13-2-Anti-angoreux

V"13%ANTI"ANGOREUX%
1!
!
Pharmaetudes!
1!
Les%anti"angoreux%
%
"#$%&'(!)*+!,%!*-%.('/)!+0'($123,)!.',4',(),5!426!7!,%)!*',88($%1)!.)*!1)44,4)*!1$(.2$3,)*9!
*,2+)!7!,%)!2*106/2)!:;$(!$,&/)%+$+2'%!.)*!<)*'2%*!)%!=>!',!.2/2%,+2'%!.)*!$;;'(+*!1'('%$2()*?@!
A('2*!14$**)*!/6.21$/)%+),*)*!*'%+!,+242*6)*!.$%*!4)!+($2+)/)%+!.)!4B$%&'(C!.6(2D6*!%2+(6*9!2%02<2+),(*!
1$4123,)*!)+!<E+$F<4'3,$%+*@!!!
!
G/3!C!"B2%+6(E+!.)*!HIJ!.$%*!4)!+($2+)/)%+!.)!4B$%&'(!$!6+6!6+$<42!!
!
1. Rappel%sur%l’angor%:%
!
1.1 Crise%d'angor%:%
K',4),(!1'%*+(21+2D)!D2'4)%+)9!$%&'2**$%+)9!.$%*!4$!(6&2'%!;(61'(.2$4)9!2(($.2$%+!.$%*!4)!<($*!
&$,10)@!")*!8$1+),(*!.)!(2*3,)!*'%+!C!+$<$19!*6.)%+$(2+69!0-;)(10'4)*+6('46/2)9!LAM9!*+()**@!
"B2*106/2)!1$,*$4)!)*+!.,)!7!4#$+06('*146('*)!1'('%$2()9!$,5!*;$*/)*!1'('%$2()*!',!7!,%!+0('/<,*@!!
!
!
1.2 Angor%stable%ou%angor%d'effort%:%
M,&/)%+$+2'%!.)!4$!1'%*'//$+2'%!.,!1N,(!)%!'5-&O%)9!*$%*!$.$;+$+2'%!.,!.6<2+!*$%&,2%!
1'('%$(2)%@!!
J(2*)!<(OD)9!16.$%+!$;(O*!4B)88'(+@!")!.6<2+!1'('%$2()!)%!$D$4!.)!4$!*+6%'*)!)*+!*,882*$%+!$,!
();'*!P!/$2*!4'(*3,)!4)*!<)*'2%*!/6+$<'423,)*!$,&/)%+)%+9!4)!/-'1$(.)!%)!()Q'2+!;4,*!,%!$;;'(+!
*$%&,2%!*,882*$%+@!
!
1.3 Angor%instable%:%
R-%.('/)!.)!/)%$1)!.B2%8$(1+,*!.,!/-'1$(.)@!JB)*+!,%)!,(&)%1)!%61)**2+$%+!4#0'*;2+$42*$+2'%@!!
!
1.4 Angor%spastique%(spontané)%=%angor%de%Prinzmetal%=%variant%angina%%
R,(D2)%+!$,!();'*9!*;'%+$%69!.S!7!.)*!*;$*/)*!.)*!$(+O()*!1'('%$2()*@!!
!
1.5%Ischémie%myocardique%silencieuse%:%
I44)!1'(()*;'%.!7!4$!;(6*)%1)!.B,%)!2*106/2)!$,!%2D)$,!/-'1$(.23,)!)%!$<*)%1)!.)!+',+!*-/;+T/)@!
I44)!;$(+$&)!4)!/E/)!;('%'*+21!4B$%&'(!*+$<4)!)+!.'2+9!;$(!1'%*63,)%+9!E+()!+($2+6)!.)!4$!/E/)!8$Q'%@!!
!
1.6%Buts%du%traitement%:%
• Augmenter%les%apports%en%oxygène%au%cœur%:%
M,&/)%+)(!4)!.6<2+!1'('%$2()!)%!$,&/)%+$%+!4)!.2$/O+()!.)*!$(+O()*!)+!4)!+)/;*!.)!
;)(8,*2'%!.)*!1'('%$2()*9!3,2!$!42),!;.+!4$!.2$*+'4)@!H4!8$,+!.2/2%,)(!4$!8(63,)%1)!
1$(.2$3,)!
• Diminuer%la%consommation%en%oxygène%du%cœur%:%
K2/2%,)(!4$!;'*+F10$(&)!)+!4$!;(6F10$(&)@!K2/2%,)(!4$!1'%+($1+2<242+6!)+!4$!8(63,)%1)!
