Gemfibrozil Pharmacology

On this episode, I discuss gemfibrozil pharmacology, adverse effects, and important drug interactions.

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Propranolol Pharmacology

On this episode, I discuss propranolol pharmacology, adverse reactions, and important drug interactions you should know.

Propranolol (Inderal) is a non-selective beta-blocker. There are many indications for it including hypertension, tachycardia, atrial fibrillation, post-MI, chronic stable angina, essential tremors, migraine prophylaxis, esophageal varices, performance anxiety disorder, lithium-induced tremor, psychotic induced akathisia, and thyroid storm.

Propranolol blocks beta-1 receptors that are commonly referred to as the cardiac receptors and beta-2 receptors that are in the lungs. Albuterol is a beta-2 agonist meaning that propranolol can block its effects. This may lead to bronchospasms and worsening of respiratory conditions. This is one of the major issues when using a non-selective beta-blocker vs a selective one.

Other adverse effects include a drop in blood pressure and pulse. Fatigue is also seen in many geriatric patients so it is important to be titrating them up slowly. If you notice patients increasing caffeine intake, starting a stimulant, or experiencing new depression symptoms that can be a sign of fatigue. Sexual dysfunction has also been seen in patients taking propranolol. Propranolol may mask symptoms of hypoglycemia. Closely monitor patients that are taking insulin and/or sulfonylureas. Abrupt discontinuation can increase the risk for acute coronary syndromes, especially if the patient is already at risk. Make sure that the medication is taken consistently and there aren’t periods of multiple missed doses.

Propranolol comes in multiple dosage forms that have been mixed up. When dispensing or administering take extra caution that the medication is correct.

Propranolol is a weak CYP1A2 inhibitor that could increase concentrations of tizanidine or theophylline. Propranolol also gets broken down by CYP1A2. Medications that inhibit this enzyme can increase the concentration of propranolol. Examples of these are ciprofloxacin and fluvoxamine. Inducers of CYP1A2 can reduce concentrations. These are rifampin, carbamazepine, and phenobarbital. A unique CYP1A2 inducer is smoking tobacco. Medications can cause additive effects when it comes to blood pressure and pulse. Be careful with any blood pressure-lowering medications including antihypertensives, PDE5 inhibitors (sildenafil), and Parkinson’s medications (Sinemet). Drugs that can lower pulse include centrally acting alpha 2 antagonists (clonidine) and acetylcholinesterase inhibitors (donepezil, rivastigmine).

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Hydrochlorothiazide Pharmacology

On this episode, I breakdown the pharmacology of hydrochlorothiazide including adverse effects, drug interactions, and other clinical pearls.

Hydrochlorothiazide has common brand names of Microzide, Hydrodiuril, and its common abbreviation is HCTZ. Extra caution should be taken with “HCTZ”; it may be mistaken for other abbreviations. Hydrochlorothiazide works pharmacologically by blocking the reabsorption of sodium in the distal tubule of the kidney. The result of the pharmacology of hydrochlorothiazide is increased water, sodium, and potassium excretion. Due to hydrochlorothiazide’s mechanism of action, it makes it advantageous when used for blood pressure, edema, and heart failure in addition to loop diuretics.

Hydrochlorothiazide’s adverse reactions are due to its pharmacology. Frequent urination should occur so, dosing hydrochlorothiazide at night should be avoided. Loss of electrolytes should also happen, and the risk for hypokalemia, hyponatremia, and hypomagnesemia increases. Other adverse reactions include the increased risk of dehydration, increased uric acid concentrations, and hypercalcemia. The risk for hypercalcemia is not as concerning in lower doses. There is a potential for a sulfonamide allergy. If the patient has had an anaphylactic reaction with a sulfonamide-containing medication, hydrochlorothiazide may want to be avoided, or at least a risk/benefit assessment should be done. Another potential adverse reaction is an increase in blood sugar, but that is not typically concerning at lower doses. Electrolytes, as well as creatinine clearance, should be monitored to make sure kidney function, and electrolyte levels remain stable. 

Drug-drug interactions that can occur with hydrochlorothiazide are additive effects that may happen when taken with other medications. The risk for an unsafe drop in blood pressure may increase if it is taken with PDE inhibitors, Sinemet, or SGLT2 inhibitors. Hydrochlorothiazide should be avoided with Lithium, the risk for toxicity increases when the two are taken concurrently due to Lithium concentrations being increased. The risk of an AKI increases if it’s taken with NSAIDs, ACE inhibitors, or ARBs; increased monitoring is warranted. Topiramate may increase the risk for hypokalemia, while vitamin D and calcium supplements may increase the risk for hypercalcemia. Hyponatremia may be more likely to occur if it’s taken with SSRIs, carbamazepine, or oxcarbazepine. Hydrochlorothiazide may blunt the effect of allopurinol if it’s used for gout. Since blood sugar levels may be increased, hyperglycemia can occur, but it’s typically not clinically significant. 

In cases of intolerability, or overdoses, the manifestations are extensions of hydrochlorothiazide’s adverse effect profile. Most commonly, electrolyte depletion and dehydration will occur.

Show notes provided by Chong Yol G Kim, PharmD Student.

