Real Life Pharmacology - Pharmacology Education For Health Care Professionals

Benztropine is a highly anticholinergic medication that is primarily used for movement disorders. Antipsychotics can cause extrapyramidal adverse effects that can help be managed with benztropine. Because benztropine is highly anticholinergic, it can cause dry eyes, dry mouth, urinary retention, constipation and contribute to falls and confusion, particularly in our elderly population. While benztropine is classified as an anti-Parkinson's agent, it is rarely used for that indication as it has a high incidence of anticholinergic adverse effects (particularly at the doses that are required for benefit).

Budesonide is a corticosteroid that can be given orally or rectally for management of Crohn's disease or ulcerative colitis. Because budesonide has a high first pass metabolism, the relative impact of systemic effects may be less than other steroids like prednisone. Remember that CYP3A4 inhibitors can increase the concentrations of budesonide. I discuss this further on the podcast. Different dosage forms of budesonide (oral versus rectal) can be used for different reasons. The site of the inflammation in Ulcerative colitis can determine which dosage form is most appropriate.

Cimetidine blocks histamine 2 receptors which can suppress acid production and reduce symptoms of heartburn. One of the major downsides to cimetidine is that it has a ton of drug interactions. I discuss many of the common ones in this episode. Cimetidine is one of a few drugs that has the potential to cause gynecomastia. I discuss the mechanism of this adverse effect in this episode. Phenytoin concentrations can rise due to the use of cimetidine. I discuss this in the drug interactions section of this episode.

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.

Sulfasalazine is a medication that can be used for diseases like rheumatoid arthritis, Crohn's disease, and Ulcerative Colitis. Because sulfasalazine can cause GI upset, this is a major reason why we try to break up the dose and give it multiple (at least two) times per day. LFT and CBC monitoring are recommended with sulfasalazine due to its low potential to cause liver dysfunction, aplastic anemia, and agranulocytosis. Sulfasalazine can impair folic acid absorption and lead to potential deficiency. A patient deficient in folic acid is at higher risk for developing anemia.

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.

Rifampin is classified as an antibiotic and an antituberculosis agent. It primarily works by inhibiting bacterial RNA polymerase. While not extremely common, rifampin is well known to cause hepatic dysfunction. You should remind patients who are taking rifampin that it can alter the color of tears, sweat, saliva and urine. It can change these fluids to a reddish/brown color. Rifampin is very well known for causing drug interactions. It is an enzyme inducer that can reduce the concentrations of numerous medications such as warfarin, apixaban, cyclosporin, levothyroxine, and oral contraceptives to name a few. Rifampin can be used to help prevent meningococcal infection. Learn more on rifampin by listening to this podcast!

Heparin is an interesting drug with a lot of unique clinical quirks. This drug ultimately inhibits the formation of fibrin. Fibrin is an essential component of a blood clot. Because heparin has blood thinning effects, it is critical to assess a patient's bleed risk. Look out for other agents that may increase the risk of bleeding. Examples include; NSAIDs, antiplatelet agents, and other anticoagulants. One classic test question about heparin that often comes up is the reversal agent. Protamine can be used to help reverse the effects of heparin. Heparin-induced thrombocytopenia is a critical adverse effect to understand. I discuss both subtypes on the podcast and let you know what to look out for. Rarer side effects of heparin include hyperkalemia and osteoporosis (only with long term use).

On this episode, I discuss montelukast pharmacology Montelukast is a leukotriene receptor antagonist. Leukotrienes play an important role in causing inflammation and smooth muscle contraction in asthma and allergic rhinitis. Because montelukast blocks the effects of leukotrienes, it can be advantageous to use this medication for allergies and asthma. It is important to remind patients that montelukast is NOT a substitute for an acute relief medication like albuterol in the management of asthma symptoms. Montelukast has been reported to cause mood and behavioral changes and it is important to monitor our patients for these rare concerns.

On this episode, I discuss clozapine pharmacology. This drug has multiple mechanisms of action: Dopamine blockade, anticholinergic activity, and alpha blocking activity all contribute to the complexity of this drug. Smoking cessation can significantly increase the concentrations of clozapine. This is because smoking can induce CYP1A2. Listen to the podcast for more details on how this can impact our patients clinically. Clozapine has 5 boxed warnings. I discuss them all in this podcast. The most well-known boxed warning is for agranulocytosis. Because clozapine has alpha blocking activity, it can cause orthostasis. We need to monitor for this. Clozapine can cause QTc prolongation. Keep an eye out for other medications that the patient may be taking that can also cause this. Examples include: amiodarone, ondansetron, quinolones, and macrolides

On this episode, I discuss carbamazepine pharmacology. This drug is most commonly used for seizures, bipolar disorder, or trigeminal neuralgia. Carbamazepine is an autoinducer and can reduce the concentrations of numerous drugs. Some examples include apixaban, warfarin, rivaroxaban, diltiazem, verapamil, and many more! Carbamazepine has the potential to cause Steven Johnson's Syndrome. This has a much greater chance of happening in patients with certain genetics. Carbamazepine can contribute to SIADH and cause significant hyponatremia. Carbamazepine has boxed warning for numerous potential events like aplastic anemia, agranulocytosis, and the above-mentioned SJS.

On this episode, I discuss the pharmacology of commonly used stimulant laxatives like sennosides and bisacodyl. Stimulant laxatives "stimulate" the GI tract smooth muscle which helps propel fecal material out of the body and thus helping to relieve constipation. Patients who are having diarrhea and are unsure of what medications they are taking should have their regimen assessed for these medications. Chronic opioid therapy is a situation where chronic stimulant laxative therapy may be used. Stimulant laxatives have very few drug interactions. However, bisacodyl effectiveness can be reduced by the use of antacids like calcium carbonate.

On this episode, I discuss ezetimibe pharmacology. Ezetimibe works by inhibiting Niemann-Pick C1-Like1 (NPC1L1) transporter. This transporter aids in cholesterol absorption so by blocking it, we can reduce cholesterol levels (and LDL) in the bloodstream. Ezetimibe is usually very well tolerated. Diarrhea, myopathy, and elevations in LFT's are adverse effects that have been reported but do not occur at high rates. Ezetimibe is dosed at 10 mg once daily. This is a nice advantage because this is a starting dose and the usual treatment dose. With the most recent cholesterol guideline updates, I do expect ezetimibe to be utilized a little more than it used to be. They place more emphasis on a target LDL and getting patients to goal. Statins are going to be used first line for cholesterol and ezetimibe will be an add on therapy to consider. They don't, unfortunately, lower cholesterol as much as high-intensity statins do.

On this episode, I cover azithromycin pharmacology. This drug primarily acts by inhibiting protein synthesis. It binds to the 50s ribosomal subunit. GI adverse effects like nausea and diarrhea are going to be the most common with azithromycin. Azithromycin has been associated with prolonging the QT interval. Drugs like amiodarone, ondansetron, citalopram, antipsychotics, and quinolone antibiotics can also prolong the QT interval. One major advantage that azithromycin has over other antibiotics is that it has a long half life which allows for once daily dosing. Azithromycin has numerous uses like pneumonia, MAC, alternative for ear infections in patients with a beta-lactam allergy, certain STD's, and also is rarely used in long term COPD exacerbation prevention.

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.