Loop Diuretics: Uses, and Side Effects

• Diuretics are considered the most effective ("high-ceiling")
• Loop Diuretics (e.g., Furosemide - Lasix) is a class of diuretic
• Conditions treated by Loop Diuretics:
  • Pulmonary edema (drug of choice)
  • Edema related to heart, liver, or renal failure
  • Refractory hypertension (when first-line agents fail)
• Adverse Effects of Loop Diuretics (OHH DANG!)
  • O: Ototoxicity
  • H: Hypokalemia
  • H: Hypomagnesemia
  • D: Dehydration
  • A: Allergy (sulfa-based)
  • N: Nephritis
  • G: Gout
• Drug interactions with Loop Diuretics:
  • Digoxin (more dig is absorbed in states of hypo K)
  • Ototoxic drugs
  • K sparring diuretics
  • Lithium (remember Na)
  • Anti-hypertension drugs
  • and NSAIDs.

EKG changes with hypokalemia and hyperkalemia

• Hypokalemia EKG changes:
  • Flattened or inverted T waves
  • U waves prominent
  • ST depression
  • Prolonged QT interval
• Hyperkalemia EKG changes:
  • Peaked T waves
  • Widened QRS complex
  • Prolonged PR interval
  • Loss of P waves
  • Risk of ventricular fibrillation

RAAS Activation and Outcome

• RAAS Activated by:
  • Low blood pressure or hypovolemia
• RAAS Outcome:
  • Vasoconstriction (via angiotensin II)
  • Fluid retention (via aldosterone), raising blood pressure

Renin Release (Kidneys)

• Renin Release Trigger:
  • Decreased renal perfusion (e.g., low BP)
  • Low sodium delivery to the distal tubules
  • Sympathetic stimulation
• Renin Release Action: The juxtaglomerular cells of the kidney release renin into the bloodstream.

Conversion of Angiotensinogen to Angiotensin I (Liver)

• Renin acts on angiotensinogen (a protein produced by the liver) and converts it into angiotensin I (inactive form).

Conversion of Angiotensin I to Angiotensin II (Lungs)

• Angiotensin I is converted into angiotensin II by the enzyme angiotensin-converting enzyme (ACE), primarily in the lungs.

Actions of Angiotensin II (Potent Effector)

• Vasoconstriction:
  • Strongly constricts arterioles → increases systemic vascular resistance (SVR) → raises blood pressure.
• Aldosterone Secretion (Adrenal Cortex):
  • Stimulates aldosterone release from the adrenal cortex → sodium and water reabsorption in the kidneys → increases blood volume and BP.
• ADH Release (Posterior Pituitary):
  • Promotes antidiuretic hormone (ADH) secretion → water reabsorption in the kidneys → increases blood volume.
• Stimulates Thirst (Hypothalamus):
  • Promotes increased water intake → contributes to restoring blood volume.

Aldosterone's Role (Kidneys)

• In the distal tubules and collecting ducts of the nephron, aldosterone:
  • Increases sodium reabsorption (water follows sodium) → expands blood volume.
  • Increases potassium excretion → lowers serum potassium levels.

Cough and Angioedema with ACEIs

• Cause: ACE inhibition leads to increased levels of bradykinin, which causes:
  • Cough
  • Angioedema (potentially life-threatening)

Major Differences Between CCB Subtypes

• Nondihydropyridines (Verapamil, Diltiazem):
  • Action: Affect heart and vessels (reduce HR and contractility)
  • Uses: Angina, HTN, dysrhythmias
  • Adverse effects: Bradycardia, AV block, constipation (Verapamil)
• Dihydropyridines (Nifedipine):
  • Action: Act mainly on vascular smooth muscle → vasodilation
  • Uses: Angina, HTN, Raynaud's phenomenon
  • Adverse effects: Reflex tachycardia, flushing, headache

Drug-Induced Reflex Tachycardia

• Beta-blockers are a secondary medication commonly combined with dihydropyridine CCBs (e.g., Nifedipine) or vasodilators to prevent reflex tachycardia.

Unique Side Effects of Vasodilators

• Hydralazine:
  • Reflex tachycardia
  • SLE-like syndrome (muscle/joint pain, fever, nephritis)
  • Hypotension causing body ton increase volume (may need diuretic to correct)
• Minoxidil:
  • Hypertrichosis (80% of users)
  • Pericardial effusion (black box warning) progress to tamponade.
  • Reflex tachycardia
  • Hypotension

First-Line Therapy for HTN (No Compelling Situation)

• Preferred Agents:
  • Thiazide diuretics (e.g., Hydrochlorothiazide)
  • ACE inhibitors/ARBs
  • Calcium Channel Blockers (CCBs)

Beta Blockers in Diabetic Patients

• Reason for caution:
  • Beta-blockers can mask early signs of hypoglycemia (e.g., tachycardia)
  • May also impair glycogenolysis, potentially prolonging hypoglycemia

Dosing Changes for Older Adults (Anti-HTN)

• Consider:
  • Start low, go slow: Initial doses should be ~50% of younger adult doses
  • Slow titration: To minimize the risk of orthostatic hypotension and falls

Preferred Agents for HTN in Pregnancy

• Preferred Medications:
  • Methyldopa
  • Labetalol
  • Nifedipine (sustained-release)
• Contraindicated: ACE inhibitors, ARBs (due to teratogenicity)

Diagnostic Criteria for Pre-eclampsia and Eclampsia

• Pre-eclampsia:
  • BP ≥ 140/90 after 20 weeks of gestation
  • Proteinuria: ≥ 300 mg/24 hours
• Eclampsia:
  • Pre-eclampsia + Seizures
  • Requires immediate delivery in severe cases

Medication for HTN and ED

• Answer: ACE inhibitors (e.g., Lisinopril)
  • They do not cause erectile dysfunction and may even have beneficial effects on endothelial function compared to beta blockers and thiazides