I

ntr
oduct
ion:

Phar
macol
ogy
:-i
sthest
udyofdr
ugsandt
hei
r
act
iononl
ivi
ngorgani
sms.
Phar
macology

Phar
macokinet
ics:
absor
pti
on,di
str
ibut
ion,
metabol
ism ,
excr
eti
on

*Pharmacodynamics:howdrugs,aloneandin
combinati
on,af
fectthebody.(r
eceptors,
dose
,t
herapeut
icuses,
mechani sm ofacti
on,adver
seef
fect
s)

Lear
nthedef
ini
ti
onst
hatf
oll
ow:

Term Def initi

on
1 Pharmacol
ogy Thest udyoft heinter
act ionof
chemi calswi thliv
ingsy stems
2 Dr
ugs Subst ancest hatactonl i
v i
ng
syst emsatt hechemi cal
(mol ecul ar)l evel
.
3 Dr
ugr
ecept
ors Themol ecul arcomponent softhe
bodywi t
hadr uginteractst obri
ng
abouti tsef fect.
4 Medical Thest udyofdr ugsusedf orthe
phar
macology diagnosi s, preventi
on, and
tr
eat mentofdi sease
5 Toxi
col
ogy Thest udyoft heundesi rable
effect sofchemi calagent son
l
ivingsuy stems; consider edan
areaofphar macol ogy.Inaddi t
ion
tot headv erseef f
ectsof
 therapeut i
cagent soni ndivi
duals,
toxicologyal sodeal swi ththe
acti
onofi ndust r
ialpollutants,
natur alorgani candi nor ganic
poisons, andot herchemi calson
speci es.
6 Phar
macodynamics Refer stot heact i
onsofadr ugon
thebody , i
ncludingr ecept or
i
nter acti
ons, doser esponse
phenomena, andmechani smsof
therapeut i
candt oxicact i
on.
7 Phar
macoki
neti
cs Ref er stot heact i
onsoft hebody
ont hedr ug, i
ncl uding
absor ptions,di str
ibution,
met abol i
sm, andusedt o
descr ibet hepr ocessesof
met abol i
sm andex cretion.

Pharmacoki
nat
ics:
st
udyoftheabsorpt
ion,di
str
ibut
ion,
met
abol
i
sm,
and
excr
eti
on.
Pharmacoki
nat
icdefi
nit
ions

Term Defi
niti
on
1 Vol
umeof Theratiooft heamountofadr ug
di
str
ibut
ion i
nt hebodyt oi t
sconcent r
ati
onin
theplasmaorbl ood.
2 Hal
f-
li
fe Thetimei ttakesf ort
heamount
orconcent r
ationofadr ugtofall
to50%ofanear l
ier
measur ement ;
3 Bi
oav
ail
abi
l
ity Thefraction(orper centage)of
 theadmini
stereddoseofadr
ug
thatr
eachesthesystemi
c
cir
cul
ati
on

7 Fi
rst
-passef
fect Theel imi nati
onofdr ugt hat
occur saf teradmi ni
str
at i
onbut
beforei treachest hesy stemic
cir
culat i
on, e.g.duri
ngpassage
throught hegutwal l
,por tal
blood,
andl i
verf oranor all
y
admi nistereddr ug
8 Ex
tract
ion Thef ractionofdr uginpl asma
thatisr emov edbyanor ganasit
passest hrought hatorgan.

Absor pt
ion:It
`st het r
ansf erofdi ssolveddr ugpar t
icl
es
from theGI Tint ot hebodyf l
uid.
Thisisaccompl ishedbysev eralway s:activetransport,
passivedi f
fusi on, andpi nocy t
osi s.
Distri
buti
on:
Mov ementofdr ugf r
om ci rculati
oni ntobodyt i
ssuesor
targetsit
es.Somedr ugsbi ndt obloodpr otein(Albumi n)
Andt heyar et husi nact i
ve.
Onlywhent hepr ot ei
nmol eculesr el
easet hedr ug(f r
ee
from ofthedr ug) ,itcandi ffusei ntothetissues, i
nteract
wi t
hreceptor s, andpr oduceat herapeuti
cef fect.
Distri
buti
onr at edependsonsev eral f
actorsli
ke:
 Capi l
laryper meabi l
ity
 Bloodf lowt ot heor gan
 Differencei npH.

pl
asmapr otei
nbinding(
Albumin):
Thebindi
ngofdrugsto
pl
asmapr ot
einsisusual
lynonspecif
ic;t
hati
s,manydrugs
mayint
eractwiththesamebindingsiteonal
bumin
mol ecul es.Adrugwi t
hahi gheraffi
nit
ymaydi splacea
drugwi thweakeraf f
ini
ty.Freedrugshav eincreased
phar macol ogicalr
esponse, si
deeffect
s, andpot ential
toxicity.Somedi seasestates(e.g.hypoalbumi nemi a:a
decr easeofal bumininthebl oodresul
t sinfeweral bumin
mol ecul esforadrugt obindwi t
handl eadtoincr eased
l
ev el offreedruginthebl oodstr
eam.

 Met
abol
i
sm ofdr
ugs

Metaboli
sm ofadr
ugsometi
mesterminatesit
’s
act
ion,butot
heref
fect
sofmet
abol
ism arealso
i
mpor t
ant.
Somedrugswhengi
venoral
l
yaremetaboli
zed
bef
oret
heentert
hesyst
emicci
rcul
ati
on.Thi
sis
cal
l
edfi
rst-
passmet
abol
ism.

1-Drugmet aboli
sm asamechani sm ofter
mination
ofdrugaction.Theacti
onofmanydr ugse.g.local
anestheti
c,phenothi
azi
neistermi
natedbefore
theyareexcretedbecausetheyar
emet abol
izedt o
biol
ogicali
nactiv
ederivat
ive.

2-Drugmet abol
i
sm asamechanism ofdr
ug
act
ivat
ionProdrugs(l
evodopa-methyl
dopa→
act
ivedrugs

3-Act
ivedrug benzodi
azepi
ne→ act
ive
met
aboli
sm

4-Drugeli
minati
onwithoutmetabol
i
sm li
thi
um-
Peni
cil
li
nGar enotmodifi
edbythebody,t
he
cont
inuetoactunti
ltheyar
eexecrat
ed.
Pati
entswit
hli
verdiseasemayrequir
elowerdosagesofa
drugoradrugthatdoesnotundergoabiot
ransf
ormati
on
bytheli
ver
.Thekidneys,l
ungs,
plasma,andint
esti
nal
mucosaalsoai
di nthemetabol
ism ofsomedrugs.

Excretion:
Itistheel i
mi nationofdr ugsf rom t hebodyt hroughthe
kidney.Somedr ugsar eexcr etedunchangedbyt hekidney.
Pat i
entswi thki dneydi sease, childrenorel derl
ymay
requireadosager eductionandcar eful monitori
ngof
kidneyf unction.Ot herdr ugsar eel iminat edbysweat ,
breastmi lk,breat h, orwithf eces.
Ther ateofur i
nar yexcr etionwi l
ldependont hefol
lowing
factors:
1-Drug’sv olumeofdi st r
ibut i
on.
2-Degr eeofpr oteinbi nding.
3-Glomer ularf il
trati
onr ate( GFR) .
4-Tubul arfluidpH.
5-Tubul arreabsor pt
ion.
 Exampl esofdr ugst hatcanbeexcr etedinbreast
mi l
k:Acet y l
salicyl
icaci d, Ant i
thy roi
dur acil
compounds, Barbiturates, Caf feine,Ethanol,
Mor phine, Nicot i
ne.
 Rout eofadmi nist
rat i
on:
Commonr out esofadmi nistrationandSomeoft hei
r
featuresincl udet hef ollowi ng:

1-Oral (swallowed)absorptionitslowerandl ess

compl etethanparentalr
outes.
Ingest eddrugsaresubjecttothef i
rstpassef fect,
themet abol
ism Occursi
nthegutwal landl i
ver
beforet hedrugreachestheSy stemiccirculati
on.
Iti
st hemostcommonr outeoft aki
ngdr ugs.This
routeispr ef
erredduetoadv antageslike:
1.Easeofadmi nist
rat
ionasev enthepat i
entcan
takemedi ci
neonhisownwi t
houtot hershelp.
 2.Thi sisnon- painfulr outealsosaf estr oute.
3.Itissui t
ablef orpeopl eofallagesi ncl uding
infants,children,adul tsoldagepeopl e.
Di
sadv antages:
1.I tisnotpossi bletogi vedr ugsint hisrout et o
comat osepat ients.
2.Notal l drugscanbegi venbyt hisr out
eduet o
chanceofdegr adat i
onl iverbeforeshowi ngi ts
actions.
3.I ncaseofemer gencyt hisr out
ei snotpr ef erredas
thet i
met akenbymedi camentgi venbyt hisrouteto
produceef fectishal fandhourt oonehour .Thati s
therei snoi mmedi ateresponse.
2-Buccal /sublingual di
r ectabsor pti
oni ntot he
systemi cvenousci rculat i
onandbi oavailabili
tyis
higher .

3-Inhalat
ion:I
nthecaseofr espiratorydiseases,t
his
routerapi
dabsor pt
ionbecauseoft helargealveol
ar
surfaceareavail
abl
e.localeff
ect-br onchodial
ators,
systemiceffect
-generalanesthesia.

4-Topi cal
Thet opicalrout eincludeappl icationtotheskinor
mucousmembr aneoft heey e-nose, thr
oat,airway
.I
tsl owert hanot herRout es.Thi sr outei
soneoft he
safestr outeast hedr ugcannotpr oductpoisonous
effects.
Adv antages: I
tcanshowl ocal effect.Thatisthedrug
actsonl yatt hesi teofappl icationandnotonwhol e
bodyl ikeinor al r
out e.
Ex.;powder s,ointment ,loti
ons
5-Nasal r
out e:Her edrugsar egivenbynose.Thi sis
meantei therforcl eaningofpoi sonsf rom stomach
orf ordeliveryofnut r i
ti
ont ot hebodyby passing
mout h.
6-Transder mal
 I
trout
esappl
icat
iontotheski
nforsystemi
ceffect
.
I
tabsorpt
ionv
eryslowl
ybutthefi
rstpassef
fectis
avoi
ded.

