Cardio: RAAS Drugs

Question 1

• Drugs that:
  
  • Prevent the formation of Angiontensin II
  • Prevent degredation of bradykinin

Answer 1

ACE Inhibitors: (“-PRIL”)

Lisinopril

Captopril

Enalapril

Question 2

Clinical use of ACE inhibitors:

Answer 2

• HTN
• CHF
• HCM
• MI
• Renal failure and fibrosis
• Diabetes

Question 3

Contraindications for ACE inhibitors and ARBs:

Answer 3

• Renal artery stenosis → Renal Failure
• Elevated serum K⁺ (>5.5 mEq/L)
• Symptomatic hypotension
• Pregnancy (chronic mgmt of Hypertension)
  
  • ​Methyldopa
  • Hydralazine

Question 4

Side effects of ACE inhibitors and ARBs:

Answer 4

• Severe hypotension
• Chronic nonproductive dry cough (ACEs)
• Dysgeusia (altered taste)
• Renal hemodynamic dysfunction
  
  • Renal Artery Stenosis (contraindicated)
    → Renal Failure
• Hyperkalemia (Lack of Aldosterone)
• Angioedema (rare)

Question 5

• Drugs that:
  
  • Nonpeptide AT₁ receptor antagonism that interferes w/ binding of Angiotensin II to its receptor
  • DOES NOT effect the breakdown of bradykinin

Answer 5

ARBs (AT1 receptor blockers) (“-SARTAN”)

Losartan

Vaisartan

Question 6

Clinical use of ARBs:

Answer 6

• HTN
• CHF

Question 7

Aldosterone receptor antagonist drugs:

Answer 7

• Spironolactone
  
  • Aldosterone receptor antagonist
• Eplerenone (Inspa)
  
  • Selective aldosterone receptor blocker

Question 8

Mechanism of action for Aldosterone antagonists:

Answer 8

• Aldosterone (a mineralocorticoid hormone) produced in the adrenal cortex and in extra-adrenal sites) whose synthesis and secretion are affected by Angiotensin II, plasma potassium levels, ACTH, and other stimuli
• Angiotensin II is the most potent stimulus
• Kidney: stimulates sodium retention by distal nephrons, potassium excretion, blood volume expansion, elevation of blood pressure
• Other sites: increases blood pressure by a CNS mechanism, stimulates myocardial fibrosis, reduces arterial elasticity and increases inflammation

Question 9

Clinical use of Aldosterone receptor antagonists:

Answer 9

• Hypertension
• CHF

Question 10

Contraindications of Aldosterone antagonists:

Answer 10

• Hyperkalemia
• Cirrhosis

Question 11

Side effects of Aldosterone antagonists:

Answer 11

• Hyperkalemia (both drugs)
• Progestational and antiandrogenic side effects (Spironolactone only):
  
  • Gynecomastia
  • Impotence
  • Menstrual irregularities

Question 12

• Increases kidney tubular fluid osmolarity - pulls water from the interstial space into the tubules via osmosis - more water is excreted into the urine and less water reabsorbed into the ciruclation
• Acts on the Proximal tubule
• Tx: Intracranial Pressure, Increased Ocular Pressure
• Can pull fluid into the blood and lead to Hypervolemia –> which can lead to peripheral and pulmonary edema

Answer 12

Mannitol

Question 13

Drug acts on the Proximal Convoluted Tubule

Answer 13

Acetazolamide and Osmotic Agents (Mannitol)

Question 14

Drug acts on the Descending Limb

Answer 14

Osmotic agents (Mannitol)

Question 15

Drug acts on the Thick Ascending Limb

Answer 15

Loop Diuretic Agents (Furosemide)

Ethacrynic acid

Question 16

Drug acts on the Distal Convoluted Tubule

Answer 16

Loop Agents (Furosemide)

Thiazides

Aldoesterone antagonists

Question 17

Drug acts on the Collecting Duct

Answer 17

ADH antagonists

Osmotic agents (Mannitol)

Question 18

• Prevents the conversion of HCO₃^- into CO₂ by carbonic anhydrase primarily at the brush border of the proximal tubule cells, necessary for the reabsorption of HCO₃^-
• Proximal convouted tubule
• Tx: Metabolic alkalosis, Altitude sickness, Glaucoma, or Intracranial HTN (Pseudotumor cerebri)
• SEx: Metabolic acidosis due to HCO₃^-, urine pH goes up, blood pH goes down, also allergic rxns to sulfa group

