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Treatment Options for Side Effects: Today and Tomorrow
Advances in drug delivery are offering new options for people with cancer, Parkinson’s, and other diseases.!--h2>
The most prominent symptoms of major diseases are well publicized. But for many patients, side effects of mainstream therapies—while lesser known—can affect their physical and psychological well-being as well. Fortunately, advances in drug delivery have offered novel treatment options, and more are being developed today. In what follows, we will examine some examples.
First, cancer treatment, including chemotherapy and radiation therapy, can result in low blood cell counts, leading to various complications. These therapies run a risk of damaging bone marrow, where blood cells are created. A low white blood cell count (neutropenia) leaves the body more open to infection, while a low red blood cell count means low hemoglobin level, which can produce anemia, bleeding, and fatigue. Neutropenia is a granulocyte disorder characterized by an abnormally low number of neutrophils, which usually make up 50 to 70 percent of circulating white blood cells and serve as the primary defense against infections by destroying bacteria in the blood.
In some cases, a doctor might recommend a course of antibiotics to prevent neutropenia-related infection before it develops. This is called prophylactic antibiotic therapy. Other medications, called growth factors or granulocyte-colony stimulation factors (G-CSF), are often used to increase white blood cell production in the bone marrow. Commonly used growth factors include Leukine® (sargramostim), Neulasta® (pegfilgrastim), and Neupogen® (filgrastim). Meanwhile, other medications are sometimes prescribed to stimulate the formation of red blood cells. These include epoetin alfa (Epogen®, Procrit®) and darbepoetin alfa (Aranesp®).
As another example, nausea is one of the most common medication side effects that patients report (both from chemotherapy and other treatments), as virtually all agents have the ability to cause stomach disturbances. Medication-related nausea can have a profound impact on patient outcomes because nonadherence to prescribed therapy can lead to treatment failure. Agents that trigger nausea include dopaminergic agonists, digoxin, opiates, nonsteroidal anti-inflammatory drugs (NSAIDs), and erythromycin.
Several treatments can counteract the nausea triggered by these agents. Specifically, dopamine antagonists, such as promethazine (Phenergan®), prochlorperazine (Compazine®), droperidol (Inapsine®), haloperidol (Haldol®), and metoclopramide (Reglan®), are especially effective for opioid-induced nausea, but can be beneficial for nausea caused by other medications as well. They are a good choice for short-term offenders, such as antibiotics and NSAIDs. The use of serotonin receptor agonists—e.g., ondansetron (Zofran®), granisetron (Kytril®), dolasetron (Anzemet®), and palonosetron—(Aloxi®) may be beneficial for long-term prevention of nausea. Further classes of drugs that can be used to treat nausea include steroids, anti-anxiety drugs and cannabinoids.
Parkinsonism and Akathisia
A further arena involves the treatment of side effects triggered by the use of antipsychotics by the elderly. Drug-induced parkinsonism, characterized by tremors, is a common side effect of conventional antipsychotic treatment; approximately 40 percent of older patients treated with conventional antipsychotics develop drug-induced parkinsonism even at very low doses. This condition can cause discomfort and often contributes to falls in older adults. Benztropine is commonly prescribed for the purpose of treating drug-induced parkinsonism. However, anticholergenic agents should be used sparingly, and only for a short time, because they may in turn trigger additional side effects in the elderly.
Akathisia is another common, drug-induced type of motor restlessness that should always be considered when evaluating agitated or restless older adults receiving antipsychotic treatment. Treatment with a benzodiazepine, low-dose propranolol, or the alpha-adrenergic drug clonidine may be effective in treating akathisia; again, however, these should be used sparingly due to the possibility of further side effects. A further type of drug-induced motor restlessness, dystonia, is characterized by sustained contraction of muscles; almost all dystonic reactions respond to anticholinergic treatments such as benztropine or diphenhydramine, although intramuscular administration of these agents may be required.
In addition to these current treatments, innovation is ongoing in the area of addressing side effects. For an example of cutting-edge treatment, consider the case of Parkinson’s disease (PD). One PD side effect is “freezing” or “off” episodes, characterized by acute immobility, occurring between one and several times daily and lasting from one to several hours cumulatively. These episodes are triggered by levodopa or enzyme inhibitors—both mainline treatments for PD. The episodes begin when the levodopa or enzyme inhibitors enter the bloodstream too slowly, or wear off quickly, or just do not enter the bloodstream sufficiently at all.
The sole drug approved as an acute rescue therapy to treat these “off” episodes is the dopamine agonist apomorphine, (Apokyn® in the U.S. and Japan; Apo-go® in Europe and Asia). Apomorphine is primarily available in an inconvenient, painful injectable form (and as an abdominal infusion pump in Europe)—problematic not only because it requires administration up to several times daily, but also because the injection can result in (for approximately 70 percent of users) irritation and nodules at the injection site on the body, since apomorphine is only stable in a highly acidic formulation.
Approximately 40 percent of patients using Apokyn experience significant nausea for the first few months of treatment with it. As a countermeasure, they are prescribed the anticholinergic Tigan® (trimethobenzimide) in the U.S. a few days before beginning Apokyn, and within three to six months almost all no longer require Tigan.
Given the ongoing demand to address side effects of current and future mainstream drugs, the innovation embodied by the examples above will continue to be welcomed by healthcare providers and patient populations alike.
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