7-Parenteralroute:Ast henameindicates,her
eare
drugsar e
giveninr outesot herthatint
esti
ne.Allt
y pesofi
nject
ions
comeundert hisroute.Butsti
llt
hisrout
ehas
advantagesov er
oral r
oute.
Advantages:
1.Itissuitabletogivedrugtocomapat i
ent
s
2.Forquickacti
onandachievi
ngi
mmedi at
e
responseinthepat
ientt
hemedicamentisgi
ven
direct
lyi
ntobloodv
essels.
3.Alsosmal l
amountofdrugi
sneededcompared
tootherroutesast
her
eisnowastageofdr
ugs
bymet aboli
sm.
4.Thosedrugswhicharenotabsorbedby
stomachorwhichwill
bedigestedbyst omach
aregiv
enbythi
sr out
e.Ex;I
nsuli
nindiabeti
c
pati
ents.
Di
sadvantagesofthisrout
e:
1.Ri skyr
oute:t
hisrouteisr
iskyasoncedrugisgi
ven,
it
cannotberet
rievedbackorstoppedeasi
ly
.
2.Painandwound;thi
sroutecaninducepaindur
ingt
he
i
njecti
onalsof
requenti
nject
ionscancausewoundor
abscesses.
3.Expensiver
oute;
onneedsasyri
nge,cott
on,
ster
il
izi
ngagentbef
oreadmi
nist
eri
ngt hei
nject
ion.
 Sot
hisaddsupt
hecost
.
4.Minimalchancesofsel
fmedicat
ion.Thepat
ient
cannotmedicamentonhisowninmostcases.
1-Intr
avenous(I .
V)
Routeof f
ersinstant
aneousandcompl et
eabsorpti
on.
Thisroutei
spot enti
all
ymor edangerous,however
becauseofhi ghbloodlevelsthatmaybepr oduced.
2-Intr
amuscul ar(I.
M )absorpti
onfasterand
compl et
ethanwi thadministr
ati
on.
3-Subcutaneous(SC)sl owerabsor pti
onthanI.
M
route.

8-Vagi
nalr
oute;Thi
srout
eispossi
bleonl
yinwomen.Alsomost
oftheti
mes,thi
sroutei
savoi
ded.Thisi
susedforl
ocal
inf
ect
ioni
n
genit
alpar
tsofwomen.
9-Rect
al(supposi
tory)
Largeramountsofdr
ugmaybeadmi nist
eredThi
s
waythanbythebuccalorsubl
i
ngual
route.

Pharmacody namic:Whent hedrugbindst oareceptpr

,a
dr
ug- r
eceptorcomplexisformed,cell
ularprot
einsunder
goanal t
erati
oninconformationwhichinduceschanges
(response).

Phar
macody
namicdef i
nit
ion
Term Def
init
ion
1 Recept
or Componentoft he
bi
ologi
csy stem wi
th
 whi chadr uginter actsto
bringachangei nf uncti
on
oft hesy st
em.
2 Agonist Adr ugthatactivatesi ts
recept oruponbi ndi ng.
3 Pharmacol ogi
c Adr ugthatbindst oits
antagoni st recept orwit
hout
activ at
ingit
.
4 Compet i
tiveantagonist Aphar macologic
ant agonistt
hatcanbe
over comebyi ncr easi ng
thedoseofagoni st .
5 I
rreversibleantagonist Aphar macologic
ant agonistt
hatcannotbe
over comebyi ncr easi ng
thedoseofagoni st
6 Physiologicantagonist Adr ugthatcount er sthe
effectofant herby
bindi ngtoadi f
ferent
recept orandcausi ng
opposi ngeffects.

 Nonreceptormedi atedaction
1-Physi
cal--
--
--
---
--osomat i
ce.g.mannitol
,pur
gat
ive.
2-Chemi cal-
---
--
---
-ant
acid
3-Chelati
on---
--
--
---
-Sodium edatat
e--
--
-Ant
idot
e
4-Adsorpti
on---
--
---
-Charcoal
5-Localanesthesia
6-Anti
cancerdrugs
7-Hormones
1Functi
onofr eceptors:
-Togiveresponse:
a-Modifi
cationorstimulat
ion
b-I
nhibi
ti
on
Drug+Recept or↔D- R-complex→ D-
R-compl
ex
→Response.

AdverseDrugReact ions:t
heundesi rabledr ugeff
ects.
Theymaybemi l
d,severe,orli
fethreatening.Theymay
occuraft
ert hefir
stdose,afterseveral doses,orevenafter
manydoses.
Sideeff
ects: mil
d,common, andnont oxicreacti
onsthat
occurswit
ht her
apeuticdosesofdr ugs.
Adverseeffects:severeandlif
e-thr
eat eningreacti
onsthat
usual
lyoccur swithhigherdoses.

Commoneff
ect
sincl
udet
hef
oll
owi
ng:
1.CNSef
fect
s:

a.CNSst imulat
ion(
e.g.agi
tati
on,confusion,
del
ir
ium, di
sori
ent
ati
on,hall
ucinat
ions,psychosi
s,
sei
zures).

b.CNSdepr ession(
e.g.dizziness,
drowsi
ness,
unconsciousness,sedation,coma,i
mpaired
respi
rat
ionandci r
culation).

2.Gastrointest
inalef
fect
s:e.
g.anorexia,
nausea,
vomiting,consti
pati
on,di
arr
hea,bleedi
ngor
ulcer
at i
on.

3.Hypersensit
ivi
ty:
Iti
slar
gelyunpredi
ctabl
eand
unrel
atedtodose.Iti
srangingfr
om mi l
dski
nrashes
toanaphylacti
cshock.

4.Hematol
ogiceffect
s(anemi
a,coagul
ati
ondisor
der
s,
bl
eedi
ngdisorders,
bonemarrowdepressi
on,
 l
eukopeni
a,agr
anul
ocy
tosi
s,t
hrombocy
topeni
a).

5.Hepatot
oxici
ty(hepat
it
is,l
i
verdy
sfunct
ionorf
ail
ure,
l
iverci
rr
hosis,bi
li
aryt
racti
nfl
ammationor
obstr
ucti
on).

6.Nephrotoxi
cit
y(nephri
ti
s,renali
nsuff
ici
encyorfai
l
ure)
I
tispotenti
all
yseriousbecauseitmayinter
fer
ewith
drugexcret
ion,t
herebycausingdrugaccumulat
ion
andincr
easedadv erseeff
ects.

7.Fever:Fev
ermayoccuraloneorwit
hother
symptoms( e.
g.ski
nrash,
joi
ntandmusclepai
n,
enl
argedlymphglands)
.

8.I
diosy
ncrasy
:unexpect
edr
eact
iont
oadr
ugt
hat
occur
sthefi
rstt
imeiti
sgi
ven.

9.Dependence:
phy si
ologi
corpsychological
.
Physi
ologi
cdependenceproducesunpl easant
physi
calsymptomswhent hedosei sreducedorthe
drugiswit
hdrawn.Psychol
ogicaldependenceleads
toexcessi
vedrugsekingbehavior
.

10. Car ci
nogeni
ci
ty:i
stheabi
li
tyofasubst
ancet
o
causecancerduetochangei
ncell
ularDNA.

11. Toxi
cEffect
s(poisoni
ng,overdose,
i
ntoxi
cati
on):r
esul
tsfrom excessi
veamount sofa
drugandmaycauser eversi
bleori
rrever
sibl
edamage
tobodyti
ssues.

12. Ter
atogeni
cit
y:i
stheabi
li
tyofasubst
ancet
o
causeabnormalfetal
devel
opmentwhentaken
duri
ngpregnancy.
Sour cesofdr ugs:
1.Pl antsour ces
2.Ani mal sour ces
3.Mi ner al Ear t
hsour ces
4.Mi crbiol ogical sources
5.Recombi nantDNAt echnol ogy
6.Semi sy nthet i
csour ces, synthet i
csour ces
1.Plantsour ce: i
st heoldestsour ceofdr ugs
Allmostal l par tsoft hepl antsar eused(l eav es,bark,f
rui
t,
andr oot s)
Leav es:
a.Thel eav esofdi git
al i
spur puraar et hesour ceof
digitoxi nanddi goxi n,whichar ecar di acgl y
cosides.
b.Tobaccol eav esgiveni cotine
c.At ropabel ladonnagi v
esat ropine
Flower s:
Poppypapuv ergi vesmor phine
Fruits:
Sennapodgi v esant hraci neispur gative( usedi n
const ipat i
on
Seed:
Cast oroi lseedsgi vecast oroil
Root s:
Ipecacuanhar ootsgi vesemet ine
Bar k:
Cinchonabar kgi vesqui nineandqui nidine
2.Ani mal sour ces:
1.Pancr easi ssour ceofi nsulinusedi nt reatment
diabet es
2.Sheept hy roi
di sasour cesoft hyroxin
3.Bl oodofani mal isusedi npr eparationofv acci
ne.
3.Mi ner alsour ces:
i
.I roni susedi nt r
eatmentofi r
ondef i
ci ency
ii
. Zi nci susedaszi ncsuppl ement ,zincoxi deusedin
woundandi neczema
i
i
i.Iodineisant
isept
ic
i
v. Goldsalt
sareusedint
reat
mentofr
heumat
oid
ar
thri
ti
s

3.
Mi crobiological sour ces
i. Peni cil
lium not atum i saf unguswhi chgi vespenici
l
li
n.
i
i. Act inobact eriagiv est reptomy cin
ii
i. Ami noglycosi dessuchasgent amy cinand
tobramy cinar eobt ainedf rom st r
eptomy cisand
micromonospor us.
4.
Recombi nantDNAt echnol ogy :
Recombi nantDNAt echnol ogyi nvol
v escleav ageofDNA
byenzy mer estri
ctionendonucl eases.
Thedesi redgenei scoupl edt or api
dlyreplicatingDNA
(v
iral
, bacterial
)t henewgenet iccombi nationi sinser
ted
i
ntot hebact erialcultur eswhi chal l
owpr oduct ionofvast
amountofgenet i
c.
Classifi
cationofdr ugs: namesofdr ugs

Dr
ugsmaybecl
assi
fi
edby
:

1-Ther
apeuti
cusee.
g.ant
imi
crobi
al,
ant
idi
abet
ic,
AHT,
anal
gesi
c.

2-Modeorsi t
eofact i
on;
a.Mol ecul arinteraction,e.
g.r eceptorblockers,
enzymei nhibitors
b.Cel l
ularsi t
e, e.g.l
oopdi uretic,catechol
ami ne
uptakei nhibitor
c.Phy siological system
e.g.Vasodi lator,li
pid-l
ower i
ng, anticoagulant.
3-Mol ecularstruct uree.g.barbiturate,glycosi
de, al
kaloi
d,
ster
oid.

