Antiparkinson Agents
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Antiparkinson Agents
In the management of Parkinson's disease, due to the chronic nature of Parkinson's disease (PD), a broad-based program is needed that includes patient and family education, support-group services, general wellness maintenance, exercise, and nutrition. At present, no cure for the disease is known, but medications or surgery can provide relief from the symptoms. While many medications treat Parkinson's, none actually reverses the effects of the disease. Furthermore, the gold-standard treatment varies with the disease state. People with Parkinson's, therefore, often must take a variety of medications to manage the disease's symptoms. Several medications currently in development seek to better address motor fluctuations and nonmotor symptoms of PD. However, none is yet on the market with specific approval to treat Parkinson's. Medication The main families of drugs useful for treating motor symptoms are levodopa, dopamine agonists, and MAO-B inhibitors. The most commonly used treat ...
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Neurology
Neurology (from el, wikt:νεῦρον, νεῦρον (neûron), "string, nerve" and the suffix wikt:-logia, -logia, "study of") is the branch of specialty (medicine), medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal cord and the peripheral nerves. Neurological practice relies heavily on the field of neuroscience, the scientific study of the nervous system. A neurologist is a physician specializing in neurology and trained to investigate, diagnose and treat neurological disorders. Neurologists treat a myriad of neurologic conditions, including stroke, seizures, movement disorders such as Parkinson's disease, autoimmune neurologic disorders such as multiple sclerosis, headache disorders like migraine and dementias such as Alzheimer's disease. Neurologists may also be involved in clinical research, clinical trials, and basic research, basic or translational research. While neurology is a nonsurgical sp ...
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Carbidopa
Carbidopa (Lodosyn) is a drug given to people with Parkinson's disease in order to inhibit peripheral metabolism of levodopa. This property is significant in that it allows a greater proportion of administered levodopa to cross the blood–brain barrier for central nervous system effect, instead of being peripherally metabolised into substances unable to cross said barrier. Pharmacology Carbidopa inhibits aromatic-L-amino-acid decarboxylase (DOPA decarboxylase or DDC), an enzyme important in the biosynthesis of L-tryptophan to serotonin and in the biosynthesis of L-DOPA to dopamine (DA). DDC exists both outside of (body periphery) and within the confines of the blood–brain barrier. Carbidopa is used in the treatment of, among other diseases, Parkinson's disease (PD), a condition characterized by death of dopaminergic neurons in the substantia nigra. Increased dopamine availability may increase the effectiveness of the remaining neurons and alleviate symptoms for a ...
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Apomorphine
Apomorphine, sold under the brand name Apokyn among others, is a type of aporphine having activity as a non- selective dopamine agonist which activates both D2-like and, to a much lesser extent, D1-like receptors. It also acts as an antagonist of 5-HT2 and α-adrenergic receptors with high affinity. The compound is historically a morphine decomposition product made by boiling morphine with concentrated acid, hence the ''-morphine'' suffix. Contrary to its name, apomorphine does not actually contain morphine or its skeleton, nor does it bind to opioid receptors. The ''apo-'' prefix relates to it being a morphine derivative ("omesfrom morphine"). Historically, apomorphine has been tried for a variety of uses, including as a way to relieve anxiety and craving in alcoholics, an emetic (to induce vomiting), for treating stereotypies (repeated behaviour) in farmyard animals, and more recently in treating erectile dysfunction. Currently, apomorphine is used in the treatment of Pa ...
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Bromocriptine
Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic malignant syndrome, and, as an adjunct, type 2 diabetes. It was patented in 1968 and approved for medical use in 1975. Medical uses Bromocriptine is used to treat acromegaly and conditions associated with hyperprolactinemia like amenorrhea, infertility, hypogonadism, and prolactin-secreting adenomas. It is also used to prevent ovarian hyperstimulation syndrome For label updates seFDA index page for NDA 017962 and to treat Parkinson's disease. Since the late 1980s it has been used, off-label, to reduce the symptoms of cocaine withdrawal but the evidence for this use is poor. A quick-release formulation of bromocriptine, Cycloset, is also used to treat type 2 diabetes.. For label updates seFDA index page for NDA 020866 When administered within ...
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Selegiline
Selegiline, also known as L-deprenyl and sold under the brand names Eldepryl and Emsam among others, is a medication which is used in the treatment of Parkinson's disease and major depressive disorder. It is provided in the form of a capsule or tablet taken by mouth for Parkinson's disease and as a patch applied to skin for depression. Selegiline acts as a monoamine oxidase inhibitor, and increases levels of monoamine neurotransmitters in the brain. At typical clinical doses used for Parkinson's disease, selegiline is a selective and irreversible inhibitor of monoamine oxidase B (MAO-B), increasing levels of dopamine in the brain. In larger doses (more than 20 mg/day), it loses its specificity for MAO-B and also inhibits MAO-A, which increases serotonin and norepinephrine levels in the brain. Medical uses Parkinson's disease In its pill form, selegiline is used to treat symptoms of Parkinson's disease.
