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Questions and Answers
What is the primary effect of dopaminergic action in the striatum?
What is the primary effect of dopaminergic action in the striatum?
How does levodopa bioavailability get affected according to the provided information?
How does levodopa bioavailability get affected according to the provided information?
What is observed about prolactin levels during levodopa therapy in Parkinson's patients?
What is observed about prolactin levels during levodopa therapy in Parkinson's patients?
What might happen if gastric emptying is slow during levodopa therapy?
What might happen if gastric emptying is slow during levodopa therapy?
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What side effect commonly occurs in patients receiving levodopa therapy?
What side effect commonly occurs in patients receiving levodopa therapy?
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What is the primary effect of combining levodopa with carbidopa or benserazide?
What is the primary effect of combining levodopa with carbidopa or benserazide?
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Which of the following conditions requires cautious use of levodopa?
Which of the following conditions requires cautious use of levodopa?
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What consequence does pyridoxine have when combined with levodopa that is not combined with carbidopa?
What consequence does pyridoxine have when combined with levodopa that is not combined with carbidopa?
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What is the usual daily dose of levodopa for therapeutic effect?
What is the usual daily dose of levodopa for therapeutic effect?
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Which of the following is a characteristic of decarboxylase inhibitors like carbidopa and benserazide?
Which of the following is a characteristic of decarboxylase inhibitors like carbidopa and benserazide?
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What does the degeneration of neurones in the substantia nigra pars compacta primarily lead to in Parkinson's disease?
What does the degeneration of neurones in the substantia nigra pars compacta primarily lead to in Parkinson's disease?
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Which of the following is a common cause of drug-induced temporary parkinsonism?
Which of the following is a common cause of drug-induced temporary parkinsonism?
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What major breakthrough in treatment for Parkinson’s disease occurred in 1967?
What major breakthrough in treatment for Parkinson’s disease occurred in 1967?
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What is a likely consequence of excessive excitatory transmitter glutamate in Parkinson’s disease?
What is a likely consequence of excessive excitatory transmitter glutamate in Parkinson’s disease?
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Which type of Parkinsonism is most likely to be idiopathic?
Which type of Parkinsonism is most likely to be idiopathic?
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What is one of the common side effects associated with high doses of bromocriptine in patients?
What is one of the common side effects associated with high doses of bromocriptine in patients?
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What is the purpose of combining levodopa with a decarboxylase inhibitor in treatment?
What is the purpose of combining levodopa with a decarboxylase inhibitor in treatment?
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What is the initial dose of bromocriptine recommended for patients?
What is the initial dose of bromocriptine recommended for patients?
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Which of the following is a side effect that may occur early in patients taking bromocriptine?
Which of the following is a side effect that may occur early in patients taking bromocriptine?
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How do the newer D2/D3 receptor agonists like ropinirole and pramipexole compare to bromocriptine?
How do the newer D2/D3 receptor agonists like ropinirole and pramipexole compare to bromocriptine?
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What is a consequence of progressive degeneration of peripheral decarboxylase DA neurons?
What is a consequence of progressive degeneration of peripheral decarboxylase DA neurons?
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How does the combination of carbidopa and levodopa affect treatment outcomes in Parkinson's disease?
How does the combination of carbidopa and levodopa affect treatment outcomes in Parkinson's disease?
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Which factor is important to consider when administering levodopa to elderly patients?
Which factor is important to consider when administering levodopa to elderly patients?
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What characteristic of pyridoxine impacts the effectiveness of levodopa when not combined with carbidopa?
What characteristic of pyridoxine impacts the effectiveness of levodopa when not combined with carbidopa?
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What is the usual starting dose of levodopa for effective therapy?
What is the usual starting dose of levodopa for effective therapy?
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What is the usual daily maintenance dose of levodopa?
What is the usual daily maintenance dose of levodopa?
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Which of the following statements about ropinirole is correct?
Which of the following statements about ropinirole is correct?
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What can be said about the side effect profile of bromocriptine compared to pramipexole?
What can be said about the side effect profile of bromocriptine compared to pramipexole?
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In the treatment of advanced PD, what is a common characteristic regarding the capacity to synthesize DA?
In the treatment of advanced PD, what is a common characteristic regarding the capacity to synthesize DA?
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What is the significance of dose titration for maximum improvement in PD therapy?
What is the significance of dose titration for maximum improvement in PD therapy?
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Study Notes
Parkinsonism
- Parkinsonism is an extrapyramidal motor disorder featuring rigidity, tremor, and hypokinesia.
- Secondary symptoms include posture and gait problems, a mask-like face, excessive saliva production, and potentially dementia.