Dr
ugnomencl
atur
e:
1-Chemicalname(acet
ylsali
cyl
icaci
d)
2-Genericname(Aspir
in)inpharmacopoei
a
3-Tradename

Themor eimpor tantmechani sms

Recept ors
Mostr eceptorsar eprot einmol ecul es.Whent heagoni st
bindst otherecept or,thepr oteinsunder goanal ter
ationin
conformat i
onwhi chinduceschangesi nsy stemswi thin
thecell t
hatintur nbringaboutt her esponset othedr ug.
Forexampl e,act ivati
onofβ-adr enocept orsbya
catecholamine(t hefi
r stmessenger)i ncreasest he
activ
ityofadeny latecy clasewhi chr aisest herateof
format i
onofcy clicAMP(t hesecondmessenger) ,a
modul atoroftheact ivityofsev er alenzy mesy stemst hat
causet hecelltoact .Ot herdr ugr ecept oref f
ectsare
medi atedthroughcont rolofmembr anei onchannel s
closelyassociatedwi tht her ecept or,e.g.calcium entry
blockers.

Whent issuesar econt

inuouslyexposedt oanagoni st
,the
numberofr eceptor
sdecreases(down- regulat
ion)and
thismaybeacauseoft achyphl
axi s(lossofef fi
cacywith
frequentr epeateddoses) ,e.
g.inast hmaticswhouse
adr enoceptoragonistbronchodilatorsexcessivel
y.
Pr olongedcont actwit
hanant agoni stl
eadst oformation
ofnewr ecept or
s(up-regulat
ion) .
I
ncompatibil
i
ty:
Def i
nit
ionofdr
ugincompat ibi
l
ity
:
DrugIncompat
ibi
l
ityref
er stoi
nteract
ions
betweentwoormor edrugs.
Ty pesofDrugI
ncompat ibil
i
ty
 1.Ther apeut i
ci ncompat i
bi li
ty
2.Phy sical i
ncompat i
bili
ty
3.Chemi cal i
ncompat i
bility
1-
Therapeut ici ncompat i
bilit
y
Def i
nitionoft her apeut i
ci ncompat i
bil
it
y
Iti
st hemodi f
icat i
onoft het herapeut ic
effectofonet oanot her.(i tisal socal l
ed
drugi nter act i
on)
Mechani smsoft her apeut ici ncompat i
bil
i
ty
Theyar edi vi
dedi ntot wogr oups:
a.Phar macoki net ics:
Inv olvet heef fectofadr ugonant her
from t hepoi ntofadmi ni stration
(absor pti
on, di stri
but ion, met aboli
sm,
excr et i
on)
b.Phar macody nami cs
Ar er elatedt ot hephar macol ogi cal
act ivityoft hei nt eractingdr ugse. g
sy ner gism orant agoni st(al tercellul
ar
transpor t,effectont her ecept orsite.

Pharmacokineti
cinteract
ions
a.
Alter
edpH
Thenon- i
onizedform ofadr ugi
smore
li
pidsolubleandmor er
eadil
yabsor
bed
from GI
Tt hanionizedform does

↑pH
Anti
aci
d,H2antagonists
decr
easethetabletdissol
uti
onof
ketoconazol e(aci dicdr ug)
Ther ef ore, thesedr ugsmustbe
separ atedbyl east2hi nt het i
meof
admi nistrat i
onofbot h.
b.Alter edbact erial flora
e.g, in10%ofpat ient srecei vedi goxi
n,
40%ormor eoft headmi nist ereddosei s
met abol i
zedbyt hei ntest inal
fl
or a(ant ibioticski llalar genumberof
thenor mal fl
or aoft hei ntest i
ne
i
ncr easedi goxi nconc.Andi ncreaseits
toxici t
y .)
c.For mat i
onofdr ugchel atesorcompl ex
Tet racy clinei nt eract ionwi thi ron
prepar ations,f or m unabsor bedcompl ex
withcal cium i nmi lk.
Ant iacid( Al umi num ormagnesi um)
hydr oxi dedecr easeabsor ptionof
ciprof loxaci n
d.Drugi nducedmucosal damageand
alteredGI Tmot il
ity
Ant icancerdr ugse. gv incr ist i
ninhibi
t
absor pat i
onofsev er aldr ugse. gdigoxin.
Met ochl opr ami de(ant iemet i
c)increase
absor ptionofcy clospor ineduet othe
i
ncr easeofst omachempt ingt ime
i
ncr easet het oxi ci tyofcy cl ospor i
ne
drugs
Displacedpr oteinbi ndi ng
Itdepenedsont heaf finityoft hedr ugt o
plasmapr ot ein
e.gpheny toi ni sahi ghl yboundt oplasma
protein(90%)
tolbutamide( 96%) ,andwar f
arin(99%),drugs
thatdisplacet heseagent sar eAspi r
in
,sulfonami desphy eny lbutazone.
CYP450f ami l
yist hemaj ormet aboli
zi ng
enzymei nphaseI (oxidati
onpr ocess) .
Ther efor e, t
heef fectofdr ugsont her ate
ofmet abol i
sm ofot herscani nvolvet he
foll
owi ngexampl e:
-Ex1. , Enzy mei nduct ion:
Pheny toi nincreaseshepat i
cmet abol i
sm
oftheophy lli
nel eadingt odecreasei ts
lev
el r
educesi tsact ion

-Ex2. ,Enzy mei nhibiti

on
Erythromy cininhibitmet abol i
sm of
astemazol eandt erfenadi ne
i
ncreaset heser um conc.Oft he
antihi
stami nicagent sl eadingt o
i
ncreasi ngt heLifethr eatening
cardiotoxicity.
Pharmacody namici nteraction
I
tmeansal terati
onoft hedr ugact i
on
withoutchangei ni t
sser um conc.By
pharmacoki netic
-Sy nergisticef f
ectoccur swhent woor
mor edr ugs, wit
horwi thoutt hesame
overef fectareusedt oget hert oyi
elda
 combi nedef fectt hathasanout come
great ert hant hesum oft hesingledrug
act i
v ecomponent sal one
-E.gsul phonami de+t r i
met hoprim
-Ant agoni sticef f
ect
E.g., prot ami neant i
dot etoant i
coagulant
act i
onofhepar i
n
-Addi tiveef fectoccur swhent wodr ugs
ormor eheav i
ngt hesameef fectare
combi ndandt her esul tisthesum of
individual effectst othedosesused.
Thi saddi ti
v eef f
ectmaybebenef ici
al or
har mf ul effect
E,gH1- blockermepy rami ne,commonl y
causedr owsi nessef fect, t
hisismor eif
suchdr ugsar et akenwi t
hal cohol,l
ead
toacci dent swor k.
2-phy si cal incompat ibili
ty:
Interact i
onbet weent owormor e
subst ancewhi chl eadt ochangei ncol or
,
odor , tast e, viscosi tyandmor phology.
3-
Chemi cal incompat ibil
ity
:
React ionbet weent woormor e
substanceswhi chl eadt ochangei nchemi cal
properti
esofphar maceut ical dosagef orm
Ty pesofchemi cal changes:
1.Oxi dat i
on
2.Hy dr olysis
3.Decar boxl ation
4.Absor pt i
onofCO2
For
mat
ionofi
nsol
ubl
ecompl
ex

Aut
onomi
cNer
voussy
stem
(ANS)

Ner
voussy
stem

Per
ipher
alNS Cent
ral
NS

Ef
fer
entdi
vi
sion Af
fer
entdi
vi
sion

ANS Somat
icSy
stem

Sy
mpathet
ic Par
asympat
het
ic
Syst
em Syst
em

 AutonomicNer vousSy stem:

The3r egulatoryfuncti
ons
1.Regulationofhear t
2.Regulationofsecr etorygl
ands(sali
var
y ,
gast
ri
c,
sweat ,andbr onchialgl
ands)
3.Regulationofsmoot hmuscl
es(muscl esof
bronchi,bloodv essels,ur
ogeni
talsyst
ems,and
gastrointesti
naltract)

*
Eff
erentDi
vi
sion:
-
 Theneur onswhi chcar rysignalfrom brai
nand
Spi nalcordtot heperipheraltissue.
*AfferentDivi
sion:-
Theneur onswhi chbringinformat i
onfrom t
he
peripher
yt ot hecentralnervoussy stem.
*Autonomi cfiberscontai n(pregangl i
oni
c,
post gangli
oni c).
Gangli
on effect
or
ANS
Preganglionic post ganglionic

*Thepri
ncipl
elocusofintegrat
ionoftheANSisthe
hypot
halamus,wheret
hef uncti
onofANSar ecoordi
nated
i
ntotheprogr
ammer si
nv olvi
ngotherdiv
isi
onsofnervous
syst
em andendocri
nesy stem.

 Transmittersoft heper i
pheralnerv
oussystem(
PNS)
 Principal neur otr
ansmittersofPNS:
 Acet ylchol i
ne
 Nor epinephr ine
 Epinephr ine
 Dopami ne
 Subt ypesofchol i
nergi
candAdr ener
gic
recept os:
 Chloner gicr eceptor
- Ni cotinic
- Muscar i
nic
 Adrenergic
- Alpha1andAl ph2
- Bet a1andBet a2
- Dopami ne

Theacti
onofsympat
heti
candpar
asy
mpathet
icsyst
em
ontheeff
ect
orsor
gans:
Organs Sympathet
ic Par
asympathet
ic
Hear
t ↑Rateand ↓rateand
contracti
lit
y contracti
l
ity
↑bl
oodpr essur
e ↓bloodpressur
e
Br
onchi Dil
atation&↓secret
ion Const r
ucti
on&
↑secreti
on
GI
T ↓mot
il
it
y&secr
eti
on ↑mot i
li
ty&
secreti
on
Uri
nary Relaxati
on Cont r
acti
on
bl
adder
Eye My dri
asis Miosis
Sal
ivar
ygland Thickandv i
scous Waterysecr
eti
on
secreti
on
Li
ver Glycogenoly
sis(
↑blood -
--
---
--
--
--
--
glucose
Fat
tyti
ssues ↑lipolysi
s(↑fat
tyacid) -
--
---
--
--
--
-

Sy
mpat
homi
met
ics
Defi
nit
ion:
Drugsthatst
imul
ateadr
ener
gicr
ecept
ors.
Adri
nergicr
ecept
ors:
Thesearet
hesit
esonwhi
ch
sympathomimeti
csact.

