nclude
a/Thepeni cilli
ns.
b/Thecephal ospor i
ns.
c/Agent sascy closer i
ne, v
ancomy cin,Bacitraci
n.
d/Imidaz oles( ant ifungal agent s).
2. Agent sact ingdi r
ctlyont heCel lmembr ameoft hemi cr
o–
organisim: af f
ect ingpr emeabi l
ityandl eadi ngtol eakageof
i
nttracelludercont ent s.Thiscl assi ncludes:
Pol ymy xins.
Ny statin( ant i
fungal )
Amphot ericin.
3. Agent swhi chaf f
ectt hefunct ionof30sor50s:
Ribosomalsubuni ts,causingar eversibleinhibitionofpr ot
ein
biosy nthesi s–t hi
scl assincl udes:
a/Chl orampheni col.
b/Tet racy cline
c/Er ythromy cin.
d/Cl i
ndamy cin.
4. Agent st hatbi nd t ot he 30S r i
bosomalsub- units:and
l
eadi ngt oal ter ationi npr oteinBi osy nthesiswhi chev entuall
y
l
eadst ocel l deat ht hisclassi ncludesAmi noglycosi des.

NOTESONPHARMACOLOGY 10
 DR/AWADELJACKZAYED

5. Agent
sthataf
fectnucl
eicAci
dmet
abol
i
sm:
Exampl
esar
e:
a/Rifampi ci
nwhi chi nhibi
tsDNAdependantRNApol ymerase.
b/Qui nolones:-whichinhibitgrase.
6. Ant imet aboli
tes:-Blockaspeci fi
cmet abol
i
cst epsthatare
essent i
alforthemi cro–or ganism.IncludesTr i
methprim and
Sulphonami des.
7. Nucl eicAci dAnal ogs:-Actbyi nhibi
t i
ngv i
ralenzymesand
which ar e essentialf orDNA sy nthesis,thus halfi
ng v i
ral
repli
cation.

ANTI
-MI
CROBI
ALDRUGS

A/SULPHONAMI
DES

Thef irstchemot herapeuticagent susedsy stemically.

Their use decl i
ned af ter discovery of Peni cil
li
ns and ot her
Antibiotics,anddev elopmentofr esistancebyBact erialstrai
ns.
Nowt heirusei sv eryr estri
cted.
Chemi cal lysul phonami desar eder i
vativesofsul fanil
ami de( which
contairni trogenandsul phur )i
nitsstructure.
Modeofact ion:-
Suphonami des ar e st ruct
ural anal ogs and compet i
ti
ve
antagoni sts ofpar a-ami no Benzoi c Aci d( PABA) ,t heypr event
normalbact eri
alut il
izati
onofPABA f orsy nthesisofFol i
cAci d.
Sensi t
ivebact eriaist hatwhi chcannotut il
izepref ormedf olicacid
.Mammal i
ancel lsar enotaf fectedbyt hismechani sm,because
foli
cAci di sessent ialfort hem andisnotsy nthesized.
Anti Bact erialspect rum: -
Strainsaf f
ectedbySul phonami desinclude:
-Str
ept ococcuspy ogenes.
-Haemophi lusinfluenz a.
-Actinomy ces.
-Escher i
acol i.
-Str
ept ococcuspr eumoni a.
-Nocar dia.
-Chamy diat rachomat is.
-Neisser i
ameni ni
ngi ti
dis.

Phar
macokineti
cs:
-
Arerapidl
yabsorbed (
exceptt
hose act
ing l
ocal
lyon the
bowel
)from GI T,appr
oxi
miatel
y 70 – 100% oft he dose i
s

NOTESONPHARMACOLOGY 11
 DR/AWADELJACKZAYED

absor bed.Maj orsi teofabsor pti

oni ssmal lintestine–Bound( by
var yingdegr eet ot hepl asmapr ot eins).Di stri
but edt oal lbody
tissues.
Met abol iz edi nliv ert oi nact i
vemet abol it
es.
Excr et edpar tl
yunchangedandpar t
lyasmet abolitesbyt heur inary
sy stem.
1. Sul phamet hoxaz ole( Gantanol ):-
Isal ongact ingsul phanomi de.Admi ni steredOr all
yf orbot h
sy stemi candur i
nar yt ractinfections.
Commonl yusedi ncombi nationwi tht r i
met hopr im( Co–
trimox az ol e–Sept ri
n)t opot entialet heant ibacterial effect.
Dose: 2t abl ets( 400mgsul phamet hazol e+50mgt ri
mt hopr im)
ev ery12Hour sf oratl eastf ivedai l
y .
Co–t r i
moxaz ol ei scommonl yusedi nt r
eat mentofal lsy stemi c
infect ions, buti sspeci ficallyusedf orUTI( ur i
naryt racti nfections)
andTy phoi dandTox opl asmosi s(combi nedwi thpy rimet hami ne).
2. Sul phadi azi ne:
Rapi dal yabsor bedwhengi venor ally, partiallymet abol olized
inliverandi sexcr et edur i
nary.
It’susei sr est rictedt oBact er i
al Meni ngiti
sbecausei tcan
crossBl oodBr ainBar rierBBBef ficient l
y,usual lyadmi nst ered
par ent ral l
y.
Dose: 60mg/ kgbodyev ery4Hour s.
3. Sul phadox i
ne:
Isal ongact ingsul phonami de,usedi ncomi nationwi th
Py rimet hami ne( Dar apr im)( 500mgsul phadoxi ne+25mg
Py rimet hami ne–Fansi dar )fortreat mentofMal aria.
Dose: Asi ngledoseof3t ablets.
4. Sul phacet ami de: -(Isptocetami de)
A shor tact ing sul phonami de used l ocal lyi n ey ei nfections
especi al l
ychl amy dia.For mulat edi nsodi um sal tfor m,asey e
dropsof20%&30%concent r
ation.
5.Sul phat hiaz ol e:-
Thi ssul phonami dei snotabsor bedbyGI Tsoi tsact ioni sl ocal,
usedf orGI Ti nf ect ions.

TRI
METHOPRI
M

Asynthesti
cdrug,chemi cal
lynotasul
phonamide.
Modeofaction:
-
Actsbyinhibti
onofDi hy dr
ofl
ateReductasewit
haff
ini
tyf
or
Bact
eri
alenzemes50000t imest hatf
orhumans.
Isapotentbroadspectrum Bacter
iost
ati
cagent.

NOTESONPHARMACOLOGY 12
DR/AWADELJACKZAYED

Emer genceofr esistantst rai

nsisi ncreasi
ngsoi susual l
y
usedi ncombi nationwi thsul phonamides,t ogi vesy nergi
sti
c
act i
on.
Usedf orUTI( urinaryt r
actinfecti
ons)andf orprophy laxi
sof
UTI .
Adv erseef fectsofsul phonami des:-
1.GI T Di st
ur bances: i ncluding Anor exia, nausea, and
vomi t
ting.
2.Hy per sesit
ivity:ueticari
a, ski
nrash,photesensiti
sty.
3.Cr ystallur
iamayaccuri fadequateamountofwat eri snot
takendur ingt herapy .
4. h aemat opoeitic di sturbances: - Acut e Haemol y t
ic
anaemi a, Agranulocy tosis,Aplasti
canaemi a
5. .
B/QUI
NOLONES

Synt
hesti
cchemother apeut
icagents,whi
char
ederiv
ati
ves
ofadoubl eri
ngedhetr
ocy cli
cnucleusknownasquonol
i
ne.The
fi
rstcl
ini
cal
lyusedqui
nolonei sNal
idi
xicAci
d.

ModeofAct i
on: -
Actbyi nhibit
ion oft heenzy meDNA gy raseleading to
blockingofDNAr eplicati
onofthesensi tiveBact eri
a.
Antibacter i
al Spectrum: -
Withexcept ionofNal idixacid(Wintomy lon)
which i s act i
ve onl y agai nst gram negat i
ve Bacill
i,ot her
quinoloneshav ebr oadspect rum incl
uding: -Esheriacoli
Salmonel l
a ssp
Shigell
a ssp
Enterobact er
Campy l
obact er
Neisseriassp
Pseudomonasaur igenosa
Enterococci
Pneumococci
Staphy l
lococci
Phar macoki netics:-
Wel labsor bedor all
yandwi delydi stri
butedi nbodyt i
ssues,
peakser um concent rationisreachedwi t hin1-3hour s.Canpass
bl
oodbr ainbar ri
or( BBB).Met abolizedi nl i
ver.Mostqui nolones
areexcr etedur inary.
Ther
apeut
icusesofqui
nol
ones:
-

NOTESONPHARMACOLOGY 13
 DR/AWADELJACKZAYED

1/Uri
narytractinfecti
ons( UTI
).
2/Prost
atit
iscasedbysensi ti
vebact er
ia.
3/ Sexuall
y t ransmi tt
ed di seases ( sy phi
l
li
s, Gonor
rhea
.Tr
ichomiasis).
4/Gastr
ointesti
nal andabdomi nal i
nfect
ions.
5/Respi
ratorytractinfecti
ons.
6/Bone.jointandsof ttissueinfect
ion.

Adverseeffects:
-
Mil
d ef f
ectsincl
uding :
-nausea ,abdomi
naldi
scomf
ort
,
headache,dizzi
nessandrashes.

1. Nal i
di xicacid(wint
omy l
on): -
(usedonlyforUTI)
Dose:-500mgev ery6hourforatleastoneweek.
2. Nor flox aci
n:
dose:-4000mgev ery12horsfor5day s.
3. Ci profloxacin:-
Dose:-250 –500 mgev er
y12hour sfor5days,f
orgonor
rheaa
singl
edoseof500mgi ssuf
fici
ent
4. Of loxaci n:
Dose:400mgev ery12Hour sfor5day s.

