Parkinsonism Overview

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Questions and Answers

What is the primary neurotransmitter depleted in Parkinson's disease due to reserpine?

Acetylcholine

Norepinephrine

Serotonin

Dopamine (correct)

Which of the following is a condition that can lead to drug-induced parkinsonism?

Antihistamine use

Neuroleptic use (correct)

Chronic alcohol use

Levodopa administration

What is a significant characteristic of Parkinson's disease as described in the content?

Constant tremors without rigidity

Presence of hyperkinesia

Progression to rigidity and inability to move (correct)

Increased muscle tone without tremors

What historical breakthrough in 1967 significantly impacted the treatment of Parkinson's disease?

Finding that levodopa produces dramatic improvement Signup and view all the answers

Which of the following statements is true regarding the effects of glutamate in parkinsonism?

It leads to neuronal death by inducing calcium overload through NMDA receptors. Signup and view all the answers

What is the primary effect of an imbalance between the dopaminergic and cholinergic systems in the striatum?

Motor defects Signup and view all the answers

Which mechanism is primarily responsible for the generation of hydroxyl free radicals in the striatum?

Oxidation of dopamine by MAO-B Signup and view all the answers

What characteristic drug is used to alleviate dopamine deficiency in Parkinson's disease?

Levodopa (l-dopa) Signup and view all the answers

Which compound has been shown to produce symptoms similar to Parkinson's disease by impairing energy metabolism?

N-methyl-4-phenyl tetrahydropyridine (MPTP) Signup and view all the answers

Which of the following is NOT a mechanism contributing to the degeneration of nigrostriatal neurons?

Increased production of lipids Signup and view all the answers

What may occur within ½–1 hour of taking bromocriptine?

Marked improvement in overall conditions Signup and view all the answers

What side effects are commonly associated with high doses of bromocriptine?

Nasal congestion and hallucinations Signup and view all the answers

Which of the following medications has largely replaced bromocriptine?

Ropinirole Signup and view all the answers

What is a significant risk when taking the 'first dose' of certain antihypertensive agents?

Marked fall in blood pressure Signup and view all the answers

In patients on long-term levodopa treatment, which problem may become more pronounced?

Excessive daytime sleepiness Signup and view all the answers

What is the typical starting dose of bromocriptine for controlling Parkinson's symptoms?

1.25 mg once at night Signup and view all the answers

Which combination medication is referred to as 'Co-careldopa'?

Levodopa with carbidopa Signup and view all the answers

What effect does combining levodopa with a decarboxylase inhibitor usually aim to achieve?

Increase effectiveness of treatment and reduce side effects Signup and view all the answers

What is the usual daily maintenance dose of levodopa?

0.4–0.8 g Signup and view all the answers

Which drug has a greater affinity for D3 receptors compared to bromocriptine?

Pramipexole Signup and view all the answers

Which combination is used with levodopa to enhance its efficacy?

75–100 mg carbidopa or 100–200 mg benserazide Signup and view all the answers

In advanced cases of Parkinson's disease, what is a key benefit of using pramipexole and ropinirole?

They afford symptom relief comparable to levodopa. Signup and view all the answers

What is the primary reason that dose titration for maximum improvement can be achieved more quickly with other drugs than with bromocriptine?

Bromocriptine causes more gastrointestinal symptoms. Signup and view all the answers

How does the use of ropinirole compare to that of bromocriptine in terms of supplemental levodopa needs?

Fewer patients using ropinirole require supplemental levodopa. Signup and view all the answers

What is the reason for selecting suitable preparations of levodopa according to individual patients?