1$(.2$3,)*@!
!
G/3!C!4$!D$*'.24$+$+2'%!1'('%$2()!)*+!(6&,46)!;$(!4$!42<6($+2'%9!$,!%2D)$,!.)!4B)%.'+0642,/!1'('%$2()9!
.)!*,<*+$%1)*9!4#IKGU!!:I%.'+0)42,/FK)(2D).!G)4$52%&!U$1+'(9!8$1+),(!.)!42<6($+2'%!.6(2D6!.)!
4#)%.'+0642,/?!)*+!4$!;4,*!2/;'(+$%+)!)+!$!6+6!2.)%+2826!1'//)!!6+$%+!4)!/'%'5-.)!.#$V'+)@!
!

!
!
2!
2 Dérivés%nitrés%:%
!
2.1 Spécialités%:%
• Dérivés%nitrés%d'action%rapide%et%courte%voie%perlinguale%:%
o Isorbide%dinitrate%:%%ISOCARD%®!!!! ! *'4!*,<42%&,$4)!C!R;($-W>X/4!
! !! ! RISORDAN®!!!*'4!2%Y)1+$<4)9!*,<42%&,$4!
o Trinitrine%:% LENITRAL%SPRAY®!! ! ! *'4!;!;,4D!)%.'<,11$4)!
NATISPRAY%®!!!!!*'4!;!;,4D!<,11$4)!:*,<42%&,$4?!
TRINITRINE%SIMPLE%LALEUF®!!!!!!!!!!!!!!;24,4)!)%('<6)!
• Dérivés%nitrés%d'action%prolongée%:%%
o Z'2)!'($4)!C!!
 Isosorbide%dinitrate%:%LANGORAN%LP%®,%RISORDAN%®%
 Isosorbide%mononitrate%:%MONICOR%LP%®%%
 Pentaérythritol%tétranitrate%:%NITRODEX%CHRONULES®%
o K2*;'*2+28*!+($%*.)(/23,)*!!C!
 Trinitrine%:%%CORDIPATCH®,%DIAFUSOR®,%DISCOTRINE®,%EPINITRIL®,%NITRIDERM%
TTS®,%TRINIPATCH®%
!
2.2 Structure%et%mode%d'action%:%
• Structure%:%
")*!.6(2D6*!%2+(6*!*'%+!.)*!)*+)(*!.B$12.)!%2+(23,)!:L[X\?9!$D)1!,%!%'/<()!D$(2$<4)!.)!&(',;)/)%+*!
%2+('*-!:FJ=[X>?@!
")!10)8!.)!824)!)*+!4$!+(2%2+(2%)@!
!
!
")*!$,+()*!.6(2D6*!*'%+!C!
- K2%2+($+)!.#2*'*'(<2.)!:G2*'(.$%!]?!
- ^'%'%2+($+)!.#2*'*'(<2.)!:^'%21'(!]?!
!
• Relation%structure"activité%:%
- ")!%'/<()!.)![=>!%#2%84,)%1)!;$*!4#2%+)%*2+6!/$2*!4)!.64$2!.#$1+2'%!
- "$!%$+,()!.,!;'4-'4!:,+242*6!;',(!8'(/)(!4#)*+)(?!1'%.2+2'%%)!4$!($;2.2+6!)+!4$!
.,(6)!.#$1+2'%!:;'4-'4!7!8$2<4)!_^!C!$1+2'%!($;2.)!`!<(OD)!)+!2%D)(*)/)%+?!
- "$!.,(6)!.B$1+2'%!$,&/)%+)!$D)1!4$!($/2821$+2'%!/$2*!4$!($;2.2+6!.B$1+2'%!
.2/2%,)!.)!8$Q'%!;$($44O4)@!!
!
Mécanisme%d’action%:!
Ce%sont%des%bio"précurseurs%=%donneurs%de%NO%

V"13%ANTI"ANGOREUX%
3!
!
Pharmaetudes!
3!
"$!&4,+0$+2'%FRF(6.,1+$*)!;)(/)+!4$!42<6($+2'%!.B,%!&(',;)/)%+![=>!7!;$(+2(!.)*!.6(2D6*!
%2+(6*9!)%*,2+)!4)![=>!)*+!+($%*8'(/6!)%![=a!:646/)%+!($.21$4$2()?9!3,2!$1+2D)!4$!&,$%-4$+)!1-14$**)!
:;$(!$**'12$+2'%!$,!&4,+$+02'%!.)!4$!1-*+62%)!)%.'&O%)?@!H4!-!$!$,&/)%+$+2'%!.)!b^_1!.$%*!4$!1)44,4)!
