By Ben Fuchs | Pharmacist Ben
Late last week the FDA approved a new drug to treat Pulmonary Arterial Hypertension (PAH). The medication, called macitentan (Opsumit, Actelion) is the second drug approved this month to treat the debilitating disease. Earlier, the regulatory body approved a medication called riociguat (Adempas).
Micrograph showing a plexiform lesion of the lung, as seen in irreversible pulmonary hypertension. Image contributed by Bulent Celasun, MD, via Wikimedia Commons.
Pulmonary Arterial Hypertension is a condition that affects the blood circulation in the pulmonary system, which is medical term referring to respiratory mechanics and the lungs. Although no one knows exactly how many people have PAH, according to the American Thoracic Society (ATS), it may affect as many as hundreds of thousands of Americans. It can best be thought of as high blood pressure of the lung arteries and can lead to all kinds of unpleasant bodily symptoms including bluish lips, hands or feet, dizziness, fatigue and lethargy, shortness of breath, fainting and swelling in the lower extremities. PAH has no surgical cure, progresses rapidly and is marked by progressive degeneration and breakdown of the blood vessels that travel from the heart to the lungs. In a normal healthy body, blood is carried from the heart, then to the lungs, where it picks up oxygen, which is then in turn delivered back to the heart and then to the rest of the organs and tissues of the body. Under conditions of Pulmonary Arterial Hypertension however, pulmonary arterial constriction, i.e. a tightening of the blood vessels in the lungs, restricts flow resulting in a sluggish circulation to the heart as well as a decrease in the amount of blood and oxygen that is ultimately delivered to the rest of the body. In addition, long term hypertension in the pulmonary arteries can lead to vascular changes including thickening of vessel walls, inflammation and the formation of plaques, all of which can further impair circulation and blood flow. Most significantly as the condition progresses, the heart, which is forced to work harder and faster to compensate for the vascular changes, becomes weakened. This can result in heart failure which is the most common cause of death in cases of PAH.
PAH can be associated with various other disease states including connective tissue disease, hypothyroidism, liver disease and heart disease, HIV infection and stimulant drug intake. However the vast majority of cases, according to ATS literature are said to be idiopathic, meaning they are associated with no known cause.
Although there is no medical cure for Pulmonary Arterial Hypertension, drug treatments have traditionally focused on vasodilators, which open up the blood vessels. However these kinds of drugs can create potential problems via lowering blood pressure in the rest of the body and ultimately decreasing the flow of blood to the lungs. Although the recently approved drugs, macitentan and riociguat, operate via novel mechanisms they are still vasodilators and can result in the same kind of problems as the more conventional PAH medications.
As with other circulatory health challenges there are many nutritional and dietary strategies that may help improve PAH. According to researchers writing in the European Respiratory Journal in April 2013, there is an increased prevalence of insulin resistance in PAH patients. Thus, restoring insulin sensitivity by reducing the intake of sugars and refined carbs may have a beneficial effect. Additionally there are nutritional supplements that can be used that improve insulin response. Niacin, thiamin, chromium and vanadium can all increase insulin sensitivity. So can the mineral magnesium, which can the potentize effects of insulin, and can provide lung and circulatory benefits. Magnesium has also been used as a medical treatment for PAH in newborns. In a 2004 study of 12 newborn babies with pulmonary hypertension published in the Journal of Tropical Pediatrics, magnesium was found to be “a safe and effective pulmonary vasodilator”, which is medical talk for “a safe substance for opening up blood vessels in the lungs”.
Finally, according to the University of Maryland Medical Center, while not specifically associated with treating pulmonary arterial hypertension, there are several nutritional supplements that can be used to improve heart health function in general. These include carnitine (500mg, three times a day), CoQ10 (200-600mg a day), Vitamin E (400 IU a day), potassium (20mg and day) and taurine (1000mg twice a day).
According to an American Society for Pharmacology and Experimental Therapeutics article published in the journal Pharmacological Reviews, recent discoveries into the pot plant peptides have triggered an “exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease” According to the September 2006 article, modulation of the cannabinoid system can potentially improve the symptoms of a wide range of medical conditions including emotional and mental disorders, nervous system and movement issues (e.g. Parkinson’s and Huntington’s diseases ) spinal cord injury and nerve pain, osteoporosis, obesity and metabolic syndrome and various circulatory health issues, including myocardial infarction, stroke, hypertension, atherosclerosis, and osteoporosis.
Some of these functional proteins require calcium for their activation. They are said to be calcium-dependent-proteins and they play a critical part in the operation of many important functions in the body. These proteins are interestingly shaped with little hooks on them, chemical hooks, and molecular hooks. Via these little biochemical appendages they ‘fish” for calcium. Chemical hooks are an iconic example of how shape affects the function and properties and features of various molecules. Without calcium-trapping hooks these vital and key proteins are as useless as any fishing pole & line would be without its hook. A fishing pole & line without a hook isn’t going to catch many fish and a calcium-dependent-protein without a hook isn’t going to catch much calcium. No hooks on these chemicals means these chemicals are going without calcium. And no calcium on these chemicals means these chemicals are essentially neutered. They’re inactive. These are chemicals that contract muscles, keep your heart healthy, and help clean the blood among other roles. In fact almost everything a cell does is somehow related to these proteins and their chemical hooks and their ability to “catch” calcium.
The Taiwanese scientists studied 2,658 pregnant women who were exposed to topical corticosteroids and compared them to 7,246 pregnant women who were not exposed. They concluded that “this study reassuringly showed no associations of maternal topical corticosteroid exposure with orofacial cleft, preterm delivery (or) fetal death…”
