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8/17/2019 Overview of Antihypertensive
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CRIT5003 – MODULE 3.3.A Andrew Couch
ANTIHYPERTENSIVE OVERVIEW AND CLASSIFICATION
CONTROL OF BLOOD PRESSURE:
Components o !"scu#"r s$stem:
Aort" – e#"st%c& stor"'e o ener'$ (potent%"# %n s$sto#e) *%net%c %n d%"sto#e+
Arter%es – #ow res%st"nce) some stor"'e o ener'$
Arter%o#es – " m",or contr%-utor to TR) contro# /ow o -#ood to p"rt%cu#"r or'"ns
"t "n$ '%en t%me
C"p%##"r%es – th%n w"##ed& e1ch"n'e o w"ter "nd su-st"nces& s#ow r"te o /ow
!e%ns – h%'h c"p"c%t"nce& #ow res%st"nce
Role of Arterioles:
2 mooth musc#e r%ch – ton%c contr"ct%on2 Res%st"nce %s proport%on"# to the r"d%us 4 ( thus " sm"## ch"n'e %n r"d%us 6
s%'n%7c"nt ch"n'e to res%st"nce – 8"'en2o%seu##e9s L"w+2 mooth musc#e tone: contro##ed -$ -$:
o D%rect %nner"t%on – nere end%n's th"t w%## "ct%"te "#ph" (contr"ct%on+
"nd ;< receptors (d%#"t"t%on+o C%rcu#"t%n' hormones ("n'%otens%n II) "dren"#%ne) "sopress%n+
o Autore'u#"t%on o /ow (met"-o#%c = m$o'en%c "ct%%t$+
ressure (drop> ch"n'e+ 6 /ow 1 res%st"nce:
Remember: (ohm’s law)
Under ideal laminar ow !ondi"ions# in whi!h
$as!%lar resis"an!e is inde&enden" o' ow
and &ress%re# "he rela"ionshi& be"ween &ress%re# ow and resis"an!e !an be de&i!"ed as
shown in the gure to the right Be!a%se ow
and resis"an!e are re!i&ro!all rela"ed# an in!rease
in resis"an!e de!reases 'low a" an *i$en +P ,lso#
a" an *i$en ow alon* a blood $essel or a!ross a
hear" $al$e# an in!rease in resis"an!e in!reases "he +P
Chan*es in resis"an!e are "he &rimar means b whi!h blood ow is re*%la"ed
wi"hin or*ans be!a%se !on"rol me!hanisms in "he bod *enerall main"ain
ar"erial and $eno%s blood &ress%res wi"hin a narrow ran*e -owe$er# !han*es in
&er'%sion &ress%re# when "he o!!%r# will a.e!" ow
http://www.cvphysiology.com/Hemodynamics/H006.htmhttp://www.cvphysiology.com/Hemodynamics/H006.htm
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CRIT5003 – MODULE 3.3.A Andrew Couch
The abo$e rela"ionshi& also indi!a"es "ha" "here is a linear and &ro&or"iona"e
rela"ionshi& be"ween ow and &er'%sion &ress%re This linear rela"ionshi
howe$er# is no" 'ollowed when &a"holo*i!al !ondi"ions lead "o "%rb%len" ow#
be!a%se "%rb%len!e de!reases "he ow a" an *i$en &er'%sion &ress%re
F%r"hermore# "he &%lsa"ile na"%re o' ow in lar*e ar"eries also al"ers "his
rela"ionshi& so "ha" *rea"er &ress%res are re/%ired 'or a *i$en ow 0n o"her
words# &%lsa"ili"# li1e "%rb%len!e# in!reases resis"an!e "o ow
As dep%cted "-oe) the "scu#"r tree %s d%%ded %nto se'ments) "nd /ow %s e?u"#%n e"ch se'ment. The res%st"nce %n e"ch se'ment determ%nes the pressure drop.
Thus % we %ncre"se "rter%o#"r res%st"nce) we shou#d note "n %ncre"se %n "rter%"#
pressure) "nd " decre"se %n c"p%##"r$ pressure.
