Frequently Asked Questions About Anti-Parkinsonian Medications

It is a slowly progressing chronic neurological disease usually developed in elderly people. It is a degenerative disorder of the extrapyramidal motor system driven by the gradual destruction and death of neurons that produce dopamine in the CNS and the signs of the health condition occur.

The main manifestations of the disease are:
– Muscle rigidity. It is a uniform elevation in muscle tone by plastic type. The hands and legs, while flexing and unbending, freeze in the position given. This form of elevated muscle tone is called "plastic wax flexibility." The predominance of rigidity in certain muscle groups leads to the formation of a characteristic “dummy posture”: the patient slouches, head tilts forward, arms bend at the elbows, and the hip and knee joints are also slightly bent.
– Hypokinesia (limited pace and range of motion) is a decrease in spontaneous motor activity. The patient can freeze and be still for hours. Active movements occur after some delay, their pace is slowed down. The patient’s steps become small and the feet are parallel to each other. The face becomes mask-like, the look is frozen, and blinks are rare. Smile and grimaces of crying appear late and just as slowly disappear.
– Tremor (shaking) usually starts in one arm, with the advancement of the disease spreading to the opposite arm and to the legs. The multidirectional moves of the thumb and fingers resemble counting change or the rolling of pills (like the old technique of creating pills in the pharmaceutical industry). Usual also are a “yes-yes” or “no-no” head shaking, a shaking in the eyelids, lower jaw, and so on. In rare cases, it covers the whole body. Shaking enhances in agitation and diminishes during sleep and intended movements.
– Postural instability (worsened posture). Postural instability is noticeable in the late stages of the disease. An individual has difficulty in overcoming both the inertia of rest and the inertia of movement. It is difficult for a patient to start a movement, and starting it is difficult to stop. A person can often lose stability and fall. Sometimes patients have defined “paradoxical kinesis”, when, due to emotional experiences, after sleeping or due to other factors, a person begins to move freely, the symptoms typical for the disease disappear but after a few hours, the symptoms return.
– Vegetative and mental disorders. Besides the motor sphere disorders, vegetative and metabolic dysfunctions are noted in Parkinson's disease. It results in either extreme weight loss (cachexia) or obesity. Secretory disorders manifest in greasiness of the skin, especially of the face, increased salivation, and excessive sweating.
– Mental disorders in Parkinson's can be induced by the disease itself, as well as antiparkinsonian drugs. Initial signs of psychosis (fear, confusion, insomnia, a hallucinatory-paranoid state with disorientation) are noted in 20% of outpatients and two-thirds of patients with severe Parkinsonism. Dementia is less pronounced than with senile dementia. Depression is observed in 47%, sleep disorders and pathological fatigue are observed in 40%. Patients are inactive, sluggish, and also intrusive, prone to repeating the same questions.
Over time the manifestations progress and shaking along with worsened posture are the main visible symptoms.

The manifestations of the condition result from the diminishing of the brain chemical dopamine. It happens when the nerve cells that transport dopamine get damaged or die, the content of dopamine also lowers.
The causes of the processes that are now described as Parkinson’s disease aren’t fully studied. It is believed that the risk factors are old age, genetic predisposition, and environmental factors.
About 15% of individuals with Parkinson's have a family history of the disease. However, the genes that can indicate the predisposition to the disease have not been identified.
Parkinson-like manifestations can also be provoked by environmental factors (pesticides, herbicides, heavy metal salts), chronic cerebrovascular insufficiency, or use of medicines that cause extrapyramidal side effects.

To date, no blood or other tests that can identify the condition exist. But there are procedures that are followed by physicians and neuropathologist when an individual has symptoms of Parkinsonism. For instance, a physical examination is made to identify the main manifestations of the disease, medical history of a patient is analyzed, and additional tests to exclude other illnesses that can have similar symptoms are made.

It isn’t a contagious disease. As we have previously mentioned, it is rather a genetic predisposition and additional negative effect from external factors. You cannot precisely find out whether you are predisposed to the disease because the genes responsible for it aren’t determined. However, if someone from your close family has the disease, there is a chance that you can inherit it.

Unfortunately, nowadays it’s impossible to forecast if an individual is going to develop the disease or not and therefore it’s impossible to do anything to prevent it. Especially, taking into account that scientists are still not sure what causes the illness.

No. This misconception arose from the fact that in 90-95% the dysfunction affects elderly people over 65. But the remaining individuals who get it can develop early onset of symptoms, for instance, as early as at the age of 40.

The progression of the disease is very individual. However, it has been noticed that the earlier it onsets, the faster it progresses and have more pronounced movement manifestations. When the disease develops in people over 70 years of age, psychical disorders are more pronounced than motion disorders.

