2 ADRENERGIC AGONIST drugs.pdfnjjjkkkjkkm

Ans

1. ADRENERGIC Agomist
By: Zakivullah yousufzai
FROM: Dy. Najeeb Lecture

ANS Phaxmacotogy

Drug acting on SNS Drugs actiny om PSNS

Sympataomimatie sympatholyhe Dveg
Dregs or cs
Adrenergic drugs ati Advenergic. ange

aR

Advenergic Agorist Ravenergic Antagonist

x When there is suddenly mevesse in stress, sympathetic
Newveeus system will Jive, and prepare the bedy Jer Tight E, Wight

% Nowmala sympainetic 4 Parasympalhelic opposing sach nu

venbemesiat

nn

Ei ehe
Va ne cece ae
sence ra ei

ec sara them: MS =
Pipas Sas cout che

az

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2. Preqanglionic — Release Ach

post ganglionic — Release Nov tginepbrine

pi meurs Prom CNS comeout (Relsse AU) are cholinergic

Beta taalion , Se chal,

depot a
open, à GE enter te u
fe ot ale do ST, Se

Te Soa. st alah ei Ma

tg

bara Ñ
Wet me o
BE:
sin
X PP m2
Se
we |
se
AR pepemin demie within, the a
Mn, Cid dom mos
aria ale lo vee
ComT
+ Boh q NE ane veabserbed by ne-Redetake À (RUN ee
hes deme ts aden she
(NE RUL is N/A dependant) ARS
dak 4th doe ag eens ips Ar

Lait Gi se hibit RT as a vesutt CAMPE 4 PHA, Se
channel een, cal beume —ve, again vole putter Mav des

NE people ove bite by gr TER Cr
Swat ( duloxetine

NOTE, ReuPlare A NE inte mentenal en OL re ma
Hey the termination of HH TVET a ie

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3. Out & enter te Civcalation

Tose

© mactivale by CoMT

@ Back Reuptake (Mein rechantn) my pharmacelegy The
Reupioked NE Biechemistry q, only ANS
TO back te vesicle A E

O destryed by MAO
cie Gen ~

} NH
POS RE
Ray benzene ing ik gd o pos have où are

Gaited Glhecol Ring
Cotiecolamime Compounds wii, amine grog Es teca 29

on oot
P PO _ "| Dopa

en u 3
le) nu DoPAMINE
? U

# what are Mencamimest

Nevelvansmittin which are devivitive «single Amina
WT pesine make man) menshmimes Like
© Depamine „@ Epineghiin O neretgineghein O Tayptethana(aie
ud] Nor- tinephrine

Ach 15 met mencamine

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©

4. Nov-spineperine is bound — with protein
Ascorbic Acid, 5,
e osmaicaly as

SR wi ATP ev

colted Chromegranin
ad as

ait x bound mor tpinep vine
“singt molecule

How Nev-fpinephvine ave Released?
Newe ending have Depolaning

Ca came
Depeloriration occur Ne move im, So Gt Channel ove
activated E Gt move in and allow verde Le use sith
menienal membrane.

Sensitive cat
Se, when

vesicle have a polen Catted " Syrapte Braun
membrane have a protein called” Sy Mtazin
am obstruct, whin

and neuronal
the Symasin have
Ge come and bind with obstruct, bah Gi

en ech cher, so azine otis D al,
so the =

Symaplobrain Come & Jose with Suntarine Eq The Nersipinephing
sde Prom the mere ending © Poin} vesicle wu mare mit

Ihis vesicle is pulled agsin by clathrin & ved Jor again 0%

ADRENERGIC RECEPTORS

B-AR
Ë +

À

AU Advenengie ecspions ane Fpasy protein

Se AR presynaptic. mene mien

TAR, BAR, BAR ———T Postsyraptic mmeminame Chiste)
meri Y Efimepiniva are veleasul, small

amount of it ads om 4 AR

So, camp tet des, Gi proteins alse open the 10 chan $

wiiacellecalas 10 Comes eut

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5. & ct become — hyperpolarized Such call

mewe ending is

is different te
Polarized , so tahititea ; Torther release

D rem tpimepiin is teduced | this Mechanism is AUTO inhibitory

Y cAMP lead do reduce activist 2, Pratean Kinase AA), Se
Synthesis metre trom smiter reduced, so

+ A,AR act as an auddoinhibiter Helecule

wuhakevey mac epinephrine is yeleased gez tt weites

le -veuse AS —N-Epinephine 15 UPHAKER, small amount

it, whe,
is shi mot taken ds vesiucle , ave

destaped by MAO
ENE is taken back by Reuplake-1 mechanism

NER is also acted gy URE I) ameter
Enzyme COMT present on postmembrone a
and! vemeve oH up nie % add CH, gmp

Due te melllatien, this molecular become

less polar pe In en
> .

