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25 Cards in this Set
- Front
- Back
What are the two major enzymes in the renin-angiotensin system?
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The renin-angiotensin system consists of two major enzymes, Renin and Angiotensin
Converting Enzyme (ACE). |
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What is the bioactive peptide in the RAS system?
what is its pharmacologic effect? |
angiotensin II
Angiotensin II is a potent vasoconstrictor that effects peripheral resistance, renal function and cardiovascular systems. |
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What is angiotensinogen?
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Angiotensinogen:
· A globular protein formed in the liver; Contains 452 amino acids (Mol. Wt. 58K-61K) · Abundant in the plasma; Hydrolyzed by Renin to release Angiotensin I. |
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What is Renin?
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Renin:
· An aspartyl protease produced by the kidney · A highly specific enzyme responsible for the hydrolysis of Angiotensinogen to form Angiotensin I. |
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What is angiotensin I?
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Angiotensin I:
· A decapeptide formed by the hydrolysis of Angiotensinogen; Negligible biological activity. · Acted upon by Angiotensin Converting Enzyme (ACE) to form the bioactive peptide Angiotensin II. |
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What is angiotensin converting enzyme (ACE?
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Angiotensin Converting Enzyme (ACE):
· A Zn2+ ion containing enzyme (Mol. Wt. 130K) · Relatively non-specific peptidyldipeptide hydrolase that requires only a tripeptide sequence as a substrate, but does not cleave peptides with a penultimate prolyl residue · Hydrolyzes Angiotensin I to the highly bioactive octapeptide Angiotensin II. · ACE also hydrolyzes other bioactive peptides such as Bradykinin and Substance P. |
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What is angiotensin II?
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· A physiologically active octapeptide formed by the action of ACE on Angiotensin I
· Angiotensin II is a highly potent vasoconstrictor and can cause rapid rise in blood pressure · It also stimulates aldosterone production and secretion, while also causing enhanced release of catecholamine and increased sympathetic discharge. |
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What is angiotensin III?
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Angiotensin III:
· A heptapeptide formed by removal of the N-terminal aspartate residue of Angiotensin II by a glutamyl peptidase catalyzed hydrolysis · Angiotensin III does not have potent vasoconstricting activity, but it is a strong stimulant for aldosterone secretion. |
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put these terms in the correct order
renin, angiotensin II, angiotensinogen, angiotensin I, ACE, angiotensin III, Na and fluid retention, blood pressure elevation, aldosterone sectretion |
Angiotensinogen
renin angiotensin I ACE Angiotensin II peptidase angiotension III aldosterone secretion Na and fluid retention blood pressure elevation |
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what are the three actions of ACE?
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The action of ACE results in,
· Generation of a potent hypertensive agent Angiotensin II · Release of a hypertensive agent Aldosterone · Degradation of a potent antihypertensive agent Bradykinin (a vasodilator) |
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what three groups can ACE inhibitors be classified as?
What class is captopril, enalapril, fosinopril? |
Sulfhydryl (SH) group containing inhibitors (e.g. Captopril)
Dicarboxylate-containing inhibitors (e.g. Enalapril) Phosphonate-containing inhibitors (e.g. Fosinopril) |
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What does captopril have in its structure that could be attributied to skin rashes and taste disturbances?
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a SH GROUP
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Is enalapril a prodrug?
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YES
· Enalapril is a prodrug; Hydrolyzed by esterases in the liver to form the highly potent ACE inhibitor drug Enalaprilat; |
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Is benazepril a prodrug?
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YES
Cleavage of the ester moiety produces the active drug benazeprilat. |
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is Fosinopril a prodrug?
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YES
Cleavage of the ester moiety by hepatic esterases generates the active drug Fosino |
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how do large hyprophobic funtionalities in the N-ring affect potency?
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increases potency
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are Zn-ion binding groups required for potency?
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YES
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why is the N-ring carboxylic acid essential in ACE inhibitors?
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because it mimics the C-terminal carboxylate of ACE substrates
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What should be avoided when taking ACE inhibitors?
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do not take metal oxides found in antacids due to binding
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when are ACE inhibitors contraindicated?
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during pregnancy (especially 2nd and 3rd trimesters)
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How are ACE inhibitors eliminated?
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Renal elimination is the primary route of elimination for majority of the ACE inhibitors;
therefore, dosage should be reduced in patients with renal impairment. |
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what is stimulation of the AT1 receptor do in comparison to AT2 receptor?
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Stimulation of the AT1 receptor is thought to mediate the majority of the known negative
effects of angiotensin II, such as vasoconstriction, secretion of aldosterone etc. In contrast, the AT2 receptor is associated with functions such as vasodilation, muscle relaxation etc. |
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Are ACE inhibitors and bilateral arterial stenosis contraindicated?
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YES YES
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What does the AT2 receptor affect pregnancy?
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AT2 are present in the fetus and may cause teratogenicity
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Are ARBs contraindicated in pregnancy?
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YES
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