Renin Angiotensin System, Vasopressin, and Kinins

Question 1

Candesartan

Answer 1

ARBs

AT1 Receptor Antagonist (blocker)

Non-Peptide

Primarily used in HTN, HF

Lack some side effects seen with ACE inhibitors

Higher affinity for AT1 than AT2, Mas receptors

Don’t effect kininase II

Blood pressure lowering due to residual AT2 receptor activation
- Via increased production of Ang(1-7)

Blockade of AT1 receptors results in loss of AII feedback inhibiton of renin release from kidney

• PROMOTE renin release
• Leads to more AI and AII production
• Made into Ang(1-7) via ACEII

Adverse Effect:

• Hypotension
• Hyperkalemia
• Pts with renal insufficiency: acute renal failure

Contraindicated in pregnant and nursing mothers

Question 2

irbesartan

Answer 2

ARBs

AT1 Receptor Antagonist (blocker)

Non-Peptide

Primarily used in HTN, HF

Lack some side effects seen with ACE inhibitors

Higher affinity for AT1 than AT2, Mas receptors

Don’t effect kininase II

Blood pressure lowering due to residual AT2 receptor activation
- Via increased production of Ang(1-7)

Blockade of AT1 receptors results in loss of AII feedback inhibiton of renin release from kidney

• PROMOTE renin release
• Leads to more AI and AII production
• Made into Ang(1-7) via ACEII

Adverse Effect:

• Hypotension
• Hyperkalemia
• Pts with renal insufficiency: acute renal failure

Contraindicated in pregnant and nursing mothers

Question 3

losartan

Answer 3

ARBs

AT1 Receptor Antagonist (blocker)

Non-Peptide

Primarily used in HTN, HF

Lack some side effects seen with ACE inhibitors

Higher affinity for AT1 than AT2, Mas receptors

Don’t effect kininase II

Blood pressure lowering due to residual AT2 receptor activation
- Via increased production of Ang(1-7)

Blockade of AT1 receptors results in loss of AII feedback inhibiton of renin release from kidney

• PROMOTE renin release
• Leads to more AI and AII production
• Made into Ang(1-7) via ACEII

Adverse Effect:

• Hypotension
• Hyperkalemia
• Pts with renal insufficiency: acute renal failure

Contraindicated in pregnant and nursing mothers

Question 4

valsartan

Answer 4

ARBs

AT1 Receptor Antagonist (blocker)

Non-Peptide

Primarily used in HTN, HF

Lack some side effects seen with ACE inhibitors

Higher affinity for AT1 than AT2, Mas receptors

Don’t effect kininase II

Blood pressure lowering due to residual AT2 receptor activation
- Via increased production of Ang(1-7)

Blockade of AT1 receptors results in loss of AII feedback inhibiton of renin release from kidney

• PROMOTE renin release
• Leads to more AI and AII production
• Made into Ang(1-7) via ACEII

Adverse Effect:

• Hypotension
• Hyperkalemia
• Pts with renal insufficiency: acute renal failure

Contraindicated in pregnant and nursing mothers

Question 5

captopril

Answer 5

ACE inhibitor

Antihypertensive Primary Use

Left ventricular systolic dysfunction: reduces mortality

Myocardial Infarcation: reduces mortality

Heart failure: reduces mortality

Adverse Effects:
- Hypotension
- Renal failure in renal insufficient patients
- Hyperkalemia
Additionally:
- Dry cough (due to bradykinin)
- Angioedema 

Blood pressure effects via: Ang-(1-7) production

Results due to shunt of AI to make Ang(1-7)

Question 6

enalapril

Answer 6

ACE inhibitor

Antihypertensive Primary Use

Left ventricular systolic dysfunction: reduces mortality

Myocardial Infarcation: reduces mortality

Heart failure: reduces mortality

Adverse Effects:
- Hypotension
- Renal failure in renal insufficient patients
- Hyperkalemia
Additionally:
- Dry cough (due to bradykinin)
- Angioedema 

Blood pressure effects via: Ang-(1-7) production

Results due to shunt of AI to make Ang(1-7)

Question 7

lisinopril

Answer 7

ACE inhibitor

Antihypertensive Primary Use

Left ventricular systolic dysfunction: reduces mortality

Myocardial Infarcation: reduces mortality

Heart failure: reduces mortality

Adverse Effects:
- Hypotension
- Renal failure in renal insufficient patients
- Hyperkalemia
Additionally:
- Dry cough (due to bradykinin)
- Angioedema 

Blood pressure effects via: Ang-(1-7) production

Results due to shunt of AI to make Ang(1-7)

Question 8

conivaptan

Answer 8

Vasopressin Receptor Antagonist

Non-peptide vasopressin receptor antagonist

V1/V2 receptor

Approved for treatment of hyponatremia caused by SIADH (syndrome of inappropriate antidiuretic hormone)

• Water retention is mediated by secretion of vasopressin
• Administered by IV to hospitalized patients to increase serum sodium conc.

Question 9

tolvaptan

Answer 9

Vasopressin Receptor Antagonist

Selective V2 receptor antagonist

Orally adminstered for treatment of hypervolemic and euvolemic hyponatremia that is resistant to to fluid restriction

• HF
• Cirrhosis
• SIADH

Question 10

aliskiren

Answer 10

Renin Inhibitor

Non-peptide based renin inhibitor that is approved for treatment of essential hypertension

Adverse effect:
- Hypotension
- Hyperkalemia
- Renal Failure in renal patients
- Dry cough
- angioedema
and GI/allergic symptoms

Has effect in patients that are Na-depleted