To tailor treatment to the specific needs of patients. Signup and view all the answers

Study Notes

Parkinsonism

Parkinsonism is an extrapyramidal motor disorder characterized by rigidity, tremor, and hypokinesia.
Secondary symptoms include impaired posture and gait, a mask-like face, and excessive saliva production. Dementia can also be a secondary issue.
Untreated, symptoms worsen progressively over years, leading eventually to immobility, difficulty breathing, and vulnerability to infections.
Parkinson's Disease (PD) is the most common form, a progressive degenerative disorder, primarily affecting older individuals. Idiopathic cases are the most common, while arteriosclerotic and post-encephalitic cases are less common.
Wilson's disease, a rare cause of copper poisoning is also a rare cause.
The primary pathological finding in PD is degeneration of neurons in the substantia nigra pars compacta (SN-PC) and the nigrostriatal dopaminergic tract. This deficiency in dopamine (DA) within the striatum disrupts muscle tone and coordinated movement.
An imbalance between the dopaminergic (inhibitory) and cholinergic (excitatory) systems, creates the motor defects, though the cholinergic system is not primarily impacted.
The exact cause of nigrostriatal neuron degeneration appears multifactorial.
Oxidative stress from dopamine metabolism and age-related/acquired defects in protective mechanisms contribute to neuronal damage.
Environmental toxins and genetics may also contribute.
Exposure to MPTP, a synthetic toxin, causes nigrostriatal degeneration and PD-like symptoms by affecting energy metabolism in dopaminergic neurons.
Glutamate excess can induce 'excitotoxic' neuronal death.
Medications like neuroleptics and metoclopramide can induce temporary parkinsonism.
Reserpine use historically caused this.

Antiparkinsonian Drugs

A breakthrough in treating PD occurred in 1967, when levodopa was found to dramatically improve symptoms.
Levodopa (L-dopa) is a precursor of dopamine which is used to treat PD because dopamine itself cannot cross the blood-brain barrier.
Dopamine precursor, peripheral decarboxylase inhibitors, and dopamine agonists are important types of drugs used to treat PD.
MAO-B Inhibitors and COMT Inhibitors are also used to potentiate levodopa to extend the efficacy of the drug.

Classification of Antiparkinsonian Drugs

Drugs affecting the brain's dopaminergic system are crucial and include dopamine precursors (levodopa); peripheral decarboxylase inhibitors (carbidopa, benserazide); dopamine agonists (bromocriptine, ropinirole, pramipexole); MAO-B inhibitors (selegiline, rasagiline); and COMT inhibitors (entacapone, tolcapone).
Drugs affecting the brain's cholinergic system are also used and include central anticholinergics (trihexyphenidyl, procyclidine, biperiden) and antihistamines (orphenadrine, promethazine).
Glutamate (NMDA receptor) antagonists (amantadine) are also used.

Actions and Effectiveness of Drugs

Levodopa, the most effective treatment, greatly improves movement disorders in Parkinson's Disease.
Levodopa's efficacy is high in early-stage disease.
Side effects like nausea, vomiting, postural hypotension, cardiac arrhythmias, and psychiatric symptoms may be problematic. Dyskinesias are common and often dose-related, potentially impairing function.
Additional drugs such as COMT inhibitors and MAO-B inhibitors are given with levodopa to enhance treatment efficacy and reduce the dose needed.
Non-ergoline dopamine agonists, such as ropinirole, pramipexole are being used increasingly as effective treatments that are less prone to early dopaminergic neuron damage and offer similar efficacy to levodopa.
Central anticholinergics like trihexyphenidyl produce substantial improvement, especially to tremor.
These drugs have little effect on the underlying disease pathology, only mitigating manifestations.
The effects of levodopa include a 'general alerting response', which can at times manifest as mild excitement or even frank psychosis.
Excessive dopamine can also lead to unwanted side effects such as increased sexual activity.
Dementia is not reversed by levodopa.

Problems in Long-term Therapy

Fluctuations in motor performance ("on-off" phenomenon) can develop after several years of levodopa treatment.
"End-of-dose" deterioration and rapid motor fluctuations are among consequences.
Progressive neuronal damage usually leads to more frequent and more severe fluctuations.
Combination therapy, with additional drugs, helps manage fluctuation issues and improves quality of life.

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Description

Explore the characteristics and symptoms of Parkinsonism, a motor disorder affecting movement and muscle control. This quiz covers the most common form, Parkinson's Disease, and its impacts on aging individuals. Delve into the pathology, secondary symptoms like dementia, and treatment insights.