This entpme is also Present in the Liver

very small amount q NER is diffuse inte general civcalólion

& tel by Ler (7 & Wma
sympalholyHe u
Syrmpathelyhe beugt

1) methyl TyResine

+ enter ‘te mewe ending & capture
A Got werk Yor momel Pate
Qu taime le oda ande q, Tin)

rotas ner activa 15 Le

So this dwg is sympathetic Aug

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6. (2)_RES. ERPINE a

This Dw] mhibit Depa,
cant be enterd into vesicle

Transporter A), So depamin

voice remain Empl
Depamin is destigel by Mio

a Tis dry alse inhibit urlake of tpt WER by vesicle

ari is du is sch as AM hypertensive, but ou dys

perten sive

© mat used as anti

(3) Guanadyil oR_Bretylium,
Guenadvil of bebita,

Tus dwg does mot allow the Pai of veside with

mewe amembiame, So the nes rosa

(4) H—metiyl Dota

A meth] depa is taken by merve endiw

3

“pom it
Y

Depa decorbasias, meh! Dopamine
a

cmt dopamine enter inte vesicle E

spa decorborlase act on I à make ml

demehyl dopa

converted into émail NE

a Methy) dopamin > met] Ne eri

ge, when Actim potential Comes, -melkgl Nor ine is Come out

bet jon is mot there

sgmpalnche aca ges down

val
oni:

+ bind Le vecepter & stimulale it

+ Antagenist, bno te vecepter but deuil Simebiteit

+ Povkial ogerist,

PRE LION LS

x mixed agonist amlagewist pind to one site 1 stimulate them, white bind
SSS

Beaker side & Gant Que Stimulation

bind Lo vecapter £ Stimuele Mock

©

7. ADRENERGIC RECEPTOR AgomsT

+ 8

dt, el PP e

enetopetel

e prenesybenzene + Prpranatel

e ATEnetot

« Phentelamime

Af these dys

+ Phewoxybemene = Ivreversible man Competitive Yecapler ecke

# Phentolamines Reversible competitive vecapter

difference Bf Praresine & Trazosine

x Prozssine = Shot half Life

lang hal Lite

y drug wich weduce synthesis of Newatransiittengdprte| Hsing

+ diy € of nembransmittevad Reser Pine
: he velase ef Nuno tvansmitera Gumadrit el
x deg Bretgtiom

Sympathoanimitic Dregs

Divectly acting agonist Iindiveetty acting dvvgs
nich it Drago cart act én
soe me ending &

Site wlaye of NE

8. DIRECTly ACTING DRVGS

ai
phenql-
Ephosine

la.
Solbutamel
brenchadiolaloy

A sic
cents + APR
Con wi
cont “re
Sympathetic Epinephrine
(narenaline)
Cardio stimulant
& Renal Wed
alter
INDIRECTLY ACTING DRUGS
1) Cocain., Act with —sevptake- 1, So NeuroTiansmittey ave
ot veuptane dy meme ending
ik yemains 8 Synaptic clef Ta tanger dime, so ac m

yeceptor Yor Jonge tine
2) Tricyclic Anti _depresse:

Bind with veuptaKet but mel

Sheng, & SUN yeduce veurioke

3) Selective sexetenin Reuptake mhibi SoA), Pile
Selective SS

4) Payqyiine, prenylerpremidg oo ase AOS imite
qgLLgL —— rá

ei a5 an antidepressant

5) Amphitamines AAMC These ang Enhamen usin

af vessche wi membrane fy release mevvotrangmi ters

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9. Biological Respence to stress under sympathetic

