Renin, Angiotensin, Aldosterone System PPT1

The section covers key components of the cardiovascular system, notably the Renin-Angiotensin-Aldosterone system (RAAS) and various drug classes including beta blockers and calcium channel blockers.

Afferent and Efferent Arteries:
- The Afferent Artery enters the nephron and is larger than the Efferent Artery, creating a pressure gradient essential for kidney function.
- Prostaglandins keep the Afferent Artery open.
- NSAIDs (e.g., ibuprofen, naproxen) block prostaglandins, leading to a narrowed artery and increased blood pressure—patients should be advised against NSAIDs if they have high blood pressure.
- Baroreceptors at the nephron entrance sense pressure and volume, aiding in regulation.

Renin:
- Activated by low pressure and volume signals received from baroreceptors, particularly in conditions like heart failure.
- Triggers the liver to produce Angiotensin I and signals adrenal glands to release Aldosterone.
- Renin can be inhibited by Aliskiren (Renin Blocker), preventing the cascade to Angiotensin and Aldosterone initiation.
- Use caution in pregnancy due to potential fetal growth effects and with renal dysfunction; also monitor for angioedema and hyperkalemia.

Angiotensin:
- Treated with medications ending in “pril” that are Angiotensin Converting Enzyme (ACE) inhibitors, blocking Aldosterone release.
- Angiotensin I requires conversion by ACE to Angiotensin II, which constricts blood vessels, promotes inflammation, increases clot risks, and contributes to structural heart changes.

Common Side Effects:
- First dose hypotension leading to potential fainting.
- Hypoglycemia due to increased glucose uptake.
- Nagging cough, especially in women, possibly due to Bradykinin accumulation in the lungs.
- Angioedema risk is heightened in African Americans and smokers, with symptoms including swelling of the tongue, lips, and throat; it can be fatal.
- Patients with angioedema should never take another "pril" medication.

Angioedema:
- A life-threatening condition indicated by voice changes.
- Patients must go to the emergency room and notify staff of ACE inhibitor usage.
- Symptoms may include hives and additional swelling.

Impact on Kidneys:
- Hypertension leads to intraglomerular hypertension, causing eventual kidney failure which often is painless until significant damage occurs.
- All type II diabetics should be prescribed a "pril" and monitored using microalbumin tests to assess kidney pressure.

Hyperkalemia with “prils”:
- Can be managed by adding a thiazide or Spironolactone/Eplerenone (both block Aldosterone).
- Potassium levels need checking within the first week after the addition of these medications to avoid potential complications like death from heart failure.

ARBs:
- Known as “sartans”, they bypass ACE and generally do not cause cough.
- Block Angiotensin II receptors in blood vessels, with a lower incidence of angioedema.

Beta Blockers:
- Categories include beta1 (affects heart) and beta2 (affects lungs).
- Labetalol: Safe during pregnancy.
- Carvedilol: Used specifically for heart failure.
- Metoprolol: Most commonly prescribed beta blocker.
- Propranolol: First introduced in 1968; not commonly used for BP due to high lipid solubility affecting the brain.
- Mechanism includes blocking fight-or-flight response by inhibiting dopamine, epinephrine, and norepinephrine.

Beta 1:
- Increases heart rate and strength of myocardial contractions.
Beta 2:
- Affects skeletal muscle and vasoconstriction in lungs and leg arteries.
- Non-cardio-selective blockers can exacerbate conditions like COPD and asthma due to broad receptor blocking.

Uses:
- Timolol drops for glaucoma, careful with dosing to prevent systemic effects.
Side Effects:
- May include bradycardia and anhedonia (loss of joy), with the risk of suicidal ideation.

Calcium Channel Blocker Classes:
- Class 1: Verapamil - First generation, blocks AV node, reduces heart workload and decreases heart rate but can lead to severe constipation and peripheral edema.

Diltiazem:
- Class 2 calcium channel blocker that dilates calcium channels, stops arterial spasms, and is used primarily for hypertension and angina.
- Less likely to cause constipation compared to Verapamil.

Class 3:
- Includes Nifedipine, Amlodipine, Nicardipine - Focus on blocking peripheral vascular calcium channels.
- Amlodipine prevents reflex tachycardia, a risk with sudden BP drops, previously Nifedipine was administered sublingually and posed risks of severe cardiovascular events.

Critical Conditions:
- Diastolic >120 warrants urgent treatment to prevent stroke, heart ischemia, or renal failure.
Sodium Nitroprusside (Nipride):
- Potent IV medication with a rapid onset and short half-life (90 seconds).
- Risk for cyanide toxicity, especially with liver disease, thus requires careful monitoring and light-sensitive storage.

Fenoldopam:
- Acts like nitroprusside by activating dopamine receptors for vasodilation and promoting sodium/water excretion; rapid onset with a 5-minute half-life.

Clevidipine:
- Calcium channel blocker with a 1-minute half-life for IV infusion.
- Common side effects include headache, nausea, and vomiting.

Labetalol:
- A beta1 blocker used IV for hypertensive crises.
- Side effects include bradycardia, dizziness, confusion, and worsening heart failure.
- Caution in patients with AV heart block or cardiogenic shock.