)+!.2/2%,+2'%!.)!J$>c!42<()!2%+($1)44,4$2()!$D)19!$,!82%$49!()4$5$+2'%!!
.)*!1)44,4)*!/,*1,4$2()*!42**)*!.)*!D$2**)$,5!!D$*'.24$+$+2'%@!
J)+!)88)+!()4$5$%+!%B)*+!;$*!*;612823,)@!H4!-!$!,%)!$1+2'%!*,(!4$!/,*1,4$+,()!<('%1023,)9!
2%+)*+2%$4)9!,+6(2%)9!<242$2()!@@@@!J);)%.$%+9!4B$1+2'%!()4$5$%+)!*,(!4)*!D$2**)$,5!)*+!;(6.'/2%$%+)!$,5!
.'*)*!+06($;),+23,)*@!
")![=a!)5)(1)9!)%!;4,*9!,%)!$1+2'%!$%+2F$&(6&$%+)@!!
!
2.3 Propriétés%phramacologiques%:%
• Cardio"vasculaires%:%
o M!.'*)!+06($;),+23,)!C!action%vasodilatatrice%veineuse!;6(2;06(23,)!ccc!.2/2%,$%+!
4$!;(610$(&)@!"$!.2/2%,+2'%9!.)!4$!;()**2'%!2%+($D)%+(21,4$2()!+646.2$*+'423,)!;)(/)+!
.)!.2/2%,)(!4)!+($D$24!1$(.2$3,)@!M,!82%$4!24!-!$!.2/2%,+2'%!.)!4$!1'%*'//$+2'%!)%!
'5-&O%)!.'%1!)88)+!$%+2F$%&'(),5@!:↓!;(6F10$(&)!`!;()**2'%!D)%+(21,4$2()!&$,10)!P!↓!
()+',(!D)2%),5?!
o M!.'*)!64)D6)!C!vasodilatation%veineuse,%coronaire%et%artérielle9!)%+($d%$%+!,%)!
+$10-1$(.2)!()84)5)!*,2+)!7!4#0-;'+)%*2'%@!M2%*29!24!-!$!$,&/)%+$+2'%!.,!+($D$24!
1$(.2$3,)@!!
 Z$*'.24$+$+2'%!1'('%$2()!C!+(O*!;(61'1)9!1$;$<4)! .)!4)D)(!4)!*;$*/)!
1'('%$(2)%9!↓!;'*+F10$(&)!
 Z$*'.24$+$+2'%!$(+6(2'4$2()!;6(2;06(23,)!.'*)F.6;)%.$%+)%
%
• Redistribution%du%flot%coronaire%vers%les%couches%sous"endocardiques%sensibles%à%l'hypoxie@!
:e!().2*+(2<,+2'%!.,!*$%&!D)(*!4)*!V'%)*!2*106/2)*?!
• Anti"agrégant%plaquettaire%
• Vasodilatation%cutanée%et%cérébrale%
• Relaxation%des%muscles%lisses%bronchiques,%biliaires,%digestifs,%urinaires.%
!
H4! )52*+)! ,%! ;06%'/O%)! .)! tolérance!)+!.#accoutumance!$,5!.6(2D6*!%2+(6*@!=%!;),+!.'%1!
'<*)(D)(! ,%)! .2/2%,+2'%! ($;2.)! .)*! )88)+*! $D)1! échappement!$,!4'%&!1',(*@!J)!;06%'/O%)!)*+!
1('2*6!$D)1!+',*!4)*!.6(2D6*!%2+(6*9!24!)*+!.#$,+$%+!;4,*!($;2.)!3,)!4)*!.'*)*!*'%+!2/;'(+$%+)*!)+!3,)!
4)*!+$,5!*$%&,2%*!*'%+!*+$<4)*!:8'(/)*!"_!ccc?9!/$2*!réversible!7!4#$((E+!.,!+($2+)/)%+@!
_',(!6D2+)(!1)4$9!4$!;()*1(2;+2'%!.'2+!E+()!discontinue!:f>!0!.#2%+)(D$44)?@!
!
2.4 Pharmacocinétique%:%
• Absorption%:%
- A(O*!/$,D$2*)!<2'.2*;'!_=!:f)(!;$**$&)!06;$+23,)!ccc?!!.'%1!$./2!)%!*,<42%&,$4!
',!)%!HZ!;',(!4)!+++!.)!4$!1(2*)@!
- R,<42%&,$4)!C!($;2.)!:f!/2%?!`!2%1'/;4O+)!
