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Nimodipine
Nimodipine, sold under the brand name Nimotop among others, is calcium channel blocker used in preventing vasospasm secondary to subarachnoid hemorrhage (a form of cerebral hemorrhage). It was originally developed within the calcium channel blocker class as it was used for the treatment of high blood pressure, but is not used for this indication. It was patented in 1971 and approved for medical use in the US in 1988. It was approved for medical use in Germany in 1985. Medical use Because it has some selectivity for cerebral vasculature, nimodipine's main use is in the prevention of cerebral vasospasm and resultant ischemia, a complication of subarachnoid hemorrhage (a form of cerebral bleed), specifically from ruptured intracranial berry aneurysms irrespective of the patient's post-ictus neurological condition. Its administration begins within 4 days of a subarachnoid hemorrhage and is continued for three weeks. If blood pressure drops by over 5%, dosage is adjusted ...
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Subarachnoid Hemorrhage
Subarachnoid hemorrhage (SAH) is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain. Symptoms may include a severe headache of rapid onset, vomiting, decreased level of consciousness, fever, and sometimes seizures. Neck stiffness or neck pain are also relatively common. In about a quarter of people a small bleed with resolving symptoms occurs within a month of a larger bleed. SAH may occur as a result of a head injury or spontaneously, usually from a ruptured cerebral aneurysm. Risk factors for spontaneous cases include high blood pressure, smoking, family history, alcoholism, and cocaine use. Generally, the diagnosis can be determined by a CT scan of the head if done within six hours of symptom onset. Occasionally, a lumbar puncture is also required. After confirmation further tests are usually performed to determine the underlying cause. Treatment is by prompt neurosurgery or endovascular coiling. Me ...
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Vasospasm
Vasospasm refers to a condition in which an arterial spasm leads to vasoconstriction. This can lead to tissue ischemia and tissue death (necrosis). Cerebral vasospasm may arise in the context of subarachnoid hemorrhage. Symptomatic vasospasm or delayed cerebral ischemia is a major contributor to post-operative stroke and death especially after aneurysmal subarachnoid hemorrhage. Vasospasm typically appears 4 to 10 days after subarachnoid hemorrhage. Along with physical resistance, vasospasm is a main cause of ischemia. Like physical resistance, vasospasms can occur due to atherosclerosis. Vasospasm is the major cause of Prinzmetal's angina. Pathophysiology Normally endothelial cells release prostacyclin and nitric oxide (NO) which induce relaxation of the smooth muscle cells, and reduce aggregation of platelets. Aggregating platelets stimulate ADP to act on endothelial cells and help them induce relaxation of the smooth muscle cells. However, aggregating platelets also s ...
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Calcium Channel Blockers
Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as medications to decrease blood pressure in patients with hypertension. CCBs are particularly effective against large vessel stiffness, one of the common causes of elevated systolic blood pressure in elderly patients. Calcium channel blockers are also frequently used to alter heart rate (especially from atrial fibrillation), to prevent peripheral and cerebral vasospasm, and to reduce chest pain caused by angina pectoris. N-type, L-type, and T-type voltage-dependent calcium channels are present in the zona glomerulosa of the human adrenal gland, and CCBs can directly influence the biosynthesis of aldosterone in adrenocortical cells, with consequent impact on the clinical treatment of hypertension with these agents. CCBs have be ...
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Troleandomycin
Troleandomycin (TAO for short) is a macrolide antibiotic. It was sold in Italy (branded Triocetin) and Turkey (branded Tekmisin). It is no longer sold in Italy as of 2018. The drug's mode of action is to bind to the ribosome, specifically in the tunnel through which the newly formed peptide egresses, thereby halting protein synthesis. Troleandomycin is a CYP3A4 inhibitor that may cause drug interaction Drug interactions occur when a drug's mechanism of action is disturbed by the concomitant administration of substances such as foods, beverages, or other drugs. The cause is often the inhibition of the specific receptors available to the drug, ...s. References CYP3A4 inhibitors Macrolide antibiotics Epoxides Spiro compounds Acetate esters {{antibiotic-stub ...