E

Tissue & organs
te be stimulated
# Xy Advenergic Receptor
* PL Advenergic veeepter

Tissue & gan
function whibited
A, Rârenegie vector

Adwenergic vector
All the issues te be stimotatea P Ÿ
have AR Except AU Be dise da be inhibited
8 . having BAR. EXCEPT:
An‘ de Orrespraie Opa Orns
mente ue pr
Heart ate Titer >> pe
Ba Mt a A
BE 7
a
y
when a person tum, bleed flow to amuscies te Mlamd blood low te

wey des de
Kidney de

Constricted, Muscle have

vessele te kid

Kidney vessele have GRR on smo muse, so

ARR So mhibeted E

A AN the issue Es organs WHR ig with
ven eg: oy & ho
a Tissue, which does met Tight ith stress

have

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shimulta &

Relared

avessele te muscle

M we pui a venal vend te

Muscle verein a Container
Ravin) ER A, Mu seal Vide
wi Emsa u muscle vende

axe dialatd

ges hase simulador,

wtititeg vecapteres Bik

@

10. what ave changer in body under wtlvence +
Advenergie system.

DAR
== (KE Wir Agé oP yg Si
SE 9) “rector pi ruse, wich has «AR

PHC muscle Shin vesicle cnstrich
2) Eyes
LS ave stimulalal, Cause Pri Conshrictien

@ PVA = constriction

© sympa emoos. spin Yous Ihe eye or Var vision
Clon come tie)
os
ES

«cillianis hos PAR

circulos Muscles
wsphinden has Lo conshic 1%

au

has LAR

Lengiidunes ruso
ir AAA

Blood Veh # Smentk muscle
to GIT los in stress menea Yor Penistahis
La const be # secretions alse decvessul

We hos of AR

bronchioles ave diated
fe more O, Come
E BAR

—

&) Lungs

bused vessels ef Langs
are constricted by hos
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ung edema

11. SVD Val of blood ejected MI

Venbicles desing one Put.

Host have mang 6

Corsv-HR
costs the

porting system,
abil Ey ventricalay eye rd

Rutomaticitys property ef

veceptes
le on SA-mode, Av-nede

Viswe te produce
depolarization spontenecusly
SAnede produce Automatica
4 Sh-node have ve
“Anode have

memotpie action m ang:
Teontractlily is

Dremebngic action on ang,
cated

ave Znoisepic action, sy is ted Key Inebogie actin
Se Sympallelic Nemoos

system tes
6) vascular system

Graine

outra

have signifient

X cerebral bleed You doesn't
veceptos, 50 ce

Aue Walatel Wy Hyccardiom products
SN ane
yc mate pra Om

Ws when ens stl

panied to fens

Covenany bleed flow is

is ar

©

12. N) METABOLIC changes

ECHA
important notion
athe der i
de take Glotese &
Convert it te

den

Aaipocyles

Oliver release glucose Le civealation (ie: gycogenctys

© Adipocytes ——> Lipolysis

O Gloconeogenesis — FER— Glucese

O BNd—K ATPase is activated ey cel start taking K
Aron blood

B, veeaplor on Muscle liber is activated it ui
Simulate Na rase

Aaithin Me Muscle — glycegemolysis occun

Muscle Spimdle alse have BL yeceptor, se under Increased

sympathelic Yow PL receptor ave Stimalaled me proper
Extensor 4 Uleror Musde tone is present, So musie Arme
occur. ey dung fear be Less el éxeilibriom
# Glucose level im the blood Mes + K Level in the bleed des
à FER Level in the blood tes # Muscle By Cogemelysis occur

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13. 8) sympathetic action on ur gen tat N tem

Myocasdium have Genes Yor
PY < AR

Sumo Jara 6 ial prep,
ae el ES
Ehen ty Pagestoen dos
ment seus geht a, AR
ones wre expressed % mere

whe wed Tor Gratin

+ chen Female become pregnant
genes ‘tor po wil be Sepressed Se pregnant À

emake, have mere

fr veaptey m Uterus Than oc AR
ives
Pightedsine will act on BL amd prevent rem baby delve
+ Aemale Excretion & Sééréhon ave mewnolegtcatly Cm hg he
Same wey is parasympathetic Nenwes system