NOTESONPHARMACOLOGY 14
 DR/AWADELJACKZAYED

.
PHARMACOLOGYLECTURES/
3

ANTI
BIOTI
CS

An ant ibioti
ci sachemi calsubst ancepr oducedbycer tain
typesofbact eri
a ,and is effecti
vei n def ending thi
sbact eria
againstothert ypesofbacteri
a( orfungi).
Pharmaceut i
cal
ly ,ant ibi
otics ar e abt ained f r
om
cultur
esofbact eriaconcer
ned wher eisi sol
atedi npur ef ormf or
cl
inicaluse.Thei sol
atedanti
bioticcanbeusedi nit
scr udef orm,
orchemi callymodi fi
edtogi v
esemisy nthesti
cant ibioti
cswi th
mor eeffi
cientact ionorbett
erpr operti
es.Fel i
mi ngdiscov eredthe
fi
rstant i
biotic,benz ylpenici
llin ,pr oduced by St reptomy ces
penicil
l
um .
(I)Penicil
lns.
i
Toget herwi thCephal ospor i
ns,penicil
li
nsar echemi cal l
yknownas
β–l act am ant ibi
otics.
β-l actam i shet r
ocy cl
icfuseddoubl eri
ngcont ai
ningoneat om of
SulphurandNi trogen.
Modeofact ion: -(ofbot hpeni cil
l
ins&cephal osporins)
Penicilli
ns and Cephal osporins ar e bactericidal( Dir
ectl
y
eli
mi natet hebact erialcell).Actbyi nhibit
ionoft hel aststepin
bacterialcel lwal lsynthesiswher et heycompet ewi tht hecellwal
l
D-al anyl–D-al anine.St oppingoft hecel lwallsynt hesisleadsto
leakageofcel lcontentsanddeat hoft hecell.
N.B:β–l act amsar et hesaf estantibi
oticsbecauset heyacton
cellwal lwhi chi snotf oundi nmammal i
ancel l
s.So, t
heiruse
cli
nicall
yi sthewi dest .
Accor dingt ot heirantimicrobialspectrum,peni ci
lli
nscanbe
classifi
edt o:
1. Benz ylpenci l
li
n( Penicil
li
nG)andPhenoxy methy lpenicil
l
in
(Penicil
linV): -

Arehi
ghl
yacti
veagai
nstsensi
ti
vest
rainsofGr
am posi
ti
vecocci
.
butar
ereadi
l
yhy dr
oly
zedbypencil
linase.Peni
cil
l
inG isacid

NOTESONPHARMACOLOGY 15
DR/AWADELJACKZAYED

unst
able so can notbe admini
ster
ed or
all
y.Bot
h ar
einact
ive
agai
nstmostst r
ainsofst
aphyl
ococcusaur
eus.

Peni cil
li
nGi st hepar entpeni cil
li
ni e.Thatobt ai
neddi r ectly
from thecul ture.I tsef fi
ciencyi st hehi ghest,butcan’ t bet aken
orall
ybecausei sdest roy edbygast ri
caci dity.
Isusedf oracut ei nfect i
onst ogi ver apidt herapeut i
cact i
on.
Pharmacoki net i
cs:
Iswel labsor bed( 100%), notst ayingl ongint hebody( Has
shortT½).met abol i
z edhepat icall
yandexcr etedur i
nar y.
Dose: -
1000000I .U( =0. 3g)ev er y3-6hour sf oratleast24hour s,
thentreat menti scont inuedbyor alpeni ci
lli
ns.
Pencil
linV ( Phenox ymet hyl penicill
in): -
I
snat uralpeni cilli
n whi chhast hesamespect rum buti saci d
stable
Dose: 250-500mgSi xhour lyf oratl east4day s.
2. Cl ox acilin: (Isoxaz oly
lPeni cll
in)
Isasemi synthest icpeni cill
inwhi chcanr esistdest r
uctionby
Pencill
inase( Hepat icenz ymewhi chdest royespeni cill
in).
Spectrum ofact i
oni st hesameaspeni cil
linGbuti ti
saci dst abl e
andcanbet akenor ally.Commonl yadmi nst er
edwi t
hAmpi cill
in
(asAmpi clox)t ogi veabr oadspect rum andr esistancet o
penicl
linase.
Duet oinhi bitionofpeni cll
inase, Cloxaci l
l
ini seffecti
v eagainst
penici
lli
asepr oduci ngSt aphy l
lococci .
Dose: -250–500mgsi xhour ly.
3. Amoxy cill
in(Amoxi l):
-
One oft he i mpor tantami no peni cil
l
ins (i ncluding Ampi cill
in,
Bacampi cill
in),t heyhav esimi larant i–bact eri
alact ivi
tybutt heir
spectrum i sbr oadert hant heabov ement i
onedpeni cill
i
ns.theyact
on bot h Gr am posi ti
v e and Gr am negat ive Bacter i
a .Act i
vity
againstGr am posi ti
veBact eriai slesscompar edwi thpeni ci
ll
inG.

Pharmacokineti
cs:-
Oralabsorpti
on israpi
d and complet
e,metabol
i
sm ishepati
c,
excr
etioni
sbot huri
nar
yandbil
iary.
Therapeut
icindi
cati
onsofAmoxy ci
l
li
n(&ot
heraminopeni
cil
l
ins)
:-

NOTESONPHARMACOLOGY 16
DR/AWADELJACKZAYED

a/UpperRespi ratoryTr actinfect i

ons.
b/Uri
nar yTr actinfections.
c/Meni ngi ti
s.
d/Salmonel lai
nfections.
4/Procai nepenicill
i
n: -
Ischemi call
ysy nthestizedf rom penici
ll
inGbyi nt
roducti
on
ofprocai newhi chpr olongst hehal fl i
feleadi
ngtodecr easein
i
nterv
alsofadmi nistr
at i
onandr educti
onofpainatinject
ionsit
e.
Isadmini steredincombi nationwi t
hPenicil
l
inG.
Thespect rum i
ssi milartoPeni cil
li
nG.
Dose:-1000000I .U.(0.3g)onceort wicedail
yforatl
eastfiv
eday s.
N.B:
-Ist hedr ugofchoi ceforSy phil
li
s.
5/Benzat hinepeni cil
l
in:-(Penadur):-
Semi sy nthestic Peni ci
ll
in pr oduced by i nt
roduct
ion of
Benzat hzine t o Peni ci
ll
i
n G . This leads to no change i n
Antibact eri
alspect rum.Thechangei sinprolongati
onofstayi
ngof
thedr ugi nt hebody( i
ncreaseinT½) .Suchmodi fi
cati
onisuseful
forlongt ermt reatmentwher eonl yonei nject
ionofBenzathzi
ne
penicil
lincanst aywi t
hef f
ecti
venessupt ofourweeks.
Dose:-
1. 200.000I .
U.to2.400.000ev eryfourweeks.
(i
nsev er ecasesi nter
valscanbeshor t
er)
6.Carboxypeni
cil
l
ins(AntipseudomonalPeni ci
l
li
ns)
i
ncludecar
bencill
i
n, t
icar
cil
li
n,andpiperaci
ll
in.
they are semisynt
hetic peni
cil
li
ns whi ch are act
ive agai
nst
Pseudomonasaer ugi
noseandcer tainProteusssp.Alsoeff
ecti
ve
agai
nstmoststrai
nsofSt aphyl
lococcusaureus.Theyaresensi
ti
ve
todestr
ucti
onbyβ. l
actamase.
7.Car benci
ll
i
n:-
(Pyopen)
Isaci
dst abl
eandsuitabl
ef oror
aladminstr
ation.
Usedi ntreat
mentofi nfecti
onsresi
stanttoot herpeni
cil
l
insand
causedby:Pr ot
eusssp,Pseudomonasaer ugi
nosa,Enter
obact
er
ssp.
Dose:-
25-30grams/day(1g/hour
).

Adverser eact
ionofPenicll
ins:-
1\Hyper sensit
ivi
tyreact
ionsiscommon( occursi
n5%- 20%of
pati
ents) .I
scausedbyal ltypesofpenici
ll
ins.Thehypersensi
ti
vi
ty
canrangef rom mildrashupt oli
fethr
eateninganaphyl
axis,
hypersensiti
vi
tyreacti
onsinclude:-

NOTESONPHARMACOLOGY 17
 DR/AWADELJACKZAYED

a/Ski
nr ashes( Stevens–Johnsonsy ndromei nseverecases
canoccur ).
b/Fev er:Transientlasti
ngf or36hour s.
c/Eosinophil
ia.
d/Angioedema.
e/Serum sickness.
f)Anaphy l
acticsicknessr eacti
ons:-commonaf t
erparentr
al
administr
ation,butcanal sooccuronor aladmi ni
str
ati
on.
2) GI Tupset(nausea, v
omi tt
ing,diarr
hea)
3) Nephr otox i
cit
y:i sveryrareandoccur sinpati
entswithrenal
i
nsuffici
ency .
4) Super i
nfection:-occurs,especi
allyonpr olonguseduet o
changest akingplacei ntheintest
inalfl
ora.Commoni nbroad
spectrum penicil
li
ns.
(I
I)Cephal ospor i
ns

Areβ-lact
am Anti
biot
icsobtainedfr
om cul
tur
esof
Cephalosr
ium acremonium.Alsoobt ai
nedfr
om cul
tur
esof
Sardi
niam fungus.Al
lcephalospor
inscontai
ntheβ–Lactam r
ing
7-aminocephal ospor
anicacid.
ModeofAct i
on:-
Cephal ospor insinhabi tBact eri
al cellwallsynt hesi
sina
mannersi mi lart oPeni cill
ins.
Pharmacoki net ics:-
Cephal ospor inshav inggoodor alabsorptionar eCephalexi
n,
Cephr adine, Cef aclor ,Cefadr oxil
,Cefixime, Cefuroxi me,soar e
usuallyadmi nist eredbyor al rout
e.Twocephal ospor i
nsare
admi nist
er edonl yi ntr
av enousl y(I
.V.)becausei ntramuscul ar
i
njectioni spai nf ul,thesear eCephat othinandCephapi ri
n.Others
canbeadmi nisteredei t
heri ntramuscul arl
yori ntrav enousl
y.
Distr
ibutioni sr api d,met abol ism i
shepat i
c.Excr etionismai nl
yby
Kidney s.
Cephal ospor i
nwhi chpenet rateBBBi ncludeCef ur
oxime,
Cefotax i
me, Cef til
ox ime.
Antibact erial spect rum
Bacter iasensi ti
vet oCephal ospor i
nsinclude: -
-Mor axellacat arrhalis -E.col i
-Klebsellassp -proteusmi rabili
s
-Enterobact eriaceae -Pscudomonasaer ugi
nosa

N.B:Cephalospor
inareBroadspectr
um Ant
ibi
oti
cs.
Therapent
icusesofcephalospor
ins:
Commonl yusedfor:
-

