Grapefruit Juice Interactions

On this episode of the podcast, I discuss my approach and strategies to handle grapefruit juice interactions.

Grapefruit juice causes drug interactions by inhibiting the CYP enzyme system. More specifically, it inhibits CYP3A4 which is responsible for the breakdown of many medications.

Quantity is always an important consideration when assessing grapefruit juice interactions. The more that is taken, typically, the more drug concentrations will be affected.

It is important to assess the use of grapefruit juice when your patient has a history of cardiovascular disease, cardiac conditions, pain, mental health disease, or gout as some medications used to treat these diseases can interact with grapefruit juice.

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Pantoprazole Pharmacology

On this episode, I cover pantoprazole pharmacology, adverse effects, and drug interactions.

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Rosuvastatin Pharmacology

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

Rosuvastatin is a hydrophilic statin which differs from some of the most commonly used statins like simvastatin and atorvastatin.

Rosuvastatin is minimally affected by CYP3A4 drug interactions so that is a small potential advantage over simvastatin and atorvastatin.

At dosages of 20-40 mg, rosuvastatin is considered a high intensity statin and can bring down LDL by over 50%.

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Atorvastatin Pharmacology

On this episode, I discuss atorvastatin pharmacology, adverse effects, monitoring parameters, and drug interactions.

Atorvastatin (Lipitor) is an HMG-CoA reductase inhibitor, the rate-limiting step in the production of cholesterol. It is used to prevent atherosclerotic cardiovascular diseases by decreasing cholesterol.

Atorvastatin is more lipophilic in comparison to other statins such as rosuvastatin. If a patient does not tolerate a statin, switching from a lipophilic to a hydrophilic or vice versa may decrease the chances of those side effects reoccurring.

It can be a high-intensity statin depending on the dose. 10-20mg is considered moderate and 40-80mg is classified as high intensity. Not all statins can reach high-intensity doses, which is why atorvastatin is so commonly used.            

The FDA as of July 2021, has requested to remove the contraindication of pregnancy from the prescribing information. Here’s more information on that specific change and why it was requested. I’d encourage you to read it. 

Atorvastatin is commonly found to have adherence issues so it should be taken whenever it is going to be best remembered by the patient.

Common adverse effects include myopathy, muscle pain, and soreness. Many elderly patients can be overlooked when they experience aches and pains, so it is important to take their medications into consideration. There are rare risks of liver injury and rhabdomyolysis. CPK and LFTs do not need to be regularly monitored if no symptoms are present.  

Remind patients that their cholesterol will not be lowered right away. They will usually have their levels rechecked in 3-6 months.

Drugs that increase rhabdomyolysis risk when used concurrently include fibrates, red yeast rice, niacin, daptomycin. Monitor these patients closely for symptoms of muscle pain. Can also monitor CPK and decrease the dose of the statin in these patients. 3A4 interactions can increase the concentration of statins. These include clarithromycin, grapefruit juice, amiodarone, amantadine, and verapamil. 3A4 inducers can decrease the concentration of statins. These include St. John’s Wort and carbamazepine. 

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Gemfibrozil Pharmacology

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

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Trospium Pharmacology

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

Trospium chloride (Sanctura) is a bladder antimuscarinic or anticholinergic. It blocks the action of acetylcholine in bladder smooth muscle. It is used for urinary frequency and overactive bladder. The immediate-release formulation is taken twice a day. There is an extended-release version that is more expensive.

As its classification suggests it is going to have anticholinergic effects that include dry eyes, dry mouth, constipation, urinary retention, GI tract slowing down, CNS sedation, and increased risk of falls. Compared to older bladder anticholinergics such as oxybutynin or tolterodine there is less CNS penetration. Hopefully, this will cause the patient to experience fewer CNS side effects. A downside to this being a newer medication is that it costs more.

Trospium is on the BEERS list. Look for medications started after the trospium that indicate anticholinergic side effects such as saliva substitutes, an increase in BPH medications, artificial tears, or constipation medications.

It should be administered on an empty stomach as food can block absorption. If the patient is currently taking it with food and seeing results there is no need to change how they are taking it.

Trospium is not metabolized by CYP enzymes minimizing drug interactions. Most interactions occur because of additive effects. Avoid using it with other medications on the BEERS list, especially other anticholinergic medications. Be cautious using other medications with sedative effects and CNS depression (benzodiazepines, sleep medications, opioids, alcohol) as they may have additive effects.

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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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Quetiapine Pharmacology

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

Quetiapine (Seroquel) is a medication seen a fair amount particularly in the geriatric population where there is psychosis associated with dementia. It is classified as an antipsychotic. Mechanistically it’s going to block dopamine receptors, specifically D2. It also has some serotonin receptor blockade antagonism. It does have other activity as well from a mechanism of action standpoint. There is alpha-blocking activity potentially as well as an antihistamine/anticholinergic type of activity. Uses of this medication are schizophrenia, bipolar disorder with associated mania, miscellaneous psychotic disorders, and Parkinson’s type disease with psychosis. Off-label you may see it used for OCD, or augmentation for PTSD and depression.

There is a boxed warning of increased risk of mortality in elderly/dementia patients. As a class, antipsychotics have extrapyramidal symptoms, metabolic syndrome, anticholinergic activity, QTC prolongation, sexual dysfunction, hyperprolactinemia, neuroleptic malignant syndrome, sedation, fall risk, and potentially a drop in blood pressure as well. With quetiapine it is important to recognize that antipsychotics can have varying degrees of how much these adverse effects happen and a lot of them are dose-dependent.

There are three important points in comparison to other antipsychotics. Quetiapine is not that great as far as metabolic syndrome risk goes. It’s in the middle of the other antipsychotics. Its extrapyramidal symptoms are better than most, which is why it’s used so often in Parkinson’s. Quetiapine tends to be more sedating than other antipsychotics. This can be helpful when patients are having psychosis worse in the evening or at night.

Metabolic syndrome is something to worry about more in younger patients. The long-term risk of diabetes and hyperlipidemia is going to be a lot higher for them than an 80-year-old using a low dose for dementia-related aggression.

3A4 is a pathway of breakdown for quetiapine drug interactions. With larger food intakes absorption can increase about 15% to 25% and that’s in the area under the curve. This is not something to be very concerned about unless patients change the way they take it. 

Quetiapine’s drug interactions are mostly additive effects. Watch out for other sedative drugs such as alcohol, opioids, and benzodiazepines. The same goes for drugs causing QT prolongation. Quetiapine has alpha-blocking activity and an added effect on patients with borderline low blood pressure or at risk for falls. It also mechanistically has a potential antihistamine burden that can play a role in adding on to anticholinergic effects. Then lastly it is metabolized partly by CYP3A4 so there is some potential there for drug interactions. Classic enzyme inducers are St. John’s Wort and carbamazepine that would lower the concentration of quetiapine.

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Phenazopyridine Pharmacology

On this episode, I discuss phenazopyridine pharmacology, adverse effects, and potential drug interactions.

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Fluvoxamine Pharmacology

On this episode, I discuss fluvoxamine pharmacology, adverse effects, and most importantly, drug interactions.

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