A 34-year-old man is being evaluated in an emergency clinic for dizziness and headache after a stressful event at work. He also reports that his face often becomes swollen and he occasionally has difficulty breathing during these spells. Family history is significant for his father who died of a stroke and his mother who often suffers from similar facial swelling. The patient’s blood pressure is 170/80 mm Hg. On physical examination, the patient appears well. Which of the following medications is most likely contraindicated in this patient?

The patient has no contraindications.

A physician is choosing whether to prescribe losartan or lisinopril to treat hypertension in a 56-year-old male. Relative to losartan, one would expect treatment with lisinopril to produce which of the following changes in the circulating levels of these peptides?

Bradykinin increase; angiotensin II decrease

Aldosterone increase; bradykinin decrease

Angiotensin II increase; bradykinin decrease

Renin decrease; angiotensin I increase

Renin decrease; angiotensin II increase

A 75-year-old woman is brought to a physician’s office by her son with complaints of diarrhea and vomiting for 1 day. Her stool is loose, watery, and yellow-colored, while her vomitus contains partially digested food particles. She denies having blood or mucus in her stools and vomitus. Since the onset of her symptoms, she has not had anything to eat and her son adds that she is unable to tolerate fluids. The past medical history is unremarkable and she does not take any medications regularly. The pulse is 115/min, the respiratory rate is 16/min, the blood pressure is 100/60 mm Hg, and the temperature is 37.0°C (98.6°F). The physical examination shows dry mucous membranes and slightly sunken eyes. The abdomen is soft and non-tender. Which of the following physiologic changes in glomerular filtration rate (GFR), renal plasma flow (RPF), and filtration fraction (FF) are expected?

Decreased GFR, decreased RPF, increased FF

Decreased GFR, decreased RPF, decreased FF

Decreased GFR, decreased RPF, no change in FF

Increased GFR, increased RPF, increased FF

Increased GFR, decreased RPF, increased FF

A 52-year-old man is brought to the emergency department by ambulance after a motor vehicle accident. He was an unrestrained passenger who was ejected from the vehicle. On presentation, he is found to be actively bleeding from numerous wounds. His blood pressure is 76/42 mmHg and pulse is 152/min. Attempts at resuscitation fail, and he dies 25 minutes later. Autopsy shows blood in the peritoneal cavity, and histology of the kidney reveals swelling of the proximal convoluted tubule epithelial cells. Which of the following is most likely the mechanism underlying the renal cell findings?

Decreased function of the Na+/K+-ATPase

Decreased activity of caspase 7

Increased activity of caspase 9

Increased function of the Na+/K+-ATPase

Increased activity of caspase 8

A 68-year-old woman presents to her primary care physician for a regular check-up. She complains of swelling of her legs and face, which is worse in the morning and decreases during the day. She was diagnosed with type 2 diabetes mellitus a year ago and prescribed metformin, but she has not been compliant with it preferring 'natural remedies' over the medications. She does not have a history of cardiovascular disease or malignancy. Her vital signs are as follows: blood pressure measured on the right hand is 130/85 mm Hg, on the left hand, is 110/80 mm Hg, heart rate is 79/min, respiratory rate is 16/min, and the temperature is 36.6℃ (97.9°F). Physical examination reveals S1 accentuation best heard in the second intercostal space at the right sternal border. Facial and lower limbs edema are evident. The results of the laboratory tests are shown in the table below. Fasting plasma glucose 164 mg/dL HbA1c 10.4% Total cholesterol 243.2 mg/dL Triglycerides 194.7 mg/dL Creatinine 1.8 mg/dL Urea nitrogen 22.4 mg/dL Ca2+ 9.6 mg/dL PO42- 3.84 mg/dL Which of the following statements best describes this patient's condition?

If measured in this patient, there would be an increased PTH level.

There is an error in Ca2+ measurement because the level of serum calcium is always decreased in the patient’s condition.

Increase in 1α, 25(OH)2D3 production is likely to contribute to alteration of the patient’s laboratory values.

The calcitriol level is unlikely to be affected in this patient.

Hypoparathyroidism is most likely the cause of the patient’s altered laboratory results.