NOTESONPHARMACOLOGY 18
 DR/AWADELJACKZAYED

- UpperandlowerRespi ratoryTr
acti
nfect
ions.
- Uri
naryTractinf
ections
- Bacteri
almeningit
is
- Postoperati
veprophy l
axis.
- Resist
antpneumoni ainfecti
ons
- Neisseri
agonorrhea(i
njectabecef
uroxi
me)

Cephalospor i
ni ncommonusei nclude: -
1/Cephalex in(Kef l
ex -Cepor ex)
Broadspect rum enabl eusef orRespi rat
oryi nfectionsandRenal
inf
ect i
onsspeci ficall
y.
Dose: -250–500mg6Hour l
yf oratl east4day s.
2/Cephradi ne( Vel osef )
:-
Usedgener al l
yf orsensiti
vesy stemi cinfections
Dose:-250-500mg6Hour lyforatl east4Day s.
3/Cefuroxime( Zinacef )
Usedgener allyf orgonococcal infections, septicemi asandpost
operat i
vel y
Dose: -1-3gr am 8Hour lyfor3Day s.Admi nisteredi ntravenously.
4/Cefaclor( Cect or): -
Usedf orallsy st emi cinfecti
onespeci all
yur inarytr actinfect
ions.
Canbeadmi ni steredor all
yorpar ent rall
y.
Dose: -1gr am ev ery8Hour l
yfor3Day satl east .
5/Cefatoxime( Claf oran)
Broadspect rum cephal osporin,buti scommonl yusedf or
Bacter i
al meni ngitisbecausei tcr ossesBBBef f i
ciently.
Dose: -Intravenousl y2gr am ev ery4t o8Hour s
Adverser eacti
ons:-
1/Hy persensiti
vi
tyr eact
ionsisthemostcommonsi deeffect,i
s
i
denticaltohy persensiti
vi
tycausedbyPenici
ll
ins(Urti
cari
a,
Bronchospasm, Anaphy l
axis)
Cephalospor i
nsshowcr osssensiti
vi
tywit
hpencill
ins.
2/Nephgr otoxici
ty:-Cephalospori
nsinhi
ghdosesar enephr oxi
c.
Severit
yofnephr otox i
cit
ydiffer
sbetweendif
ferenttypes.
3/Diarrheaiscausedbycephal ospori
ninsomepat ients.

(
II
I)βLact
amsei
nhi
bit
ors

Someagentscanbindtoβ-Lact amaseenzy
meandi nhibi
t
i
tsact
ivi
ty,t
husprev
enti
ngdegredati
onofβ-lact
am ant
ibiot
ics
whi
chconsequent
lyl
eadstoprolongat
ionofT½ andobt ai
ning

NOTESONPHARMACOLOGY 19
DR/AWADELJACKZAYED

bett
er/therapenti
cef f
ects.β-lactamasei nhibi
torsaregi venin
combinationwi t
htheβLact am admini
stered.
Clav
ulanicacid:
-
I
s pr oduced by St r
ept
omy ces cl avul
igerus, has poor
anti
microbialef
fect.Soisnotusedsepar atel
yasanAnt ibi
otic.I
s
usedincombi nati
onwi t
hβ–Lact amsasa( succide)i
nhibit
or

Parmacokinetics:
Well absor bed or al
ly, can be admi ni
stered par entrall
y.
Metaboli
sm ishepat ic,
excreti
onisuri
nary.
Therapeuti
cuse: -
Used incombi nati
onwi th Amoxicil
l
in(Augment i
n)f oror al
administ
rati
on. Theyl eadst o pot
entiati
onoft het herapeuti
c
eff
ectofAmox icil
li
n.
Dose:-1Tabl et(300mgAmoxi ci
l
li
n+75mgcl avuli
nicacid)ev ery
8Hours.
(
IV)
-TheAMI
NOGLYCOSI
DES
ThisclassofAnt i
biot
icsisobtai
nedfrom dif
ferentt
ypesof
Bacteri
a and Fungi i ncl
uding St reptomyces gr i
seus
(Streptomy ci
n)Strept
omy cesfr
adie(Neomy cin)
,Strept
omyces
kanamy cet
ieus(Kanamy ci
n),
Micr
ospora(Gentamycin).
Chemicall
yAminoglycosi
desconsi
stoftwoormor eamino
sugarsjoi
nedbyaGl y
cosidi
cbondtoaHexosenucluesusuall
y
si
tuated i
nt hecenter.Thishexoseiseit
herStr
epti
dineor2
deoxyst
reptamine
Mechanism ofActi
on:-
Aminogl
ycosi
dear er apidl
yBacterici
dalanti
biot
ics.Actby
enteri
ngint
ocy t
oplasm oft hebacter
ialcellwheretheybindto
Polysomes and i
nterf
erwi t
h prot
ein biosy
nthesi
s bycausing
misreadi
ngandpremat ur
et ermi
nati
onofTr ansl
ati
onofmRNA

Ant i
bateri
alSpect r
um: -
Theantibacter
ialspectr
um ofAmi noglycosides(Gentamy
cin,
Streptomy ci
n,Kanamy ci
n,Tobr amy cin,Ami kaci
n) is mainly
confinedtoGr am negativeBacil
lii
ncluding:-
-Pseudomonasaer ugi
nosa -Ent erobacterspp.
-EscheriaColi -Klebsell
a 5pp.
Proteusmi rabil
i
s -Sderrali
aspp.
-Enterococcusf oecali
s -Staphy ll
ococcusaur eus.

NOTESONPHARMACOLOGY 20
DR/AWADELJACKZAYED

Phar macoki net i

cs:-
Ami nogl ysidesar epoor l
yabsor bedbyGI Tbecauseoft hei
r
highpol arit
y(onl ylesst han1%i sabsor bed) .Theyar einact ivated
i
nt he i ntestine,so t he Ami nogl y cosi des ar e admi nistered
par ent r
al l
ywher et heyar er apidlyabsor bed.Wi thexcept ionof
Strept my cin,bi ndingofAmi nogl ycosi dest o plasmapr ot ei
ni s
negl igible,sot heirdi stribut i
oni nbodyt issuesi sv eryl ow.They
can’ tpenet ratBBBandshoul dbei nject edi ntr
athecal l
yt oat tai
n
effect iveconcent rat i
on i n CSF.Excr et i
on ofAmi nogly sidesi s
urinar y.
Adv er ser eact i
ons: -
1/Ot otoxi cit
y :
-Admi nst rat
ionofAmi nogl y cosidesr esultsi nbot h
vest ibular and audi tory dy sfunct ion. Thi s occur s due t o
accumul ationint he per i
lymph and endol y mph ofi nnerear .
Otot oxi cityisirrever si
bl eandi sduet odest ructionofv est ibularor
Cochl earsensor ycel l
s.
2/ Nephr otox ici
ty : - Resul ts due t o accuml ation of
Ami nogl cosides i nt he pr oximalt ubul arcel l
s.Ref lect ed by
prot einur eaandappear anceofgr anul arcast s.GFRi sr educed
afterday sofbegi nningt reatment .Sev ereacut enecr osi smay
occur ,mi ldincr easei npl asmacr eatininei sdet ected.
3/Neur omucul arbl ockade: -
Occuronadmi nistrati
onofl ar gedoses, relativelyuncommon.
4/ St rept omy ci n may cause Opt i
c dy sfunct i
on i nf or m of
enlar gementofBl indspotandper i
pher alneur i
tis.
5/Mi l
d adv erse ef f
ect si nclude:ski nr ash,eosi nophi li
a and
exfol iativeder mat itis.
(
a)St
rept
omy
cin

TherapeuticusesofStr
eptomyci
nar enowr estr
ict
edt
o:-
1/Bacteri
alendocardi
ti
s:i
ncombinati
onwi thPenici
l
li
ns.
2/Tuberculosi
s:-i
ncombinati
onwithIsoniazed.
3/Pl
ague
Doses:
-1gram dail
yfor2-
3month(forT.B.
)
1gram dail
yfor4weeks(f
orEndocardit
is.
)
1–4gr amsdail
yfor7-
10Day s(
ForPlague)
(
b)Gent
amy
cin
Importantint r
eatmentofmany serious Gram Negati
ve
Baci
l
lar
yinfect
ions.I
scommonlyusedfort
reatmentof:-
1/Sensi
tiv
ecompl i
cateduri
nar
yTractinf
ectionsusual
lyin

NOTESONPHARMACOLOGY 21
DR/AWADELJACKZAYED

combi nat i
onwi t
haβLact am.
Dose: -80mgev er y8Hour seforatl east3Day s.
2/Pneumoni a:-Effectiveinpnemoni acausedbyv ari
ousGr am-
negativeBaci l
li
.Shoul dbeadmi ni
ster edaf t
ersensi
ti
vil
yTest.
Givenincombi nationwi thaβ–l actam, .
Dose: -80mg8Hour lyforatleast3Day s.
3/Meni ngiti
s:-Usef ulinMeni ngit
iscausedbyGr am negati
ve
Bacill
i
.Shoul dbeadmi nist
eredintr
athecal ly.
Dose: -30mgperml CSFev er
y24Hour s.
4/Topi cal uses:-
Giveni nt opicalf orms( oi
ntment s,cr eams,eye(ear)dropsor
oi
mt ment s)f ort reatmentofi nf ectionscausedbysensi ti
ve
Bact eri
a.

(
c)Kanamy
cin:
-(Kant
rax)

Canbeadmi nister
edor all
yorpar entr
all
y.UseofKanamycin
islimit
ed because i ts anti
bact eri
alspect r
um isthe l
east
compar edtootherAmi noglycosides.
Usesincl
ude:
-
1/Tr
eatmentofTuber culosi
si fbacteriaisresi
stantt
oother
anti
T.B.Drugs.Dose1gdai ly.
2/Usedorallyf
orprophylaxisincasesofHepat iccoma.
Dose:-4-6gramsdai ly(i
ndi vi
deddoses)f or36to72Hours.
d)Neomy cin

Theantibact
ereialspectr
um isbroad.
Therapenticuses:-
1/Sensiti
veinfect
ionsint heskinandmucousmembr anes
(i
ncombi nati
onwi ther ythromycin) 2/Forpreprat
ionof
Bowel f
orSurgeory.
2/Dose: -4-12grams
N.B.Thehi ghdosei snotdanger ousbecausenoabsor pt
ion
takesplaceandt heact i
onislocal
.
(e)Amikacin(Amiki
n)

A br oad spectr
um Ami nogl
ycoside. I
s resist
ant t o
Ami nogl
ycosi
de –inact
ivat
ing enzyme.Used f or Bact
eria
resist
anttoGentamyci
n.
Dose:- 15mg/ kgbodywei ght(
insingleordi
vi
deddoses)for
atleast5Days.

