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group_3_presentation_1_-_parkinsons [2019/02/01 17:38] gilli1 [Dopamine Agonist] |
group_3_presentation_1_-_parkinsons [2019/02/01 19:04] (current) gilli1 [Drugs and Medication] |
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| ===== History ===== | ===== History ===== | ||
| - | <box 25% round right | > {{ :essay.png?200|}} </box| Figure 2: The first page of the essay written by James Parkinson.> | + | <box 18% round right | > {{ :essay.png?200|}} </box| Figure 2: The first page of the essay written by James Parkinson.> |
| Traditionally, descriptions of PD can be found as early as 1000 BC for Indian texts, in addition to those within ancient Chinese sources.<sup>[2]</sup> PD was initially described by James Parkinson in 1817 through this work in “Essay on the shaking palsy”.<sup>[3]</sup> This was originally thought to be a movement disorder with three fundamental signs: bradykinesia, rigidity, and tremors.<sup>[3]</sup> Parkinson at that time described the disease as: “involuntary tremulous motion, with lessened muscular power, in parts not in action and even when supported; with a propensity to bend the trunk forward, and to pass from a walking to a running pace: the senses and intellects being uninjured”.<sup>[2]</sup> With time, postural changes and instability were included as a fourth fundamental sign.<sup>[4]</sup> | Traditionally, descriptions of PD can be found as early as 1000 BC for Indian texts, in addition to those within ancient Chinese sources.<sup>[2]</sup> PD was initially described by James Parkinson in 1817 through this work in “Essay on the shaking palsy”.<sup>[3]</sup> This was originally thought to be a movement disorder with three fundamental signs: bradykinesia, rigidity, and tremors.<sup>[3]</sup> Parkinson at that time described the disease as: “involuntary tremulous motion, with lessened muscular power, in parts not in action and even when supported; with a propensity to bend the trunk forward, and to pass from a walking to a running pace: the senses and intellects being uninjured”.<sup>[2]</sup> With time, postural changes and instability were included as a fourth fundamental sign.<sup>[4]</sup> | ||
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| ===== Causes ===== | ===== Causes ===== | ||
| - | Parkinson’s is a cause of decreased neuronal activity. The neurons in the brain will begin to deteriorate or die down over a period of time. The neurons that are primarily degraded produce dopamine for the body. This decrease in dopamine will lead to symptoms such as tremors, rigid muscles, impaired balance, etc. There are also certain changes that can occur in the overall physical structure of the brain. This is primarily through the abundance of Lewy bodies. Inside of these Lewy bodies there is an accumulation of alpha-synuclein protein. These clumps of Lewy bodies will interfere with neuronal function and can cause accelerated Parkinson’s. Parkinson’s will primarily manifest from genetic mutations. These mutations are rare, but if present they will affect the brain makeup and dopamine levels. The familial mutations include changes in the LRRK2, PARK7, PINK1, PRKN, or SNCA genes. These mutations are not the only changes that Parkinson’s could potentially effect; however, these are often present in a lot of the cases. Overall, family history only plays a 15% role in the inheritance of this disease. Another cause of Parkinson’s can be through environmental toxins. There are certain chemical substances that can lead to Parkinson’s. Along with the environmental risk factors it can also be dependent on age and sex. It is commonly found in older people and is much more likely to develop in males. | + | PD is a result of decreased neuronal activity. These neurons in the brain begin to deteriorate or die down over a period of time.<sup>[10]</sup> The neurons that are primarily degraded in PD produce dopamine for the body. This decrease in dopamine leads to symptoms such as tremors, rigid muscles, impaired balance, etc. There are also certain changes that can occur in the overall physical structure of the brain. This is primarily through the abundance of Lewy bodies which contain an accumulation of alpha-synuclein protein.<sup>[11]</sup> These clumps of Lewy bodies will interfere with neuronal function and can accelerate the progression of PD.<sup>[11]</sup> This disease will primarily manifest from genetic mutations, which are rare, but if present will affect the brain makeup and dopamine levels. The familial mutations include changes in the LRRK2, PARK7, PINK1, PRKN, or SNCA genes.<sup>[12]</sup> These mutations are not the only changes that PD could potentially affect; however, these are often present in a lot of the cases. Overall, family history only plays a 15% role in the inheritance of this disease.<sup>[12]</sup> PD can be triggered through environmental toxins, particularly certain chemical substances.<sup>[10]</sup> Furthermore, PD can also be dependent on age and sex such that is is more common in older adults and males.<sup>[10]</sup> |