A 63-year-old man comes to the physician because of fatigue and muscle cramps for 6 weeks. He also noticed several episodes of tingling around the mouth and in the fingers and toes. He has osteoarthritis of his knees and hypertension. Current medications include ibuprofen and ramipril. He has smoked one pack of cigarettes daily for 35 years. Tapping over the facial nerve area in front of the ear elicits twitching of the facial muscles on the same side of the face. His serum alkaline phosphatase activity is 66 U/L. An ECG shows sinus rhythm with a prolonged QT interval. Which of the following is the most likely underlying cause of this patient's symptoms?

Destruction of parathyroid glands

Albright hereditary osteodystrophy

Pharmacological targeting of RAAS for USMLE Step 1: High-Yield Physiology Lessons

ACE Inhibitors - Pril's Power Play

ACE Inhibitor Action on RAAS and Bradykinin Metabolism

Mechanism: Inhibit Angiotensin Converting Enzyme (ACE) to block Angiotensin I → Angiotensin II conversion. Also prevents bradykinin breakdown.
Result: ↓ Angiotensin II leads to vasodilation & ↓ aldosterone. ↑ Bradykinin contributes to vasodilation and side effects.
Key Side Effects: Dry cough, angioedema (↑ bradykinin), hyperkalemia, first-dose hypotension.
Contraindications: Pregnancy (teratogen), bilateral renal artery stenosis.
Mnemonic (📌): Captopril's CATCHH (Cough, Angioedema, Teratogen, Creatinine ↑, Hyperkalemia, Hypotension).

⭐ ACE inhibitors are first-line therapy for hypertension with compelling indications like diabetes mellitus (for diabetic nephropathy) and chronic kidney disease.

Angiotensin II Receptor Blockers - Sartan's Shield

Mechanism: Selectively block the Angiotensin II Type 1 (AT1) receptor.
- Inhibits the primary effects of Angiotensin II, leading to arterial/venous dilation and ↓ aldosterone secretion.
Drugs: Losartan, Valsartan, Irbesartan (ends in -sartan).
Key Advantage vs. ACEi: Do not increase bradykinin levels.
- Results in a much lower risk of cough and angioedema.

⭐ ARBs are a first-line substitute for patients who cannot tolerate ACE inhibitors due to cough.

Adverse Effects:
- Hyperkalemia
- Hypotension
- ⚠️ Teratogenic: Contraindicated in pregnancy.

Pathway Bookends - Renin & Aldosterone Blockers

Direct Renin Inhibitor: Aliskiren
- Mechanism: Directly blocks renin, preventing the conversion of angiotensinogen to angiotensin I.
- Side Effects: Can cause hyperkalemia, hypotension, and acute kidney injury.
- Contraindications: Similar to ACE inhibitors and ARBs, especially pregnancy.
Aldosterone Antagonists
- Drugs: Spironolactone, Eplerenone.
- Mechanism: Compete with aldosterone for receptors in the distal convoluted tubule and collecting duct.
- Side Effects:
  - Hyperkalemia is a major risk.
  - Spironolactone: Can cause gynecomastia, impotence, and menstrual irregularities due to its antiandrogen effects.
  - Eplerenone: More selective for the mineralocorticoid receptor, with fewer antiandrogen side effects.

⭐ Spironolactone is particularly useful in managing ascites secondary to liver cirrhosis and in heart failure to improve survival.

RAAS pathway and pharmacological inhibition

Comparative Side Effects - The RAAS Clash

Side Effect	ACE Inhibitors (-pril)	ARBs (-sartan)	Aldosterone Antagonists
Cough	Yes (↑ Bradykinin)	No	No
Angioedema	Yes (↑ Bradykinin)	Lower Risk	No
Hyperkalemia	Yes	Yes	Yes (significant)
Teratogenicity	Yes	Yes	No
Gynecomastia	No	No	Yes (Spironolactone)

High‑Yield Points - ⚡ Biggest Takeaways

ACE inhibitors (-prils) prevent Angiotensin I conversion, causing dry cough & angioedema due to increased bradykinin.

ARBs (-sartans) block AT1 receptors directly, making them a suitable alternative for patients with ACE inhibitor-induced cough.

Aliskiren is a direct renin inhibitor, blocking the rate-limiting step of the RAAS pathway.

Aldosterone antagonists (e.g., spironolactone) are K+-sparing diuretics; major side effects include hyperkalemia and gynecomastia.

ACE inhibitors and ARBs are potent teratogens and are absolutely contraindicated in pregnancy.

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