V-
TETRACYCLI
NES

NOTESONPHARMACOLOGY 22
 DR/AWADELJACKZAYED

Chemi callytetracy cl
insar ederi
vati
vesofthePol ycycl
icnucl
eus.
Naphthacenecar box amide.Theyar eobtai
nedf rom cult
uresof
Str
eptomy cesaur eofaciensandSt rept
omy cesrimosus.Thereare
6types: -
1/Chlortetr
acy cli
ne
2/Oxytetracy cl
ine
3/Tetracycline(semi -synthesti
c)
4/Demecl ocy cli
ne
5/Dox ycycli
ne(semi –sy nthest
ic)
6/Minocy cli
ne
Mechani sm ofAct i
on:-
Tet r
acy cli
nesactbyi nhi
tingBacteri
alprotei
nbiosythesi
sby
bi
ndingt ot he30SBact erialRi
bosomeandpr event
ingaccessof
Aminoacy lt RNAt ot heaccept or(A)si
teoninRNARi bosome
compl ex.
Anti –mi crobialspect rum:-
Tetracy cli
nehav eabr oadspect r
um.Theyar
eeffecti
ve
againstaer obicandanaer obicGr am posi
ti
veandGram negat
ive
Bact eri
a.Sensi tiv
emi croorgani smsi
nclude:
-
-Al
l Gram posi t
ivemi croorgani sms(i
ngeneral)
-Neisseriagonor r
hea
-Neisseriameni ngit
idis
- Haemophi l
lusinfl
uenza
- Staphy l
ococcusaur eus.
- Streptococcusspp
- Pseudomonaspseudomal lei
- Treponomapal li
dum
- Vibriochol era
- Brucel l
aspp.
- Propioni bacteri
um.
- Rickettsiae
- Spirochet es
- Chlamy diaspp
- My coplasmaspp.

Therapeuti
cuses:
-
Duetodevelopmentofresistancebymanystr ai
ns,and
appearanceofsupperi
orAnti
biotics,useofTet
racycli
nesdecli
nes
butsti
lli
susedinthesecases:-
2/DiseasescausedbyMy coplasmas
3/DiseasescausedbyChlamy dia(DrugofChoice)

NOTESONPHARMACOLOGY 23
 DR/AWADELJACKZAYED

4/Sexuall
ytransmit
tedDi
seases
5/Brucell
osi
s
6/DiseasescausedbyShigel
laspp.
7/Actinomycosis
8/Acne
9/Sensiti
veuri
narytr
acti
nfect
ions.

Phar macoki net ics:-

Absor ptioni si ncompl et ef rom GI T. (
About30%i n
chlortetracy cline,60- 80%i nTet racy cl
ine) .Butabsor ptionof
Doxy cy clineandMi nocy cl i
nei sal mostcompl ete.Absor ptioni s
++ ++
i
mpai redbyDi valenti onsl ikeCa &Mg i fconcur rently
admi nist eredduet ochel at ion.Di stri
butionofTet r
acycl inet hrough
thebodyi swi de.Hepat i
cmet abol i
sm occur sbutissi gni fi
cantonl y
i
ncaseofMi nocy cline.Excr et i
onofTet racy cl
ineismai nlyur inary
althoughmi norbi l
iar yex cr etioni st akingpl ace.
N.B.Tet racy clinear eav ailabl einawi dev ariet
yofPhamaceut ical
formsf oror al, parent ral andTopi calappl icat i
on.
Adv erser eact ions: -
1/Gast roint est inal effect s:-irritation,nausea, vomitti
ng, epigastri
c
distress.
2/Hepat otox ici t
y:-hepat icdamage, j
aundi ce,azotemi a, aci dosis,
i
rrever sibleshock.
3/Renal Toxi ci ty:
-Tet racy clinemayaggr av ateuremi ainpat i
ents
withr enal diseases, az otemi ai si ncreased.
4/Di scol or ationofenemal ofTeet hiscausedi nchil
dr enr ecei vi
ng
Tet r
acy clinesorAdul tswhouset hem f orl ongt ime.
5/Phot osensi t i
v i
ty.
6/Hy persensi tiv i
tryr eact i
ons( urtiti
caria, skinRash, erupt i
ons)

Doses:-
 Chlortetr
acycl
ine,
ox y
tetr
acy cl
i
neandTet
racy
cli
ne:-
250–500mg6Hour lyforatleast4Day
s.
*Doxycycli
ne
I
niti
aldoseof200mgt hen100–200mgdai l
yforatl
east5
Days.
 Minocy cl
ine:
-
250-
500mg6Hour l
yforatleast4Days.

VI
-Chl
orampheni
col

Isananti
biot
icpr
oducedbyStr
ept
omy cesvenzuelaeandcan
bechemical
l
ysynthesi
zed.Chemi
cal
lyi
tcontai
nsaNi t
robenze

NOTESONPHARMACOLOGY 24
DR/AWADELJACKZAYED

ri
ngandi sader i
v ativeofdi chlor acet icaci d.
ModeofAct ion: -
Chl or ampheni col act sbyi nhi bi t
ionofpr oteinsynt hesisi n
bacter i
a( andt oal esserext enti nEukar yot i
ccells).Thei nhibit
ion
i
smai nl ybybi ndi ngr ever siblyt ot he50SRi bosomal subuni t
,
l
eadi ngt opr ev ent i
onofbi ndingoft heami noaci dcont ainingend
oftheami noacy ltRNAt ot heaccept orsi teont he50Sr ibosomal
subuni t. Thuspept i
debondf ormat ioni sbl ocked.So, theact i
onof
chlorampheni col isBact er iostatic.
Antimi cr obial spect rum : -
Chl or ampheni col isabr oadspect rum ant i
biot
icef fective
against: -
-Salmonoel l
aTy phi -Brucel l
a spp.
-Haemophi llus -Cl ost ridium spp
-Strep.peneumoni a -St aphy. aur eus.
-Klebsel laspp -pseudmonasaur igi
nosa.
-Vibr i
ochol er a -Shi gel laspp.
-Enter obact erspp -Ri cket tsia.
-Chlamy diaspp -My copl asma
Ther apeut icUses:
Despi tei t
shi ghef ficiencyandbr oadant i
bacteri
al spect rum,
Useofchor ampheni col i
sr estrictedt ospeci fi
cdiseasesbecause
ofdanger ousadv er ser eact i
onsi tpr oduces.I susei ncaseswher e
benef i
tsofchor ampheni col ov erwei ghsr i
sksofi tstoxicity.Such
casesi ncl ude: -
a)Ty phoi df ev er: -
Usedi fmor esaf edr ugs(egAmoxi cil
li
nandCo–
Tri
mox az ole)ar enotsuf f i
ent l
lyef fect ive.
Dose: 1gr am 6hour l
yf or4weeks.
b)Bact er i
al Meni ngi t
is:-
pr efer redi nt reatingmeni ngi t
iscausedbyH.i nfluenza. Given
bylumbarpunct uref or2- 3dayi nadoseof100mg/ kgbody
weightperday.
c)Anaer obici nfect ions:
especi al lyofbowel andpel visi ndoseof250–500mg6
hour l
yf oratl east4day s.
d)Brucel losi s: -
UsedwhenTet racy cl i
nesar einef fect i
ve,indoseof750mg–
1gr am 6hour lyf oratl east4day s.
e)Ri cket tsial di seasesr esi stantt ot et racy cl
ines.
f)Topi cal lyusedf orey e, earandski ninf ections.
Phar macoki net ics:
Wel labsor bedbyor al rout e,par ent ralabsor pt
ioni sal so

NOTESONPHARMACOLOGY 25
 DR/AWADELJACKZAYED

rapidwhenadmi nisteredi nfor m ofchlorampheni col sodi um

succinat e.Bi oavailabitit
yi sabout70%, distri
butioni sgoodand
reachesal lti
ssuesi ncl udingCSF, hepatical
lymet abol izedt o
i
nact ivemet abolit
echl or ampher i
colglucouronide. Excr eti
oni s
mainl yurinar y.T½ i s4hour s.
Adv erser eact i
ons: -
1\Hy persensi t
ivi
tyr eactions: -Notcommon, mayi ncludeski n
Rashes, f
ev er, Angioedema
2\Haemat ologictox icitythemosti mpor tanteffecti sont hebone
mar row.I tcasusesanemi a,l
eukopeni a,ort hrombocy t openia,The
mostdanger ousef f
ecti sApl asticanemi aleadingt of atal
pancy topeni a.
3\GI Tt oxicity:-nausea, vomitting, unpleasantt aste, diarr
hea.
N.B: Tox icit
yofchl orampheni col i
smor epr ominenti nneonat es
duet odel ay edexcr etion.

PHARMACOLOGYLECTURES/4

VI
-MACROLI
DES

Chemi cal l
yhav ealar gemol eculewhi chcontainsmany
member edl actoner i
ngsl i
nkedt oanumberofdeoxysugar s.
Theyar ethr ee.Er ythromy cin,Cl ari
thromy cinandazi t
hromy ci
n.
Modeofact ion: -
Macr olidesar ebact er ostati
cant ibiot
icsobtai
nedf rom
Streptomy ceser ythreus.Theyactbyi nhibit
ingproteinbybinding
reversiblyt o50SRi bosomal subuni toft hesensiti
vemi cro-
organism . Act i
vityis100f ol dsef fi
cientongr am-positiv
emi cro-
organism .
Therapeut i
cuses: -
1. My copl asmal pneumoni ainfections.
2. Chl amy dial infections.
3. Di phther ia.
4. St reptococcal infecti
onsast onsil
li
tis.Pharyngi
ti
sandot her
upperr espi rat orytractinfect i
ons.
5. Gast roent er i
ti
scausedbyCamphy lobacter.
6. Tet anus.
7. Sy phi l
li
s.
8. Gonor r
hea.
N.B:

NOTESONPHARMACOLOGY 26
 DR/AWADELJACKZAYED

Er ythromy cini
sthefirstalt
ernat
ivepr
escri
bedforPeni
cil
l
ins
sensit
iv epat ients.
Dose:-
Er ythromy cinhasthestandarddose250–500mg6hour ly
foratleast4day s.
Azi thromy cin:asingl
edailydoseof500mgf or3days
Cl arithromy ci
n:500mgev ery12hoursfor5days.