Answer 18

Acetazolamide

Question 19

• Inhibits Na⁺ K⁺ 2Cl_^- channel in the thick ascending limb of the loop of Henle - Loop diuretics - OH DANG!
• Na⁺ and K⁺ abolish the Hypertonicity of the Medulla (urine cannot be collected in the collecting ducts)
• Marked diuresis –> Ca²⁺ excretion
• Tx: Edema (CHF, Cirrhosis, Nephrotic syndrome, PE), moderate to severe HTN, Acute ion overdose, and Hypercalcemia
• SEx: Azotemia, Ototoxicity, Hyponatremia, Hypokalemia, Hypercalciuria, Hypocalcemia, Dehydration, Allergy to sulfa (furosemide, not ethacrynic acid), Nephritis, Gout

Answer 19

Furosemide (Lasix)

Ethacrynic acid (Edecrin)

Bumetanide (Bumex)

OH DANG!

• Ototoxicity
• Hypokalemia, Hypercalcuria
• Dehydration
• Allergy to sulfa (Furosemide)
• Nephritis
• Gout

Question 20

• Thiazide diuretics
• Inhibit Na⁺, Cl^- co-transporter, which blocks the reabsorption of Na⁺ and Cl^- in the **Distal Convoluted Tubule - **competing for the Cl^- site
• NaCl is excreted along with water into the urine –> increases Ca²⁺ reabsorption
• Action is addivitve to Ethacrynic acid and Furosemide
• Tx: Mild to moderate HTN, mild CHF, Nephrogenic diabetes insipidus, Idiopathic Hypercalcuria
• SEx: Hyperglycemia, Hyperlipidemia, Hyperuricemia, Hypercalcemia, Sulfa allergy - HyperGLUC

Answer 20

Hydrochlorothiazide

Chlorothiazide

Metolazone

• HyperGLUC
  
  • HyperGlycemia
  • HyperLipidemia
  • HyperUricemia
  • HyperCalcemia

Question 21

• Competitive antagonist at the Aldosterone receptor in the Collecting tubule (indirectly inhibits Na⁺) reabsorption (1st)
• Directly blocks Na⁺ channels in the Collecting tubule (2&3)
• K⁺ sparing properties:
  
  • Less K⁺ secretion occurs due to inhibiton of Na⁺ reabsorption in the Distal Tubule (Na+ reabsorption and K⁺ secretion are coupled in this segment of the nephron) –> they do not greatly increase flow
• Tx: Prevents K⁺ waisting w/ other diuretics, CHF
• SEx: Hyperkalemia, Spironolactone causes Gynecomastia

Answer 21

Spironolactone

Triamterene

Amiloride

Question 22

• Centrally acting sympatholytics
• Selective α₂-agonist - Brain stem - reduces cental sympathetic outflow - decreased CO and SVR
  
  • BP = CO x SVR
• Drug of choice for Hypertension in Pregnant patients
• SEx:
  
  • M: Sedation, Positive Coombs test in 10% of patients (reversible upon discontinuation of drug)
  • C: Sedation, Dry mouth, Severe rebound Hypertension with abrubt discontinuation

Answer 22

Methyldopa

Clonidine

Question 23

• Selective** α1-receptor antagonist**; α1-blockade decreases SVR by preventing arteriolar vasoconstriction - decreased BP
• Primarily α1-receptors on arterioles, Bladder sphincter
• Tx: Mild to Mod HTN, and BPH - α1-blockers to treat urinary hesitancy for pts. w/ benign prostatic Hypertrophy (preventing bladder sphincter contraction)
• SEx: First-dose syncope orthostatic hypotension, Reflex tachycardia, Secondary Na⁺ retention in Kidney (use w/ diuretic), Urinary incontinence

Answer 23

Prazosin

α1-receptor blocker - ends in ‘osin

Doxazosin

Terazosin

Question 24

• β-receptor blockers (ANS, decrease Renin release))
• Reduce HR, Contractility, Inhibit Renin
• β1-receptors on heart and kidney, β2-receptors on arterioles
• Tx: HTN, Angina, Pts. w/ previous MI, CHF
• SEx: Asthma (Bronchoconstriction (β2)), Vasospastic, Bradycardia, Blunted response to hypoglycemia - dangerous in Diabetics (masks Hypoglycemic events) on insulin therapy, **Sexual dysfunction, **small increase in LDLs and TGs

Answer 24

Propranolol

Carvedilol

Metoprolol

Esmolol

Atenolol

Tinolol

Question 25

Drug that blocks the production of Renin:

Answer 25

Aliskiren

Prevents the conversion of:
Angiotensinogen → Angiotensin I