A 34-year-old male is being seen by his primary care physician for normal follow-up.  The patient’s PMH includes asthma, chronic kidney disease, and depression. The patient’s home medication list includes albuterol 90 mcg inhale 2 puffs PO Q4-6H PRN for shortness of breath and escitalopram 10 mg PO QD. Currently, the blood pressure after the best of two readings is 145/94 mm Hg. Upon second look at his last visit, it was also elevated at 148/92 mm Hg six months ago. The patient maintains a healthy diet and exercises at least 150 minutes of moderate intensity, aerobic exercise throughout the week. The decision is made to diagnose our patient with hypertension and medication therapy will be initiated.  Which of the following are true regarding the pharmacology of potential anti-hypertensive therapy agents for our patient? Select all that apply.  

A. Diovan may cause hyperkalemia due to decreased production of aldosterone, therefore increasing the retention of potassium. 

B. Hygroton’s mechanism of action is blocking the Na/Cl transporter in the renal collecting tubule. 

C. Norvasc is a generally well-tolerated medication with side effects of peripheral edema and headache. 

D. Lotensin has renal protective effects in many patients through vasodilation of the efferent glomerular arteriole. 

E. Coreg would be indicated as a first-line anti-hypertensive therapy for our patient due to its selective effects on beta-1 receptors on the myocardium. 

Answers with rationale: A, C, and D 

Brand/Generics covered: Diovan (Losartan), Hygroton (Chlorthalidone), Norvasc (Amlodipine), Lotensin (Benazepril), and Coreg (Carvedilol) 

Explanation: 

Hypertension is one of the most common disease states and can be contributed to multiple risk factors. Diets high in sodium, physical inactivity, co-morbid conditions (CKD, dyslipidemia, diabetes), age, socioeconomic status, and family history are risk factors for developing hypertension. Secondary hypertension is rare but can be caused by such things as obstructive sleep apnea (OSA), hyperaldosteronism, and drugs such as sympathomimetics (e.g. pseudoephedrine).  Blood pressure is determined through cardiac output (the volume of blood pumped by the heart) and total peripheral resistance (resistance in the blood flow in the arteries). When the heart increases cardiac output and/or the arteries vessels narrows, the result would be an increase in blood pressure.  

The body has its own mechanism in regulating blood pressure. The system that regulates blood pressure is the renin-angiotensin-aldosterone system. Renin is an enzyme that cleaves angiotensinogen to angiotensin I. Angiotensin I is converted to Angiotensin II by angiotensin converting enzyme (ACE). Angiotensin II plays a vital role in vasoconstriction of the arterioles and stimulating the release of aldosterone (key in regulating electrolyte balance and water retention). Some medications that lower blood pressure work on the renin-angiotensin-aldosterone system and therefore water/electrolyte balance. 

According to the American College of Cardiology and American Heart Association 2017 guidelines for the treatment of high blood pressure in adults, the first-line class of therapeutics for the treatment of hypertension are angiotensin converting enzyme inhibitors (ACEi), Angiotensin receptor blockers (ARBs), thiazide diuretics, and calcium channel blockers (CCBs). The blood pressure goal for hypertensive patients is less than 130/80 mm Hg. 

Answer choice A is correct as the mechanism of action of ARBs is reducing the production of aldosterone by blocking the activation of type 1 angiotensin II (AT1) receptors. Aldosterone is a hormone that reabsorbs sodium in exchange for potassium. Inhibiting aldosterone production leads to an increase reabsorption of potassium in the blood, thus causing hyperkalemia. 

Answer choice B is incorrect as the mechanism of action of thiazide diuretics is the blocking of Na/Cl receptors in the distal convoluted tubules in the kidneys. Aldosterone antagonists, such as spironolactone,  work in the renal collecting tubule, also knowns as the collecting ducts, exchanging sodium for potassium. 

Answer choice C is correct as Norvasc (amlodipine) is a dihydropyridine calcium channel blocker. Peripheral edema and headache are the side effects of note with this drug class due to peripheral vasodilation. Non-dihydropyridines CCBs (Verapamil and Diltiazem) are not considered first-line agents due to lack of outcome data showing decreased morbidity and mortality in uncomplicated hypertension. 

Answer choice D is correct as ACEi such as Lotensin (benazepril) reduces the efferent glomerular arteriole pressure through vasodilation. The reduction of pressure thus is renal protective by decrease the strain on the efferent glomerular arteriole. Many patients with albuminuria (high amounts of a protein called albumin) will benefit from starting an ACEi or an ARB due to this effect. It is important to note however that in certain patients, ACEi or ARB can cause acute kidney injury and are additionally contraindicated in patients with bilateral renal artery stenosis. 

Answer choice E is incorrect as beta blockers, particularly non-selective beta blockers such as Coreg (carvedilol), are contraindicated in patients with asthma due to beta-2 receptor blockade causing vasoconstriction of bronchioles. This leads to narrowing of the airways which can exacerbate the patient’s asthma and can be fatal. Selective beta-1 blockers such as Lopressor (Metoprolol tartrate) and Tenormin (Atenolol) can be used in asthma patients as they do not work on beta-2 receptors at low-moderate doses (can be nonselective in higher doses). Beta blockers are also not considered first-line agents for the initial treatment of hypertension but can used as add-on agents in certain concomitant, compelling indications such as post-MI or heart failure (specific beta blockers such as metoprolol succinate, carvedilol, or bisoprolol).  

Managing hypertension is essential to a patient’s health as chronic hypertension leads to morbid conditions such as cardiovascular disease. The role of the pharmacist is to know which medications are indicated for the patient and what factors are considered when choosing one medication over another. The importance of understanding the pharmacology of medications is vital when giving recommendations to the healthcare team as this knowledge often translates well to adverse effects and patient counseling pearls. 

References: 

ACC/AHA 2017 Guidelines 

Basic & Clinical Pharmacology Ch. 11 & 12 (Access Pharmacy) 

NAPLEX Exam Competencies Covered: 

2.1 – Pharmacology, mechanism of action, or therapeutic class 

2.2 – Commercial availability; prescription or non-prescription status; brand, generic, or biosimilar names; physical descriptions; or how supplied 

3.7 – Adverse drug effects, toxicology, or overdose 

3.11 – Evidence-based practice

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