Adv
er sereacti
ons:-
1. Allergicreacti
onsfever,eosi
nophi
ll
ia,ski
nerupt
ions.
2. GI Treaction:nausea,v omit
ti
ng,diar
rhea.
3. Chol estati
chepatit
is.
4. Tr ansientaudit
oryimpairment.
5. Rar elymaycausecar diacarry
thmias.

VI
I-
Pol
ymy
xinBandCol
i
sti
n(pol
ymy
xinE)

Thesedr ugsar eextremel ynephr otoxici fadmi nistered

parent ally, sot heyar enowr estri
ctedt ot opical applicationonly
.Polymy xinBandCol i
sti
nar eant i
bioti
csobt ainedf rom Baci ll
us
polymy xaandBaci ll
uscolistinusr espect ivel
y. Theyar echemi cal
ly
si
mpl epept ides.
Modeofact i
on: -
Becauset heyar eamphi pathicagent scont ainingbot h
l
ipophobi candhy drophil
icgr oups, theyi nteractst r
ongl ywi th
phosphol i
pidsl eadi ngtodi sruptionoft hebact er i
alcell membr ane
andconsequent lydeat hoft hecel l.
Antibact eri
al spect rum :-
Rest ri
ctedt ogr am negat i
v ebact eria.Sensi t
iveBact eri
a
i
nclude:
-Ent er obact er -E-col i
-Klebsel laspp -Sal monel la.spp
-Past eur ell
aspp -Shi gell
aspp.
Phar macoki netics:-
Bot har enotabsor bedor all
y,alsopoor lyabsor bedf rom
mucousmembr anesandsur faceoft hel argeBur ns.
Therapeut i
cuses: -
N.BUsesar eonl ylocalinf r
om ofoi ntment, cream , dr ops,
dustingpowder sandl oti
ons.
1. i nf ectionsofey e(conj unct i
v i
ti
s).
2. i nf ectionsofear( External otit
is).
3. i nf ectionsoft heskins.
4. Bur ns( combi nedwi thot hersy stemi cant ibacterials).

NOTESONPHARMACOLOGY 27
 DR/AWADELJACKZAYED

5. Sensi tiv
ei nfecti
ousdi
arr
heaini
nfantsandchi
l
dren(
the
onlyor aluse) ,
Theacti
onisl
ocalonthebowel.
Adverser eactions: -
- Nephr otoxicity(Extr
emeleadi
ngtostoppi
ngofsyst
emicuse)
.
- Hy persensitvitymaybedetected.
-
VI I
I-Vancomy cin
Isant i
bi oticpr oducedbySt reptococcusor i
ent ali
s.Hasav er
y
compl i
cat edchemi calstruct urecont ai ningGl ycopept i
des.
Ant ibact er i
al spect rum:-
Ismai nl yact iveagai nstGr am posi ti
vebact eria.Sensi ti
ve
strainsi ncluy de: -
-Staphy ll
ococcusaur eus -Staph. epidermi s
-Str ep.pneumoni a -Cor ynebact er
ium spp
-Enter ococcusspp. -Clostridium spp
-Lact obaci l
lus -St rep.v ir
idans
- St aph.hemol y ti
cus.
Phar macoki net i
cs: -
Poor lyabsor bedbyor al route,soi sadmi nistered
i
nt rav enousl y, par tiall
yboundt opl asmapr ot
eins, dist r
ibuti
oni s
widei nal lbodyt issuesi ncludi ngCSF.Notsi gni fi
cant l
yaf f
ectedby
met abol ism ( 90%oft hedosei sexcr et edunchanged) ,Excreti
onis
renal .
ModeofAct ion: -
Vancomy cini nhibit
ssy nt hesisoft hecel l wallinsensi t
ive
bact er i
a- IsBact er icidal
.
Ther apeut i
cuses: -
1. Psendomembr anouscol itis
2. Ser iousi nf ect ionsresi stantt oot herAnt ibacter ials.
3. Di pht her i
a
4. Endocar di tis.
Adv er seef fect s:-
- Hy per sensi tivity :
-muscul arRashandanaphy l
axis.
- Phebi t i
sandpai natinject ionsi te
- I.V.admi nist rat i
oni ninf usionf orm maycausechi l
ls,
tachy car diasandf lushing.
Dose: -125–250mg6Hour lyf oratleast4day s.

IX-
Baci
tr
aci
n
I
sanant
ibi
oti
cproducedbyBaci
ll
ussubt
il
is.
Chemi
cal
l
yisapoly
pepti
de.

NOTESONPHARMACOLOGY 28
 DR/AWADELJACKZAYED

Pharmacokineti
cs:
-
UseofBacitr
acinisrest r
ict
edtoTopical
appl
i
cat
iononl
y.
Antibact
eri
alspectrum:-
-Gram posi
tivecocci -Nei sseri
aspp
-Haemophil
lusspp -Tr eponemapalli
dum
-Act
inomyces -Ent erobact
eri
aceae

ModeofAct ion: -
Actbyi nhi bi
tionofcellwall synthesis.
Therapenticuse: -
Usedt opi call
yinform ofoi ntment s,powdersorsol
uti
onsf
or
tr
eatmentof :-
1. Ski ninf ections(e.g.pyoderma, Abcesses)
2. Opht halmi cinfecti
ons( conjuctiva,cornea)
Dose:-Applicationf or2to3t imesdai ly
.
Adverseef f
ect s:-
- Seriousnephr otoxici
ty
- Hypersensi tivi
tyreacti
on( Al
lergy, urt
icari
a)

ANTI
-TUBERCULOTI
C DRUGS
ThePr
imar
yAnt
i-
TBDr
ugsi
ncl
ude:

1\I
soni
azi
d(I
NH)

I
sani mportantpr i
maryAnt i-
TBDrug,
chemicallyi
st he
Hy drazi
deofisonicotinicacid.
Ant i
bacter
ialacti
vity:-
I
NHi sbacteriostat
icforresti
ngBacil
l
i,butbacteri
cidalf
or
thoser api
dlydiv
iding.INHi sselecti
vef
orMy cobacteri
a.Itcan
penet r
atethecellwal lwhil
eStreptomyci
ncannot( i
ngr owing
stage).
Mechani sm ofAct ion:-
Itissuggest edt hatIsoniazedinhibitcellwall
synthesi s(specifi
callyinhi
bitsbiosynthesisofmy col
icacidwhich
i
sf oundonl yi nMy cobacteria)
Pharmacoki neti
cs:-
Absor ptionisr apidfr
om GI Torpar entall
y ,
dist
ri
butestoall
bodyt issuesi ncludingCSF, signifi
cantl
yaf fectedbymet aboli
sm i
n
l
iver,excr etedur i
nary
Therapeut i
cuses: -
- I
NHi st hemosti mpor t
antant iT.
Bdr ugi nthewhol eworld,i
s

NOTESONPHARMACOLOGY 29
 DR/AWADELJACKZAYED

activeagai nstallty pesofMy cobacteria.

- Py r
idox ine(15-50mg\ day )shouldbeadmi ni
ster
edwithINH
tomi ni mizet hesi deef fects.
Dose: -10-20mg\ kgbodywei ghtaccor dingtoseveri
tyofthecase
.Max imum dai l
ydosei s600mg.
Adv erser eact i
ons: -
-Rashes -Fev er
-Peripher alneuriti
s -Jaundice
- haemat ological changes( Agranulocytosis,eosi
nophil
i
a,
thombocy topenia, anaemi a).
- Epigast icdistress.
Ov erdose; -
Causescoma, seizures,metabol i
cacidosisand
hyper glycemi a.
Ant i
dot e: Ispyridox i
negi v
eni nadoseappr oximatel
yequival
entto
i
ngest edI NH.
2\Rifampi ci
n

Isasemi -
synthest icant i
bioti
cchemi callyobtai
nedf r
om
Rif
amy cinwhi chispr oducedbyst rpt
omy cesmedi trr
anei –The
str
uctur eofRi fampi cini scompl exmacr ocy cl
ic.
Antibact er
ialactiv
ity
Ri fampicininhi bitsgrowt hofmostgr am positi
veandgr am
negativebact eria,alsoact iveagainst
– E.col i
– Pseudomonasspp
– Prot eusspp
– Klebsel l
aspp
– Staph. aureus.
– Nei sseriameni ngi ti
dis.
– Haemophi l
lusinfluenza
– Rifampi ciniseffect iveagainstal l
ty pesofMy cobacteri
a
(t
uber culosis,Kansasi ,i
ntracel
lulare,
ov icem, scrof
ulacem)
Modeofact i
on
Actbyi nhibi
tionofDNAdependentRNApol y
mer aseoft he
My cobact eri
um andot hermi croorganisms, l
eadi
ngt oblocki
ngt he
i
niti
ationofchai nfor mat ioninRNAsy nt hesis.

Phar
macoki neti
cs:
Oralabsorptioniswell,
peakplasmaconcentrati
onobt ai
ned
af
ter2-4hour s,afterabsor
pti
on,Rif
ampici
niseliminatedrapi
dly
bybi
leandunder goesent er
ohepati
cCycle.T½ isappr oxi
mat el
y
4hours.Widelydistri
butedt
hroughoutbodyti
ssuesincludi
ngCSF

NOTESONPHARMACOLOGY 30
 DR/AWADELJACKZAYED

.Excr etionismainlyur i
nary, bil
iaryexcr
etionispresent.
Ther apeut i
cUses: -
1. Tr eatmentofT.B(i ncombi nati
onwi thINH) ,
isafir
stli
ne
drugf orT. B.
Dose: 600mgdai ly(inasi ngledose)
2. Tr eatmentofGonor rhea
Dose: 900mgsi ngledosedai l
yfor3successi vedays.
3. Tr eatmentofmeni ngitis.
Dose: 600mgdai ly(singledose)f oratleast2day s.
Adv erseef fect
s:-
-Rashes -Fever
-Nausea&v omit
ti
ng -Jaundice
-Apot entenzy meinducer( shor t
ensthehal fl
if
eofmanydr ugseg
β-Blocker s,ver
pami l
, quidine, digoxin,oralanti
co-agul
ants
,steroids) .

