Real Life Pharmacology - Pharmacology Education for Health Care Professionals

Rivaroxaban is a factor 10a inhibitor that inhibits clot formation and thins the blood. Rivaroxaban needs to be monitored for bleed risk. Checking periodic CBC can help us assess if hemoglobin and hematocrit are remaining stable. Enzyme inducers like rifampin, St. John's Wort, and carbamazepine can reduce concentrations and increase the risk of treatment failure. NSAIDs and antiplatelet medications can significantly increase the risk of bleed with rivaroxaban. Rivaroxaban should not be used with dual P-glycoprotein and CYP3A4 inhibitors. Examples include ketoconazole, itraconazole, and ritonavir.

Valproate (valproic acid, Depakote) has numerous uses which includes migraines, seizures, and bipolar disorder. In a patient who is taking valproate, it is important to monitor for signs and symptoms of confusion as this drug can cause elevated ammonia levels. When switching between dosage forms of valproate, you must recognize that the bioavailability is not the same between each different dosage form. This could lead to toxicity or treatment failure. Valproic acid has a boxed warning for hepatotoxicity and liver function needs to be monitored. Valproic acid can increase lamotrigine levels which ultimately could lead to an increased risk of lamotrigine induced SJS.

On this episode I discuss the pharmacology of donepezil. Donepezil is an acetylcholinesterase inhibitor. In dementia, that is a deficiency in acetylcholine and donepezil helps preserve this neurotransmitter. Donepezil can cause weight loss, GI upset, and diarrhea. This is an important monitoring parameter in our dementia patients. There is the possibility for donepezil to cause bradycardia and insomnia. Keep an eye out for these adverse effects as they can and do happen in real practice. Anticholinergics are notorious for blunting the effects of donepezil. We must look out for drug interactions from older anticholinergics like diphenhydramine, amitriptyline, and hydroxyzine.

Linezolid is an antibiotic used for bacterial infection. It primarily works by inhibiting bacterial protein synthesis. Linezolid is primarily bacteriostatic against most bacteria which means that it inhibits the growth and doesn't necessarily kill the bacteria itself. Caution must be used with linezolid and serotonergic drugs as there is a risk for serotonin syndrome. Clinical risk/benefit analysis needs to be done. Linezolid overall has good coverage for VRE and MRSA. It is an option for MRSA pneumonia where daptomycin is not. Linezolid has both an oral and an IV option which allows for good continuity of inpatient and outpatient use.

On this episode, I cover pioglitazone pharmacology. The primary mechanism of action with pioglitazone is that it is an agonist at Peroxisome Proliferator Activated Receptor Gamma receptor. This improves insulin sensitivty in the periphery. Two common side effects exist with pioglitazone. This drug can cause weight gain and also contribute to edema. Pioglitazone has a boxed warning and is contraindicated in patients who have symptomatic heart failure. There are a few potential interactions with pioglitazone. Trimethoprim and gemfibrozil can inhibit the breakdown of pioglitazone. A couple of advantages of pioglitazone include that it is generic (inexpensive) and that it is dosed once daily.

On this episode I breakdown nitrofurantoin pharmacology. Nitrofurantoin is an antibiotic that is used in the treatment of UTI's. Nitrofurantoin has activity by creating reactive metabolites that can disrupt protein synthesis and ultimately kills the bacteria causing the infection. It is important to remember with nitrofurantoin, that in the setting of systemic infection and/or kidney involvement, the drug may not be very effective. Nitrofurantoin can potentially reduce the effectiveness of certain vaccines. Be sure to look this up prior to administration. Nitrofurantoin can cause pulmonary symptoms as well as neuropathy. This is very important to monitor for.

Hydralazine Pharmacology Hydralazine works as a direct vasodilator. It primarily works on the arterioles versus the venous system. Hydralazine can cause a unique adverse reaction. It can cause a Lupus type syndrome that can result in fever, myopathy and symptoms that mimic arthritis. I discuss drug interactions with hydralazine and how you need to be aware of certain medications that can have additive effects and also those that can oppose the effects of the drug. One of the downsides to using hydralazine is that patients don't like to take it as often as it requires. It is typically dosed three to four times per day. Orthostasis is a risk with any drug that reduces blood pressure and hydralazine is no different.

On this episode of the Real Life Pharmacology Podcast, I discuss aspirin pharmacology. The two most common adverse effects with aspirin are GI upset and increasing the risk for bleeding and bruising. A commonly asked test question about aspirin is whether it can be used in pediatrics and what risk we encounter if we use it. Another rare effect with aspirin is tinnitus which I discuss further on this episode. It is critical to pay attention to other medications that can thin the blood in a patient taking aspirin. Examples include anticoagulants like warfarin, apixaban, rivaroxaban; antiplatelets like clopidogrel or prasugrel; or NSAIDs.