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| ===== Pathophysiology ===== | ===== Pathophysiology ===== | ||
| - | <box 20% round right | > {{ :screen_shot_2019-02-01_at_5.30.26_pm.png?200|}} </box| Figure 3:> | + | <box 18% round right | > {{ :screen_shot_2019-02-01_at_5.30.26_pm.png?200|}} </box| Figure 3:Chemical synapses in the nervous system> |
| PD is caused by a deficiency of the neurotransmitter dopamine due to the degeneration of substantia nigra in the basal ganglia.<sup>[13]</sup> The substantia nigra contains dopamine secreting neurons whereas the basal ganglia is part of the brain which controls coordinated movement.<sup>[14]</sup> | PD is caused by a deficiency of the neurotransmitter dopamine due to the degeneration of substantia nigra in the basal ganglia.<sup>[13]</sup> The substantia nigra contains dopamine secreting neurons whereas the basal ganglia is part of the brain which controls coordinated movement.<sup>[14]</sup> | ||
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| As PD progresses, dopaminergic neurons will continue to deteriorate, affecting the excitatory response and inhibitory response from the thalamus. This has been found to disrupt voluntary motor control leading to the characteristic symptoms of PD.<sup>[16]</sup> | As PD progresses, dopaminergic neurons will continue to deteriorate, affecting the excitatory response and inhibitory response from the thalamus. This has been found to disrupt voluntary motor control leading to the characteristic symptoms of PD.<sup>[16]</sup> | ||
| - | <box 20% round right | > {{ :screen_shot_2019-02-01_at_5.30.17_pm.png?200|}} </box| Figure 4: > | + | <box 18% round right | > {{ :screen_shot_2019-02-01_at_5.30.17_pm.png?200|}} </box| Figure 4: Dopamine levels in a normal neuron versus Parkinson’s affected neuron > |
| === Nigrostriatal Pathway === | === Nigrostriatal Pathway === | ||
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| In patients with PD, Lewy bodies are present in many of the remaining cells in the substantia nigra. Lewy bodies mainly consists of the alpha-synuclein proteins. It has been found that alpha synuclein plays a role in the progression of PD however, the way in which the Lewy bodies affect the neurons are not known.<sup>[11]</sup> Nonetheless, there has been evidence suggesting that they act as toxins. <sup>[20]</sup> | In patients with PD, Lewy bodies are present in many of the remaining cells in the substantia nigra. Lewy bodies mainly consists of the alpha-synuclein proteins. It has been found that alpha synuclein plays a role in the progression of PD however, the way in which the Lewy bodies affect the neurons are not known.<sup>[11]</sup> Nonetheless, there has been evidence suggesting that they act as toxins. <sup>[20]</sup> | ||
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| ===== Diagnosis ===== | ===== Diagnosis ===== | ||
| - | Currently, there is no definitive test to determine whether or not someone has PD however, medical history and clinical tests are used to test for symptoms of PD.<sup>[24]</sup> <box 30% round right | > {{ :screen_shot_2019-01-31_at_1.10.55_pm.png?300|}} </box| Figure 6: UK Brain Bank Criteria. > Misdiagnosis for PD is quite common since symptoms overlap with a number of other diseases, resulting in either a lack of diagnosis or inaccurate diagnosis of PD.<sup>[23]</sup> | + | Currently, there is no definitive test to determine whether or not someone has PD however, medical history and clinical tests are used to test for symptoms of PD.<sup>[24]</sup> <box 27% round right | > {{ :screen_shot_2019-01-31_at_1.10.55_pm.png?300|}} </box| Figure 6: UK Brain Bank Criteria. > Misdiagnosis for PD is quite common since symptoms overlap with a number of other diseases, resulting in either a lack of diagnosis or inaccurate diagnosis of PD.<sup>[23]</sup> |
| The following tests are currently used to assess presence of PD: | The following tests are currently used to assess presence of PD: | ||
