Furosemide Pharmacology

Furosemide is a loop diuretic most commonly recognized by its brand name, Lasix. Pharmacologically, it acts by inhibiting the reabsorption of Na/Cl in the thick ascending limb of the loop of Henle. The inhibition of electrolyte reabsorption results in a loss of fluids causing diuresis. Since it has a diuretic effect, it is commonly used to treat congestive heart failure, general edema, ascites due to cirrhosis, and to aid in fluid elimination. 

If a patient has a new prescription of furosemide, it’s important to look for drug-induced causes of edema. Common causes of drug-induced edema are the calcium-channel blockers (amlodipine, nifedipine, diltiazem, verapamil), some anticonvulsants (pregabalin, gabapentin), pioglitazone, and NSAIDs. In times when oral furosemide is not readily available, 40 mg of furosemide is equivalent to roughly 20 mg torsemide, or 1 mg bumetanide. If IV furosemide is desired and the patient is already on an oral formulation, generally, the approximate equivalent IV dose is 50% of the oral dose. Dosing is approximate and based on urine output. Serum creatinine, electrolytes, weight, blood pressure, should generally be monitored due to the pharmacology of furosemide.

Common adverse drug reactions of furosemide associated with its pharmacology are hypokalemia, and its symptoms such as cramping and uncommonly cardiac problems, hypotension, hyponatremia, dehydration, decrease in renal perfusion, uric acid elevation, transient increases in glucose, angioedema and hypersensitivity reactions, ototoxicity, and nephrotoxicity. Drugs that can exacerbate furosemide’s adverse drug reaction profile are ARBs, ACEis, NSAIDs, aminoglycoside, SGLT2 inhibitors, PDE5 inhibitors, a1a blockers. Electrolyte supplementation may be provided to patients on furosemide to counteract any imbalances that may precipitate. 

In cases of overdose, the common symptoms are exacerbations of the adverse drug reactions and mechanism, dehydration, electrolyte imbalances, hypochloremic alkalosis, reduction in blood volume, and hypotension. Supportive treatment of symptoms is necessary to treat furosemide overdoses, fluid and electrolyte replacement is a rational method of treatment. Serum electrolytes, CO2 level, and blood pressure should be monitored in overdose situations. Hemodialysis does not accelerate furosemide elimination.

Show notes provided by Chong Yol G Kim, PharmD Student

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Resources

  1. Information taken directly from the podcast episode
  2. Dosing goals diuresis end of paragraph 2: 2013 ACCF/AHA guideline for the management of HF https://doi.org/10.1161/CIR.0b013e31829e8776
  3. Last paragraph on overdose, furosemide FDA label

Simvastatin Pharmacology

Simvastatin use has declined over time due to more potent statins being available and due to numerous drug interactions.

Grapefruit juice can inhibit CYP3A4 which will increase the concentrations of simvastatin.

Genetic variations in SLCO1B1 can lead to patients being more susceptible to simvastatin toxicity.

Simvastatin is a lipophilic statin. I discuss why this is important and how it might impact clinical decisions.

I discuss important drug interactions on the podcast, be sure to check out my latest project which is a 200+ page book on managing drug interactions in primary care.

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Colestipol Pharmacology

Colestipol is a bile acid sequestrant that can be used in the management of hyperlipidemia.

By binding bile acid in the gut, colestipol can lower LDL that is bound to bile acid by eliminating it through the feces.

Numerous drug interactions existed as colestipol can bind many drugs. This is a downside to its use and why it isn’t a preferred hyperlipidemia agent.

In patients with elevated triglycerides, colestipol should be avoided.

I discuss important drug interactions on the podcast, be sure to check out my latest project which is a 200+ page book on managing drug interactions in primary care.

Metolazone Pharmacology

Metolazone (Zaroxolyn) is a thiazide-like diuretic. It promotes the loss of water and sodium through the kidney.

The most common indication I see metolazone used for is for additional fluid loss in heart failure.

Potassium must be monitored as it can cause significant hypokalemia which is exacerbated when metolazone is used in combination with loop diuretics.

Hyperuricemia is a potential adverse effect with metolazone; this is critical to monitor for in patients at risk for gout attacks.

I discuss important drug interactions on the podcast, be sure to check out my latest project which is a 200+ page book on managing drug interactions in primary care.

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Diltiazem Pharmacology

Diltiazem is a non-dihydropyridine calcium channel blocker that can be used in atrial fibrillation as well as hypertension.

One big downside to diltiazem is that it does have a few drug interactions via CYP3A4.

Aripiprazole, apixaban, and certain statins are all examples of medication that can have concentrations increased by adding diltiazem to a patient’s regimen.

Diltiazem works a little differently from dihydropyridine calcium channel blockers (like amlodipine) as it works on the heart AND the vessels.

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Metoprolol Pharmacology

Metoprolol is a beta-blocker commonly used in the management of hypertension, heart failure, and atrial fibrillation.

There is an extended release dosage form and immediate release dosage form with metoprolol. The advantage of the extended release product is that it doesn’t require as frequent dosing.

Metoprolol is selective for beta-1 receptors. It is less likely to interact with asthma medications.

CYP2D6 plays an important role in breaking down metoprolol. Alterations in this enzyme’s activity can alter concentrations of the drug.

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Cilostazol Pharmacology

Cilostazol has antiplatelet and vasodilatory effects. Because of this, it can manage symptoms of intermittent claudication.

GI upset, headache, and edema are common adverse effects associated with the use of cilostazol.

Cilostazol is recommended to be given on an empty stomach.

In patients with heart failure, cilostazol use is contraindicated.

CYP3A4 interactions are prevalent with cilostazol. Inhibitors of CYP3A4 can increase the concentrations of cilostazol.

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Prasugrel Pharmacology

Prasugrel is a P2Y12 inhibitor that is used in the setting of ACS.

Be aware of patients who may be taking over the counter medications that can increase their bleed risk while taking prasugrel.

Prasugrel is on the Beers list and in general, should be avoided in most situations for patients who are 75 years of age or older.

Morphine has the potential to impact antiplatelet agents like prasugrel and make them less effective. Be sure this is clinically considered prior to using morphine with prasugrel.

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Clopidogrel Pharmacology

Clopidogrel is an antiplatelet agent that is often used in combination with aspirin to help reduce the risk of an MI.

The risk of bleed is a high priority with the use of clopidogrel. Patients must be monitored for signs and symptoms of bleeding and bruising.

Clopidogrel is a prodrug that is converted to its active metabolite by CYP2C19.

Fluconazole can inhibit CYP2C19 which may reduce the effectiveness of clopidogrel.

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Cholestyramine Pharmacology

On this episode, I discuss the pharmacology of cholestyramine.

Cholestyramine was originally developed as an agent to manage cholesterol, but has fallen out of favor for some of the more effective agents like statins.

Cholestyramine is notorious for binding drug interactions. It can reduce concentrations of drugs like amiodarone, digoxin, oral contraceptives, immunosuppressive and many more!

In patients with chronic diarrhea, cholestyramine is occasionally used off label to help manage symptoms because it tends to have constipating effects.

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