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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  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

Hydroxyzine Pharmacology

Background: – Hydroxyzine Pharmacology Hydroxyzine, common brands Atarax, and Vistaril, is a first-generation antihistamine. It is a part of the piperazine drug class[1], sharing structural similarities to other antihistamines like Cetirizine, but also drugs of other classes like ranolazine, buspirone, clozapine. Being an H1 blocker, hydroxyzine is commonly used for itching, anxiety, analgesia, urticaria, and insomnia. The main adverse drug reactions associated with hydroxyzine are the anticholinergic effects common with most antihistamines, dry mouth, headache, urinary retention, QTC prolongation, drowsiness[2].

Interactions: Due to hydroxyzine’s pharmacology and mechanism of action, it can exacerbate or worsen gastroparesis by decreasing smooth muscle contraction in the GI tract, and has similar effects on benign prostatic hyperplasia by worsening urinary retention. Hydroxyzine is metabolized into its active drug, cetirizine, by CYP3A4 and CYP3A5[3]. As such, hydroxyzine’s efficacy can be increased with concomitant use of rifampin, carbamazepine, St. John’s Wort; and its efficacy can be decreased with concomitant use of certain azole antifungals, verapamil or diltiazem, or grapefruit juice. The anticholinergic effects can also be compounded when taken with other anticholinergic drugs and can decrease the efficacy of certain dementia medications, like clonidine. Although uncommon, the risk of QTC prolongation, and Torsades de Pointes, can be increased when taken with potassium channel blocking agents like amiodarone or sotalol, or other agents like certain antibiotics and antipsychotics[4][5].

PK/PD & toxicity: Hydroxyzine has an onset of action between 15-60 minutes and a duration of action between 4-6 hours[3]. The half-life of hydroxyzine varies with age. On average, it is 7.1 hours in children, 20 hours in adults[6], and 29 hours in the elderly, and should be dosed appropriately[7]. Its volume of distribution is 16±3 L/kg with high concentrations found in the skin than in plasma[3]. Its clearance is 31.1±11.1 mL/min/kg in children and 9.8±3.3 mL/min/kg in adults. The active drug of hydroxyzine is excreted around 70% unchanged in the urine[6]. Overdoses can be characterized by sedation, but can also cause nausea, vomiting, and seizures. General supportive care of the symptoms is needed for treatment. Vomiting should be induced if it has not occurred. Immediate gastric lavage is also recommended[8].

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Show notes written by Chong Yol G Kim, PharmD Student

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References

[1] Fifer EK. Drugs Used to Treat Ocular and Nasal Congestion Disorders. In: Roche VF, Zito SW, Lemke TL, Williams DA. Eds. Foye’s Principles of Medicinal Chemistry 8e. Lippincott Williams & Wilkins; Accessed May 15, 2021.

[2] Katzung BG. Histamine, Serotonin, & the Ergot Alkaloids. In: Katzung BG, Vanderah TW. eds. Basic & Clinical Pharmacology, 15e. McGraw-Hill; Accessed May 15, 2021.

[3] Altamura AC, Moliterno D, Paletta S, Maffini M, Mauri MC, Bareggi S: Understanding the pharmacokinetics of anxiolytic drugs. Expert Opin Drug Metab Toxicol. 2013 Apr;9(4):423-40. doi: 10.1517/17425255.2013.759209. Epub 2013 Jan 21.

[4] Schlit AF, Delaunois A, Colomar A, Claudio B, Cariolato L, Boev R, Valentin JP, Peters C, Sloan VS, Bentz JWG: Risk of QT prolongation and torsade de pointes associated with exposure to hydroxyzine: re-evaluation of an established drug. Pharmacol Res Perspect. 2017 Apr 21;5(3):e00309. doi: 10.1002/prp2.309. eCollection 2017 Jun.

[5] Nachimuthu S, Assar MD, Schussler JM. Drug-induced QT interval prolongation: mechanisms and clinical management. Ther Adv Drug Saf. 2012;3(5):241-253. doi:10.1177/2042098612454283

[6] Paton DM, Webster DR: Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines). Clin Pharmacokinet. 1985 Nov-Dec;10(6):477-97.

