Antihypertensives (RAAS) Flashcards
What are the three types of Primary Hypertension (92% of hypertension)?
- Low Renin (25% A. Americans and elderly)
- Normal Renin (60%)
- High Renin (15%)
Reflex circuit with sensing via stretch receptors located in the carotid sinus and aortic arch that opposes attempts to reduce arterial pressure with drugs. Works second-to-second.
sympathetic baroreceptor reflex
Controls the slow, but ultimate regulator of blood pressure because of its infinite gain
Renal-blood volume pressure control
α1-adrenergic receptors
Blood vessels
- arterial & venous vasoconstriction
- maintains venous return w/ changes in posture
α2-adrenergic receptors
Brain and periphery
Presynaptic Feedback Inhibitory Receptors:
- decreases sympathetic tone
β1-adrenergic receptors
- Increase HR
- increases heart contractility
- stimulates renin secretion
β2-adrenergic receptors
- Fight or flight response
- dilates skeletal muscle vasculature
- dilates bronchioles
What are the Angiotensin-Converting Enzymes (ACE)?
-pril
- Captopril
- Enalapril (enalaprilate) | prodrug (active form)
- Lisinopril
- benazepril
what are the Angiotensin II Receptor drugs (ARBs)?
-artan
- Losartan
- Valsartan
- Candesartan (irreversible binding)
- Aliskiren (expensive, new, unpopular)
How do you calculate Mean Arterial Pressure (MAP) and what is considered a normal MAP?
MAP = diastolic (systolic - diastolic) / 3
normal: 100 mmHg
22 year old female comes into your office with hypertension. She is an athletic, healthy, well-maintained invidivdual w/ no family hx of hypertension. What is most likely the cause of her hypertension?
Secondary Hypertension due to oral contraceptives
Malignant hypertension and unilateral renovascular diseases are a consequence of what?
High Renin secretion
Low aldosterone secretion
Primary hyperaldosteronism and low-renin essential hypertension are a result of what?
Low renin secretion
high aldosterone secretion
What has the biggest impact on resistance of a fluid to flow?
radius (to the fourth power)
A blood pressure goal of 140/90 is recommended for who?
- < 60 years
- diabetic patients w/o CKD (all ages)
- CKD patients (all ages)
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For which group of people is a blood pressure goal of < 150/90 indicated?
patients age 60 or older
Patient presents with a blood pressure greater than 140/90. Describe how you would treat an African American patient versus a non-black patient?
African American:
- 1st - thiazide or calcium channel blocker (CCB)
- no ACE (-) (ACEI) or Angiotensin receptor blocker (ARB) due to hypertension in this population being a result of low renin
Nonblack:
- Thiazide or CCB or ACEI or ARB
African Americans with hypertension are not typically treated with ACE inhibitiors (ACEI) or Angiotensin Receptor Blockers (ARB) due to statistics which show African American patients tend to have a type of low renin hypertension. However, regardless of race all patients with hypertension AND CKD or diabetes are treated with ACEI or ARB or a combination of both. Why is this?
Chronic Kidney Disease (CKD) & Diabetes:
Both result in high glomerular pressure. ACEI and ARB dilate efferent arteriole allowing relief from some of that glomerular pressure
preserves remaining kidney function
Why are β-blockers no longer used for control of hypertension?
- does not prevent MIs, heart failure, or death as well as other therapies
- associated with significantly higher incidence of stroke than other therapies
Once angiotensin I is cleaved by ACE to form angiotensin II, angiotensin II acts to increased EC fluid volume. How does it accomplish this?
- stimulates thirst
- stimulates aldosterone secretion
- stimulates ADH secretion
- cardiovascular remodeling (so BV can vasoconstrict easier)
Due to various causes in chronic hyptension you always see…
an increase in total peripheral resistance
What effect do ACEI, ARBs, and CCBs have on hypertensive vascular remodeling?
- decrease in media thickness of BVs
- decreased aortic stiffness
What is the first move in management of essential hypertension?
Lifestyle modification
Once on a BP med you have to stay on one the rest of your life
The MOA of ACE inhibitiors is to stop the action of ACE kinase in convertin angiotensin I to angiotensin II. What unwanted consequence occurs as a result of this therapy?
ACE kinase also converts converts bradykinin into inactive metabolites.
there is a build-up of bradykinin
The use of ACE inhibitors correlates with a build-up of bradykinin within the body. What does bradykinin build-up cause?
- Vasodilation
- decrease in GFR (result: increase in serum creatinine)
- Cough (#1 reason people stop using ACEIs)
- Proinflammatory
- Angioedema
What are the most popular ACEIs? Why?
benazepril and lisonopril
- both have longer half-lives allowing for 1 dose/day
Medication fell out of favor due to patients experiencing a loss of taste due to a constant metallic taste in their mouth
ACEI - Captopril
What’s the number one reason patients stop using their ACE inhibitor? What’s the second reason?
#1 reason = cough
#2 reason = angioedema (swollen tongue, choking)
Competitive non Peptide angiotensin II receptor antagonist
Losartan - selective for AT1 (1000x more than AT2)
What are the benefits of Angiotensin II Receptor Blockers over ACEIs?
- less severe cough symptomology (no bradykinin effect)
- less severe angioedema
Less severe symptoms as compared to ACEIs
Angiotensin II Receptor Blocker (ARB) with a half-life of 5-9 hours and characterized by irreversible binding
Candesartan
An ARB with a half-life of 6-10 hours that is not a prodrug
Valsartan
What patients should NOT use a β-blocker?
- Asthmatic patients (bronchodilation needed)
- diabetics (beta receptors offset hypoglycemia)
What type of hypertension is more commonly seen in children?
Secondary hypertension (so identify cause)
NO ACEIs or ARBs in sexually active girls
What two patient populations should not receive ACEIs?
- Pregnant patients during ALL three trimesters (fetal harm, malformations)
- bilateral renal stenosis patients (precipitates kidney failure)