Clonidine is classified as an antihypertensive. Clonidine pharmacology involves having agonist activity at central alpha 2 receptors. This leads to lower sympathetic outflow and a reduction in blood pressure. Clonidine has numerous reported uses in addition to its antihypertensive effect. It can potentially be used for ADHD, menopausal type symptoms, and opioid withdrawal. Clonidine has historically been on the Beers' list of drugs as it can cause some CNS side effects like sedation, dizziness, and rarely delirium. Clonidine is unique in the antihypertensive class as it does have a patch formulation. Because of the blood pressure lowering effect of clonidine, we have to be aware of patients who report dizziness. Monitoring is critical. Clonidine can also lower heart rate and contribute to dry mouth. Keep an eye out for drugs that can have a cumulative effect on these symptoms. Drugs like beta-blockers, non-DHP CCB's, and digoxin can all have a cumulative effect with clonidine and lower pulses. Monitoring is important.

Memantine is classified as an NMDA receptor antagonist. Memantine pharmacology is complex as is the pharmacology of any medication working in the brain. This drug can help reduce the activity of glutamate, an excitatory neurotransmitter which can play a role in Alzheimer's dementia. Memantine has an extended release dosage form that is dosed once per day compared to twice per day for the immediate release. However, the cost of the extended release is much more expensive, so it is recommended to begin with the immediate release. Memantine is cleared by the kidney. In patients with reduced kidney function, you must review to assess if the memantine dose needs to be adjusted. When using memantine or other dementia medications, be sure to look out for medications that can cause dementia type symptoms. CNS depressants like benzodiazepines, sleep medicines, and anticholinergics are all examples of meds that could exacerbate dementia.

On this episode, I discuss magnesium pharmacology and the clinical applications. Magnesium plays numerous important functions in the body and you may see patients take these supplements under the direction of a healthcare professional and sometimes on their own. It is very important to remember that magnesium can cause GI upset and diarrhea. This is often overlooked in our polypharmacy patient. Magnesium can accumulate in renal disease. This is important to remember especially in patients who have a tendency to take a lot of supplements without discussing them with a healthcare professional. PPI's are a notorious cause of low magnesium. Loop diuretics can increase magnesium excretion and also cause low magnesium levels. Magnesium can bind up numerous drugs reducing concentrations and leading to treatment failure. A few examples include quinolone antibiotics, tetracycline antibiotics, and levothyroxine.

Trazodone pharmacology is complex. It can inhibit serotonin reuptake, block histamine receptors, and possibly have alpha-blocking activity. Side effects of trazodone include sedation, dizziness, and dry mouth. Rarely, priapism may occur. I've seen this nugget come up on pharmacology exams! While trazodone is classified as antidepressant, it is often used to help manage insomnia. Trazodone can possibly prolong the QT interval. Risk of other medications and patient specific parameters should be considered. Trazodone concentrations can be increased with the use of CYP3A4 inhibitors and reduced with 3A4 inducers.

The GLP-1's are a relatively newer class of medications used to lower blood sugars in diabetes. GLP-1's work by simulating the effects of incretin hormones in the body. They can help promote fullness, lower weight, and stimulate insulin release following a meal. GLP-1's can cause significant GI side effects. Nausea is by far the most common adverse effect. It can even lead to diarrhea and vomiting in some cases. There is boxed warning on the GLP-1 agonists. Be aware of patients who have had a history of thyroid cancer as this may be a contraindication. GLP-1 agonists can help lower A1C and stimulate weight loss which is a huge benefit for most patients with Type 2 diabetes.

Iron supplements frequently cause GI upset. Monitor patients for nausea, vomiting, and constipation issues. There are three main salt forms of iron. Ferrous fumurate has the most elemental iron, ferrous sulfate (2nd most), and ferrous gluconate has the least. Iron can bind up antibiotics and reduce their effectiveness. Two classic examples include the quinolone and tetracycline antibiotics. Anemia can be caused by numerous concerns, however, iron deficiency is a very common cause. Ferritin is a lab that we commonly monitor in a patient who may be iron deficient. Iron deficiency can also lead to symptoms of Restless Leg Syndrome.

On this episode, I cover common loop diuretics. They include furosemide, torsemide, and bumetanide. Loop diuretics are potent agents that can help in the management of heart failure and ascites. Loops diuretics help promote the loss of excessive fluid through the urine. A common patient complaint from loop diuretics is that they can cause frequent urination. Because of this, we typically dose these drugs earlier in the day. Kidney function and electrolyte monitoring is critical with the use of loop diuretics. Enjoy the episode!