- Untreated, it progresses to a severe stage where patients are rigid, immobile, and susceptible to infections or embolisms.
- Parkinson's disease (PD) is a progressive degenerative disorder mainly affecting the elderly.
- Idiopathic causes account for most cases, while some are attributed to arteriosclerosis.
- Wilson's disease, a rare copper poisoning disorder, is another possible cause.
Neurological Degeneration in PD
- The substantia nigra pars compacta (SN-PC) and the nigrostriatal dopaminergic tract are predominantly affected in PD.
- This leads to dopamine (DA) deficiency in the striatum, contributing to muscle tone imbalances and movement coordination issues.
- A deficiency arises from an imbalance between dopaminergic (inhibitory) and cholinergic (excitatory) systems in the striatum.
- Oxidative stress caused by DA metabolism may trigger neuronal damage.
- Age-related declines in protective mechanisms, environmental toxins, and genetic predispositions exacerbate this vulnerability.
- Mitochondrial dysfunction in aging further exacerbates neuronal damage.
- Exposure to MPTP-like chemicals, present in some drugs, accelerated age-related/pre-disposed neuronal damage contributing to parkinsonism.
- Excess glutamate can induce neuronal death through NMDA receptors.
Treatment Breakthrough and Classification
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A groundbreaking 1967 discovery demonstrated levodopa's potential to treat PD effectively.
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Levodopa, the precursor to DA, is significantly effective, but doesn't cross the blood-brain barrier, necessitating its use with other substances.
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Several types of drugs are crucial in treating parkinsonism.
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Drugs affecting brain dopaminergic system:
- Dopamine precursor: Levodopa
- Peripheral decarboxylase inhibitors: Carbidopa, Benserazide
- Dopaminergic agonists: Bromocriptine, Ropinirole, Pramipexole
- MAO-B inhibitor: Selegiline, Rasagiline
- COMT inhibitors: Entacapone, Tolcapone
Levodopa Actions
- Levodopa exhibits a highly effective therapeutic effect in Parkinson's disease.
- Although ineffective on its own, it's a precursor to dopamine, enabling its uptake and conversion within the brain.
- Levodopa significantly improves various motor symptoms (e.g., hypokinesia, rigidity, tremor).
- Secondary symptoms like posture, gait, handwriting, speech, facial expression and mood also improve.
- Levodopa can also be used to produce a non-specific "awakening" effect in hepatic coma.
Side Effects of Levodopa
- Common side effects include nausea, vomiting, postural hypotension, and cardiac arrhythmias.
- Development of abnormal movements (dyskinesias) can occur with prolonged use.
- Behavioral effects such as anxiety or psychosis can also manifest.
- Additional side effects include alterations in taste, altered dopamine regulation in the cardiovascular system; or the potential for dopamine to act via excitatory receptors in the vomiting centre leading to nausea and vomiting.
Other Important Drugs in PD Treatment
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Peripheral Decarboxylase Inhibitors (PDIs): Carbidopa/benserazide are given with levodopa to decrease peripheral metabolism, and hence increase the amount of levodopa available to reach the brain, thereby reducing nausea and vomiting as well as needing a smaller dose of levodopa to give the same effect.
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Dopamine Agonists (e.g., Bromocriptine, Ropinirole, Pramipexole): These directly stimulate dopamine receptors in the brain, useful as monotherapy in early PD or as an adjunct to levodopa in later stages. These drugs have a slower onset of action compared to levodopa.
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MAO-B Inhibitors (e.g., Selegiline, Rasagiline): These are helpful in delaying the progression of the disease and reducing the need for higher doses of levodopa, and also reduce the motor fluctuations and 'wearing-off' associated with later-stage disease. They also have a lesser incidence of dyskinesia compared to levodopa.
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COMT Inhibitors (e.g., Entacapone, Tolcapone): These drugs inhibit the breakdown of levodopa in the periphery, increasing its availability to reach the brain, resulting in the reduction in required doses of levodopa to achieve a therapeutic effect.
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Anticholinergics (e.g., Trihexyphenidyl, Biperiden): These drugs counter the effects of excess acetylcholine, improving tremors, rigidity and other symptoms in early and milder cases of the disease.
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Glutamate Antagonists (Amantadine): Less effective than levodopa, amantadine acts on the NMDA receptor (and also has some dopamine facilitator properties), may be supplemented to levodopa in more advanced cases/ patients with dyskinesias.
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Description
Explore the various aspects of Parkinsonism, an extrapyramidal motor disorder characterized by rigidity, tremor, and hypokinesia. Understand its symptoms, progression, and the neurodegenerative changes associated with Parkinson's disease. This quiz delves into both idiopathic causes and rare conditions like Wilson's disease.