Ef
fect
oror gan&Response Recept
or Ty
pe
I
-Vascularsmoot hmuscles:
a-Hear t:
1-I ncreased --
--
--
--
- Bet
a1
Cont ract
il
it
y
2-Increased
Hear trat
e
3-Increased
conduct ionveloci
ty
b-Bloodv essels:
 1-V.Cofski n, Al
pha1 -
--
--
-
mucosa, v
iscer
a
2-V.Dofcor onary -
--
--
--
-- Bet
a2
andskel etal
ar
teri
oles
c-Reninrel
ease -
--
--
--
-- Bet
a2

I
I-Non-v ascul arsmoot h
muscl es: Al
pha1 -
--
--
--
a-Ey e: cont ractionof
di latorpupi l
lae
(my dri
asi s) -
--
--
--
- Bet
a2
b-Br onchi al
Rel axat ion
c-G. I.T. Bet
a2
1-Rel axat i
on( ↓tone
andmot il
ity) Al
pha1 -
--
--
--
2-Cont ractionof
sphi nct ers
d-Ur inar y: -
--
-- Bet
a2
1-Rel axat ion(↓ tone) Al
pha1 -
--
--
--
2-cont ractionof
sphi ncter
e-Spl enni ccapsul e Al
pha -
--
--
--
--
cont ract i
on
g-Pr egnantut er us Al
pha
1-cont raction Bet
a2
2-Rel axat i
on
I
II-Glands Al
pha -
--
--
-
a-Sal iv ary:v i
scous
sal iva
 b-Pancr eas: Al
pha -
--
--
--
-
1-Reducedexocr i
ne
secr eti
on Al
pha -
--
--
--
--
2-Reducedi nsuli
n
secr eti
onf rom ß-cel
l
s -
--
--
--
- Bet
a2
3-I ncreasedi nsul
i
n
Secr et
ionf r
om ß
Cell
s -
--
--
--
--
- Bet
a2
I
V-Met abolic(liver)
1-Li polysis
2-Gl ycogenol y
sis
3-Gl uconeogenesi s
Al
pha -
--
--
-
V-Facil
it
ati
onof
neuromuscular -
--
--
--
--
- Bet
a2
VI-Anti
-all
ergi
c
I
nhi
biti
onofhist
amine
Rel
easefrom mastcel
l

Mechani smal classificati

onofsy mpat homimet i
cs:
A-DirectlyonAdr energicrecept ors:
1-adr enalineonal pha,bet a
2-Nor -adrenal i
nemai nlyonal pha
3-I sopr enalinei smai nl
yonbet a
4-Dopami neonbot hdopami nergicreceptorsand
alpha&bet aadr enor eceptos
5-Pheny l
ephr inemai nlyonal pha.
B-Indir
ect lyact i
ng: Amphet amine,
Met hamphet ami ne,Mephent eramine,and
Ty r
ami nest i
mul at erel
easeofnor -adrenal
inethat
Onal phar ecept ors.
C-Directandi ndi r
ect( Dual)Ephedr i
neand
Met ar ami nol.
N.B:Adr enal i
ne, nor-adrenalineandI soprenal
ine
 Arecat
echol
amine,whi
leamphetamineand
Ephedr
inear
enon-cat
echol
amines.

Phar
macologicaldi
ff
erencesbet
weencat
echol
ami
neand
non-
cat
echolamines:

Catecholami nes Non- catecholamines

1-Dopami ne, nor-
adrenali
ne 1-Amphet ami ne,
andadrenal ineoccur Ephedr ine,
natur
all
yi nbody ,i
soprenal
ine Pheny lephedrine,
doesnot . Mephent yramine,
Tyrami ne,salbutamol,
Terbut ali
nedonotoccur
naturallyinthebody .
2-Charactristics:
a.Unst able a-Stable
b.Nev erorall
y b-Usual lyoral
c.Hy droly
sedby c-Nothy drol
ysedbyMAO
MAOandCOMT orCOMT
d.Rapi donsetand
shor tdurat
ion d-Rel ati
velydelayedonset
andl ongerdur ati
onof
e.WeakCNS action.
stimulanteffect
s e-St r
ongerCNSst i
mulant
effects.

Adr
enocept
ors
α1-
recept
ors α2–r
ecept
ors ß1- ß2-
recept
ors
recept
ors
Vasoconst r
ict
ion -i
nhi bi
ti
onof Tachy cardi
a Vasodi l
atati
on
-↑bloodpr essure nor epeniephrine ↑my ocardialBronchodi l
atat
ion
-my dri
asis release(negat i
ve cont racti
lit
y- ↑muscl e&li
ver
-contracti
onof f eedbacki nhibit
ion) ↑l
ipolysis glycogenolysis
urinarysphincter -inhibit
ionof
-↓GITt oneand i nsul inrelease -Relaxuteri
ne
mot il
it
y smoot hmuscl es
-↓GI Ttone&
mot il
it
y

αandß-agoni st
ADRENALI NE(Epinephrine)
Sour
ce&Chemi stry:
Natural
: f
rom medul l
aofsuprarenalgland
Synt
hesis:Tyrosine(anami noacid)→Dopa
di
hydroxyphenylalanine)→Dopami ne
(aneurotrnsmitter)→Nor epenephri
ne
(neurotransmitterandhor mone)→ Epi nephr
ine
(majorhor moneofadr enalmedulla)

Acti
on: Althoughi tactsonbot halpha&bet areceptor
s,
thebetaef fect spredominate.
1-↑forceandr ateofheartcont racti
ons
2-Const r
uct ionofbl oodvessel s→↑bloodpr essure.
3-Relaxofbr onchialsmoothmuscl es→
bronchodi l
at ation.
4-Vasoconst racti
on(v i
sceraandski n)
5-Urinaryret ent i
on
6-↑bloodgl ucose.
7-Ant i
-hi
stami neandant i-
allergi
cact i
on
8-Ey e( my driasis)
9-Exocr inegl andsViscidsal i
varysecret
ion.
10-Endocr ine: st
imulat
ionADH, ACTH&cor ti
solrel
ease
*
Ther apeut i
cuses: -
I
-Local :
1-Decongest ant(nose),Haemost ati
c(epistax)
2-Pr olongedt heacti
onandr educethetoxicit
yofl
ocal
anaesthetics.
I
I-Systemi c:
1-Acut ebronchialasthmaS. C
2-Allergy,urti
cari
aandshock.
3-Compl eteheartblock.
(Int
racar
diali
njecti
on)
4-Hy poglycaemi cshock(inducedbyinsulin)

*contr aindications:
-Cor onar yhear tdisease(Angi na)
-Hy per thyrodism
-Hy per tension
-Diabet esmel l
itus
*Toxici ty:
I
-Mi nor :
1-C. N. S: Anxiet y,tr
emor s,headacheandi nsomni a
2-C. V. S:Pal pitation,angi napai ns.
I
I-Maj or(i .e.fatal ): i
fadr enalinei s:
a-Rapi dlyI .
V.inject edor
b-Ov erdoseagewi thhal othane, cyclopropane,
Thef oll
owi ngi sexpect ed:
1-Sev erehy pertension, cerebralhaemor rhage.
2-Vent riculararrhy t
hmi a,pulmonar yoedema.
N.B: C.V.t oxicityiscont r
ol l
edbypr opranolol and
phentol ami net obl ockbet aandal phaef fectsrespectivel
y.

*Preparat
ions:
I
-S.C(1mg/ml )
2-I
nhalati
on(10mg/
ml)
:Acut
ebr
onchi
alast
hma

2-Nor
adr
enal
i
ne(NE)
-Mainl
yalphaagonist(weakß-agoni
st)
-Acti
onandusesasadr enal
ine
-Giv
enbyI Vinf
usiononlyduetostr
ongvasoconst
ri
cti
on
→ necrosisoft
issues.

3-Dopami ne:-
-Action:-
1-Actingon αandßr eceptors.
2-Deplet i
ngNAf rom storagev esicl
es
3-Agoni statspecifi
cdopami ner ecept
ors(↑r
enal
bl
oodf l
ow)
-Usedmai nl
yintr
eat mentofshock→↑r at
eand
f
orceofhear tcont r
act
ions
-Giv
enonl ybyI Vinfusi
on.

*
ß1&ß2-Agoni
st:

Isoprenali
ne:-(I
soprot
erenol
)
(Isopr opyl
nor-adr
enali
ne)synt
heti
ccatechol
amine.
-well absorbedbymucousmembr aneandbyinhalat
ion.

Uses:-
1-Acutebronchi alAsthma:Drugofchoice,
byinhal
ati
on
(onset:4mi n,duration:1hour)orsubl
i
ngual(onset:
3-4
min,durati
on: severalhour
s)
2-Heartblock(15mgsubl i
ngual/½hr)drugof
choice.
3-Cardiacarrest.

-Toxi
cit
y:
1-Palpit
ati
onandhy potension
2-Anginalpain,ar
rhythmias
3-Overdose:Tremor ,excit
ationanddi
zzi
ness
-Dose:-
Subli
ngual t
ablet10-15mgt i
d
Sol
uti
onf ornebuli
zation0.5-1%
α2-agonist
s:-
Feedbacki nhibitionofr eleaseofnor adrenali
ne
(pre-synapt icall
y)
1-Clonidine(Cat apress)
-Usedascent ralacti
ngant i
hhypert
ensivet otreat
mildt omoder atehy per t
ension.
-Givenor ally
-Sedat ioni sthemostcommonsi deef fects.
2-Met hyldopa: (Al domet )
-Conv ertedi nadr ener gi
cner veendingst ofalse
transmi tter(α-met hylnoradr
anali
ne) →
stimul ationofα2-r eceptorspresynapticall
y→↓
sy mpat het i
cef f
ect.
-Usedascl oni di
ne.
ß1-agoni st:-

Dobutamine:
-usedin:1-Sev erheartfail
ure
2-Cardiogeni
cshock
-Notcausev asoconstri
ction
-GivenbyslowI Vinfusion.
Nasaldecongestantagent s:

-Hav e -sti
mulantseff
ect.
-As:-Naphazoli
ne,Tet
rahydrozoli
ne,
Xylometazol
ine
-Givenmainlyasnasaldecongest anti
nal
ler
gicr
hini
ti
s,
col
ds, si
nusi
ti
sasnasal dropsorspr ay
s.
-Usingthesedrugsforlongperiodscauseatr
ophyof
nasalmucosaandl ossofsmel l
.

Indirectacti
ngsy mpat homimet i
c:-
-Ephedr i
ne:
-
-Alkaloidobtainedfrom Ephedraplantandalso
preparedsy nthet
icall
y
-Stimulat
e αandßr eceptorsdir
ectl
yandindir
ect
lyby
i
ncr easerel
easingofnor adrenali
nefr
om store
 -morest abl
ethanadr enal
ineandhaslonger
durat
ionofact i
on.
-Sti
mul ateCNS→i nsomni a
-Giv
enor al
l
y,parenterall
yandnasaldrops.
-Usesandsi deeffectaresimil
artoadrenal
ine.

