Enalapril: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
David Canner (talk | contribs)
7,699 edits
No edit summary
No edit summary
 
(One intermediate revision by one other user not shown)
Line 1: Line 1:
<applet  load="" size="480" color="" frame="true"  spin="on" Scene ="Enalapril/Enal/1" align="right" caption="Enalaprilat, the metabolite of Enalapril, also known as Vasotec"/>
<StructureSection load='' size='340' side='right' caption='Enalaprilat, the metabolite of Enalapril, also known as Vasotec' scene='Enalapril/Enal/1'>
===Better Known as: Vasotec===
===Better Known as: Vasotec===
* Marketed By: Merck & Co.<br />
* Marketed By: Merck & Co.<br />
Line 11: Line 11:
===Mechanism of Action===
===Mechanism of Action===
Angiotensin II has been implicated in cardiac, renal and vascular diseases. <ref>PMID:17083068</ref> Bradykinin, a small peptide that counterbalance the effects of Angiotensin II by acting as a strong vasodilator upon binding AT2, is degraded by the same ACE-1 enzyme. Since ACE-1 is the primary producer of Angiotensin II and degrader of Bradykinins, inhibition of ACE-1 has proven an effective treatment for Hypertension and Congestive Heart Failure. Enalapril is quickly metabolized into Enalaprilat, the more active metabolite of Enalapril predominantly by the Hepatic enzyme CYP3A4. Enalaprilat binds to the active site of <scene name='Enalapril/Ace/1'>Angiotensin-Converting Enzyme</scene>, preventing ACE-1 from binding and converting Angiotensin I into Angiotensin II. <scene name='Enalapril/Enalalprilat/2'>Enalaprilat is bound </scene>to ACE-1 via electrostatic interactions with His 353, Ala 354 (Backbone oxygen), Glue 384, Lys 511, His 513, Tyr 520 and Tyr 523 along with the zinc cation. <ref>PMID:15236580</ref>
Angiotensin II has been implicated in cardiac, renal and vascular diseases. <ref>PMID:17083068</ref> Bradykinin, a small peptide that counterbalance the effects of Angiotensin II by acting as a strong vasodilator upon binding AT2, is degraded by the same ACE-1 enzyme. Since ACE-1 is the primary producer of Angiotensin II and degrader of Bradykinins, inhibition of ACE-1 has proven an effective treatment for Hypertension and Congestive Heart Failure. Enalapril is quickly metabolized into Enalaprilat, the more active metabolite of Enalapril predominantly by the Hepatic enzyme CYP3A4. Enalaprilat binds to the active site of <scene name='Enalapril/Ace/1'>Angiotensin-Converting Enzyme</scene>, preventing ACE-1 from binding and converting Angiotensin I into Angiotensin II. <scene name='Enalapril/Enalalprilat/2'>Enalaprilat is bound </scene>to ACE-1 via electrostatic interactions with His 353, Ala 354 (Backbone oxygen), Glue 384, Lys 511, His 513, Tyr 520 and Tyr 523 along with the zinc cation. <ref>PMID:15236580</ref>
 
