Angiotensinogen a hormone released in the liver. It will encounter an enzyme called RENIN. Renin’s job is to find Angiotensinogen and cleave off part of the protein and form an inactive hormone called ANGIOTENSIN l. From there, a different enzyme called Angiotensin Converting Enzyme or ACE will convert the Angiotensin l to the active hormone Angiotension ll. It is active and will go to the kidney and activate the ANGIOTENSIN 1 RECEPTOR or AT1R then
ANGIOTENSIN ll tells the kidney to: - increase Na+ retention - increase H20 retention - increase Aldosterone (they all causes increase blood pressure)
It is good for people who have low blood pressure but for people who have normal blood pressure too much of it will cause their blood pressure to be high.
RAA SYSTEM DRUG TARGETS: 1. It blocks the conversion of Angiotensin l to Angiotensin ll. It is called ACE l 2. This drug prevent Angiotensin ll from working on the kidney by blocking the receptor that Angiotensin relies on. It is called Angiotensin ll Receptor Blocker or ARBS
MOST COMMON ACE INHIBITOR DRUGS (ending in “pril”): - Lisinopril (Prinivil, Zestril) - Lininopril/HCTZ is a combination product with Thiazide (Prinzide, Zestroetic) - Enalapril (Vasotec) - Ramipril (Altace) most commonly used
ANGIOTENSION l RECEPTOR BLOCKER DRUGS or ARBS (ending in “sartan”): - Losartan (Cozaar) - Olmesartan (Benicar) - Valsartan (Diovan)
Clinical use of ACE l and ARBS: - HYPERTENSION - HEART FAILURE esp following a heart attack - Hypertension that causes kidney problem like Proteinuria which the kidney spills protein into the urine as the result of kidney damaged caused by high blood pressure
ADVERSE EFFECTS OF ACE l AND ARBS: 1. Symptoms of low blood pressure (orthostasis) - that is why we advice patient not to get up or rise quickly 2. Hyperkalemia - it happens because if we block the Angiotensin ll the Na+ can’t be reabsorbed which means the K+ will stay in the blood causing K+ level in our blood to be high. 3. Acute Kidney Injury - Serum Crea in your blood will increase. This is because the Angiotension ll is very important hormone to regulate blood flow to the kidney AND if we block the effect of Angiotensin ll we prevent the kidney’s ability to maintain its own blood flow which can cause damage to the kidney 4. Angioedema (very rare) - most common with ACE l than ARB’s
5. Dry Cough (why it happened) - ACE l does not only involve in converting Angiotensin l to ll but it also involve in breaking down BRADYKININ into PROTEIN. So if we are taking ACE inhibitor, we are blocking the conversion of Angiotensin l and ll, and we are also blocking the conversion of Bradykinin causing the Bradykinin to increase and thus cause Dry Cough.
Quick facts about Bradykinin: The activation of the kinin system-bradykinin is particularly important in blood pressure regulation and in inflammatory reactions, through bradykinin ability to elevate vascular permeability and to cause vasodilatation in some arteries and veins. The biological effects of kinins are mediated by specific receptors called B1 and B2.The activation of this system is particularly important in blood pressure regulation and in inflammatory reactions, through bradykinin (BK) ability to elevate vascular permeability and to cause vasodilatation of arteries and veins of the gut, aorta, uterus and urethra. The kinin system is involved in many clinical situations including respiratory allergic reactions, septic shock, hypertension and its treatment, hypotensive transfusion reactions, heart diseases, pancreatitis, hereditary and acquired angioedema, Alzheimer disease and liver cirrhosis with ascites. Apart from being a pro-inflammatory mediator, bradykinin is now recognized as a neuromediator and regulator of several vascular and renal functions. Bradykinin (BK) has multiple pathophysiologic functions such as induction of vascular permeability and mitogenesis, and it triggers the release of other mediators such as nitric oxide in inflammatory and cancer tissues. (from nlm)
WHO SHOULD NOT TAKE ACE-l and ARB’s? 1. Those with high K+ level 2. Angioedema 3. Pregnant women (category D) 4. Acute Kidney Injury 5. Bilateral Renal Artery Stenosis (the body can’t regulate the blood flow to the kidney)
SOURCE: Sean P. Kane (ClinCalc Academy)
Visit his YouTube channel for more info about drugs