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| ===== Drugs and Medication ===== | ===== Drugs and Medication ===== | ||
| - | Currently there is no cure for PD but various drugs and medication can provide relief from the symptoms. Over the recent years, extensive research has been conducted allowing for significant results in treatments for PD. Although there are numerous medications available, the use of these drugs are dependent on the disease stage and the age of onset. The main groups of drugs used for treating PD, especially for the coordination of movement, are: levodopa, MAO-B inhibitors, and dopamine agonists. | + | Currently there is no cure for PD but various drugs and medication can provide relief from the symptoms. Over the recent years, extensive research has been conducted allowing for significant results in treatments for PD. Although there are numerous medications available, the use of these drugs are dependent on the disease stage and the age of onset. The main groups of drugs used for treating PD, especially for the coordination of movement, are: levodopa, dopamine agonists, and MAO-B inhibitors. |
| - | <box 28% round right | > {{ :screen_shot_2019-01-31_at_8.08.40_pm.png?200|}} </box| Figure 7: Dopaminergic synapse in the substantia nigra with levodopa.> | + | <box 20% round right | > {{ :screen_shot_2019-01-31_at_8.08.40_pm.png?200|}} </box| Figure 7: Dopaminergic synapse in the substantia nigra with levodopa.> |
| ==== Levodopa ==== | ==== Levodopa ==== | ||
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| Selegiline was the first MAO-B inhibitor to be used for individuals living with PD.<sup>[26]</sup> This is a drug with a mild to moderate benefit and is used as a monotherapy in early onset of PD. Once the disease is progressive it is used as an adjunctive therapeutic with either levodopa or dopamine agonist.<sup>[26]</sup> Side effects of this drug include headache, nausea, loss of balance, and gastrointestinal symptoms. | Selegiline was the first MAO-B inhibitor to be used for individuals living with PD.<sup>[26]</sup> This is a drug with a mild to moderate benefit and is used as a monotherapy in early onset of PD. Once the disease is progressive it is used as an adjunctive therapeutic with either levodopa or dopamine agonist.<sup>[26]</sup> Side effects of this drug include headache, nausea, loss of balance, and gastrointestinal symptoms. | ||
| - | ====== Future Therapeutics ====== | + | ===== Future Therapeutics ===== |
| ==== A2A Antagonists ==== | ==== A2A Antagonists ==== | ||
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| ==== AFQ056 ==== | ==== AFQ056 ==== | ||
| - | This is selective antagonist of the mGluR5 receptor which can help mediate symptoms of dyskinesia. This drug is particularly effective at reducing the amount of dyskinesia as a direct result of levodopa.<sup>[31]</sup> This drug had statically significant impact on patients that were on levodopa treatment.<sup>[31]</sup> This drug is too given in conjecture with traditional treatments and can dramatically reduce certain symptoms. It is still early in the testing process, but has shown excellent progression thus far. | + | This is selective antagonist of the mGluR5 receptor which can help mediate symptoms of dyskinesia. This drug is particularly effective at reducing the amount of dyskinesia as a direct result of levodopa.<sup>[31]</sup> This drug had statically significant impact on patients that were on levodopa treatment.<sup>[31]</sup> This drug is given in conjecture with traditional treatments and can dramatically reduce certain symptoms. It is still early in the testing process, but has shown excellent progression thus far. |
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| + | ===== Conclusion ===== | ||
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| + | PD is one the most common neurodegenerative diseases, directly impacting many globally. A decrease in the production of dopamine triggers various symptoms, slowly affecting the body. Though there is no test or cure for PD, there are future therapies researchers are working on to help those affected by Parkinson’s disease. | ||
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| + | With what we know, there is still more work that needs to be done. Researchers are continuing to understand the progression of PD and how best to overcome it. | ||
| ===== References ===== | ===== References ===== | ||