[7] Simons KJ, Watson WT, Chen XY, Simons FE: Pharmacokinetic and pharmacodynamic studies of the H1-receptor antagonist hydroxyzine in the elderly. Clin Pharmacol Ther. 1989 Jan;45(1):9-14. doi: 10.1038/clpt.1989.2.

[8] FDA Approved Drug Products: Vistaril (hydroxyzine pamoate)

Vitamin B12 Pharmacology

On this episode, I cover clinical tips and practice pearls surrounding vitamin B12 pharmacology.

Vitamin B12 deficiency plays a critical role in the development of macrocytic anemia.

There are medications that you have to be aware that can deplete vitamin B12. Metformin, colchicine, and PPIs are some common examples.

A lack of intrinsic factor can lead to B12 deficiency. Intrinsic factor is necessary for adequate GI absorption of vitamin B12.

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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Ketamine Pharmacology

On this episode, I discuss ketamine pharmacology.

Ketamine is primarily broken down by CYP2B6 which fortunately does not have a lot of common medications that can interfere with its action.

Ketamine can cause psychiatric type adverse effects such as hallucinations, nightmares, and vivid dreams.

At lower to moderate dosages, ketamine does have some mild sympathetic activity which can raise blood pressure and heart rate.

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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Topiramate Pharmacology

On this episode of the Real Life Pharmacology Podcast, I cover topiramate pharmacology.

Topiramate is indicated for migraine prevention, seizures, and weight loss which are the most common uses that I see this medication used for.

Topiramate has carbonic anhydrase activity, so rarely, use of this drug may induce metabolic acidosis.

By far, the most common patient complaint I get with the use of topiramate is that it causes cognitive slowing or impairment.

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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Colchicine Pharmacology

On this episode I discuss colchicine pharmacology, adverse effects, drug interactions, and pharmacokinetics.

Colchicine ultimately works by reducing the activity of neutrophils that help contribute to pain and inflammation associated with gout.

Colchicine does have some drug interactions with medications and grapefruit juice via CYP3A4.

The most common dose limiting side effect of colchicine is diarrhea.

Colchicine can be used as a potential alternative to NSAIDs or corticosteroids in the management of a gout flare.

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Fexofenadine Pharmacology

Fexofenadine is a 2nd generation antihistamine that is primarily used for allergic rhinitis. I cover fexofenadine pharmacology on this podcast episode.

Fruit juices can actually impair the absorption of fexofenadine and increase the risk of treatment failure.

Fexofenadine is mildly anticholinergic but overall has low to no CNS penetration.

Because fexofenadine has low CNS penetration, the risk for sedation and dizziness is much lower than older antihistamines like diphenhydramine.

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.

Be sure to check out our free Top 200 study guide – a 31 page PDF that is yours for FREE!

Empagliflozin Pharmacology

On this episode I discuss empagliflozin pharmacology and how this medication lowers blood sugar.

Empagliflozin is associated with an increased risk of genitourinary tract infections.

Be aware that patients who are prone to hypotension, may have an increased risk of this issue with empagliflozin use.

Empagliflozin has cardiovascular and renal function benefits in addition to its blood sugar lowering effects.

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.

Be sure to check out our free Top 200 study guide – a 31 page PDF that is yours for FREE!

Rifaximin Pharmacology

On this episode, I discuss rifaximin pharmacology.

Rifaximin is most commonly used in hepatic encephalopathy and C. difficile infection.

Rifaximin systemic absorption is minimal so that is why it is primarily only used for GI conditions.

Drug interactions with rifaximin are fairly minimal compared to its cousin rifampin which has tons of drug interactions.

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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Naproxen Pharmacology

On this episode of the Real Life Pharmacology Podcast, I discuss naproxen pharmacology.

Naproxen can raise the concentrations of lithium and increase the risk for toxicity.

Compared to most other NSAIDs, naproxen tends to have a lower cardiovascular risk.

Naproxen can contribute to renal insufficiency, GI bleed risk, and CHF exacerbations.

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.

Be sure to check out our free Top 200 study guide – a 31 page PDF that is yours for FREE!