3/Et
hambut
ol
Synthest
icanti
bact
eri
aldrugacti
veagainstnearlyall
strai
ns
ofMycobacter
ia.Hasnoeff
ectonothertypesofbact eri
a.Is
eff
ect
iveagainstINHandStreptomyci
nresi
stantMy cobateri
a.

Phar macoki netics:

80%ofor all
yadmi nist
ereddr ugisabsorbedf rom GI
T, onl
y
25%oft hedosei saf fectedbymet abolism ,
excret
ionisuri
nary.
Ther apeut i
cuses: -
Tr eatmentofdi ff
er entformsofT. B.whengi v eni
n
combi nat i
onwi thisoni az id.
N.B: Ethambut olisnotr ecommendedf orchil
drenbelow5y ears
(becauseofi t
sdi stur banceofv i
sualacui t
y).
Dose15mg\ kgbodywei ghtdaily.
Adv erser eact
ions: -
- Dimi nshedv isual acuit y.
- Rashes.
- Fev er.
- GITupset.
- Headache, dizziness, ment alconf
usion.
- Opt icneur i
tis.
4\St
rept
omy
cin
Wast hef
irstdrugusedfortr
eatmentofT.
B.,wasgivenin
l
argedoseswhichincreaset
oxici
tyandemergenceofresi
stant

NOTESONPHARMACOLOGY 31
 DR/AWADELJACKZAYED

strains.Wi t
happearanceofothermor esafeandef f
ecti
v eantiT.
B
drugs, useofSt rept
omy ci
ndecli
ned(duet oresi
stantstrai
nsand
toxicit
yoft hedrug).Treat
mentofT. Bneeduseof3dr ugsin
combi nation.Streptomyci
nisusedbysomer egi
mensf or2-3
mot hst henreplacedbyanotherant
iT.B
DoseofSt reptomycininT.
Bt r
eatment:-
15mg\ kgbodyweight(intwodivideddoses)Amaxi mum
of 2gr amsshoul dnotbeexceeded.

5\Py
razi
nami
de

Synt hest i
cAnt iT. B.,chemi call
yisananal ogofnicoti
nami de.
ActivityofPy razinami dei sr estri
ctedt oMy cobact eri
um
tuber culosi s.
Phar macoki netics: -
Wel labsor bedor all
y, distri
butioniswi dei ndiff
erentbody
ti
ssues, met abol izedandi nact ivatedinliver,excreti
oni suri
nary.
Ther apeut i
cuses: -
Acomponentofshor tterm (6mont hs) mul ti
pledrugtherapy
ofT. Bot hercomponent sincl udeRi fampicin,INHorSt r
eptomy cin.
Dose: 15-30mg\ kgbodywei ghtor all
y
Adv erser eact i
ons:
- Hepat ot i
xicit
y(j aundi ce, hepat i
cnecrosis)
- Hy per ur i
cemi a( EpisodesofGout)
- GITdi stur bances( Anor exi a,nausea, vomi tt
ing).

6\Et
hionami
de

Synthest i
c ant iT. B.Der iative of t hi
oiso-
nicotinamide .
Eff
ectiveonlyagai nstMy cobacterium t uberculosis.
Pharmacoki netics:-
Oralabsor ptioniswel l,T½ i s2hour s,dist
ri
butionisrapid
andwi dethroughal lbodyt issues( includi
ngCSF),met aboli
zed&
i
nactivatedbyl i
v er,exeretioni surinary.
Modeofact i
on: -
Notcer tai
n, suggest edtobet ypicaltot hatofSulphonami des
.
Therapeuticuses: -
Secondar yant iT.B.dr ugadmi nisteredwi thprimar ydrugs
(St
reptomy cin, I
NH).

NOTESONPHARMACOLOGY 32
 DR/AWADELJACKZAYED

Dose:
250mgt
wicedai
l
y(or
all
y)

Adverser eacti
ons:
- GITdi sturbances(anorexia,
nausea, v
omi t
ti
ng),
- post uralhy pot
ension,ment aldepr
ession,dr
owsness.
- Blurr
edv i
sion,dipl
opia, di
zziness.

Ant
i–Mal
ari
alDr
ugs

Antimal arials can be cl assified accor di

ng to stage of
parasitet heyaf f
ectt o:-
1\Schi zonot ocides: -actagainstlatentoract i
vet i
ssueforms.
a)Tissueschi zontocides: -
Primaquinechl orquanide(Proguani
l).
b)Blood schi zont ocides :-Chlor
oqui ne,qui nine,mef logui
ne,
artemet her,ant if
ol at
esandant i
biot
iccompounds.
2\Gamet ocytocides: -
Effecti
v e agai nstsexualer t
hr ocyti
cf orms ofPl asmodia
preventingt r
ansmi ssionofmal ariatoMosqui t
os.
3\Spor nt oci
des: -actbypr eventi
onoff ormationofmal ari
aoocyst
andspor ozoitesini nfectedmosqui tos

(
1)4–Aminoquinol
i
nes
Chl
oroqui
ne.

I
st hemostcommonl yusedant i
mal ar i
al.I
sasy ntheticant i
mal ari
alcont ai
ningthe4ami noqui nol i
ner i
ng.
Activit
y:-
Chloroquineishi ghlyef f
ectiveagai nster yt
hrocy ticformsof
plasmodi um v ivax,P. ovale,P.mal ari
eand sensi tivest rainsof
P.falci
parrum .Isgamet ocy toci
dal i
nt he3f irstspp.
Modeofact i
on: -
Not y et certain ,suggest ed t o be by i nt eraction of
chloroquine( andot her4-ami noqui nolines)wi thpar asitenucl ei
c
acids( DNA, RNA)bi osy nthesi
s. Act iondependsont heabi lityof
the er y
throcy t
es to accumul atet he dr ug selectively. In bl ood
concent r
ationofchl oroqui netoahi ghlev elleadst or aisingi npH
i
nf oodv acuol eofsensi ti
vemal ariapar asite.
Phar macoki neti
cs:-
Chloroquineiswel labsorbedf rom GI T,par entalabsor pti
on
i
sal sor apid. Dist
ri
but i
oni sslow butwi det oallbodyt i
ssues

NOTESONPHARMACOLOGY 33
 DR/AWADELJACKZAYED

(i
ncludi ngCSF).met abolism i shepat i
c,t hemaj ormet aboli
te
hav i
ngant imal ar ialact ivi
ty.Theexcr etioni smai nlyur i
nary,a
portioni sex cretedbi li
ar y.
Ther apeut icuses
- Themostcommonl yusedant imalarial,i
st hedr ugofchoi ce
i
fpar asiteissensi t i
ve. Thatisduet obei ngl esst oxicandmor e
effect i
vecompar edwi t
hot herdr ugs.
- Effect i
vei npr ophy lax i
sagai nstmal ariacausedbysensi ti
ve
Plasmodi a.
- Usesot hert hanAnt imal ari
alofchl or oquinear e:Tr eatment
ofHepat i
cAmoebi asis,Rheumat oi
dAr thr i
ti
sandDi scoidlupus
erythremat osus.
Adv erseef f ect:-
- Gast roi ntest inal upset (Nausea, vomiting)
- Transi entmi ldHeadache
- Visual Di stur bances
- Urt i
caria.
- Car diovascul aref fect:-Tachy carr
dia,Hy pertensionandECG
abnor mal iti
es.
- Ret i
nopat hy( especi allyincaseofHi ghdosesandpr olonged
use)
- Ot otoxicity.
Dose r egimen: -
Or al:4t abl ets(1g)asi ni
t i
aldose,2t ablets(
500mg)af t
er6
Hour st hen500mgdai l
yf or3day s.
Parental
:
-1inj
ect
ion(
200mg)i
nit
ial
l
y,1i
nject
ionaf
ter6Hour
s,1
i
njecti
ondai
l
yfor3day
s
Thenewr egimenofWHOi s:-
4tabl
ets(
1i nj
ection)i
niti
all
y,2tabl
et(1i
nject
ion)af
ter6hour
st hen
2tabl
ets(
1inject
ion)ev ery12hoursfor3day s.
Amodiaquine( f
lavoqui
n) :-this4– ami noqui
noli
neisnol onger
usedbecauseofhepat otoxici
ty.
(
2)Py
rimt
hami
ne(
Dar
apr
im)
I
schemi call
yaDiami nopyri
midine.
Anti protozoal activi
ty:
-
I
sasl owact i
ngbloodschi zontoci
de.Activi
tyisgr
eaterthan
chloroquani de. Not ef f
ect i
ve agai nst hepat i
c forms of
P.Falciparam.I n combi nati
on wi th Sulphadi
azi
ne is used for
therapyofToxopl asmosis.
Modeofact ion:-
Actbyi nhibit
ingDihydrofol
atereductaseofPlasmodia(Anti
-

NOTESONPHARMACOLOGY 34
 DR/AWADELJACKZAYED

f
olat
e)

Phar macokinet i
cs
AbsorptionbyGI Tissl ow butcompl et
e,boundtoplasma
prot ei
ns,T ½ i s85Hour s,met abolism i shepati
c,excr
eti
onis
uri
nar y.
Ther apenti
cuses: -
-Incombi nationwithsulphdoxine,isgi venasasecondl i
ne
drugfortreatmentofchloroquine–r esi
stantmalar
ia
- usedpr ophy l
act
ical
l
yagai nstP.falciparum.
Adv ersereactionst
:-
-Rashese, depressi
onofhemat opoiesis.
-Highdosesmaycausemegal oplasti
cAnaemi a.
Dose
Treat ment:75mg( combinedwi t
h1. 5gsul phadoxi
ne)asasingl
e
dose.
Prophy laxi
s:50mg\week.
(
3)Chl or oguani de(Proguani l)
Chemi cal lyisasy nthest i
cbi gunidedr ug.Relat
eddr ugsar e
Tri
az ine( Cy cloquani l)andChl oroquanil (
Lapudr ine).
Modeofact ion: -
Actbysel ect i
vei nhibi ti
onoft hebifunctional (
Dihydrofolate
–reduct aset hy mi dylatesy nthest ase)oft heplasmodui m, l
eadi ng
toinhi biti
onofDNAsy nthesi sanddepl etionofFol atecof actors.
Theact i
oni sv er yslowcompar edt oquinolineDr ugs.
Phar macoki net ics:-
Absor ptioni sadequat ebutsl owf rom GIT, T½ is20Hour s,
met abol izedhepat i
callyt ot heact i
vemet aboli
teTr i
azi
neandot her
i
nact ivemet abol i
tes.Excr etioni suninary.
Ther apent icuses: -
Forpr ophy l
axisofmal ari
acausedbyPl asmodi um v i
vax
(Gi
v eni ncombi nat i
onwi thchl oroquine)
Adv erseReact ion:
- Nausea, Headache, vomi tti
ng, diar
rhea.
- Haemat uria.
Dose: 200-300mg/ weekl y (forDr ophylaxis).