*
Adr
ener
gicDepr
essant
s;

Definiti
on: Dr ugst hatbl ocksy mpat homi met i
ceff
ect :
Classificat ion:
I
-Sy mpat hol y t
ics: Drugst hati nterfer ewith:
1-St or age, release, uptakeofnor adrenaline;
a-Guanet hidine, i
nhi bitther el easeofst or
edNA
-usedmai nlyf orhy per tension.
-Notusedwi delyduet osi deef f
ects.
b-Reser pine, depl etet heNAf rom storagev esicl
es.
c-Bi osy nthesi s(Al domet)ofcat echolaminesby
Adr ener gicner v eendi ngs.I tcompet eswi t
hDOPA,
for mat ionoft heweakv asoconst rict
oralpha
met hy lnoradr enal i
net hatr eplacesnoradr enal
ine
i
ni t
sst oragesi tes.
I
I-Adr enol y ti
cs: Drugst hatbl ockadr energic
recept orsbycompet i
tivei nhibition:
a-Al phaadr ener gicbl ocker s:
1-Er gotal kaloids
2-Tol azol ine
3-Phent ol ami ne
4-Phenoxy benzami ne
d-Chl orpr omazi ne
e-Yohi mbi ne
b-Bet aadr ener gicbl ocker s:
1-Pr opr anol ol
2-Oxpr enol ol
3-Atenol ol
3-Met opr ol ol
4-Ti mol ol
 5-Nadol
ol
6-Pr
actol
ol

α-blocker s
Af
fectmai nlyonbl oodpr
essur ebydecreasing
Sympat hetictoneonbloodv essel
s→↓per i
pheral
Vascularresistance→dilat
ationofbloodv essel
s→
Hypotensi on.

1-Phenoxybenzamine:
-
-Non-competit
iveandi
rreversi
blebl
ockof
α-r
eceptors(byconvalentbonds).
-Actfor24hour s.

-Ther
apeuticuses: -
1-Asant i
hypertensi
ve
2-InPheochr omocytomat umorofadr enalmedull
a
→ hi
ghsecr eti
onofnor adrenal
i
neandadr enal
i
ne
→ hy
per t
ension.
3-I
nperipheralvasculardi
seases(v asodil
atati
on)

-Sideef
f ect:-
1-Posturalhypotensi
on
2-Refl
ext achycardi
a
4-Nasal sti
ffness
5-Nauseaandv omit
ing
6-Sexual dysfuncti
on.

2-Phent ol
ami ne:-
-Shor tdurationofact i
on.(about4hr)
-Act i
onandusesasphenoxy benzamine.
-Compet i
ti
v eandr eversi
bleacti
on.
3-Prazocine: -(Mi nipr
ess)
-Selecti
ve α1- blocker.
-Usedmai nlyasant ihypertensi
ve→ rel
axat
ionof
arteri
alandv enoussmoot hmuscl es.
 -Hasl esssi deef f
ectthanphenoxybenzamine&
phent
ol amine.
4-Doxazoci n(car dura)andTamsul osin(omnic)
Select
ive α1- bl
ocker .
-Usedmai nlyfortreatmentofbenignprost
atic
hypertr
ophy .(decr easetoneinsmoot hmuscleoft
he
bladderneckandpr ostat
e).
5-Yohimbi ne:-
-Sel
ective α2–bl ocker
-Useful i
nimpot ence.

ß-bl
ocker
s

1-Non- sel
ecti
veß-bl ockers:-
As:
-Pr opranolol(Inder al)
,Oxprenolol
,Timolol
,
Nadol ol
.
Therapeuticuses:-
1-Hyper t
ension
2-Angi napectori
s→ ( ß-blocker
s→ pr event
increaseincar diacwor k→↓oxy genr equi
rement
ofhear t).
3-Car diacarr
hy t
hmi aandM. I
4-Glaucoma(asey edr ops)→↓i nt
raocular
pressure.

Adversereact ion:
-
1-Severbrady cardia
2-Severhy potension
3-Heartblock
4-bronchospasm
5-Heartfailure
6-Hypoglycemi a(↓gl
ycogenol
ysi
sand↓gl
ucagon
secret
ion)
Contrai
ndicat i
on:-
1-Bronchial asthma
2-Congesti
vehear
tfai
l
ure
3-Hypotensi
on

-Givenor all
yandI .
Vsl owl y.
-Mustbest oppedgr adual ly
.
2-Sel ectiveß1-bl ocker s:-
As:-At enolol(Tenor ami ne)
Met aprolol(Lopr essor)
-Usedmai nlyforhy per tensionandangi na
-Noef fectonbr onchi andgener all
ylesssi
deeffect
s
t
hannon- selectiveß-bl ocker s.
3- α1-andß-bl ocker s:-
As: -Labet olol,Car vedilol(Dilatrend)
-Causev asodil
at ati
onandbr adycardia
-Usedmai nlyasant i
hy pertensionandper i
pher
al
v ascul ardisease.

Parasympathomimeti
cs:
Choli
nergi
c(Chol i
nomimeti
c)
Thesesubstancesactonacetyl
choli
nereceptor
s
(choli
noceptor
s)atallthesi
tesi
nt hebodywhere
acetyl
chol
ineisthetr
ansmitt
erofthenerveimpulse.

Par
asy
mpat
homimet
ics
│

Dir
ectacti
ng I
ndi
rectacti
ng
(onrecept
ors) (onenzy me)
│

Rever
sibl
e Ir
rev
ersi
ble
Anti
choli
nest
erase ant
ichol
i
nestr
ease
Cl
assi
fi
cat
ion:
1-Di r
ectact ing:
*Chol i
neest er s(car bachol ,bet hanechol )whi ch
Actonmuscar inicrecept ors:-whi chpr esentonef fectors
organs, nerv es, hear t
, smoot hmuscl esandgl ands.(M1,
M2, M3- recept ors)
*Alkal oids(pi l
ocar pine, muscar ine)whi chact
select i
v elyonend- or gansofpost ganglonic,
choliner gicneur ons.
*Indirectact i
ng:
1-Chol inest erasei nhi bit
ors, orant i
chol i
ne
i
nhibitor s(phy sost igmi ne,neost i
gmi ne,py ri
dost i
gmi ne,
whichi nact i
v atet heenzy met hatdest r
oysacet y l
choline.
-Acet ylchol inenotusedt her apeut i
callybecauseof
i
tsv eryshor tdur ationofact ionduet orapi d
hydroly sisbyenz y me.
-Inther egionofchol inergicner v
eendi ngandi n
erythrocy t
est her eisanenzy met hatspeci fi
call
ydest r
oys
acetylchol ine; truechol inesteraseoracet ylcholinesterase.
Invarioust issues, especi all
ybl oodpl asma, therear eother
esteraseswhi char enotspeci ficf oracet ylcholi
nebut
whichal sodest royot herest ers.Thesear ecol l
ednon-
specificorpseudochol i
nest erase.

A-Bethanicol:
-
-Actmai nlyonmuscar inicreceptos
-Sameact i
onasacet ylcholi
nebutlongerdur
ati
on
andmor esel ecti
veacti
ononey e,
GITandbladder
.
-Usedor al
lyandpar entrall
yorey edropsf
or:-
1-glaucoma
2-Urinaryretention
3-Par al
yti
cileus

B-Car
bacol:-
-AsBethani
colbuthasal
soni
cot
ini
cact
ivi
ty.
-Usedonlyforgl
aucoma.

C-Pi
l
ocar
pine:
-
 -Actmainl
yonmuscar inicr
eceptor
-Thechi
efcli
nicaluseofpil
ocarpineist
olower
i
ntr
aocul
arpressureinchroni
csimpl egl
aucoma.

-Si
deef f
ectsofchlonergi
cdrugs:-
1-Di
arrhea
2-Miosis
3-Nausea
4-Sweatingandincreasesal
i
v at
ion
5-Hypotensi
on

I
ndi
rectact
ingpar
asy
mpat
homi
met
ics:
-

1-Rev ersibleant i
choli
nesterase:-
-Actbyi nhibitionofacetylcholi
nester
ase→↑
acet y
lchol i
nei nsynapti
cspace→↑chol inergi
c
action.
1-Phy sost agmi ne:-
-Isanal kaloidobt ainfr
om t heseedof
plant(phy sostigma)
1-Usedsy ner gist
ical
lywit
hpi locar
pinetoreduce
intraocularpr essure(glaucoma)
2-Inat r
opi net oxi
city

-St
imul
ateCNS

2-Neost i
gmi ne:-
-Syntheticanalogactasphy sosti
gmi
ne
-Noef fectonCNS
-Mor eact i
ononv oluntar
yskelet
almuscl
esat
neuromuscul arjuncti
on
-Givenor al
lyandpar entral
l
y

-Therapeuti
cusesofneostigmine:-
a-Di agnosi
sandtreatmentofmy astheni
agr
avis
(autoi
mmunedi seasemanifestedbyweaknessand
rapidfati
gui
abi
li
ty)
b-Anti
dot
eofcurar
epoisoni
ng
c-
Sti
mulat
ethebowelsandbl
adderaf
tersur
ger
y

3-Pyr
idosti
gmine:-
-Issimil
artoneosti
gminebuthasal
esspowerf
ul
act
ionthati
ssloweri
nonsetandsl
ight
lyl
ongeri
n
dur
ati
on
-I
tusedinmy ast
heniagrav
is.

4-Edrophonium:-
-Usedmai nlyi
nmyastheni
agr
av i
s
-Moreselectiv
eact
iononskel
etalmuscl
es.