+ female ejaculation & orgasm are Controlled by Sipupallehe rem
pen

Delresure Musde hes
BAAR, Se dani thre
it elotes

le

Ejaculation = sympathetic ns

ejecalatony duct, vos déforme,
prostate che ave Wird

Rinrnal Urethral sPhinclee
& combi, so My have AR

NAAR, So ducing stra
Henri e prod
under stressful Gen difions Urination.
WS Remo tes — mn tes ch tse;
aan, * Venocenstriction
4 Re ef Aldosteren — TNA E, He retention
hie eat oe det ne cent
NUE SRE Lea ANO

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14. Sharecteristic Physiological & Pharmacological
Action by Stimulation of specific Adrenergic-R

Vascalay

ae ES. on ES
“1 Aa Heart a" 6”
© mydriasis ov orn
Ot fileerection —@ deeweate mine FFE a © 1
janie Aron Ardo res |
constriction @ des Lipolysis from + Atria.
mesi muscle ¿ase Smostrery A rat
od E
© cti © PRET panty Be
aa © iues a
Sthinctey id _
=a

vasailay smeuh muscle

4

vasoconstriction

>
ee

arteria have
ANR, te by
stint
Stele ston,
canal Cae
Mores tend

a font Area
ne diet A
ot eee fat

a) Br

oon aMesiel to venevs side
eres im artery daños diastole 15 flay
spend m TER
TIRA in arteriole fer à
arteriete ack as a tape whem ope is ee.
een pressure in pipe des
A ug Venous vessde ave Gpacitence vessele?
Blc do boa vslume is Present im vences side.

+ Co o systole BP
¡antic OF + Diastelicoc TPR

systie ce
Fash TER

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15. Systemic BP =
SYStOME: pressure im mager systemic arteries hen LEY
Ventvicle is Pumping

Diastolic odia UE

y Pressure im mage systemic
relaxing
ii: Rortic valve à closed
AAR — Stimulated by m venvies will Cause les of bled

te wight het, so There is tes venous velum

back
strike Yelome & tes CO; Se during

frend diastolic volume , tes

mere Heed Comes te arterith so sgstalic Brite

systole

ste
eS

Diagtetic
er

+ when dug A ds given systolic is momal & diastehie decresse, go the

ng is bing TPR Cavtenistodialater)

+ when dig Bob given systolic is memal & diastole BP AS the an
is ting TAR Catericle constrictes)

diastolic is memal E, systlic Be ter the dg

# when dry © D qien
ie fing cardiac ovitut
y vibe dre D ds pren diastolic is moral 2, systole pds, de dong
is Ving Gdiac "ect pot
then dou Er given syste de mére à diaslele 15 deevan so
dwg ls Hing FRR à Ting Cardiac output
+ when ding Gis given systolic des h diasteie Tes, so the doug,
Ving tardiac output & tes TPR

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16. Pupitoyg diatation,

ds; mydriasis a"

PROSTATE
=
When Piel meresse in Size, iL Constrich Urra, & the met

will develepe Berign prostatic hgpertrerhs (BPH)

ete sud pales we
made These go are [E mias)

drag which diolle postale gmat

ed, blockers ave Excel Anti HTN in BON Palliat
o polie PR
&LAR (crease Tone of internal urethral sphincter

00 ML

gn TB
P, stimulant Adirocyke

+ Depamine
+ Doputamine

Pr Stimulant ave always Cardio stimulant
Balhkmotvapy; ted eilibility of specitiged Conde so

Wis tes in strength of Gntrachion
without py stimulate, Te fakes mere time te
Beach te peak. with Pi Stimulation veloc}y À
Imevense, so bess Time is date te Yeh
de paar this is Ave Eat}
ve noto] — Ted VE 24 Contraction

+ THR? Ve Chronebor'y

Swe" tetes
maso DN Guen

etes = To = t systelic BP

is we moteery,

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17. one of TyPical function of Bı blocker is te
Cavdiowmbibitor-
Pi-blocker ip mel only Cardiombbile but alse whibit
Jura glomerular Apparcdus GUA) cols Renin Production in the
bedy is deevesse , 50 Syd

