• Blockade of Renin Secretion:
  •  clonidine (Catapres)
    • Mechanism of Action:
      1. decrease in CNS-mediated renal stimulation
      2. direct intra-renal effect
  •  methyldopa (Aldomet)
  •  propranolol (Inderal) (and other b-adrenergic receptor blockers)
    • Mechanism of Action:
      • blockade of renal b-adrenergic receptors

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• Renin Inhibitors:
  • Orally active (unapproved) renin inhibitors:
    • Remikiren
    • Enalkiren
  • poor bioavailability
    • poor absorption
    • first-pass effect
  • increased plasma renin levels (interrupts angiotensin II negative feedback effect on renin secretion)

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• Converting Enzyme Inhibitors (ACE):
  • Examples: Captopril (Capoten),  Enalapril (Vasotec)
  • Conversion blockade: angiotensin I angiotensin II
  • Degradation blockade:
    1. bradykinin (important in ACE inhibitors hypotensive effects)
       •  reduced bradykinin degradation: responsible for certain adverse effects-- cough, angioedema.
    2. substance P
    3. enkephalins
  • Clinical Use: ACE inhibitors--
    1. management of hypertension
    2. management of congestive heart failure
    3. may reduce renal vascular injury in diabetic patients

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• Angiotensin Antagonists:
  • Amino acid substitutions:
    • Saralasin -- antagonist
      • some agonist activity
      • IV administration only
      •  less effective in lowering blood pressure compared to ACE inhibitors because:
        1. partial agonist properties
        2. ACE inhibitors enhance bradykinin vasodilation
  • Receptor Blockers:
    • Losartinl (Cozaar), valsartin:
      • competitive antagonist at AT₁ receptors
      • Effective orally
      • Antihypertensive effects comparable to those obtained with enalapril (ACE inhibitor)
      • no agonist activity
      • Clinical uses: Receptor Blockers
        1. hypertension
        2. congestive heart failure (possible)

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