Hypertension, pulmonary

Untoward effects of both E and NE (usually to a lesser degree) are anxiety, headache, cerebral hemorrhage (from vasopressor effects), cardiac arrhythmias, especially in presence of digitaUs and certain anesthetic agents, and pulmonary edema as a result of pulmonary hypertension. The minimum subcutaneous lethal dose of E is about 4 mg, but recoveries have occurred after accidental overdosage with 16 mg subcutaneously and 30 mg intravenously, followed by immediate supportive treatment. 

DHPs are also used to treat vasospasms of peripheral arteries (e.g., Raynaud s phenomenon) and pulmonary hypertension. 

During COPD, the following symptoms occur, usually in the order mucus hypersecretion, ciliary dysfunction, airflow limitation, pulmonary hyperinflation, gas exchange abnormalities, pulmonary hypertension and cor pulmonale. Acute exacerbations appear to be mainly triggered by bacteria, viruses or environmental pollutants. They lead to a worsening of lung functions, wasting and increased mortality their psychosocial impacts include depression and anxiety that may be associated with the will to die. 

In addition, ETB receptors are upregulated in vessels with atherosclerotic lesions and in pulmonary vessels of patients with severe pulmonary hypertension. The upregulation can be attributed to increased ETB receptor expression in smooth muscle cells and to ETB receptors expressed on infiltrating macrophages. 

As endothelins mediate potent vasoconstrictor effects, ECE inhibitors and endothelin receptor antagonists were developed for the treatment of cardiovascular diseases, such as acute and chronic heart failure, pulmonary hypertension and subarachnoid haemorrhage. As ETa recqrtors have potent mitogenic responses and may promote progression of ovarian and prostate cancer and bone metastases ETA receptors are also considered as a potential targets for anti-tumour activity. 

Bosentan (Tracleer ) Actelion, Switzerland ETA/ETB receptor Grade III and IV PAH and chronic thromboembolic pulmonary hypertension (European approval in 2002 as orphan medicine) Program for CHF was terminated in phase III... 

In low doses, inhaled NO may have a beneficial therapeutic effect, since NO in the inspired air leads to pulmonary vasodilation. In persistent pulmonary hypertension of the newborn, NO inhalation has already been used with some success. NO inhalation as the treatment for acute respiratory distress syndrome, however, has been disappointing. Only transient improvements of oxygenation were detected and the outcome of placebo-controlled trials did not show any improvement... 

MDMA overdose as well as the concomitant consumption of selective serotonin reuptake inhibitors (SSRI) with other dmgs that exert serotoninergic effects (such as inhibitors of monoamine oxidase) can rapidly lead to the serotonin syndrome. Its symptoms, which are reversible upon cessation, of the drug include confusion, muscle rigidity in the lower limbs, and hyperthermia suggesting an acute reaction to serotonin overflow in the CNS. Blocking the function of SERT outside the brain causes side effects (e.g., nausea), which may be due to elevated 5HT however , impairment of transporter function is not equivalent to direct activation of 5HT recqrtors in causing adverse effects such as fibrosis and pulmonary hypertension. 

Inhaled NO has been used for treatment of persistent pulmonary hypertension of newborn infants, critical respiratory failure of preterm infants, and acute hypertension of adult cardiac surgery patients. PDE-5 inhibitors such as sildenafil are also effective for treatment of pulmonary hypertension. The combination of PDE-5 and NO inhalation yields additive beneficial effects on pulmonary hemodynamics. On the other hand, measurement of exhaled NO is a noninvasive and reproducible test that is a surrogate measure of airway inflammation in patients with bronchial asthma. 

Prostacyclin (epoprostanol) is one of the few drugs effective for the treatment of Primary Pulmonary Hypertension (PPH) a rare but frequently fatal illness of young adults. Increased blood pressure in the pulmonary circulation leads to right-heart failure. Continuous infusion of epoprostanol leads to a decrease in blood pressure however, it is unclear whether this is due to direct dilator activity of the IP receptor acting on smooth muscle, or a more indirect mechanism. 

Primary pulmonary hypertension is a disease of unclear etiology that is characterized by abnormally high mean pulmonary arterial pressures, in the absence of a demonstrable cause. A wide variety of pulmonary and cardiac diseases can lead to secondary pulmonary hypertension. 

Long exposure to Si02 dust can result in fibrosis of the lung or silicosis which may eventuate in pulmonary hypertension and cor pulmonale. Susceptibility to tuberculosis is enhanced. The tolerance level for cryst forms of Si02 is calculated from the formula 250/(%SiO2 +5), and for amorph forms the tolerance level is 20 millions of particles/cu ft of air... 