DU fogiotensin TL mediated Vase censtriclin is tow thaw diadtelie BR

Qu be Less 5 MIM AT meliatel venoconstriction wil alle be Las

Venous relum wi be le End diastolic Volume des — Co

astoke Brees,

Qaidosteron mit alse be Lew, ge aldesteren medial Soll te way
Yetention is la, so Bleed Volume is le venous vetum 10,0

Cob, se syitelic ap is Len

So These dm are used Antihypertensive digo, so fi blockess

des Be by Gavdinmbatitions E, wibilin of worin Ang.nd. system

pr

muscle have
more Y veceptor
& Less 2, veceptos

= x tes TOR

ly Stimulant
Bi sKmulont —» des TPB

Roynad’s ABR à There ig increased tendency ef vasesfastick)
SF distal bled Vesele, when Expese to cad, vessele constrid se
sah, that Fersen develop Genesis, à even necrosis im wor
Pongads aiseote

y so.Prepramelal is Conbindicaleh Yr Mond ve

patient sith perephvat

disease

# propramstel Should met be given in Alma patient

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18. frpranclet is contraindicated Yor palient
Diabetes meiitus (EDDM) be they have
hypoglycemic attack: they dera

O nntions Leo

© palpitation o

eg CRE spnpaheie siler

© Trem Pees AT

Weil, Insuline dependant

mare Chance te develop

YA eBecker (ea Perr Ts Faken by onu dependant Din Patient
& whenever he deep Mpféemis he will mot develop Mania
symptoms, so such pakient mot taking sugar, & also Liver ‘ill met
Cane gares, so They have mme chance Le desa Aife threo,
Fee comia

+ Ba stimulant have Tokelytic effect om utes.

el Basis of Advenergie Drugs E imbraceleculow

nana Mechanigm

al adrenegic receptors ave

Fr, also called
Sexpentine og

Gepmten coupled veces te

ng act en PREC
rad gost setae
row tyme path
the

the activates pres Man
pesares the Yonge
Preteens

Pnesghoreit
Target pardas

it. > ch
a? RT Subs

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19. Hein

activity of PICK dependant
ate eue Fonction

As E ges ed ca

became hgevpolarinch
X,AR bind with

© Gi
O Ge (G-net)

when AR bind te de, the ate bind with

G-channed & block them , so mo Gt wilur
œceur dus ds me Way tad how A, ack in Presgrap fie membrane
miraceliecular Lu Yor BB à By are same.
ae Pr

AP Simon use
Gardiostimeistion

Cate channels are Phoebe
$ activated, mare in
& G dependant activity ts

A, can simula
Adame Brey

te Au ie Present on SRyavemeds, SA LAV node
TE dependent, de action Potential tes
ee ER at activity also dépend on ER, So ave moitie actin

action fotentia

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20. ADRENERGIC Receptors

a

à Gi

y a TE de

1.08 enr “hay LS
or a

ro

DESENSITIZATION. uno, mis act m rectos and

intracenecalay signaling, by time pass tha vecepter and

EU
Sigralisg become less Rico and Ahein vespmce Le
agonist decrene a"
ES Epi Receptor > RE] han action
Receptor hes been phosphevgatel , umen his veceter de
bind with

Phospherglsted , than anelher pretein come &

ge Arcampment does md again bind mil,

Phosthenylaled receptor
caused by BAR Kinane (PARK)

receptor , Phosphorylation is

tw tke Prescence of this protein
Y descarta this

presta avrest the

mechanism

signaling Mechaniim , so tissue
Rd RAPID DESENSITIZATION , This is an Lampe 4
Homolegus | vesonsilizalian
Rapid desensitization

==

Meg

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21. Hetreleges cesenstizain

e comen agent act m BH cita FERN, uni tase
Phosphaqlation of many Proteins

Wit this Phosphorylation 16 caused LA AR than vesponce of Le

Ugand also des this de 15 cated Hetlequ Desensibizatien

Transiet sequestwation

if vecepter are tee much Stimulated

than phospheylata vector ove

iwlernalired by clathvin, byt after some

time they again Express on surface &

renga Tor action agin gut IR meer

becor foo much tham receptor wi be A
Catabolized ly Endoseme

Down Regulation of Rect? tor
le

pers bm ne AR

om 4 mens
Kran crea

Desensitization

Rapid di
desensitization an m gota on

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22. Structure acti Y £ S¥-mPathomimatic Amines