</StructureSection>
===Pharmacokinetics===
===Pharmacokinetics===
{| class="wikitable" border="1" width="50%" style="text-align:center"
<table style="background: cellspacing="0px"  align="" cellpadding="0px" width="42%">
|-
<tr>
!  colspan="8" align="center"| ACE-Inhibitor [[Pharmacokinetics]] Comparison at Equivalent Dosages <ref>PMID: 7867683</ref><ref>DOI: 10.1111/j.1365-2710.2005.00646.x</ref><ref>PMID: 16075412</ref><ref>PMID:7527101</ref>
<td style="width:100%; vertical-align:top;border-width:0px; border-style:inset">
|-
<div style="height:100%; width: 100%">
! Parameter
{{:ACE Inhibitor Pharmacokinetics}}
! [[Captopril]]
</div>
! [[Lisinopril]]
</td>
! [[Ramipril]]
</tr>
! [[Enalapril]]
</table>
! [[Benazepril]]
! [[Perindopril]]
! [[Trandolapril]]
|-
! [[Pharmacokinetics#Tmax|T<sub>max</sub>]] (hr)
! .98
! 6.5
! .67
! 1.06
! .5
! .75
! .72
|-
! [[Pharmacokinetics#Cmax|C<sub>max</sub>]] (ng/ml)
! 1210
! 79
! 16.4
! 314
! 149
! 105
! 1.68
|-
! [[Pharmacokinetics#Bioavailability_.28F.29|Bioavailability]] (%)
! 72
! 25
! 28
! 60
! 97
! 24
! 10
|-
! [[Pharmacokinetics#Protein_Binding|Protein Binding]] (%)
! 97
! 0
! 73
! 20
! 97
! 20
! 80
|-
! [[Pharmacokinetics#Half_Life_.28T1.2F2.29|T<sub>1/2</sub>]] (hr)
! .56
! 10.1
! 1.93
! 1.6
! 10
! .9
! .68
|-
! [[Pharmacokinetics#Area_Under_the_Curve_.28AUC.29|AUC]] (ng/ml/hr)
! 1673
! 1016
! 21.9
! 450
! 140
! 182
! 1.86
|-
! [[Pharmacokinetics#Inhibitory_Concentration_.28IC50.29|IC<sub>50</sub>]] (nM)
! 1.1
! 5.5
! 5.0
! 5.4
! 1.7
! 2.4
! 2.5
|-
! Dosage (mg)
! 10
! 20
! 5
! 20
! 10
! 4
! 2
|-
! Metabolism
! Hepatic (CYP2D6)
! None
! Hepatic
! Hepatic (CYP3A4)
! Hepatic
! Hepatic
! Hepatic (CYP2D6 & CYP2C9)
|}


==References==
==References==

Latest revision as of 16:03, 10 January 2024

Better Known as: Vasotec

Mechanism of Action

Angiotensin II has been implicated in cardiac, renal and vascular diseases. [1] Bradykinin, a small peptide that counterbalance the effects of Angiotensin II by acting as a strong vasodilator upon binding AT2, is degraded by the same ACE-1 enzyme. Since ACE-1 is the primary producer of Angiotensin II and degrader of Bradykinins, inhibition of ACE-1 has proven an effective treatment for Hypertension and Congestive Heart Failure. Enalapril is quickly metabolized into Enalaprilat, the more active metabolite of Enalapril predominantly by the Hepatic enzyme CYP3A4. Enalaprilat binds to the active site of , preventing ACE-1 from binding and converting Angiotensin I into Angiotensin II. to ACE-1 via electrostatic interactions with His 353, Ala 354 (Backbone oxygen), Glue 384, Lys 511, His 513, Tyr 520 and Tyr 523 along with the zinc cation. [2]

Enalaprilat, the metabolite of Enalapril, also known as Vasotec

Drag the structure with the mouse to rotate

Pharmacokinetics

ACE-Inhibitor Pharmacokinetics Comparison at Equivalent Dosages
Parameter Captopril Lisinopril Ramipril Enalapril Benazepril Perindopril Trandolapril
Tmax (hr) .98 6.5 .67 1.06 .5 .75 .72
Cmax (ng/ml) 1210 79 16.4 314 149 105 1.68
Bioavailability (%) 72 25 28 60 97 24 10
Protein Binding (%) 97 0 73 20 97 20 80
T1/2 (hr) .56 10.1 1.93 1.6 10 .9 .68
AUC (ng/ml/hr) 1673 1016 21.9 450 140 182 1.86
IC50 (nM) 1.1 5.5 5.0 5.4 1.7 2.4 2.5
Dosage (mg) 10 20 5 20 10 4 2
Metabolism Hepatic (CYP2D6) None Hepatic Hepatic (CYP3A4) Hepatic Hepatic Hepatic (CYP2D6 & CYP2C9)

For Pharmacokinetic Data References, See: References

References

  1. ↑ Ferrario CM. Role of angiotensin II in cardiovascular disease therapeutic implications of more than a century of research. J Renin Angiotensin Aldosterone Syst. 2006 Mar;7(1):3-14. PMID:17083068
  2. ↑ Natesh R, Schwager SL, Evans HR, Sturrock ED, Acharya KR. Structural details on the binding of antihypertensive drugs captopril and enalaprilat to human testicular angiotensin I-converting enzyme. Biochemistry. 2004 Jul 13;43(27):8718-24. PMID:15236580 doi:10.1021/bi049480n


Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

David Canner, Alexander Berchansky
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=Enalapril&oldid=4017107"