Agonists and Functions of Prostaglandins

• Agonists
  • Epoprostenol: An agonist discussed in relation to prostaglandins.
  • PGE1:
  • Responsible for: Vasodilation.
  • Agonist for PGE1: Alprostadil (used to keep the ductus arteriosus open).
  • PGE2 and PGF2:
  • Responsible for: Increasing uterine tone.
  • Agonist for PGE2: Dinoprost.
  • Agonist for PGF2: Dinoprost (same as for PGE2).

Aspirin and COX Inhibition

• Aspirin:
  • Inhibits COX-1 and COX-2:
  • Mechanism: Irreversible inhibition of cyclooxygenase.
• NSAIDs and Acetaminophen:
  • Mechanism: Reversible inhibition of cyclooxygenase.
• Celecoxib:
  • Inhibits: COX-2 selectively.
  • Noted as being particularly high yield for examinations.

Effects of Salicylate Overdose

• Overdose Impact:
  • Early disturbance: Respiratory alkalosis.

Diuretics Overview

• Common Electrolyte Disturbance: Hyponatremia across all diuretics.
• Specific Diuretics:
  • Carbonic Anhydrase Inhibitors, Loop Diuretics, Thiazides: All lead to hypokalemia.
• Effects:
  • Volume contraction or alkalemia stimulated by: Angiotensin II.
  • Promotes sodium-proton exchange in proximal convoluted tubule.
  • Increases bicarbonate (HCO3).
• Importance:
  • Understanding the Renin-Angiotensin System (RAS) pathway is critical as it appears in many exams.

Diuretics: Site and Toxicity

• Carbonic Anhydrase:
  • Works on: Proximal convoluted tubule.
  • Uses: Metabolic alkalosis, urinary alkalization, glaucoma, altitude sickness, increased intracranial pressure.
  • Toxicities: Renal tubular acidosis, calcium phosphate stones, non-anion gap metabolic acidosis.
• Osmotic Diuretics:
  • Uses: Increased intracranial pressure, drug overdose, oliguria, glaucoma.
  • Toxicities: Hypovolemia, pulmonary edema, congestive heart failure.
• Loop Diuretics:
  • Block a co-transport system in: Ascending loop of Henle.
  • Specifically: Sodium-Potassium-Chloride co-transport system.
  • Toxicities: Ototoxicity, hypokalemia, hypomagnesemia, dehydration, sulfur allergy, alkalosis, interstitial nephritis, and gout.
• Thiazide Diuretics:
  • Site: Distal convoluted tubule.
  • Toxicities: "HyperGLUC" (hyperglycemia, hyperlipidemia, hyperuricemia, hypercalcemia).
• Potassium-Sparing Diuretics:
  • Types: Triamterene and Amiloride (block epithelial sodium channels), Aldosterone antagonists.
  • Site of action: Collecting ducts.
  • Associated with: Type IV renal tubular acidosis (only RTA with hyperkalemia).

Nephrolithiasis Classification

• Calcium Oxalate Stones:
  • Shape: Envelope-shaped.
  • Causes: Low urine pH, hypercalcuria, hyperoxaluria.
• Calcium Phosphate Stones:
  • Shape: Needle/star-shaped.
  • Causes: High urine pH.
• Struvite Stones:
  • Shape: Coffin lid-shaped.
  • Associated with: UTI due to urease positive bacteria (e.g., Proteus mirabilis).
  • Other urease-positive organisms: Klebsiella, Pseudomonas, Staphylococcus.
• Uric Acid Stones:
  • Shape: Rhomboid-shaped.
  • Causes: Gout, tumor lysis syndrome (elevated uric acid from cell breakdown).
  • Importance of rasburicase in treatment due to tumor lysis syndrome.
• Cystine Stones:
  • Shape: Hexagonal.
  • Associated with: Hereditary disorder affecting renal tubular reabsorption of amino acids (cystine).
  • Remember: Cystine stones are hexagonal.

Immunodeficiencies and TB

• Disseminated TB:
  • Implied Immunodeficiency: IL-12 receptor deficiency.
• Drug Requirement:
  • Frequent PPD testing recommended for drugs inhibiting IL-12:
  • Example: Infliximab (inhibits TNF-alpha).
• Th1 Response:
  • Function: Activates INF-gamma.
  • Consequence: IFN-gamma activates macrophages to release IL-12 and TNF-alpha; critical for defense against TB.
  • Loss of Th1 or these components results in susceptibility to TB.

Tumor Markers in Neuroendocrine Tumors

• Tumor Markers:
  • Chromogranin A, Synaptophysin, Enolase.
  • Associated with: Neuroendocrine tumors.
• Histological Feature:
  • All neuroendocrine tumors share similar histological characteristics.