BH Phenyl = Ethyl - Amine

>= ES ER
Prem ON
ts
Wow this structure fit inte receptor
For dy to bind with veceglen AMR, he du
Nase Side Chang. Ge E bind roy E Proc mr) SH
des Ce wet A ymmpatherioatic drags Rshosd
tase A Carbon diffusion ki
‚rin pere Benzene zug & wi, THR
O A RS
‘a acts

shovid be meeded te

what ave these

This du hot ott on ob ti, se sm
Vind wit Vecapter

Di om Benzene ving s catecol vi

:
E EE Regine
r

an acting, symPatiomimatse dos

pr
= hixed acting sigmpathemi mabic day

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23. O Direct acting du diveetly acts om vecepter

O Lndivectty ang au m presgnaglic mente
the velense of ME whith thaw

and increase,
act on receptor
O Mixed action Spprpatherimaic dings , gl

ad m dived
Advenergic vecepter &

ji ack dreckig 5 Pike release of WE

AU Gatecctamine have high poten oy,

e MEL quil te bind Sheng wih veagter
+ PEIN o ability te bind Shomyly & activa the vecapter

> Ch CH NH

When oh greur are remove, mow this
Structure easily enter inte meme ending My of Lipid selubi

luhen eu gaup axe
yemeved | tha. structure
become ree Lip Sel

E, incrense the velesst of ner CNemetramsmited) , such da
ave Now Converted inte INDIRECTLY ACTING RUGS

nr une Orr

Were m 3% lth carbon ot are FEKETE Rese m and Blom Cavbon the OF

co NN cd Catechol amins
x mer à is absent this is cllal Nencaletelamine
Diveclly sympathowimatic drys anes ‘

‘an oe ©

a Ty are given paventraly
a hos tow duvaliin of action

indivediy sympathemimatie acing Ans ae:
«Less polar Compound

+ they ave given om

+ has high duradion ef action

emet cross BBB We cf Polanly (ted half fe)

©

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24. AP cakechclamime are taken cvaily , they ave met abserbet
well be they ave Polar, whatever Small amount ave absabul
E, that is Cdestayed in GIT by COMTE, MAO eramos

caise desteyel dj MAO in Ma Liver
+ Liver Fe émail amount of ComT

3 LO) enero

ComT remove te of grep

E, add methyl te catechol ving

COMT 4 catecholamine is Taken ovally i bistability
is less, se they ave Taken paventrally (oy sim)
© Ephid vin Je colecholamine
© Amphitamine
These ave indivedtly acting dig, sofia] are taken ovally
Nen- catecholamine aye having longer duration ef action by y
axe wet token up by mao X ComT
suben Calecholamine ave ven faventrally they Gmt Goss BBB
be of Ligia SolDbilily, go thay dent have direct action om ENS
# Non Glechelamine are Les felar, and mere Lipid seluble
se they mere The quese Of ER

They Css BBB amd > effects amd side effects m avs.

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25. wp WAY different sympatnomim. sue ony produce
vy

different actin m different adrenergic veceptor

en
AI ee cn Ti Ey Efinermine
|
nage m bind te 4, By fa recupe, due te this
na al ei a

catica Balanced
Epinephrine is Galet Bi

je ac on all adremergic recapiers

y, on R 4
o vine
Wu cH x Jus EPinePhvi

Nersginephine age the ably Le stimulate ot, E By Adrenenie ve sehen
ba nd significantly stomolate the By receto

ith almost Same affinity

As The amine group group increases the action foward ight ch Bay tes,

ow ae
“> en tsoproterencl
5 cn

15 amine gro ds much higher so À
doesmit act on x, but have action on Pi Pe

e on em, :
Den mac] Tevbutatin
ue me e voy Hagin 0

ack on 4,5 By but ado Pp, best used

in Asthma Yor branchediala

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26. Alter the structure of Catecholamine & make Thum
Now- catecholamine.
© Remove Hare grap Prom Egimephaine 2 add Meat group = Ephedrine

e ane acts We

€ ha mire, | Epinephrine
gO ] as.

= = ‚non entechelamine

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eier cally

REM

Opa A

Nan caked

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