Pill Pushing©

Side effects like you've never seen - (11/1/2018)

By Dr. Ron Gasbarro

Medical researchers consider a side effect that occurs in 1% or more of people taking a specific medication to be caused by that medication. Examples of common drug side effects include nausea, vomiting, fatigue, dizziness, dry mouth, headache, itching, and muscle aches and pains. Boring! Let’s get into the good stuff: the very rare, very weird side effects that some drugs can cause. 

Urine - The colors of the rainbow
Usually, urine is in the yellowish family. If it is brown, reddish, or anything in between, an infection could be brewing that should be checked out. Otherwise, through the magic of your body chemistry, urine can be a virtual Crayola™ box of different hues and shades. 

Examples include: 
Reddish orange: Rifampin (Rifadin®, Rimactane®), an antibiotic often used to treat tuberculosis, can turn urine the color of an autumn sunset. This is also true of phenazopyridine (Pyridium®), a drug that relieves urinary tract discomfort. Laxatives containing senna (e.g., Senokot®) can also cause this color. 
Purple: Phenolphthalein can cause urine to become the color of violets. This reagent was used as an ingredient in laxatives. However, the drug has been removed from pharmacy shelves because of a relatively recent association between it and colon cancer.  
Green: The antidepressant amitriptyline (Elavil®), which is also used for neuropathic pain and enuresis, as well as the muscle relaxant methocarbamol (Robaxin®) can turn urine into an emerald hue. 
Blue: The diuretic triamterene (Dyrenium®), and methylene blue, a chemical compound used in medications like Urised® to help reduce irritation caused by bladder infections, can make the urine cerulean in color.
Black:  Antibiotics such as metronidazole (Flagyl®) and furazolidone (Furoxone®), and the blood pressure medicine methyldopa (Aldomet®) appear to be blackish because it darkens upon contact with toilet bowl cleaners containing bleach.
If your urine turns an unusual color for any reason, check with your pharmacist or prescriber. 

Can’t book ‘em Danno – He has no fingerprints!

Fingerprint loss is a rare possibility when taking the drug capecitabine (Xeloda®), a drug used to treat breast, colon, and rectal cancer. The cause of fingerprint loss is related to a side effect of the drug called hand-foot syndrome (HFS), which causes redness, tingling, and dryness of the hands and feet. These side effects can develop into more serious symptoms, like the peeling and blistering of the hands and soles of the feet. Other cancer drugs can cause HFS, but it occurs most often in people taking capecitabine. Once the drug is stopped, the skin normalizes and fingerprints return. 

I wouldn’t wear white slacks if I were you 
Orlistat (Xenical®, now sold over the counter in a lower dosage as Alli®) is formulated to prevent the body from absorbing fat and therefore decrease the actual calorie intake of its users. During the premarketing clinical trials, as much as 30% of ingested fat was excreted unabsorbed by subjects. Patients must follow a low-fat diet of around 15 grams of fat per meal. If they do not, the results can be catastrophic and embarrassing. According to the manufacturer, Roche Laboratories, side effects of Xenical include "gas with oily discharge, an increased number of bowel movements, an urgent need to have them, and an inability to control them, particularly after meals containing higher amounts of fat than are recommended." 

Sex and/or the roulette wheel
Ropinirole (Requip®) and its competitor pramipexole (Mirapex®) are both indicated for Parkinson’s disease and restless leg syndrome (RLS). Chemically similar, both drugs have the same effects as a chemical called dopamine, which occurs naturally in the brain. Low levels of dopamine in the brain are associated with Parkinson's disease. Relatively early on after FDA approval, reports of gambling and sex addiction surfaced. This prompted the manufacturers to include the following statement in their package inserts: Reports suggest that patients can experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge or compulsive eating, and/or other intense urges, and the inability to control these urges while taking these. In some cases, although not all, these urges were reported to have stopped when the dose was reduced or the medication was discontinued. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or their caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending, binge or compulsive eating, or other urges while being treated with one of these dopamine agonists. 

In addition to public warnings about the gambling side effect, there are also lawsuits filed by people who claim they have gambled away their nest eggs after they began to take drugs in this class, according to a CBS New report. For example, Jacquie Rice, a retired Texas banker was prescribed a dopamine agonist and says she gambled away her entire retirement of $250,000. Max Wells, also from Texas, filed a lawsuit against the drug company as well as the Las Vegas casinos where he lost millions. So, what happens in Vegas, stays in Vegas. That apparently includes your money. 

