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Renin Angiotensin Mechanism.

Drugs Acting on "Renin-Angiotensin-Aldosterone System (RAAS)".

Drugs Acting on "Renin-Angiotensin-Aldosterone System (RAAS)".

  • The drugs which alter the functioning of  Renin-Angiotensin-Aldosterone System (RAAS) comes under this category and are employed in the management of hypertension and various cardiovascular disorders.

Classification: 

A) Drugs inhibiting "Renin" release:

  1. Propranolol.
  2. Clonidine.
  3. Methyl DOPA.

B) Drugs that blocks the actions of "Renin":

  1. Alaskirin.
  2. Remiskirin.

C) Angiotensin Converting Enzyme (ACE) Inhibitors :

  1. Captopril.
  2. Enalpril.
  3. Lisinopril.
  4. Ramipril.
  5. Quinapril.

D) Angiotensin Receptor Blockers (ARB):

  1. Losartan.
  2. Valsartan.
  3. Telmisartan.
A) Drugs inhibiting "Renin" release:
  • Renin is an enzyme secreted by "juxtaglomerular apparatus." (specialized structure formed by the distal convoluted tubule and the glomerular afferent arteriole.)

  • Renin is responsible for conversion of inactive "Angiotensinogen" to "Angiotensin I".
  • The drugs under this class release are known to inhibit release of renin from kidneys. e.g.
  1. Propranolol.
  2. Clonidine.
  3. Methyl DOPA.
B) Drugs that blocks the actions of "Renin":
  • These drugs blocks the action of renin on Angiotensinogen released by the liver.
  • e.g.
  1. Alaskirin.
  2. Remiskirin.

C) Angiotensin Converting Enzyme (ACE) Inhibitors :
  • Angiotensin Converting Enzyme is an endothelial enzyme present in lungs.
  • The enzyme is responsible for the conversion of Angiotensin-I to Angiotensin-II.
  • Angiotensin-II is a powerful vasoconstrictor and also has a direct action on adrenal gland causing release of the powerful mineralocorticoid Aldosterone.
  • The hypotensive action results from, inhibitory action on RAAS and stimulatory action on kinin-kallikrein system.
  • e.g.
    1. Captopril.
    2. Enalpril.
    3. Lisinopril.
    4. Ramipril.
    5. Quinapril.

    Uses of ACE inhibitors:

  1. Hypertension.
  2. Reverse Ventricular Hypertrophy.
  3. To decrease preload, afterload or sympathetic activity.
  4. Congestive Cardiac Failure: Cardio protective effect.
  5. Myocardial infarction: increases survival rate.

        Adverse Effects of ACE inhibitors:

  1. Persistent dry cough (due to bradykinin release/accumulation).
  2. Hyperkalemia.
  3. Neutropenia.
  4. Severe hypotension.
  5. Allergic manifestations.
  6. On prolonged use causes renal inefficiency.
D) Angiotensin Receptor Blockers (ARB):
  • Angiotensin II is formed under the effect of two enzymes:
a.      Angiotensin converting enzyme
b.      Kinase
  • When ACE inhibitors are given, angiotensin II is still formed under the effects of kinase.
  • It acts on two types of receptors:
  1. Angiotensin I receptor (AT-1)
  2. Angiotensin II receptor ( AT-2)
  • When angiotensin I receptors are stimulated, they produce effects similar to angiotensin II.
  • When angiotensin II receptors are stimulated, they produce effects that of opposite to angiotensin II (hypotensive activity, beneficial in treatment of hypertension).
  • Basically they competitive block AT-1 receptors, thus have effects of angiotensin II through angiotensin II receptors.

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