Captopril Etc….

The Renin-Angiotensin-Aldosterone system is responsible for long-termregulation of blood pressure as follows:

• Acts as a potent systemic vasoconstrictor.• Directly stimulates thirst centre in the CNS to promote water intake.• Stimulates synthesis and release of Aldosterone from the adrenal cortex.

Aldosterone acts on the kidney to:

• Retain Na+ (and therefore water), leading to an increase in blood volume.• Stimulate release of Anti-Diuretic Hormone (ADH), also called arginine

vasopressin.• From the posterior pituitary. ADH promotes renal sodium and water

retention, thus increasing urine osmolality (concentration) via decreased water excretion.

• ADH also raises blood pressure moderately by direct vasoconstrictor effects.

• Drugs which interfere with the RAAS have various beneficial effects upon cardiovascular structure and function, as well as well-documented effects on lowering of blood pressure.

ACTS ON THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM (RAAS)

afferent arteriolar resistance

-+

arterial pressure

Glomerular hydrostatic pressure

GFR

macula densa NaCl

renin

angiotensin II

efferent arteriolar resistance

Proximal tubule NaCl reabsorption

Macula densa feedback mechanism

for autoregulation

afferent arteriolar resistance

ACE Inhibitors.• Angiotensin-converting Enzyme Inhibitors:• Captopril• Enalapril• Lisinopril• prevent conversion of Angiotensin I to Angiotensin II• Net result:• Arterial vasodilation• Lowering of blood pressure.

• Additionally, they have recently been shown to improve overall vascular function and to reduce ischaemic events and mortality separate from their beneficial effects upon blood pressure.

• Angiotensin II Receptor Blockers - ARB’s (e.g. losartin, candesartan, valsartin) can be used as an alternative to ACE inhibitors in symptomatic patients who are unable to tolerate ACEI. These drugs have been shown to have a similar effect on morbidity and mortality.

Captopril • Alone and in combination with thiazide-type diuretics. - Blood pressure

lowering effects additive.• In CHF with diuretics and digitalis. • Left Ventricular Dysfunction improves survival in patients ≤ 40% ejection

fraction• Taken one hour before meals – empty stomach. • Initiation of therapy - consider recent diuretic therapy and possibility of

severe salt/volume depletion. • Neutropenia / agranulocytosis has occurred, thrombocytopenia, and

pancytopenia• Rash, often with pruritus, and sometimes fever- treat with antihistamine• Flushing or pallor rare• Hypotension may occur – • Tachycardia, chest pain, and palpitations [1 of 100 patients]

• Dose Start 0.1 mg/kg 8 Hourly. Increase to 2 mg/kg as required. • [Less hypotension in tube fed patients if mixed with feeds]