Thus res%st"nce %n the "rter%o#es %s er$ %mport"nt. It determ%nes:
2 Arter%"# -#ood pressure2 D%@erent%"# /ow to or'"ns2 C"p%##"r$ pressure %n e"ch or'"n (e' *%dne$s – BR+
o There'ore in!reasin* "he !a&illar &ress%re in "he 1idnes in!reases
2FR
CONTROL OF BLOOD PRESSURE
CENTR,L CONTROL:
ensor: ;"roreceptor (c"rot%d -od$ "nd "ort%c -od$ w"## stretch+
E@ector: !"somotor Centre (!MC+ – &or"ion o' med%lla oblon*a"a "ha" re*%la"es
BP
2 $mp"thet%co $stem%c res%st"nceo 8R> contr"ct%#%t$
o !enous return
o Ren%n secret%on (%" ; receptors on ce##s %n *%dne$+
2 "r"s$mp"thet%c
http://www.cvphysiology.com/Hemodynamics/H007.htmhttp://www.cvphysiology.com/Hemodynamics/H007.htm
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CRIT5003 – MODULE 3.3.A Andrew Couch
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RE!S!ON: Arterial Barore"e#tors: lo!a"ion and s"im%l%s3res&onse
The sin*le mos" im&or"an" ree4 "ha" main"ains ar"erial blood &ress%re in "he
shor" "erm
Stret"h re"e#tors
Loc"t%on:
Caro"id Sin%s (" swe##%n' "t the or%'%n o the %ntern"# c"rot%d "rter$+
2 cont"%ns " re#"t%e#$ h%'h de'ree o e#"st%c t%ssue "nd #ess smooth musc#e
(c"rot%d s%nus w%## stretch more th"n other esse#s+
2 %nner"ted -$ " -r"nch o the '#ossoph"r$n'e"# nere (Ith+
,or"i! ,r!h – "ort%c -"roreceptors
2 %nner"ted -$ "'"# nere (th+
;"roreceptors "re st%mu#"ted -$ -oth the r"te o ch"n'e o pressure (%n pu#s"t%#e
pressure the pressue %ncre"ses r"p%d#$ dur%n' the s$sto#%c ph"se+) "nd the me"n
"rter%"# pressure.
Re'er "o &i! below:
The -"roreceptors wor* -$:
A decre"sed "rter%"# pressure resu#ts %n DECREAED -"roreceptor 7r%n' r"te
wh%ch resu#ts %n:
+ Incre"sed s$mp"thet%c "somotor "ct%%t$
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REN,L CONTROL:
Renin
Ren%n re#e"se %s st%mu#"ted -$ < mech"n%sms:
. $mp"thet%c -et"2 "drener'%c receptor st%mu#"t%on %n "pp"r"tus
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2 Ren"# "rter$ stenos%s2 Chron%c *%dne$ d%se"se2 r%m"r$ h$per"#dosteron%sm (Conn9s – adrenal adenoma; -%#"ter"# %d%op"th%c
"dren"# h$perp#"s%"& con'en%t"# "dren"# h$perp#"s%"+2 OA
2 Th$ro%d d%se"se2 h"eochromoc$tom"
Pathogenesis of HTN
Resett%n' o -"roreceptor "nd ren%n response to m"%nt"%n " h%'her -#ood pressure
Fhen we %n%t%"##$ commence p"t%ents on "nt%2h$pertens%e ther"p$) there %s
'ener"##$ " counter"ct%on -$ compens"tor$ receptors -$ -"roreceptors "nd the
ren%n s$stem:
Com&ensa"or Rea!"ion:
3 "J> 8
li1el L3"&e !a87 media"ed2 E#ectr%c"# (d%rect %nner"t%on+
!ACULAR MOOT8 MUCLE (!M+ IER!ATIO BACTOR (s"im%la"or ?
inhibi"or):
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@S5 !on"ra!"ion *enerall wor1s b
"he 'ollowin* me!hanism:
3 S"im%la"ion o' L3"&e $ol"a*e
*a"ed Ca87 !hannels res%l"s in
in!reased 0C Ca87 ions3 This is '%r"her !on"rib%"ed "o b
release o' Ca87 ions 'rom SR3 Ca77 "hen binds !almod%lin whi!h in"era!"s wi"h $%osin light "hain
(inase )*LC+,o Calmod%lin is a !al!i%m3bindin* messen*er &ro"ein e4&ressed in all
e%1aro"i! !ells
3 -ith "onsu$#tion of an ATP $ole"ule. this #hos#hor%lates *%osinlight "hain
3 Th%s resu#ts %n "ct%n2m$os%n %nter"ct%on "nd su-se?uent contr"ct%on o !M.
M$os%n L%'ht Ch"%n
hosph"t"se (MLC+
resu#ts %n
dephosphor$#"t%on o
MLC "nd hence
re#"1"t%on
Fhen ot"ss%um
ch"nne#s open)
h$perpo#"r%K"t%on o
the ce## occurs. Th%s
resu#ts %n decre"sed
C"
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0n re'eren!e "o "he
abo$e dia*ram:
Al%ha&'(
Remember al&ha38 re!e&"ors are !lassi!all lo!a"ed on $as!%lar &re3A%n!"ional
"erminals where is 0N-0B0TS "he '%r"her release o' noradrenaline in a 'orm o'
ne*a"i$e 'eedba!1 -owe$er# "here are a 'ew &os"3sna&"i! ,38 re!e&"ors# whi!h
wor1 as 'ollows:
!%" "n inhi#ito!) 2prote%n decre"sed cAM %ncre"sed M$os%n L%'ht Ch"%n
%n"se
"here'ore in!reases !on"ra!"ion
Al%ha&*(
orep%nephr%ne re#e"sed rom s$mp"thet%c nere term%n"#s "ct on ") wh%ch "re
coup#ed to ? receptors (coup#ed to LC+& th%s resu#ts %n re#e"se o IC C"
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in!reased mosina!"in in"era!"ion; B8 howe$er res%l"s in de!reased 0C
Ca87 and de!reased mosina!"in in"era!"ion
FURT-ER RE@0S0ON:
*us"arini" / )si$ilar to al#ha /, 0 1e2o"rine glan3s
3 21PCR (Th%s asso!ia"ed wi"h PLC# 0P# D,2 e"!)