-Sideef f
ect saschol i
nomi met i
cs(di r
ectacting)
2-I rreversibleantichol i
nest erases: -
-Bindcov alentl
ytoacet ylcholinest erase→↑
acet y l
chol i
neact ion(i r
rev ersiblephosphor yl
atingt
he
activecent erofenzy me)
-Hight oxicusedasi nsect i
cidesasor ganophosphorus
compounds(di met hoate, parathi onandmel athi
on).
-Or ganophosphor uspoi soni ng:-
1-Br ady cardia
2-Br onchospasm
3-Mi osi s
4-Incr easesal i
vati
onandsweat ing
5-Conv ulsionandcoma
6-Depr essionofr espi ratoryandcar diovascular
cent ers→ deat hduet or espirat oryfail
ure.
-Treat ment :-
1-At ropine(ant agoni zemuscar i
ni ceffect)
2-Pr ali
doxi measchol i
nest eraser eactivator
(effect i
v ewi t
hin12hrofpoi soni ng)
3-Di azepam maybeneededf orconv ul
sion.
4-Mechani cal v
ent i
lati
on

Par
asy
mpat
hol
yti
cs:
 Par
asy
mpat
hol
yti
cs

Anti
-muscar
ini
c Ant
i-
nicot
ini
c
At
ropi
ne

Gangli
onblocker
s Neuromuscul
ar
Nicoti
ne blocker
s

Non-depolari
zi
ng Depolar
izi
ng
Compaetiti
ve Succenyl
chol
i
ne
Tubocurari
ne

Ant
imuscr
ini
cdrugs:-
Ef
fect
sofmuscar i
nicblocki
ngdr ugs
Organ Effect Mechanism
CNS Sedat i
on,anti
motion Blockof
si
cknessact ion, muscar i
nic
antiparki
nsonaction, receptor
s,
amnesi a,deli
ri
um unknown
subtypes
Ey
e My driasis BlockofM3
receptor
s
Br
onchi Bronchodi l
ati
on, BlockofM3
especiallyi
fconstri
cted receptor
s
GIt
ract Relaxation,sl
owed BlockofM1, M3
perist
alsis receptor
s
GUt
ract Relaxationofbladder Bl ockofM3
 wall
,urinaryr
etenti
on receptors
Hear
t Ini
ti
albradycardia, Init
ialbradycardi
a
especiall
yatlowdose, from stimulati
on
thentachycardia ofthev agal
nucleus;
tachycardiafrom
blockofM2
receptorsinthe
hear t
Vessel
s Blockofmuscar
ini
c BlockofM3
vasodi
lat
ion receptorson
endot heli
um of
vessel s
Gl
ands Mar kedr eductionof BlockofM1, M3
sali
v ation;moderate receptors
reduct ionof
l
acrimat i
on,sweating,
l
essr educti
onof
gastricsecr et
ion
Skel
etal Noef fect
muscle

*Atropine:-
-Extr
actf r
om atropa-bell
adonna.
-Compet it
iveantagonistformuscari
nicr
ecept
ors.
-Acti
on:-
1-My driasi
s
2-Decr easeacti
v i
tyofGIT(antispasmodicact
ion)
3-Urinaryretent
ion
4-Brady cardi
aatlowdoses(0. 5mg)butathi gh
dose(5mg)causet achycar
dia.
 5-Decreasesal
iva,sweatandl
achr
ymal
secr
eti
on
-Therapeuti
cuses:
-
*Invest
igat
ionoftheeye

*Gast roint esti

nal spasm.
*Bef oresur gery→ i nhibi
tsecreti
onofupperand
lowerr espiratorytract.
*Ant idot ef ororganophosphor uspoisoni ng.
-Poi soni ng
Drymout h, mydriasis,bl
urredv i
sion,hotdr y
Skin, and, inaddition,hyperthermia,anxiety,
Hal lucinat i
on,del i
ri
um, restl
essness, excitement,
Tachy car dia.
-Treat ment :-ofat r
opi nepoisoninginv ol
vesgi ving
acti
vatedchar coal t
oadsor bt hedr ug,
anddi azepam f orexcitement .
-Scopl ami ne:-(Hy ocine)
-Shor terdur ati
onofact i
ont hanatropine.
-Mor eef fectonCNS.
-Usedmai nlyinmot i
onsickness, anti
spasmodi c

-Ipr
atropium:-(At r
ovent)
-Usedmai nlyasaer solspar
yfortr
eatmentof
bronchialasthma→ br onchodi
lat
ion
-Pir
enzepi n(gastrozepin)
-Selecti
veM1bl ocker
-Usedi npepticulcer→↓gast ri
cacidi
ty

-Tr
ihexphenidyl
(Artan)
-Usedmai nlyi
npar kinsoni
sm→↓r i
gidi
tyand
tremors.
-Hyoci
ne-N-butylbr
omi de(Buscopan)
-I
tisanef f
ectiverelaxantofsmoot
hmuscl e
-usefulf
orcolic.

Localanest
het
ics(LAs):
E.g.Li
docai
ne,
procaineandcocai
ne
Thesearedr ugsusedt opreventpaininspeci
fi
edareain
thebody.
N.B:
Addit
ionofthev asoconstri
ctoradrenal
inetoLAssolut
ion:
1)AdrenalineproducesVC→ del ay
st hel
ocal
anestheticsabsorpti
on→ pr ol
ongsdurati
onofaction
and↓t heirsystemictoxi
cit
y.
2)Al
soadr
enal
i
ne↓bl
eedi
ngf
rom t
heoper
ati
onsi
te.
Mechanism ofact
ion:
LAsblockNa+channels→ preventr
api
dinfl
uxofNa+
i
onsessentialf
orthetr
ansmissi
onofnerv
eimpulse
acr
osst henerv
ecellmembrane(hyper
polar
izi
ed).

Li
docaine:
Cl
ini
caluses:-
1.Surf
aceanest
hesi
ae.
g.ski
nandcor
nea
2.Regi
onal
anest
hesi
ae.
g.l
i
mbs
3.Lesscommone.
g.ar
rhy
thmi
aandepi
l
epsy
.
Adverseeff
ects:
-
 Systemicef
fects→ abdomi
nalpai
n,conf
usi
on,
ski
n
rashesandmy ocar
dial
depr
essi
on.
 Local
eff
ect
s→ edemaandhemat
oma.

Sedat
ives&Hypnoti
cs
Sedatives:
Dr ugscalmthepati
ent
Hy pnot
ics:Drugsinducenormalsl
eep
Classif
icat
ions(Accordi
ngt omechani
sm )
:
 A.
Drugsf
aci
l
itat
eGABAact
ion:
Barbit
urat
es Benzodiazepines Non-
BZD
1.Ult
ra-short(1/
4-1/2h) 1.
Short
:tr
iazolam, Zol
pidem
ThiopentoneNa( I
V medazol
am
anaesthetic)

2.
Short(
2-3h)
:pent
o- 2-
Int
ermedi
ate:
Bar
bit
one Al
prazol
am

3.
Inter
mediaten(4-
6h) 3.
Long:Diazepam,
tr
Amy l
obarbit
one cl
onazepam
4.
Long( 6-
8h)
phenobarbi
tone

B.5-
HT1AAgoni
st:
1.Buspir
one:5-HT1AAgoni
st→ ↓r
eleaseof5-
HT
(pr
e-synapt
ical
l
y)
2.Sel
ect
iveAnxi
oly
tic
C.
OtherswithAnoxi
olyt
iceff
ects:
Alcohol
,Anti
-
Depressants,Ant
i-
Histami
nics,
Beta-bl
ocker
s&
cloni
dine.
General Guide-l
inesi
ntherapywi th(sedatives/Hypnoti
cs)
Drugs Di seases
1.Onset:Smal ldoses(Avoi
d Anoxi et
y :
shoul dbe
Abuse) accompani edby
2.Off
set :Gradual(Avoi
d: psy chotherapy&Rel axat
ion
convulsion/Rebound technique
i
nsomni a)
3.Durat
ion: short(Avoid
abuse) I
nsomni
a:shouldbestar
ted
4.Dose: ↓i
n(ol d̋ Ri skof onl ywhen(othermethods
fal
li
ngf rom Ataxia̋ , l
i
ver f ail
)
cir
rhosis)
5.Cl
ass: Better
a)Shor t-
actingHy pnoti
cs:
lessHangov er
b)Long- acti
ngAnxi olyt
ics
:Av oi
dResi dual
Anxi ety

Bar
bit
urat
es

Defi
nit
ion:arederiv
ati
vesofbarbit
uri
caci
d
Pharmacokinati
cs:
 Absorption:GI
T-I
nject
ionsi
tes

 Distr
ibuti
on:Al
l-
over
,BBB,concentr
atedi
n(Br ai
n,
ki
dney&l iver)
&dependson(ionizat
ion,
li
pid-
solubil
i
ty&BBB)

 Metabol
ism:
Ult
ra-shor
tescapesqui
ckl
;
yfr
om
ci
rcul
ati
onbyti
ssueuptake

 Excr
eti
on:
↑by(
NaHCO3-
↑ioni
zat
ion)
Mechanism:
1)Bi ndwithabindi
ngsit
eonCl‾channel
s→↑fr
equency
ofopeningofchannel
s→ ↑Cl
‾inf
lux→ Hy
per
-
polar
izat
ion→ ↑i
nhibi
tor
yeff
ectofGABA.
2)↓Rel
easeofExi
tat
oryt
ransmi
tt
ers.
3)Di
rectGABA-
mimet
icef
fect
Thiopentone;
highl
yli
pid-sol
ubl
e→ ent
ersCNSv
ery
rapidl
y,t
henRe-Dist
ri
butedtoot
herti
ssue.

Acti
ons:
CNS:
a)Sedati
on( 30-
100mg),
Hypnosi
s(100-
300mg)upt
o
Anaesthesia
b)Ant
i-
Conv
ulsant
c)↑Anal
gesi
aofNSAIDs(r
eli
eveanoxi
ety&psy
chi
c
symptomsofpai
n)
CVS:
↑dose→↓BPthr
ough
a)(
-)VMC
b)Bl
ocksy
mp.Gangl
i
a→↓sy
mp.Tone
c)Hi
stami
ner
elease→VD
Respi
ratory:Depr ession&↓sensi t
ivi
tytoCO2
Ki
dney:↓urine( ↓BP, ↑ADH, di
rect(
-)tubul
artr
anspor
t
mechanism)
Li
ver:i
nducer → Dr ugi nt
eracti
ons
Smoothmuscl es&skel et
al muscl
es: rel
axat
ion(
weak)
Si
deeffects:
1)Narrowsaf ety
2)Tol
erance&Addi
cti
on
3)Hangover(per
sist
enceofef
fects(
conf
usi
on,
headacheanddrowsi
ness)aft
ersl
eep)
4)Ni
ght–mar
es(
↓REM)
5)Par
adoxi
cal
exci
tement(
idi
osy
ncr
asy
-ol
d)
6)Hy
per
sensi
ti
vi
ty
Therapeuti
cuses;
1.Pre-Anaset
heat
icmedi
cat
ion
2.I
.Vanest
hesi
a
3.Anxi
ety
4.I
nsomni
a(wi
thoutpai
n)
5.Epi
l
epsy(
Grand-
mal
)&conv
ulsi
on
6.↑Bi
l
irubi
n
Contr
aindicat
ions:
1.All
ergy
2.I
diosy
ncr
asy
3.Headi
njur
ies
4.Respi
rat
orydi
seases
5.Shock(
Hemor
rhagi
c)
6.Li
ver,
kidneydi
seases
7.Pr
ophy
ria(
↑Hbmet
abol
i
sm)
Bar
bit
urat
epoi
soni
ng:
1)↓BP
2)Respi
rat
orydepr
essi
on
3)Car
diacdepr
essi
onl
eadi
ngt
orenal
fai
l
ure
4)Coma
5)Deat
h
Tr
eatment:
 Ar
ti
fi
cial
respi
rat
ion
 Gast
ri
clav
age
  Al
kal
ini
zat
ionofur
ine(
NaHCO3)
,I.
Vmanni
tol
or
l
asi
x→↑excreti
on
 Ci
rcul
ator
ysuppor
t(Dopami
ne,
Adr
enal
i
ne)
 Hemodi
aly
sis
 Bl
oodorDext
ran(
↓BP)
Benzodiazepines:Bi
ndwiththeirreceptor
son(ɣ-subunit
s)
ofGABAr eceptor
s(post-
synapt i
c)→ facil
it
ateacti
onof
GABAon( α&βsubuni ts)→ openCl ‾channel
s→ Hy per
-
pol
arizati
on→↓Neur onalf
iri
ng.
Acti
on/uses:
1)Brain:(Midazol
am/Diazepam )
a)Sedat
ion/Amnesi
a
b)Anaesthesi
a(Adj
uvant–pr
e-anaest
het
ic-
Endoscopy)
2)Li
mbi
csy
stem:
a)Anxi
oly
tic/Euphor
ia
b)Anoxi
ety(Di
azepam-
Alpr
azol
am )
c)Pani
cat
tacks(
Alpr
azol
am)
d)Opi
oidwi
thdr
awal
(Di
azepam )
3)Mot
orCor
tex:
a)Ant
i-
conv
ulsant
b)Epi
l
epsy(
Clonazepam/
Stat
us(
Diazepam)
4)Ret
icul
arf
ormat
ion:
Sleep
 Onset
/↑Dur
ati
on/↓REM (
ir
ri
tabi
l
ity
)
I
nsomni
a(Tr
iazol
am )/sl
eepwal
ki
ng
 (
Diazepam)
5)Sy
napses:
spi
nal
/supr
aspi
nal
)
a)Skel
etal
muscl
esr
elaxat
ion
b)Spast
icdi
sor
ders(muscl
espasm-spi
nal
cor
d
i
njur
y)(Di
azepam )