- _',(!4)!+++!.)!8'%.9!24!)52*+)!.)*!8'(/)*!"_!;'!',!+($%*1,+$%6)*!:'%!'<+2)%+!$2%*2!4$!
*$+,($+2'%!.)*!*-*+O/)*!)%V-/$+23,)*?!
- J,+$%6)!C!4)%+)!`!;('4'%&6)9!2%+)%*2+6!D$(2$<4)!
!
• Distribution%:%%
- "$(&)!:/'461,4)*!+(O*!42;';024)*?!

!
!
4!
- _$*!.)!42$2*'%!$,5!__!:)**)%+2)44)/)%+!*',*!8'(/)!42<()!.$%*!4)!;4$*/$?!
- U'(+)!42$2*'%!+2**,4$2()!
!
• Métabolisme%:!06;$+23,)!ccc9!+(O*!($;2.)9!2/;'(+$%+9!)+!/6+$<'42+)*!2%$1+28*!
!
• Elimination%:!)**)%+2)44)/)%+!,(2%$2()@!K)/2FD2)!+(2%2+(2%)!e!g!/2%@!
!
2.5 Indications%:%
- A++!1,($+28!.)!4$!1(2*)!.#$%&'(!C!fO()!2%+)%+2'%9!;',(!4)*!.6(2D6*!7!$1+2'%!($;2.)!*',*!8'(/)!.)!
*;($-!',!.)!1'/;(2/6!*,<42%&,$4!
- A++!;(6D)%+28!.)!4$!1(2*)!.#$%&'(!C!8'(/)*!*,<42%&,$4)*9!'($4)*9!;)(1,+$%6)*!!
- A++!.)!8'%.!.)!4#$%&'(!.#)88'(+!C!;',(!4)*!.6(2D6*!7!$1+2'%!;('4'%&6)!:8'(/)*!"_!',!;$+10*!.)!
+(2%2+(2%)?!
- M.Y,D$%+!.$%*!4#2%*,882*$%1)!1$(.2$3,)!:8'(/)*!'($4)*?9!)%!$**'1!$,5!2%02<2+),(*!1$4123,)*!
- H.^!)%!;0$*)!$2&,h!HZ!
- i.O/)!$2&,!.,!;',/'%!)%!HZ!
!
2.6 Règles%de%bon%usage%:%
J'//)%1)(!;$(!.)!8$2<4)*!;'*'4'&2)*!;',(!42/2+)(!4)*!)88)+*!*)1'%.$2()*9!&E%$%+*!)%!.6<,+!.)!+++!
")!/$4$.)!.'2+!$;;()%.()!7!2.)%+282)(!4$!.',4),(!)+!%)!;$*!06*2+)(!7!;()%.()!4$!+(2%2+(2%)!$,5!!;()/2)(*!
*2&%)*!.#$4)(+)!!
"B$**'12$+2'%!7!.B$,+()*!$%+2F$%&'(),59!)*+!.)!(O&4)9!1$(!24!)52*+)!,%!;06%'/O%)!.B610$;;)/)%+!
+06($;),+23,)!$D)1!4)*!.6(2D6*!%2+(6*!:2%)8821$12+6!.,!+($2+)/)%+!$;(O*!3,)43,)*!/'2*!.)!;(2*)!
1'%+2%,)?!
H4!8$,+!$/6%$&)(!.)*!8)%E+()*!+06($;),+23,)*!:2%+)(D$44)*!42<()*!*$%*!;(2*)9!;)%.$%+!j!7!f>!0?!e!
;)(/)+!,%)!()*)%*2<242*$+2'%!.)!4#'(&$%2*/)!
H4!)52*+)!,%!;06%'/O%)!.)!.6;)%.$%1)!:%)!Y$/$2*!2%+)(('/;()!,%!+($2+)/)%+!<(,+$4)/)%+?!⇒!
G2*3,)!.)!()<'%.!
!
2.7 Effets%indésirables%:%
- L-;'+)%*2'%!$(+6(2)44)!'(+0'*+$+23,)!:$++)%+2'%!$,5!;)(*'%%)*!k&6)*?!:*,(+',+!*2!$**'1!7!4$!
[286.2;2%)?!
- J6;0$46)*!D2'4)%+)*!:.2/2%,)%+!)%!3,)43,)*!Y',(*?!!
- l',886)*!D$*'/'+(21)*!C!10$4),(9!84,*0!8$12$49!D$*'.24$+$+2'%!1,+$%6)!$D)1!N.O/)!