But I didn’t weigh this much last night!
In the 2 decades since its arrival, the sedative zolpidem (Ambien®) has been linked to sleepwalking, sleep driving, and even sleep cooking and sleep eating. In 2013, the FDA ordered Sanofi-Aventis, the manufacturers of zolpidem, and all other manufacturers of zolpidem to change their dosage recommendations. This was in response to over 700 reports of zolpidem-related driving accidents, including drowsy driving and sleep-driving (patients getting out of bed while not fully awake and driving). Other reported activities have included eating, walking, making phone calls, or having sex after taking zolpidem and later having no memory of the activity.

Zolpidem seems to unlock a primitive desire to eat in some patients, according to emerging medical case studies that describe how the drug's users sometimes sleepwalk into their kitchens, raid their refrigerators and consume thousands of calories. The next morning, the nocturnal eaters remember nothing about their foraging. But they wake up to find telltale clues: mouthfuls of peanut butter, corn chips in their beds, kitchen counters overflowing with flour, missing food, and even lighted ovens and stoves. Some are so embarrassed, they delay telling anyone, even as they gain weight.

A California woman reported that she would awaken to find candy bar wrappers next to her bed and Popsicle sticks on the floor near the refrigerator. She blamed other family members before finally believing their claims that she was unconsciously eating at night.

What light through yonder window breaks? It is your ED drug!
Erectile dysfunction medications, such as sildenafil (Viagra®) and tadalafil (Cialis®)can cause strange things to happen to one’s vision. Patients taking these drugs have reported experiencing not only blurred vision but also blue vision and problems distinguishing between the colors blue and green. In 2005, researchers at the University of Minnesota theorized that ED drug users can experience permanent vision loss due to blood flow to the optic nerve being cut off, known as nonarteritic ischemic optic neuropathy.

The ED drugs are effective in erectile dysfunction because they inhibit phosphodiesterase 5 (PDE-5), an enzyme that enhances the effects of nitric oxide, which is released during sexual stimulation to relax the smooth muscle of the penis and facilitate blood inflow. However, the drug also has a milder inhibiting effect on PDE-6, an enzyme actively present in retinal photoreceptors. This causes an increase in the concentration of cyclic GMP, resulting in a depolarization of the rod cell – and increased light sensitivity and the infamous "blue vision." The ocular effects are short-lived and generally peak within 1-2 hours after the drug is taken. Side effects are usually dose-related, meaning the greater the dosage, the greater the risk. 

When side effects become the main course

Sildenafil – Perhaps the most fortuitous discovery was when sildenafil (Viagra®) was being tested as a medication for hypertension and angina. The discovery that sildenafil could lead to an erection was an unplanned event. During the heart clinical trials, researchers discovered that the “little blue pill” was more effective at inducing erections than treating angina. Pfizer realized ED was an unmet medical need and a major opportunity for financial gain. Yes, to the tune of tens of billions of dollars!

But the beat goes on. Results from a 2014 meta-analysis published in BMC Medicine suggest that phosphodiesterase type 5 (PDE5) inhibitors, like Viagra, have anti-remodeling properties and may improve cardiac contractility (inotropism). These researchers hypothesize that Viagra and other PDE5 inhibitors may be useful in treating cardiac hypertrophy and early-stage heart failure.

Levodopa – Does a medication used to control Parkinson’s disease (PD) result in increased creativity? Levodopa is used with another medicine called carbidopa (Sinemet®) to treat the symptoms of PD (stiffness, tremors, spasms, poor muscle control). These symptoms may be caused by low levels of the neurotransmitter dopamine. Levodopa is converted to dopamine in the brain.

Creative thinking requires a combination of originality, flexibility, and usefulness. A 2014 study published in the Annals of Neurology showed that PD patients treated with dopaminergic drugs demonstrated enhanced verbal and visual creativity as compared to neurologically healthy controls. Several doctors noticed that their PD patients receiving levodopa were producing copious amounts of paintings, poems, and novels. The study compared the boost in the creativity of PD patients on the drug with those who did not have PD. Visual and verbal tests and examined their responses based on creativity. While the results showed no relationship between compulsive behavior and the increase in creativity the researchers were observing, they did find that those PD patients taking higher doses of levodopa not only scored better than those without PD but that they also were also more creative in their responses. Whether or not a new Pablo Picasso or Emily Dickinson will emerge among PD patients is the question.


Ron Gasbarro, PharmD, is a registered pharmacist, medical writer, and principal at Rx-Press.com. Read more at www.rx-press.com  

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