the renin angiotensin andosterone system
TRANSCRIPT
The Renin Angiotensin Aldosterone System (RAAS)By: Darya Osman Hussein Daoud
Content
What is the Rennin-Angiotensin-Aldosterone System?
Role it plays in Hypertension
Drugs affecting system
What is it?
A hormone system Regulates blood pressure and fluid balance Involve kidney and Liver
Important Factors
Renin Angiotensinogen Angiotensin I Angiotensin II Aldosterone
Renin
A.K.A. Angiotensinogenase
Released from Kidney
Hydrolyzes angiotensinogen
Angiotensinogen
Produced and released by liver Level increased by corticosteroids, estrogen and thyroid hormone Composed of 453 A.A. but the 1st 12 are the most important
Angiotensin I Produced in the kidney through action of Renin on Angiotensinogen Has no biological activity Precursor to Angiotensin II
Angiotensin II Produced by ACE in lungs Main hormone responsible for increase in blood pressure Stimulates Na reabsorption and H+ secretion in proximal tubules of kidney
Angiotensin III
Has 40%activity of angiotensin II Has aldosterone producing activity Causes increase in mean arterial pressure
ACE
Angiotensin Converting Enzyme Acts in the lungs Catalyzes conversion of Angiotensin I to
Angiotensin II Degrades bradykinin and other vasoactive
peptides
Types of drugs
I. Angiotensin Converting Enzyme inhibitors (ACE inhibitors)
II. Renin inhibitors
III. Angiotensin II Receptor Blockers (ARBs)
IV. Aldosterone receptor antagonists
I. ACE Inhibitors (Captopril, Enalapril,Lisinopril)
Used as 1st line treatment for hypertension in patients with: High risk of CAD Diabetes History of stroke Heart failure MI Chronic kidney disease
I. ACE Inhibitors
Action: Reduce peripheral vascular resistance No increase in CO,HR or contractility Cause vasodilation of arterioles and veins Decrease aldosterone secretion Reduce cardiac work by decreasing pre and afterload
I. ACE Inhibitors
Pharmacokinetics: Orally bioavailable Given as drug or prodrug Captopril and Lisinopril do not require hepatic activation (used in hepatic
impairment) Fosinopril not eliminated by kidney (used in renal impairment) Enalaprilat only one given via IV
I. ACE Inhibitors
Clinical Use: Hypertension Heart failure Ventricular dysfunction following MI Diabetic nephropathy
I. ACE Inhibitors
Adverse effects: Hypotension Dry cough Angioedema Renal failure Skin rash Hyperkalemia Altered taste Teratogenic
I. ACE Inhibitors Advantage
Protect kidneys from kidney damage/failure in diabetics
Prevent micro-albuminuria
II. Renin Inhibitors
Selective inhibitor – Aliskiren
Action: Lowers BP Usually used as monotherapy
Side effects: Causes diarrhea at high doses Contraindicated in pregnancy Causes cough and angioedema
III. ARBs (Losartan, Valsartan, Candesartan) Action:
Lower BP by decreasing vasoconstrictor tone
Mechanism of Action: Block action of angiotensin II on angiotensin II receptor
III. ARBs
Pharmacokinetics Given orally T ½ = 1 – 2 hours
Clinical Use Hypertension CHF nephropathy
III. ARBs
Adverse Effects Hypotension Dizziness Hyperkalemia (rare)
Special points No dry cough No angioedema