CORE EXAM 1 Questions And Answers
With Verified Solutions Already Passed
Latest Updated 2025
What bond does RENIN cleave? - ANSWER✔✔ Leu-Val peptide bond in
Angiotensinogen
What bond does ACE cleave? - ANSWER✔✔ Phe-His peptide bond in
Angiotensin 1
Enalapril Prodrug Approach - ANSWER✔✔ Adds a ester to lower the pKa of the
NH group and removes the charge of the free COOH
ACE Nonspecific or Specific? - ANSWER✔✔ NONSPECIFIC enzyme therefore
it hydrolyzes peptides of similar structure (bradykinin, substance P, enkephalins)
RENIN - ANSWER✔✔ Highly specific aspartyl proteinase. produced and secreted
in the kidney. Crystal structure determination allowed a modern, rational,
structure-based drug design strategy
Development of ARB's - ANSWER✔✔ Saralastin, Screen non-peptide chemical
libraries, found a "lead" compared it the structure of Angiotensin II, found what
parts were missing/were the same. Developed Losartan
Losaratan - ANSWER✔✔ Found through lead modifications. Contains a 4 N+ ring
that contains a full (-) charge, very rare. The ring mimics the carboxylic acid (-)
charge. (phenyltetrazole)
, ARB's Contain... - ANSWER✔✔ Coo- Mimic (COO-, phenylcarboxylate,
phenyltetrazole)
Mimic of Histadine Side Chain (Imidazole Ring or Equivalent)
Mimic of Isoleucine (N-butyl)
Mimic of Phenylalanine (Substituted Phenyl)
LOSARTAN - ANSWER✔✔ contains an active metabolite (COOH). Selective for
AT1 receptors over AT2 receptors. Do not use if Cr is below 30, need to check
renal impairment since it is not metablized by glucuronide conjugates
Telmisartan - ANSWER✔✔ Eliminated completely through BILE DUCT. Dose
must be DECREASED in patients with hepatic impairment or biliary obstructure
disorders
All ARB's except irbesartan have low bioavaiability because.. - ANSWER✔✔ of
poor lipid solubility (COOH, OH, tetrazole, too polar/ionized)
ACE Inhibitor Requirements - ANSWER✔✔ -Zinc Coordinating Ligand
(carboxylate, sulfhydryl, phosphonate) (interacts with ACE's transition state
analog)
-Non-hydrolyzable bond to replace peptide bond
-Terminal carboxylate (binds to + charged arginine in ACE active site)
-Lipophilic replacements for Phe, Histidine, Leucine (all provide binding affinity
to ACE)
DONT USE THIAZIDES IN PATIENTS WITH GOUT - ANSWER✔✔
With Verified Solutions Already Passed
Latest Updated 2025
What bond does RENIN cleave? - ANSWER✔✔ Leu-Val peptide bond in
Angiotensinogen
What bond does ACE cleave? - ANSWER✔✔ Phe-His peptide bond in
Angiotensin 1
Enalapril Prodrug Approach - ANSWER✔✔ Adds a ester to lower the pKa of the
NH group and removes the charge of the free COOH
ACE Nonspecific or Specific? - ANSWER✔✔ NONSPECIFIC enzyme therefore
it hydrolyzes peptides of similar structure (bradykinin, substance P, enkephalins)
RENIN - ANSWER✔✔ Highly specific aspartyl proteinase. produced and secreted
in the kidney. Crystal structure determination allowed a modern, rational,
structure-based drug design strategy
Development of ARB's - ANSWER✔✔ Saralastin, Screen non-peptide chemical
libraries, found a "lead" compared it the structure of Angiotensin II, found what
parts were missing/were the same. Developed Losartan
Losaratan - ANSWER✔✔ Found through lead modifications. Contains a 4 N+ ring
that contains a full (-) charge, very rare. The ring mimics the carboxylic acid (-)
charge. (phenyltetrazole)
, ARB's Contain... - ANSWER✔✔ Coo- Mimic (COO-, phenylcarboxylate,
phenyltetrazole)
Mimic of Histadine Side Chain (Imidazole Ring or Equivalent)
Mimic of Isoleucine (N-butyl)
Mimic of Phenylalanine (Substituted Phenyl)
LOSARTAN - ANSWER✔✔ contains an active metabolite (COOH). Selective for
AT1 receptors over AT2 receptors. Do not use if Cr is below 30, need to check
renal impairment since it is not metablized by glucuronide conjugates
Telmisartan - ANSWER✔✔ Eliminated completely through BILE DUCT. Dose
must be DECREASED in patients with hepatic impairment or biliary obstructure
disorders
All ARB's except irbesartan have low bioavaiability because.. - ANSWER✔✔ of
poor lipid solubility (COOH, OH, tetrazole, too polar/ionized)
ACE Inhibitor Requirements - ANSWER✔✔ -Zinc Coordinating Ligand
(carboxylate, sulfhydryl, phosphonate) (interacts with ACE's transition state
analog)
-Non-hydrolyzable bond to replace peptide bond
-Terminal carboxylate (binds to + charged arginine in ACE active site)
-Lipophilic replacements for Phe, Histidine, Leucine (all provide binding affinity
to ACE)
DONT USE THIAZIDES IN PATIENTS WITH GOUT - ANSWER✔✔