*us"arini" 4 )si$ilar to al#ha 4, 0 inhi5itor%
"ar3ia" tissue
6 2i PCR (Th%s inhibi"s adenll !!lase# and red%!es !,5P &rod%!"ion)6 Remember "ha" 5%s!arini! 8 re!e&"or a*onism is also asso!ia"ed wi"h a
21PCR# and res%l"s in in!reased e%4 o' Po"assi%m !%rren" > res%l"in* in
h&er&olari=a"ion
*us"arini" re"e#tors: 71 0 7i 0 71 0 7i 0 71 )*/ 0 *4 0 *8 0 *9 0 *,
Ni"otini" Re"e#tors: )Ligan36gate3 "hannels,
U&on in"era!"ion wi"h an a*onis" (e* ,!h# ni!o"ine e"!)# !on'orma"ional !han*e
o!!%rs# and "he !hannel o&ens# allowin* &osi"i$el !har*ed ions "o mo$e "hro%*h
i" > i" is a non3sele!"i$e !a"ion !hannel The mo$emen" o' !a"ions !a%ses
a de&olari=a"ion o' "he &lasma membrane (whi!h res%l"s in an e4!i"a"or
&os"sna&"i! &o"en"ial in ne%rons )# b%" also b "he a!"i$a"ion o' $ol"a*e3*a"ed
ion !hannels
TO SU**AR!SE:
@S5 CONTR,CT0ON:
0n!reased Ca87 so%r!e:
E4"ra!ell%lar ($ia L3"&e Ca87 !hannel)8 0n"ra!ell%lar s"ores 'rom Sar!o&lasmi! re"i!%l%m (0P media"ed)
@S5 REL,,T0ON:
0nhibi"ion o' 5LCG b in!reased !,5P ($ia B8 re!e&"ors)
0n!reased 5LCP ('rom in!reased !25P 'rom in!reased Ni"ri! O4ide)
De!reased 0n"ra!ell%lar Ca87
-&er1alaemia
0n!reased re3%&"a1e in"o SR s"ores ($ia B8 2s"im%la"or e.e!")
https://en.wikipedia.org/wiki/Cationhttps://en.wikipedia.org/wiki/Depolarizationhttps://en.wikipedia.org/wiki/Excitatory_postsynaptic_potentialhttps://en.wikipedia.org/wiki/Excitatory_postsynaptic_potentialhttps://en.wikipedia.org/wiki/Neuronhttps://en.wikipedia.org/wiki/Voltage-gated_ion_channelhttps://en.wikipedia.org/wiki/Voltage-gated_ion_channelhttps://en.wikipedia.org/wiki/Cationhttps://en.wikipedia.org/wiki/Depolarizationhttps://en.wikipedia.org/wiki/Excitatory_postsynaptic_potentialhttps://en.wikipedia.org/wiki/Excitatory_postsynaptic_potentialhttps://en.wikipedia.org/wiki/Neuronhttps://en.wikipedia.org/wiki/Voltage-gated_ion_channelhttps://en.wikipedia.org/wiki/Voltage-gated_ion_channel
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0N @,SCUL,R S5OOT- 5USCLE:
!n"rease3 "A*P )7s,
3 Be"a 8 (adrenaline)3 ,8 > (adenosine)3 0P (P208) 3 0P &ros"a!!lin re!e&"or
De"rease3 "A*P )7i,
3 ,l&ha38 (noradrenaline and adrenaline)
A"ti;ate3 71 )thus in"rease3 !P8,
3 ,l&ha3# ,n*io"ensin# @aso&ressin# endo"helin
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ote th"t the endothe#%um p#"$s "n %mport"nt ro#e %n "scu#"r smooth musc#e
tone. Re#"1"t%on "ssoc%"ted w%th endothe#%um der%ed "ctors %s oten "ssoc%"ted
w%th J ch"nne# re#"ted h$perpo#"r%K"t%on.
2 %tr%c O1%de2 rost"c$c#%n (I
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ANTI&HYPERTENSIVE DRU2S
CLAIBICATIO:
An'%otens%n re#"ted (ACEI) A A A
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@,SOD0L,TORS:
2 L2t$pe C"
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