(
4)Mef
loqui
ne(
Lar
iam)
Synt
hesti
cant i
malar
ial
–chemi call
yisa4aminomet hanol
,
usedforprophyl
axisandtr
eatmentofchloroqui
ner
esist
antP.
eal
cipar
um malaria.I
sabloodschri
zontoci
de.Notef
fecti
ve

NOTESONPHARMACOLOGY 35
 DR/AWADELJACKZAYED

againstear lyhepat i
cst ages.
ModeofAct ion: -
Actst obebyi nterferingwi t
hDNA r epli
cati
onofpar asi
te.
Phar macoki net ics:-
Givenor al l
y,absor pt i
oni sveryslow( peakplasmaconc.
reachedaf ter17Hour s).Hi ghlyboundt oPl asmapr oteinsand
widel ydistri
but edi nbodyt issues, hepticall
yi ssl
owlymet aboli
zed.
Excr etedur i
nar y.
Ther apent i
cuse: -
-Alonei susedonl yforpr ev enti
onandt reatmentofchl oroqui
ne
resistantmal ar i
a.
-prothy l
axisf ornon- i
mmunei ndi
viduals( Travell
ors)
Adv erser eact ions: -
-GI Tdi sturbances( nausea, vomitti
ng, diarrhea)
- Diz zi
ness, atax i
a, di
sor ientati
on, sei
zur es.
Dose: -250- 500mg( i
ndi vided2doses)

(
5)Pr
imaqui
ne
Sy nthestic8-met hoxyquinolineant imalarial
.Isact i
ve
againstlatehepat icstagesandl atenttissuef ormsofP.v ivax&
P.ovale.Isusef uli
nirradicat
ionofr elapsingmal aria.Isactive
againsthepat i
cstagesofP. Falciparum, butnotact iveagainst
eryt
hrocy ti
cst ages,soi snotusedi ncaseofP.Fal ciparum.
ModeofAct ion:-
Byaf f
ectingaffectingoxidation–r educt i
onenzy mesoft he
parasite.
Pharmacoki neti
cs:-
Isusedonl yorally(par
ent r
allycauseshy potensin)
Absorpt i
onf rom GITiscompl eteandr apid.Wi delydistri
butedin
bodyt i
ssue, inacti
vatedbyhepat i
cmet aboli
sm, urinaryexcreted.
Therapenticuses:-
-
Reservedf orTerminalpr ophyl
axisandradical cur
eofP.v
ivax&
P.oval
emal ari
a( Giv
ent ogetherwihchloroquine)
Adversereactions
-
Epigastri
cdistress(Anor exi
a,Nausea,vomitting)
-
Mi l
danaemi a, cy
anosis,leukocyt
osis.
-
RarelyHy pert
ensionandAr ry
thmia.
Dose : 60-120mg/ dayi nasingledosefor14Day s.

(
6)Qui
nine

NOTESONPHARMACOLOGY 36
 DR/AWADELJACKZAYED

Themostanci entAnt imalar ial.Nat ur al alkaloidobt ained

from Ci nchonabar k.Hasacompl icat edchemi calstruct ure
cont ainingqui nol i
ner i
ngandqui nucl idiner ing.
Qui ninei spr imar lyabl oodschi zont ocide.Ef f
ectonpr e
–er y throcy t
icf ormsi sl i
ttl
e.I sGamet ocy tocidal forP.v ivaxand
P.mal ar iae( butnotP. falciparum) .
Notusedpr ophy l
act i
cal ly.Isless
effect i
v eandmor et ox icifcompar edt ochl or oqui ne.
Modeofact ion:-
Ty pical t
ot hatofchl oroqui ne( i
nt erferswi thpar asi teDNA
andRNAbi osy nthesi s).
Phar macoki netics: -
Readi lyabsor bedf rom or al andpar ent ral r
out es,di stri
but ion
i
swi dei nbodyt issues.T½ i s15Hour s.Boundt opl asmapr oteins.
Ext ensi v elymet abol izedi nliver( 80%oft headmi nistereddose) ,
ex cret edur inaryandaci difyingur i
nei ncreasest her ateof
ex cret ion.
Ther apeut icuses: -
- Tr eat mentofchl oroqui ne–r esi stantMal aria.
- Gi v eni nitiall
yI .
V.f orsev erelyi l
l mal ariapat ientf orpr ompt
effect .
Adv erser eact i
ons: -
Qui ninei shi ghlyt oxic.Adoseofmor et han2gr amsor all
yi s
fatal .Adv erser eact i
onsaccompany ingTher apeut icdosesof
qui ninei nclude: -
1/GI Tdi stur bances: Nausea, v
omi tting, diarrhea, cramps.
2/Ski nr ashes, f
ev er ,Angi oedema.
t
h
3/I mpai rmentoft he8 cr anial ner ver esul ti
ngi nTi nnitus,
decr easedAudi t
or yacui ty,verti
go.
4/Bl ur redv i
sion, phot ophobi a,dipl opia, nightbl i
ndness, my driasis.
5/Hy pot ensi on( ifdr ugi sadmi nist ered( I
.V)r api dly)
6/Heamogl obinur ia,anur ia&r enal f
ai l
ure
7/Hi ghdosesofQui ninel eadt oabor ti
on.

(
7)Hal
ofanf
ri
ne(
Hal
fan)
Synthesti
cant imalari
alhav i
ngchemi calstr
ucture
resembli
ngQui nine.Usedagai nstP.f al
ciparum resi
stantto
chlor
oquine.
Modeofact i
on:-
Actbycombi ni
ngwi thferr
iprotoporphy r
inIXinparasit
es
formingtoxiccompl exesthatdamagecel l membr ane.
Pharmacoki net
ics:-
Givenonlyor al
ly,absorpti
oni swell butslow, di
str
ibuti
oni
s

NOTESONPHARMACOLOGY 37
 DR/AWADELJACKZAYED

wideT½ i smor ethan10hours.Af

fect
edbymetaboli
sm i
nli
ver
andexcreteduri
nary.
Therapeuti
cUses: -
Alt
ernat
iveforMefl
oquineandQuini
nei
nterat
mentof
chlor
oquineresi
stantmalar
ia.

Adversereacti
on:-
- GITupset( Nausea,
vomi
tti
ng,di
arr
hea).
- Pruri
tus,ski
nRashes
Dose:-8mg\kgbodywei ght6hourl
yfor3Day
s

(8)Anti
bact eri
al dr
ughavinganti
mal ari
alacti
vit
y
1\Sulphonami des:sl owact i
ngbloodschizontocides,
usedi
n
combinationwi t
h Py r
inethemine.
eg:sulphadox i
ne, sulphadiazi
ne.
2\Tetracycli
nes:
Usefulintreatmentofacut emalari
ai ncombi nat
ionwi
th
chl
oroquine.
eg:Dox ycli
negiv enbidf or5Dayswithchloroquine.

-
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--

ANTI–AMOEBI
CDRUGS
1\Metr
oni
dazole:
-(Fl
agyl)
Synt
hest
ic(2Nit
roi
midazol
e)der
ivat
ive.

Ant i
par asit
ic&ant i microbialAct i
vit
y: -
Met ronidazoleisef f
ect i
veagai nsttheseProtozoa:-
- Entamaoebahi stolyt
ica–Tr ichomonasv aginal
is.
- Gar dialambel l
a.
Alsot hesebact erialsppar esensi ti
ve:-
-Bact eroidesspp -Clostri
dium spp
-Hel i
obact erspp -Fusobact eri
um spp
Modeofact ion:-
Met ronidazoleact i
vityneedsi tsreducti
onbysensi ti
ve
organismst opr oducemet abolitest hati
nterf
erewi t
hhelical
structureofDNAl eadingt oimpai rementofDNAf uncti
on.
Phar macoki net i
cs:-
Absor ptioniscompl eteandpr omptf rom GITdist
ributi
oni
s

NOTESONPHARMACOLOGY 38
Scanned by CamScanner
Scanned by CamScanner
Scanned by CamScanner
Scanned by CamScanner
Scanned by CamScanner
 DR/AWADELJACKZAYED

widet oal lbodyt issues.Onl y10%t headmi nstereddosebi nds

withpl asmapr oteins, met abol i
zedbyl i
verandasmal lport
ionby
i
ntest inalf l
ora.Excr etioni sbot hur i
nar yandbi l
iary.
Ther apeut icUses: -
- Amoebi asis:-met r
oni dazol eisamoebi cideandi st hedrugof
choice.Act i
veagai nstal lsy mpt omat i
cf or ms.
- Trichomoni asi
s: -forbot hmal eandf emal e.
- Giar di
asi sagainstbot hacut eandchr oni ccases.
- Ser i
ousanaer obici nfect i
ons: -giveni ni nfusionfor min
combi nati
onwi t
hanot herAnt ibioti
c.
Adv erser eaction:-
1\Headache 2\Nausea 3\Dr ymout h.
4\Di arrhea 5\Abdomi nal crmps 6\Di zzi
ness.
7\Ver ti
go 8\Ur t
icaria 9\Fl ushing.
N.B: -Concur r
entdr inkingofal cohol i
cwi thmet ronidazoleresult
s
i
nAbdomi naldistress, vomi t
ting,flushingandheadache.
Dose: -
- Amoebi asis:750mg( threet ablets)3t imesf or5day s
- Giar di
sis: 250mg(1t ablet)3t i
mesf or5day s.
- Trichomoni asi
s: 250mg( 1tablet)3t i
mesdai l
yf or7day s.