Individuals who do not receive therapy for the condition, on average, are unable to care for themselves within 8 years after the disease onset and in 10 years become bedridden. Patients who receive appropriate treatment, on average, become dependent on caregivers within 15 years after the disease onset.

The progression of the disease cannot be reversed but it can be effectively slowed down with the timely start of the therapy.

The health condition stage is a level of progress of the manifestations. In Parkinson’s disease the following stages are identified:
– Stage 0: no signs of disease are present;
– Stage I: a) Shaking in one limb, usually, the hand, are occurring; b) Shaking in one limb and one side of the body is occurring.
– Stage II: a) Shaking of both sides of the body; b) Bilateral manifestations of postural impairment. The individual is able to overcome the inertia of movement caused by the push.
– Stage III: Pronounced posture deterioration and restriction of movements;
– Stage IV: Severe symptoms development, disability; individual needs help for daily activities but can stand/walk without support.
– Stage V: Patient is bedridden and needs constant care.

The life span of individuals affected by the disease is on average the same as for people without it. Nevertheless, persons with dysfunction have additional risks such as choking, falling, and so on due to the manifestations of the disease.

No. Unfortunately, the disease cannot be completely cured currently. Scientists still work on the understanding of the causes and principles of the health condition. But for now, they have come up only with the solutions that can lower the manifestations and slow down the development of the symptoms but do not eliminate it completely.

Currently, the disease is incurable; all existing treatments are aimed at alleviating its symptoms (symptomatic treatment). The main drugs that eliminate motor impairment are:Levodopa (more often in combination with peripheral DOPA- inhibitors or less commonly with COMT inhibitors), dopamine receptor enhancers and MAO-B inhibitors.
– Dopaminergic formulations: Dioxyphenylalanine (Dopa) is a substance that is formed in the organism from a predecessor of dopamine.  In Parkinson's disease, the level of dopamine is significantly diminished, so substances to elevate its level in the CNS are used. Unfortunately, dopamine cannot be taken for this goal because it is unable to penetrate the brain barrier.
Levodopa, a levorotating isomer of Dopa, is the most effective type of Dopa and is frequently used. But a bigger share of the substance enters the liver and transforms into dopamine, which cannot enter through the hemato-encephalic barrier. To avoid it, the pills are combined with DOPA inhibitors (benserazide, carbidopa). For instance, you can buy Sinemet (Carbidopa + Levodopa formulation).
It diminishes muscle stiffness and postural changes. As for tremor and salivation, the beneficial effect is achieved in around 60%.
The formulation can be combined with central anticholinergic blockers and must not be used along with MAO inhibitors.
When using the formulation possible adverse reactions such as digestive disorder symptoms, low blood tension, arrhythmias, hyperkinesis, etc. can occur.
In individuals below 60–70 years, the use Levodopa is not advised due to the diminishing of its efficacy in long-term therapy.
Treatment of individuals older than 70 years, even in the initial stages, is encouraged to be started with Levodopa, which is explained by lower efficacy of other groups of medicines and more frequent somatic and mental negative reactions at this age.
– Dopamine agonists. Dopamine receptor agonists (pergolid, apomorphine, etc.) are also used as the main treatment. The formulations from this group are specific central agonists of dopamine receptors. By imitating the action of dopamine, they have the same pharmacological effects as Levodopa. Compared to Levodopa, they don’t cause as much other movement disorders, but more often provoke other adverse reactions such as edema, sluggishness, hallucinations, nausea, and others.
– MAO inhibitors of type B and catechol-O-methyltransferase.
This group of drugs selectively inhibits the activity of enzymes that break down dopamine. MAO-B inhibitors (for instance, Selegiline) and COMT inhibitors (e.g., entacapone and tolcapone) slow down the steady progression of Parkinson's disease. Pharmacological effects are similar to Levodopa, although their intensity is much lower. They can enhance the effects of Levodopa, without increasing and even reducing its total dose.
– Dopamine reuptake inhibitors.
Indirect dopaminomimetics (amantadine, gludantan) increase the sensitivity of the receptors to the corresponding mediator. These medicines enhance the release of dopamine from presynaptic endings and inhibit its reverse neuronal capture. Drugs in this group cause the same pharmacological effects as Levodopa, that is, they mainly suppress hypokinesia and muscle rigidity, affecting tremor significantly milder.
– Anticholinergics.
The most frequently used medications from the group are trihexyphenidyl (cyclodol), triperiden, biperiden, and tropacin. The use of the formulations is reasonable for the normalization of choline and dopaminergic processes as due to the disease they are impaired so the drugs "align" neurotransmitter interactions. A distinctive feature of central anticholinergics is that they have a greater effect on tremor and less affect rigidity and bradykinesia. Due to their peripheral effect, salivation decreases, to a lesser extent, perspiration and skin greasiness also are reduced.