Toxi
cit
y:
 sl
eep↑↑/CVS&RC(
-)
 Ttt:f
lumazeni
l(compet
it
iveant
agoni
stonBZD
receptor
s)
Zol
pidem/Buspi r
on
Mechanism:
 Zolpi
dem: Bi
ndwit
h( BZDOmaga1r eceptor
s)→
faci
li
tat
ionofGABAact i
ononi t
sreceptor→ openCl
‾
channel
s→ Hy per
-polar
izat
ion→↓neuronalfi
ri
ng.

 Buspir
on:5-
HT1Aagoni
st→↓r
eleaseof5-
HT(
pre-
synapt
ic)
AdvantagesofZol pi
dem ov erBDZ:less(Hangov er(short
),
Distur
bancei nREM orReboundi nsomni s
DisadvantagesofZolpidem: vomit
ing/Dy sphor
ia
AdvantagesofBuspi r
one: (nosedationlearni
ngabili
ty,
dependencedel ay
ed,mot orcoordi
nat i
onorAdditiveCNS(-)
withalcohol)
 Delayedonset
 Dosesnot
tt(
insomni
aorpani
cat
tacks)
Analgesi
cs:
(Narcot
ics&Non- Narcot
ics)
Hi
story
: Opi
um isextract
edf r
om poppyseeds
pr
oducing:euphori
a,analgesia,
sedati
on,rel
i
efof
di
arr
heaandcoughsuppr essi
on.
Opioid:i
sanat ur
alorsynt
het
icdrugt hatbi
ndsto
opioidrecept
orproduci
ngagonisteff
ect(incl
udi
ng
endogenouspept i
des).
Narcoti
cs:
Defini
ti
on: gr
oupofdrugswhichreli
vepainbycentr
al
acti
on.

Mechani sm ofact i
on:
*Analgesiai sinducedbybi ndi
ngt ospeci f
icopioi
d
receptorwhi char epresentinbrai
nandspi nalcord
*Endogenousopi oi
dareendor phi
ns, dynorphi
ns,
endomor phinandenkephal i
nswhi chbindt oopioi
d
receptors.
*Stimulationofopi oidrecept
orsinhibittherel
easeof
substancePwhi chisresponsibl
ef orpain
transmissi on.

Classifi
cat i
on:
Nar coti
c( opioi
d) Non- Nar cotic( NSAIDs)
Opi um Alkaloi
ds: Pot antAnt i-
A. PhenanthrineGroup: i
nflammmat ory:
1-Mor phine A.Acet yl
-salicyli
cAci d
2-Met hylM.( codei
ne) :Aspi ri
n
B. BenzylIso-Quinol
ine: B.Acet i
caci d
1-Papav eri
ne:non- derivatives:Indoci d-
speci f
icSm. Ms Sulindac
relaxanti
on C.Pheny l-
Acet i
caci d
derivatives:Di cl
ofenac&
2-Nar
cot
ine:
Ant
i- Fen- Dicl
of enac
Tussi
ve D. Py r
azol one
derivatives:Pheny l
butazone, Dipy r
one&
Aza- Propazone
E.Pi roxicam: Feldene
(Long- actingonce/ day)
Semi
-sy
nthet
ic: Moder ateAnt i
-
 A.Di
-AcetylMor
phine i
nflammat or
y:
(Her
oin) A.Fenami cacid
B.Di
-Hydro-
Morphine derivat
ives:Me-F&Flu-F
C.Apo-morphi
ne(centr
al B.Propionicaci
d
emeti
c) derivat
ives:Ket
obrofen,
I
bubr ofen&Napr oxi
ne

Synthet i
c: Wit
houtAnti-
A.Sel ecti
v eAgonist
s:on i
nfl
ammmat or
y:
Mur ecept ore.g.fent
anyl
, -
Acetaminophene
meper idine&met hadone (Paracetamol)
B.Sel ective
Antagoni sts:Nal
oxone
highaf fi
nit
yf orMu
receptor
Nalorphine: notapure
antagoni st

C.Mi xedAgoni st
s–
antagonistandpar t
ial
agonist:Pentazocin
Narcoti
cAnal
gesi
cs(Opi
oids)
Morphi
ne

Phar
macoki natics:
Admi nistrati
on:I.
M,I.
V,SC
Metabol ism: i
nliv
er(M-6-
Glucur
onidev
erypot
ent
Analgesic.
Execrationbyki dney
Crosspl acenta→Neonat easphyxi
a

Acti
on:
A)CNS
Depressi
on Exci
tat
ion
1.
Analgesi
a,Euphor
ia 1.
Miosis
2.
Respir
ator
ycenter 2.
Nausea,
vomi
ti
ng(
+)
3.
Coughcenter CRTZ
4,
Sleep:
sedati
on,
Hypnosi
s+analgesi
a

B)Ot hers:
1.GIT:↓Mot i
l
ity, constipati
onduet odecr ease
i
nt estinalper istalsis&bi li
arypr essur
e
2.CVS: ↓HRbyv agalact i
on( br
ady car
dia),blood
vessel s: VD. hi staminer elease..
3.Sm. Ms: prolongedl abor&Br oncho-constrict
ion
4.Hor mones: ↓LH, FSH, ACTH- Testesterone,corti
sol
,
↑ADH, GH, Prolact in
Cont raindication:
1.Age: Young, v er
yol d(badmet abol i
sm )
2.Headinj
uri
es:miosi
s,Respi
rat
orycent
er
depr
essi
on( ↑CO2→VD→↑CSFpr essur
e)
3.Respi
rat
orydiseases:
hist
ami
ner
elease,
RCdepressi
on
4.Li
verdi
sease:
met
abol
i
sm
5.Bi
l
iar
ycol
i
c:spasm
6.Acut
eabdomen:
masksy
mpt
oms
7.Pr
egnancy
:addi
cti
on,
wit
hdr
awal
sy
mptoms
8.Del
i
ver
y:Neonat
alasphy
xia

Ther
apeuti
cuses:
1.
Severpai
ne.g.postoperat
ive,
trauma,
cancer
,
fr
act
ureandcolic
2.
Premedicati
onofanesthesi
a
3.
Pulmonaryedema
4.
Coughsuppression
5.
Diar
rhea

Si
deeffects:
1.
Vomiting
2.
Constipati
on
3.
Hypotension
4.
Respi
rat or
ydepressi
on
5.
Endocrinedist
urbance
6.
Uri
naryr et
enti
on
7.
Pysi
cal dependence

-
Mi scel
laneous:
Tramadol -weakMuagoni st
Codeine -usedanti
-t
ussive
Met hyl
mor phi
ne -usedasanalgesicin
combinati
onwi thaspir
in
Dext
romet
hor
phan -usedasanti-
tussive
-i
tisfr
eeofanal gesi
c
andaddicti
on

Di
phenoxy
lat
eand -t
heyar esynthet
ic
l
oper
amide opioidswithsomeant
i-
choli
nergicacti
vi
ty
-t
heyt r
eatmentof
diarr
hea

Di
oni
ne Anal
gesici
nsurgi
cal
opht
halmicpr
epar
ati
ons

NSAIDs:
Inf
lammat i
on: i
s8phases: -
Inj
ury,
cellst
ructuralchanges,met aboli
c(hypoxi
c)
changes,acti
vationofchemi calmedi at
ors,
haemody namicchanges, andper meabili
tychanges
l
eukocytesmi grati
onandphagocy tes.
Inf
lammat or
ymedi at
orsareHi st
ami ne,5-
HT,
l
eukot
ri
ne…andPGs

Cel
lmembr
anephosphol
i
pids

Phsophl
i
paseA2

Ar
achi
doni
caci
d

Cy
cloxy
genase l
i
poxy
genase

PGG2
l
eukot
ri
ens

PGE2 PGF2 PGI2 PGH2

Thromboxanes
TXs:foundi
nplat
elet
sresponsi
blef
orcoagulat
ion.
`LTs:
causesal
ler
gyreacti
onandbronchospasm l
ike
LTB4anasthmamedi at
or.

*S0byi nhi
bit
ionofCOXwemaygetst omachul cer
,
bl
eeding,al
soar i
skofbronchospasm andall
ergyas
NSAIDs,getsleepdi
stur
banceanddelayedlabor.

**buttheyfoundt hatCOXi s:
1-COX1( const
ituti
ve)
2-COX2( i
nducibleininf
lammat i
on)
3-COX3onl yproducedduringpain,
inhi
bit
edby
paracet
amol .