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Neuroleptic Malignant Syndrome
Neuroleptic malignant syndrome (NMS) is a rare but life-threatening reaction that can occur in response to neuroleptic or antipsychotic medication. Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fast heart rate. Complications may include rhabdomyolysis, high blood potassium, kidney failure, or seizures. Any medications within the family of neuroleptics can cause the condition, though typical antipsychotics appear to have a higher risk than atypicals, specifically first generation antipsychotics like haloperidol. Onset is often within a few weeks of starting the medication but can occur at any time. Risk factors include dehydration, agitation, and catatonia. Rapidly decreasing the use of levodopa or other dopamine agonists, such as pramipexole, may also trigger the condition. The underlying mechanism involves blockage of dopamine receptors. Diagnosis is based on symptoms. Management includes stopping the triggering medication, r ...
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Entacapone
Entacapone, sold under the brand name Comtan among others, is a medication commonly used in combination with other medications for the treatment of Parkinson's disease. Entacapone together with levodopa and carbidopa allows levodopa to have a longer effect in the brain and reduces Parkinson's disease signs and symptoms for a greater length of time than levodopa and carbidopa therapy alone. Entacapone is a selective and reversible inhibitor of the enzyme catechol-''O''-methyltransferase (COMT). When taken together with levodopa (L-DOPA) and carbidopa, entacapone stops catechol-''O''-methyltransferase from breaking down and metabolizing levodopa, resulting in an overall increase of levodopa remaining in the brain and body. Carbidopa/levodopa/entacapone (Stalevo), a medication developed by Orion Pharma and marketed by Novartis, is a single tablet formulation that contains levodopa, carbidopa, and entacapone. Medical uses Entacapone is used in addition to levodopa and carb ...
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COMT
Catechol-''O''-methyltransferase (COMT; ) is one of several enzymes that degrade catecholamines (neurotransmitters such as dopamine, epinephrine, and norepinephrine), catecholestrogens, and various drugs and substances having a catechol structure. In humans, catechol-''O''-methyltransferase protein is encoded by the COMT gene. Two isoforms of COMT are produced: the soluble short form (S-COMT) and the membrane bound long form (MB-COMT). As the regulation of catecholamines is impaired in a number of medical conditions, several pharmaceutical drugs target COMT to alter its activity and therefore the availability of catecholamines. COMT was first discovered by the biochemist Julius Axelrod in 1957. Function Catechol-''O''-methyltransferase is involved in the inactivation of the catecholamine neurotransmitters (dopamine, epinephrine, and norepinephrine). The enzyme introduces a methyl group to the catecholamine, which is donated by S-adenosyl methionine (SAM). Any compound having a ...
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Tolcapone
Tolcapone, sold under the brand name Tasmar, is a medication used to treat Parkinson's disease (PD). It is a selective, potent and reversible nitrocatechol-type inhibitor of the enzyme catechol-''O''-methyltransferase (COMT). It has demonstrated significant liver toxicity, which has led to suspension of marketing authorisations in a number of countries. In comparison with entacapone, another nitrocatechol COMT inhibitor, tolcapone has a longer half life (2.9 hours vs. 0.8 hours) and can better penetrate the blood–brain barrier, acting both in the central nervous system and in the periphery. However, entacapone is less toxic for the liver. Medical uses Tolcapone is used in the treatment of Parkinson's disease as an adjunct to levodopa/carbidopa or levodopa/benserazide medications. Levodopa is a prodrug for dopamine, which reduces Parkinson symptoms; carbidopa and benserazide are aromatic L-amino acid decarboxylase (AADC) inhibitors. Without administration of tolcapone, t ...
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Duodopa
Carbidopa/levodopa, also known as levocarb and co-careldopa, is the combination of the two medications carbidopa and levodopa. It is primarily used to manage the symptoms of Parkinson's disease, but it does not slow down the disease or stop it from getting worse. It is taken by mouth. It can take two to three weeks of treatment before benefits are seen. Each dose then begins working in about ten minutes to two hours with a duration of effect of about five hours. Common side effects include movement problems and nausea. More serious side effects include depression, low blood pressure with standing, sudden onset of sleepiness, psychosis, and increased risk-taking behavior. Carbidopa prevents the breakdown of levodopa outside the brain. In the brain, levodopa is broken down into dopamine, its active form. Carbidopa also helps prevent some of the nausea which levodopa causes. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medic ...
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Slow-release
Modified-release dosage is a mechanism that (in contrast to immediate-release dosage) delivers a drug with a delay after its administration (delayed-release dosage) or for a prolonged period of time (extended-release R, XR, XLdosage) or to a specific target in the body (targeted-release dosage).Pharmaceutics: Drug Delivery and Targeting
p. 7-13
Sustained-release dosage forms are s designed to release (liberate) a drug at a predetermined rate in order to maintain a constant drug concentratio ...
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Dopamine Dysregulation Syndrome
Dopamine dysregulation syndrome (DDS) is a dysfunction of the reward system observed in some individuals taking dopaminergic medications for an extended length of time. It typically occurs in people with Parkinson's disease (PD) who have taken dopamine agonist medications for an extended period of time. It is characterized by self-control problems such as addiction to medication, gambling, or sexual behavior. Signs and symptoms The most common symptom is craving for dopaminergic medication. However other behavioral symptoms can appear independently of craving or co-occur with it. Craving is an intense impulse of the subject to obtain medication even in the absence of symptoms that indicate its intake. To fulfill this need the person will self-administer extra doses. When self-administration is not possible, aggressive outbursts or the use of strategies such as symptom simulation or bribery to access additional medication can also appear. Hypomania, manifesting with feelings of ...
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