Until recently, d-fenfiuramine was used to control appetite, in preference to d-amphetamine, because it has a lower affinity for the catecholamine transporter and so its uptake into noradrenergic and dopaminergic neurons is much less than that of amphetamine. This is thought to explain why, at anorectic doses, this compound lacks the psychotropic effects and dependence-liability that are real problems with if-amphetamine. Unfortunately, despite this therapeutic advantage, this compound has had to be withdrawn from the clinic because of worries that it might cause primary pulmonary hypertension, valvular heart disease and even long-term neuropathy. 

Recent use (within 24 h of sildenafil or vardenafil or within 48 h of tadalafil) of a phosphodiesterase-5 inhibitor for erectile dysfunction (or pulmonary hypertension)... 

Pressure overload (e.g., systemic or pulmonary hypertension, aortic or pulmonic valve stenosis)... 

Non-cardiac Anemia, anxiety disorders, carbon monoxide poisoning, cocaine use, esophageal reflux, peptic ulcer, pleuritis, pneumonia, pneumothorax, pulmonary embolus, pulmonary hypertension, thyrotoxicosis... 

The long-term (i.e., more than 3 months after the first event) goals of therapy are to prevent complications such as the postthrom-botic syndrome, pulmonary hypertension, and recurrent VTE. 

Pulmonary hypertension develops late in the course of COPD, usually after the development of severe hypoxemia. It is the most common cardiovascular complication of COPD and can result in cor pulmonale, or right-sided heart failure. Hypoxemia plays the primary role in the development of pulmonary hypertension by causing vasoconstriction of the pulmonary arteries and by promoting vessel wall remodeling. Destruction of the pulmonary capillary bed by emphysema further contributes by increasing the pressure required to perfuse the pulmonary vascular bed. Cor pulmonale is associated with venous stasis and thrombosis that may result in pulmonary embolism. Another important systemic effect is the progressive loss of skeletal muscle mass, which contributes to exercise limitations and declining health status. 

Common adverse reactions seen with phentermine use include heart palpitations, tachycardia, elevated blood pressure, stimulation, restlessness, dizziness, insomnia, euphoria, dysphoria, tremor, headache, dry mouth, constipation, and diarrhea. Phentermine should be avoided in patients with unstable cardiac status, hypertension, hyperthyroidism, agitated states, or glaucoma. In combination with fenfluramine or dexfenfluramine, pulmonary hypertension and valvular heart disease have been reported. The risk of developing either serious adverse effect cannot be ruled out with use of phentermine alone. Since phentermine is related to the amphetamines, the... 

Use of diethylpropion for a period longer than 3 months is associated with an increased risk for development of pulmonary hypertension. When used as directed, reported common central nervous system adverse effects included overstimulation, restlessness, dizziness, insomnia, euphoria, dysphoria, tremor, headache, jitteriness, anxiety, nervousness, depression, drowsiness, malaise, mydriasis, and blurred vision. In addition, diethylpropion can decrease seizure threshold, subsequently increasing a patient s risk for an epileptic event. Other organ systems also can adversely be affected, resulting in tachycardia, elevated blood pressure, palpitations, dry mouth, abdominal discomfort, constipation,... 

ET measured in the plasma appears to be a spillover of the ET that is (locally) released by the endothelium. It is known that low levels of ET (ranging from 0.25 to 5.0 pg/ml) are normally present in the circulation (B8, P12). These levels are increased by 3-10 times in patients with renal failure (S30), diabetes (V3), hypertension, bums (H32), myocardial infarction, primary pulmonary hypertension (N8), and cardiogenic shock (LI, L9, L10, PI, W8). ET is assumed to be released... 

Albert Tauber. I d like to give a reference that everyone knows. Sickle-cell is commonly evoked as a great reductionist victory. I treat many patients with sickle-cell anemia, and I can tell you that the genetic defect is not the disease, because the disease manifestation is highly variable. Some patients have an enormous number of pain-crises. Some patients have a lot of haemolysis that s red-cell destruction. Other patients have pulmonary hypertension. And it s obvious that the disease that we call sickle-cell anemia is an extraordinarily complex phenomenon interacting with many many different systems and many other genes. And the bottom line, from a clinical perspective, which is the phenomenon that we call sickle-cell anemia, is that the sickle-cell gene is necessary but not sufficient for the disease. 

After many health problems and deaths, the FDA removed Pondimin and Redux from market. Since then, there have been 200 reported cases of primary pulmonary hypertension relating to fen-phen and dexfen-phen. Of those cases, 40 have resulted in death. The FDA has received more than 100 reports of heart valve damage directly related to fen-phen or fenfluramine therapy there are no reports from individuals taking phentermine alone for weight loss. 

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