- J-$%'*)!;$(!/6+06/'&4'<2%6/2)!:4'(*!.)*!2%+'521$+2'%*?9!!
- L-;'D'46/2)!:*,(.'*$&)?!
- M&&($D$+2'%!.)!.',4),(*!$%&2%),*)*!:;$(!+$10-1$(.2)!(684)5)!*2!.6;$**)/)%+!.)*!.'*)*?!!
!
2.8%Contre"indications%:%(formes%injectables%et%patchs)%
- K68$244$%1)!$2&,h!.,!*-*+O/)!12(1,4$+'2()!:10'19!1'44$;*,*?!!
- ^2&($2%)*!
- A(',<4)*!426*!7!.)*!;()**2'%*!2%+($F1($%2)%%)*!',!2%+($F'1,4$2()*!*6DO()*!:&4$,1'/)!7!$%&4)!
8)(/6?!
- J$(.2'/-';$+02)*!'<*+(,1+2D)*!
- L-;'+)%*2'%!$(+6(2)44)!*6DO()!:1'44$;*,*?!
- K61'%*)2446!)%!1$*!.)!&('**)**)!)+!.#$44$2+)/)%+!
- M%6/2)!*6DO()!
- ^-';$+02)!'<*+(,1+2D)!:_I?!

V"13%ANTI"ANGOREUX%
5!
!
Pharmaetudes!
5!
2.9 %%%IAM%:!
- R24.6%$824!ZHMbGM]!C!(2*3,)!.#0-;'+)%*2'%!<(,+$4)!:JH?!
- ^6.21$/)%+*!/$Y'($%+*!4)!(2*3,)!.#0-;'+)%*2'%!$(+6(2)44)!C!$41''49!$%+20-;)(+)%*),(*9!
$%+2.6;()**),(*!+(21-1423,)*9!+($%3,2442*$%+*9!.2,(6+23,)*!`!D$*'.24$+$+),(*!
!
3 Molécules%apparentées%aux%DN%:%Sydnonimines%:%
!
Molsidomine%CORVASAL®%ou%MOLSIDOMINE®,!,+242*6!_=!
Linsidomine%CORVASAL®%9!,+242*6!)%!HZ!',!2%+($F1'('%$2()!
!
3.1%Propriétés%pharmacologiques%:%
^61$%2*/)!.#$1+2'%!;('10)!.)*!.6(2D6*!%2+(6*!:42<6($+2'%!.)![=?!/$2*!*$%*!)88)+*!.#$11',+,/$%1)@!
I88)+!$%+2F$&(6&$%+!;4$3,)++$2()!
!
")! /'4*2.'/2%)9! ,+242*6! _=9! )*+! ,%)! ;('F.('&,)! 3,2! .'2+! E+()! /6+$<'42*6)! )%! .6(2D6! $1+28! :',!
42%*2.'/2%)?@!J)!.)(%2)(!)*+!,%!.'%%),(!.)![=a!:4)!&(',;)/)%+![=a!)*+!&()886!*,(!4$!/'461,4)*!4'(*!
.,!/6+$<'42*/)!06;$+23,)?@!
!
3.2%Pharmacocinétique%:%
- M<*'(;+2'%!.2&)*+2D)!($;2.)!:mX!n?!
- M1+2'%!)%!>X!/2%!_=9!/$5!)%+()!f!)+!\09!.2/2%,+2'%!.)!4#)88)+!$;(O*!o!7!p0!
- ^6+$<'42*/)!06;$+23,)!)%!.6(2D6*!$1+28*!
- I42/2%$+2'%!(6%$4)!
!
\@\!Indications%:%
- A($2+)/)%+!;(6D)%+28!.)!4$!1(2*)!.#$%&'(!:_=?!
- A($2+)/)%+!.)!4#$%&'(!2%*+$<4)!:HZ?!
- A($2+)/)%+!.)*!*;$*/)*!$(+6(2)4*!1'('%$2()*!:HJ?!
!
3.4%Effets%secondaires%
- J6;0$46)*!
- L-;'+)%*2'%!
!
3.5%Précaution%d’emploi%:%Doses%progressives%pour%éviter%les%effets%secondaires%
!
\@p!Interactions%:%
- R24.6%$824!1'%+()F2%.23,6!
- ^$Y'($+2'%!.)!4#0-;'+)%*2'%!$D)1!D$*'.24$+$+),(*!
- M**'12$+2'%!$,5!.6(2D6*!%2+(6*!.61'%*)2446)!
!
\@g!Contre"indications%:!
- L-;'+)%*2'%!
- L-;'D'46/2)!
!
!
!