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

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Torsemide Pharmacology

On this episode, I discuss torsemide pharmacology, adverse effects, drug interactions and pharmacokinetics. Torsemide is commonly known as Demadex. It is a loop diuretic, and like other loop diuretics, it acts by inhibiting the reabsorption of Na+ and Cl- in the ascending loop of Henle. What results is a decrease in the reabsorption of water, causing a loss of electrolytes as well as water. The pharmacology of torsemide makes it useful in cases of heart failure, cirrhosis, or hypertension. Torsemide, and other loop diuretics, can also be a part of the prescribing cascade. For example, pregabalin and gabapentin, along with amlodipine and pioglitazone can cause or worsen edema, resulting in a new prescription of torsemide. 

Torsemide is typically initially dosed between 5-20 mg, depending on the use. If the indication isn’t very severe it might be dosed lower, between 5-10 mg, or higher if it’s a more severe indication starting at 20 mg and titrated up. It should be cautioned in patients with a history of dehydration and renal failure, and it is contraindicated in cases of anuria, hepatic coma, and hypersensitivity. It may sometimes be necessary to be converted to furosemide or bumetanide, or torsemide from the other two. The conversion is, 20 mg of torsemide is equivalent to 40 mg of oral furosemide, which is equivalent to 1 mg bumetanide. 

The adverse effects go hand-in-hand with its pharmacology, these include dehydration, increased urination, increased risk of acute renal failure, electrolyte imbalances, and ototoxicity. Also related to the pharmacology of torsemide, electrolytes, renal function, as well as blood pressure should be monitored. Kinetics may vary depending on what loop diuretic it is. It is generally more consistent with furosemide, but torsemide can sometimes have less variability as well as a longer half-life in comparison.

For drug-drug interactions, additive effects are the main concern. When combined with Sinemet or PDE inhibitors, there may be an unsafe drop in blood pressure. If it’s combined with SGLT2 inhibitors there can be increased diuresis. There can also be an increased risk of renal issues when taken with an NSAID, ACE inhibitors, or ARBs; if an NSAID is necessary, the dose or duration should be limited, and the kidney function should be monitored. The risk for ototoxicity increases when taken with aminoglycosides, and drugs that can cause edema should be monitored.

The main signs and symptoms of intolerance, or overdose, are extensions of its adverse effects and are related to its pharmacology. Commonly, it will be dehydration, hypotension, or symptoms of either. When treating overdoses, symptomatic relief is necessary; it is commonly achieved by fluid and electrolyte replacement.

Show notes provided by Chong Yol G Kim, PharmD Student.

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

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Sacubitril Valsartan Pharmacology

On this episode, I breakdown the sacubitril valsartan pharmacology.

The drug for this week is the combination drug sacubitril/valsartan, also known as Entresto. Entresto has a novel dual mechanism of action to treat HFrEF. Sacubitril, currently, is the only FDA-approved medication that is a neprilysin inhibitor. For background, neprilysin is an enzyme that breaks down natriuretic peptides. The inhibition of neprilysin results in an increase in natriuretic peptides, which causes vasodilation, fluid loss, and a decrease in blood pressure. Valsartan is an angiotensin II receptor blocker; it prevents angiotensin II from binding to AT1 to reduce blood pressure by reducing vasoconstriction, synthesis, and release of aldosterone and ADH, cardiac remodeling, and renal reabsorption of sodium. The unique pharmacology of Entresto makes it advantageous to use in HFrEF and is even now one of the preferred agents.

Common adverse reactions that occur when taking Entresto are related to its dual mechanism pharmacology. The most common adverse reactions of Entresto are hyperkalemia, angioedema, hypotension, and renal impairment. Entresto is contraindicated in pregnancy due to fetotoxicity; it requires a 36 hour washout period when transitioning from an ACE inhibitor due to the increased risk of angioedema. 

Entresto is initially dosed at 24/26 mg twice a day if the patient is on a low dose ACE inhibitor/ARB, or if the patient has not taken anything. If a patient is taking over 10 mg of enalapril equivalents a day or 160 mg of valsartan equivalents a day, then the preferred initial dose is 49/51 mg twice a day. Regardless of initial dosing, the target dose is 97/103 mg twice a day. In cases of severe renal impairment, or moderate hepatic impairment, the initial dosing should start at 24/26 twice a day; titration remains the same. 

The pharmacology of Entresto leaves room for many potential drug-drug interactions. There’s a risk of duplicate therapy with other ACE inhibitors or ARBs. An exacerbation of adverse drug reactions can also occur when taking medications that can lower blood pressure, like Sinemet, or medications that can increase the risk for hyperkalemia, like trimethoprim, and spironolactone, or medications that can increase the risk of renal impairment, like NSAIDs. Entresto has also been shown to increase the risk of lithium toxicity.

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

Show notes provided by Chong Yol G Kim, PharmD Student.

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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

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

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Flippin’ Pharmacology Flash Cards

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Meded101 Guide to Nursing Pharmacology (Amazon Highly Rated)

Guide to Drug Food Interactions (Amazon Best Seller)

Drug Interactions In Primary Care (Amazing Resource for Practicing Clinicians)

Perils of Polypharmacy (Great Resource for Those Who Work in Geriatrics)

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.

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

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.

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

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.

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