2/Dil
oxanidefuroate(
Fur amide):
chemical
lyisadichloroacet
amideder i
vat
ive.I
sdir
ect
amoebicidedrug.
Pharmacokineti
cs:-
Absorpti
oniswel l
andrapi d.Dist
ri
buti
oniswide,metabol
ism i
s
hepati
c,excreti
onisurinaryasGlucouroni
de

Ther apeuti
cUses: -
- Effecti
veintreat
mentofasy mptomati
cpasser sofcyst
sofE.
histolyt
ica.
- FortretmentofExt r
aintesti
nalamoebiasi
s, di
loxani
de
furoateshouldbeadmi ni
steredwithanot
herAnt i
-amoebic
drug.
Dose: -500mg(or all
y)3t i
mesdai lyf
or10day s.
Adv ersereacti
ons:-
Mi ldincludi
ngf lat
ulance,vomitt
ingandUr t
icari
a

PHARMACOLOGYLECTURES/
5

ANTI
-FUNGALDr
ugs

NOTESONPHARMACOLOGY 39
 DR/AWADELJACKZAYED

A)sy stemi cAnt ifungal Drugs: -

1)Amphot ericinB: -
An ant ifungal ant i
biotic obt ained f r
om cul tures of
Str
ept omy cesnodosus.Chemi callyisaPol ymacroli
de. Iswat er
i
nsol ubl esof or mul atedasi ntr
av enousi nf usion.
Modeofact i
on: -
Act sbybi ndingwi thst erols( mainlyEr gost er
ol)foundi nt he
cel
lmembr aneoft hesensi ti
vef ungi ,thisl eadst ofor mat ionof
poresandl eakageofcel lcont ents.
Pharmacoki net i
cs:-
Amphot ericinBi snotabsor bedbyGI T,soi sadministeredI .V.
wher ei tbi ndswi thpl asmapr oteins( 90%). Dist
ri
buti
oni swi de
i
ncludi ngCSF.Met aboli
zedsl owl yi nthel i
v er.Excr
etioni sbot h
uri
nar yandbi liary.
Therapeut i
cUses: -
1\Candi diasis ofoesophagus : -t herapeut ic dose is 0. 15-0.2
mg\ kgbodywei ghtdai l
y.
2\Meni ngiti
scausedbyCocci dioides: -I njectedinto CSFi na
maxi mum doseof0. 5mg\kgbodywei ght\ day.
3\ Mucor my cosis, i nvasive Asper gill
osi s ,Cryptococcosi s,
Fusar i
osi s.
4\Topi call
yi susef ul f
ortreatmentofCut aneousCandi diasis.
Adver seReact i
ons: -
-Fever - Chi ll
s- Hy perpnea.

2)Flucytosine: -
Asy nthest i
cFl uor i
natedpy ri
midineAnti-fungal.
It
sant if
ungal spect rum includes:-
- Cryptococcusneof ormans
- Candi daspp.
- Candidagl abr ata
ModeofAct ion:-
I
s deami nat ed bysensi t
ive Fungito pr oduce the pot
ent
Antimetabol iteFl uor ouracil
,thisisei t
herincorporatedi nRNAor
i
nhibitsThy mi dy l
atesy nthestaseofthesensi t
ivefungi .
Pharmacoki netics: -
Wellandr api dlyabsor bedbyGI T,widelydistri
butedi
nbody
ti
ssues, bindingt opl asmapr oteinsisinsi
gnifi
cant. Onl
y20%oft he
admi ni
stereddosei saf fectedbymet abol
ism .Excreti
onisuri
nary.

NOTESONPHARMACOLOGY 40
 DR/AWADELJACKZAYED

Ther apeut icUses: -

- Candi diasi sofur inar ytract .
- I
nf ect ionscausedbyy eastandf ungi( incombi nat i
onwi th
Amphot er icinB)
- Cry pt ococcal meni ngiti
s.
Adv erseef fect s: -
- l
eukopeni aduet obonemar r
owdepr essi on.
- Nausea, v omi t
t i
ng, diarrhea.
-
B)Imi daz ol esandTr i
az oles: -
Antifungal Act ivit
y: -
-Candi daal bi cans -Candi dat ropi calis
-Candi dagl abr ata -Cry pt
ococcusneof ormans
-Blast omy cesder mat it
idis -Hi st
opl asmacapsul atum .
-Der mat ophy tes -Coccidioi desi mmi tis
ModeofAct ion: -
Actby i mpai rmentofbi osy nthesi s ofEr gost eroloft he
cytopl asmi cmembr anel eadi ngtodi srupt ionofFungal cell.
1\Ket oconaz ole: -(Ni zoral )
Isgi venor allyf ort r
eat mentofmanysuper ficial andsy stemic
fungal infect ions.
Phar macoki net ics: -
Showi nt raindi vidual v ar i
ati
onsi nor alabsor ption.
Absor ptioni si mpai redbyconcur rentadmi ni
strat i
onofAnt acids
.Met abol ized ex tensi velyi nt he l i
v er . Reaches Ker atinocytes
effi
cient l
y.Met abol izedsl owl yinthel iver,excr etedur inary.
Ther apeut icUses: -
Usedi nt reat mentof: -
-Blast omy cosi s - Hi stoplasmosi s-Ri ngwor m –Ti neav ersicolor
-Candi dav ul vov agi nal i
s–Or alandoesphageal candi di asis.
Adv erser eact ion: -
- Nausea, anor exiaandv omi tti
ng.
- Aller gicr eact ions.
- Menst rual dist urbancesi nFemal es.
- Decr easedLi bidoi nMal es.
-
3\Fl uconazol e: -
Chemi cal lyisf luor i
nat edbi st
riazol e.
Phar macoki net ics: -
Absor pt ion f rom GI Ti s almost compl ete. Can al so be
admi ni ster ed par ent rall
y( I.V).Di stribut i
on i swi det o allbody
ti
ssuesi ncl udi ng CSF .Excr etion isur inar y.Pr otein bi nding is
i
nsigi nficant( 11%) .

NOTESONPHARMACOLOGY 41
 DR/AWADELJACKZAYED

Ther
apeuticUses:-
- Candidaiasi
s:Inadoseof100-200mgdai l
yisef f
ecti
ve
agai
nstoesphagealcandidiasi
sandor opharyngealcandi
diasi
s.
Adoseof400mgcant reatBonemar rowcandi di
asis.
- Crypt
ococcosis :A dose of200mg\ day is eff
ici
entfor
tr
eat
mentofcr ypt
ococcal meningi
ti
s.
Adv
erseReact
ion:
-
1. Nauseaandv omi
tt
inganddi
arr
hea.
2. Headache–skinRash.
3. Alopeci
a.

C\Gr i
seof ul
vin: -
Ischemi call
ynoti mi dazole,wat erinsoluble.Isf ungi st
at ic
against Der mat ophy t
es, Mi cr ospor a, Epi sermophy ton and
Tri
chophy t
on. HasnoAnt ibacterial activit
y.
Phar macoki net i
cs: -
Or alabsor ptionissl ow,hasT½ of24hour s,
met abolized
sl
owl yto6met hylgri
seofulvi
n, deposi tedinKer ati
nprecur sorcel ls
.Excr etedur i
nar y.
Ther apeut i
cUses: -
-My cot i
cdi seasesofski n, hai
randNai lscausedbysensi tiveFungi
.Thesei ncl
ude:Ti neacapi t
is(inf ectionofhai r),Ri
ngwor m( Skin),
Athet e’
sf oot.
Dose: -
10-15mg\kgBodywei ghtf orchi l
dren/ day .500mg–1gf or
adults/day.
Treat menti scont inuedfor6mont hst o1y ear.( Unt
ili
nfect edski n.
Hairornai li
sr eplacedbynor mal one)
Adv erseef fects:-
Hasmi ldadv er
seeffectsincl uding:-
Headache,Per i
pheralneur i
ti
s,ment alconf usion,Blurr
edv i
sion
andFat i
gue.

B)TOPICALAnt ifungalDr ugs:-

Useoft hesedr ugsi sconf i
ned tot hestrat
um corneum,
squamousmucosa, andcor nea.Diseasesinvol
vedincl
ude:-
-Dermat ophytes( Ringwor m) -Candi diasis
-Tineaversicolor -Ti
neanigra
-FungalKer at
itis
1\Ny stati
n( My costati
n) :
I
s an Ant i
fungalant ibiot
ic obtained fr
om Cultures of

NOTESONPHARMACOLOGY 42
 DR/AWADELJACKZAYED

Strept omy cesnour sei.Modeofact ionistypicalt

oAmphot eri
nB.
Phar macoki net ics: -
Isnotabsor bedor all
y,notusedsy stemat i
call
ybecauseof
highNephr ot ox icity.
Ther apeut i
cUses: -
- Vagi nalcandi diasis:gi v
eni nfor m of100. 000I.Upesseri
es
twicedai lyf oratl east5day s.
- Or alcandi diasi s:gi veni nf orm oftopicalsuspensionforuse
Buccal cavity.
- Ski nfungal infect ions: Appl i
edasoi ntment sorcreams.
-
2\I mi dazolesandTr i
azoles: -
For mul ated as dust ing powder s,oi ntments,creams or
l
ot i
ons.Theyi ncl ude: -
- Clot r
imaz ole( Canest en)
- Ket oconaz ole( Ni zoral ).
- Mi conaz ol e.
3\Tol naft
at e: -
Isat hi ocar bamat e. Effecti
veagai nstmostcut aneousfungal
i
nf ections. Appl iedi nform of1%oi ntmentorcr eam.

Ant
hel
mint
icDr
ugs
1\Benzi nidazoles:
I
ncl udeThi abendazol e( Mi
ntezol), Mebendazol e( vermox)
andAl bendazol e( Zent al)
.Theyhav ebr oadspect r
um as
anthelmi nticdr ugsi ncluding:
-Ascar iasis -Capi ll
ariasis.
-Enter obiasis -Tr ichuri
asis.
-Ancy lostomaDuodeual e -Necat orAmer canus.
Phar macoki netics:
Poor lysol ubleinwat er,
sotheirGI Tabsor pti
oni sr estr
ict
ed.
Thiabendazol ei srapidl yabsorbed, met abolizedinliverand
excretedur i
nar y.Mebendazol eabsor ptionisv eryslow, highly
affectedbyf irstpassmet aboli
sm ,intensivelyboundt oplasma
proteins.absor pti
onofal bendazoleisal sosl ow,hashi ghf i
rst
passmet abolism, hasact i
v emetaboliteunlikeThi abendazol eand
Mebendaz ole.
Modeofact i
on: -
Benzi midazol esi nducemanybi ochemi calchangesi nthe
sensitivenemat odesi nhibiti
onofmi tochondr i
afumar ate

NOTESONPHARMACOLOGY 43