Sali
cylates:
**Sali
cy l
atesassal ts,est
ersoramidesar eall
hydrol
y zedintosal
icy l
i
cacid.
M.O.A: 1)Anti
pyret
icsbyr esett
ingofhy pothal
amus
temper atur
eanddi lati
onofper i
pheralbloodvessel
s
2)Analgesiabybothper i
pheralandcentraland
decreasingPGs
3)Ant
i-i
nfl
ammatorybyi
nhi
bit
ionofsy
nthesi
sand
rel
easeofPG
Generalchar
act
ers:

*Aspir
inisthepr otype, Heterogenousstr
uctur
es
*Possessasi nglecommonmodeofact ion
(Reversibl
eBlocki ngofPGsy nthesi
s).
*Otheracti
onsr elatedtoi nf
lame): (
-)COX:by
(Di
clofenac,i
ndomet hacin)
*Theoreti
call
y,selectiv
eCOX2( -
)mightbe
advantageousbecause( itwouldbeconf i
nedto
i
nflammat oryti
ssue)

Pharmacoki nat
ics:
-Absorpt
ion: Al
mostcompl et
efr
om GIT.Tendnot
st
undergo1 passel iminat
ion
-Di
stri
buti
on: HighPPB-smallVd-t
1/2:short(
1-5hr
),
l
ong( 10-
60hr ).

Sal
i
cyl
ates:

Act
ions:
Anti-
Pyr
eti
c Anti-
infl
ammat or
y
5mg/ day)
1.Mechani sm: 1.(
-)PGsy nt hesi
s:
↓PGE1&PGE2 -Di
rect(-)COX
2.↓hi
ghbody -I
ndir
ect:
temper at
ur e ↑Corti
sone→↓PG
3.Actson 2.(
-)Kalli
krensy st
em
hypothalamus→heat →↓BK( r
esponsi bl
efor↑
l
osst hrough: Cap.Per meabi l
it
y)
cutaneousVD 3.(
-)protease&
&Diaphor eti
cact
ion Hydrolase( damage
4.Toxicdose:→: ti
ssueenzy me)
 1.Uncoupl ingof 4.(-
)Anti
gen/ant
ibody
oxidative reacti
on(↑ACTH
phosphor yl
ati
on→↑ →↑cor t
isone)
ofoxi dativ
e
met abolism
→↑t emper atur
e
2.RC( -
)
3.Children:Super
-
sensi t
ivi
ty
→↓t emper at
ure

Others:
1.Analgesi
a:inmi ld-moderat
epain.Maximum
effi
cacy<opi oids&nodependencepl ateletfuncti
on:
(-
)TXA2→↓pl ateletAggregati
on→ protectagainst
vascularocclusion.
2.↑Gest at
ion&l abour
4.1r
ydy smenor rhoea: Mefenamicaci
d

Si
deeff
ect
s&Cont raindicati
ons:
Syst
em Sideef f
ect s CI
GI
T N,V/gast rit
is/ulcerat
ion PU
duet oinhibitprotecti
v ePG
instomach→ pept i
cul cer
Ki
dney Anal gesicNephr opathy : Renal
(chronicuse→ i
mpairment
↓GFR→Na+/ H2O
retenti
on→↑BP,
precipi
tatesRF
Li
ver Rey ҆sSy ndrome: Chi
l
dren
(encephalopat hy,li
ver
damage)
I
mmune Hy per-
sensi ti
vit
y:(Rhinit
is, Al
l
ergy
,
 ur
ti
car
ia) Bronchial
Asthma
Joint s Hy per-uricemia(inlowdose Gout( low
) dose)
Blood Bleedi ngt endencyduet o Bleedi
ng
I
nhi bitPGH2→TXso tendency
prev entpl atel
etaggregati
on
Chroni c Tinni t
us, Dizzi
ness, GIT
toxicit
y
Acut e Respi ratoryAlkalosi
s
Toxi ci
ty foll
owedbymet aboli
c
Acidosi s&Respi r
atory
Acidosi s

Par
acet
amol
(Noant
i-
inf
lammmat
ory)

Uses/Doses: PU,Chil
dren,
Aller
gictoaspi
ri
n&
Hemophili
a.500(2-3/d)
Sideeff
ects:Analgesi
cNephropathy:i
rr
eversi
ble
chroni
cnephriti
sin(largedose/longti
me)

Livertoxi
ci t
y( 15gm ) :
-Nausea&v omiti
ng→ ( 24-
48hours)f atalli
ver
damage
-Mechani sm: Saturati
onofnor malconjugation
enzymes→conv ersi
onofdrugby( mixedf uncti
on
oxidases)t ot oxicmetaboli
te(N-Acet y
l-P-
Benzoqui none) →Accumul ation&reactwi thcell
protei
n→ damage
Treatment :Asear lyaspossible
a.Acety lcystei
ne( or
al/
IV)→↑conj ugat etoxi
c
met abol i
te
b.met hionine(oral):cont
ai n
Generalanest
heti
c
Anestheti
cisstat
eofrev
ersi
blelossofconsci
ousness,
ref
lexeswithskel
etal
musclerel
axati
on.

St
ageofanesthesi
a:
1)St
ageI(analgesi
a)  Thepat ienti
s
consciousbutdr owsy
 ↑senseofhear ing
2)St
ageI
I(exci
tement)  Thepat i
entlosses
consciousness
 Respirat
ionis
i
rregular
 Vomi t
ingmayoccur
3)StageI
II(
surgi
cal  Thepat i
entis
anaest
hesi
a) unconsciousness
 Nopai nrefl
exes
 Respirat
ionisregular
4)StageIV(medul
l
ary  Respirat
ory
paral
ysi
s) depressionand
hypotension

Ai
m ofpr
e-anest
heti
cmedicati
on:
1.Reli
efofanxi
ety(sedat
iveandhy
pnot
ics)

 OralBZDse.g.diazepam orl
orazepam ar
emost
ef
fecti
ve(↓anxiety)

 Theyalso↓theamountofgeneralanest
het
ic
requi
redtoproduceunconsci
ousness
2.Reduct
ionofparasympat
het
icbr
ady
car
dia,
secr
eti
on
(par
asympathol
yti
cs)

 Byusingmuscari
nicantagoni
ste.
g.At
ropi
ne,
scapolami
nee,
glycopyr
olate.
  Usedtopreventsal
ivati
on,bronchi
alsecr
eti
on
andtoprotecthear
tfrom bradycar
dia

3.Nar
cot
icAnal
gesi
cs:

 Opi
oidanal
gesi
ce.g.mor
phi
ne,f
entanylgi
ven
bef
oretheoper
ati
ontopr
oduceanalgesi
a
4.Ant
i-emeti
cse.g.met
oclopr
amideandandanset
ron
→topr ev
entnauseaandvomit
ing.
Ty
pesofanest
hesi
a:
I
- Intr
avenousanest
het
ic
Theyareusedforrapi
dinduct
ionofanest
hesi
a
wit
hin(20-30seconds)
1.Thi
opentone
I
sabar
bit
urat
ethatenhancestheef
fectof
GABAi
nhi
bit
oryneur
otransmit
ter
.
I
tisgi
venI
.Vandr
api
dlycr
osst
heBBB
I
thasnoanal
gesi
cpr
oper
ti
es
I
tissl
owl
ymet
abol
i
zed
 Adverseeff
ect→ r
espi
ratoryandmy
ocar
dial
depressi
onandanaphy
laxis.
2.Propof
olandEtomi
date(simi
l
art
othi
opent
one
butmorerapi
dlymet
aboli
zed)
3.Ket
ami
ne(
Ket
alar
)
 M. O.
A→ antagoni
stoftheexcit
atory
neurotr
ansmitt
ergl
utamicacidatiti
s
recept
or
  Thedrugproducesdi
ssociat
iveanesthesi
ain
whichthepati
entmayremainconscious
al
thoughamnesicandinsensi
tiv
etopai n.

I
I- I
nhal
ati
onanest
het
ics
Mechansim ofact i
on:
1-Li
pidt heory 2-I
onchannel
I ti ssuggested  Theyinhi bi
t
thatthe nicoti
nic
anesthetic receptorsand
dissolvein mayaf fectGABA
membr aneli
pid andGl utamate
andaf fect
sits (i
nhibit
ory
phy si
calstat
e neurotransmit
ter
s
)

Pharmacoki netics:
Drugswi thlow Drugswi thhigh
solubili
tyinbl ood sol ubili
tyinblood
Lowbl ood: gas Highbl ood: gas
parti
tion parti
tion
coefficient coefficient
Theyhav er apid Theyhav eslow
rat
esofi nduct i
on r atesinduct i
on
andr ecov erye.g andr ecov ery
nit
rousoxi de e.ghal othane

Cl
assif
icat
ion:
A. Volat
il
egases
1)Ni
tr
ousoxi
de(
N2O)
 Hasar
api
donsetofact
ionandr
ecov
erydue
 t
olowsol
ubi
l
ityi
nbl
ood
I
thasanal
gesi
cact
ivi
ti
es
I
thasweakskel
etal
muscl
erel
axantef
fect
.
2)Vol
ati
l
eli
qui
ds
Hal
othane
Ismor esol
ubl
ethanni
tr
ousinbl
oodand
theref
orehassl
oweronsetandr
ecov
eryr
ate
I
thasweakanal
gesi
cact
ivi
ty
I
thasweakskel
etal
muscl
erel
axantef
fect
.
Local anesthetics( LAs):
E.g.Lidocaine, procaineandcocaine
Thesear edr ugsusedt opreventpaininspeci
fi
edareain
thebody .
N.B:
Addi t
ionoft hev asoconstri
ctoradrenal
inetoLAssolut
ion:
3)Adrenalinepr oducesVC→ del ay
st hel
ocal
anestheticsabsor pti
on→ pr ol
ongsdurati
onofaction
and↓t heirsy stemictoxi
cit
y.
4)Al
soadr
enal
i
ne↓bl
eedi
ngf
rom t
heoper
ati
onsi
te.
Mechanism ofact
ion:
LAsblockNa+channels→ preventr
api
dinfl
uxofNa+
i
onsessentialf
orthetr
ansmissi
onofnerv
eimpulse
acr
osst henerv
ecellmembrane(hyper
polar
izi
ed).

Li
docaine:
Cl
ini
caluses:-
4.Surf
aceanest
hesi
ae.
g.ski
nandcor
nea
5.Regi
onal
anest
hesi
ae.
g.l
i
mbs
6.Lesscommone.
g.ar
rhy
thmi
aandepi
l
epsy
.
Adverseeff
ects:
-
 Systemicef
fects→ abdomi
nalpai
nconf
usi
on,
ski
n
rashesandmy ocar
dial
depr
essi
on.
 Local
eff
ect
s→ edemaandhemat
oma.