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CYP3A
Cytochrome P450, family 3, subfamily A, also known as CYP3A, is a human gene locus. A homologous locus is found in mice. The CYP3A locus includes all the known members of the 3A subfamily of the cytochrome P450 superfamily of genes. These genes encode monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The CYP3A cluster consists of four genes: * CYP3A4, * CYP3A5, * CYP3A7, and * CYP3A43. The region also contains four pseudogene Pseudogenes are nonfunctional segments of DNA that resemble functional genes. Most arise as superfluous copies of functional genes, either directly by DNA duplication or indirectly by reverse transcription of an mRNA transcript. Pseudogenes ar ...s: * , * , * , and * . as well as several extra exons which may or may not be included in transcripts produced from this region. Previously another CYP3A member, CYP3A3, was thought to exist; however, it is now thought that t ...
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Cytochrome P450
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown. In 1963, Estabrook, Cooper, and Rosenthal described the role of CYP as a catalyst in steroid hormone synthesis and drug metabolism. In plants, these proteins are important for the biosynthesis of defensive compounds, fatty acids, and hormones. CYP enzymes have been identified in all kingdoms of life: animals, plants, fungi, protists, bacteria, and archaea, as well as in viruses. However, they are not omnipresent; for example, they have not been found in ''Escherichia coli''. , more than 300,000 distinct CYP proteins are known. CYPs are, in general, the terminal oxidase enzymes in electron transfer chains, broadly categorized as P450-containing systems. The term "P450" is deriv ...
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First Pass Metabolism
The first pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism whereby the concentration of a drug, specifically when administered orally, is greatly reduced before it reaches the systemic circulation. It is the fraction of drug lost during the process of absorption which is generally related to the liver and gut wall. Notable drugs that experience a significant first-pass effect are buprenorphine, chlorpromazine, cimetidine, diazepam, ethanol (drinking alcohol), imipramine, insulin, lidocaine, midazolam, morphine, pethidine, propranolol, and tetrahydrocannabinol (THC). First pass metabolism may occur in the liver (for propranolol, lidocaine, clomethiazole, and NTG) or in the gut (for benzylpenicillin and insulin). After a drug is swallowed, it is absorbed by the digestive system and enters the hepatic portal system. It is carried through the portal vein into the liver before it reaches the rest of the body. The liver ...
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Thrombosis
Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thrombocytes) and fibrin to form a blood clot to prevent blood loss. Even when a blood vessel is not injured, blood clots may form in the body under certain conditions. A clot, or a piece of the clot, that breaks free and begins to travel around the body is known as an embolus. Thrombosis may occur in veins ( venous thrombosis) or in arteries ( arterial thrombosis). Venous thrombosis (sometimes called DVT, deep vein thrombosis) leads to a blood clot in the affected part of the body, while arterial thrombosis (and, rarely, severe venous thrombosis) affects the blood supply and leads to damage of the tissue supplied by that artery ( ischemia and necrosis). A piece of either an arterial or a venous thrombus can break off as an embolus, whi ...
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Congestive Heart Failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, and leg swelling. The shortness of breath may occur with exertion or while lying down, and may wake people up during the night. Chest pain, including angina, is not usually caused by heart failure, but may occur if the heart failure was caused by a heart attack. The severity of the heart failure is measured by the severity of symptoms during exercise. Other conditions that may have symptoms similar to heart failure include obesity, kidney failure, liver disease, anemia, and thyroid disease. Common causes of heart failure include coronary artery disease, heart attack, high blood pressure, atrial fibrillation, valvular heart disease, excessive alcohol consumption, infection, and cardiomyopathy. These cause heart failure by alterin ...
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Diaphoresis
Perspiration, also known as sweating, is the production of fluids secreted by the sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distributed over much of the body and are responsible for secreting the watery, brackish sweat most often triggered by excessive body temperature. The apocrine sweat glands are restricted to the armpits and a few other areas of the body and produce an odorless, oily, opaque secretion which then gains its characteristic odor from bacterial decomposition. In humans, sweating is primarily a means of thermoregulation, which is achieved by the water-rich secretion of the eccrine glands. Maximum sweat rates of an adult can be up to 2–4 liters per hour or 10–14 liters per day (10–15 g/min·m2), but is less in children prior to puberty. Evaporation of sweat from the skin surface has a cooling effect due to evaporative cooling. Hence, in hot weather ...
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