ANTI-DEPRESSANTS-3 MAO INHIBITORS-PARKINSON DISEASE-SELEGILINE-RASAGILINE

 Depression and Parkinson's Disease (PD)

Although this post is the third in a series of antidepressants, it is important to note that depression is one of the most common causes of Parkinson's disease.

Depression, anxiety, and psychoses are just like any other illness which just needs full support from the family. This is because dementia and Parkinson's Disease are often caused by unnecessary worries and depression.

MAO (MONO AMINE OXIDASE):-

Monoamine oxidase (MAO; EC 1.4.3.4.) is a mitochondrial enzyme system that is widely embedded in cells throughout the body, with high levels of exposure in gastrointestinal and liver, and neuronal tissues. This enzyme promotes the oxidative amino degradation of various types of monoamines and has the potential to break down any monoamine that is endogenous (produced inside the body) or exogenous (which can be a medicine given externally).

This enzyme disrupts and inactivates the monoamine neurotransmitters such as noradrenaline, dopamine, and serotonin, released for intercommunication of the neurons. Monoamine oxidase inhibitors, also known as MAOIs, are drugs that have been developed to inactivate this enzyme for neurodegenerative and depressive disorders such as Parkinson's Disease (PD).

MONOAMINE OXIDASE INHIBITORS(MAOIs)

These MAO enzyme inhibitors are of two types. They are MAOI-A and MAOI-B.

MAO-A and MAO-B inhibitors are in clinical use for the treatment of mental and neurological disorders (Parkinson's disease), respectively.

The clarity in studies of the active components of the molecules of these enzymes has led to the development of new compounds that inactivate these enzymes.

However, most of these enzyme inhibitors are irreversible. Although these are very decisive, the consequences are severe. So doctors do not prescribe many of these medications for depression now. However, they are still used especially for Parkinson's disease. Examples are Selegiline and Rasagiline.

The most important of these side effects is the Cheese Effect

People taking these drugs should avoid the following foods that may contain the amino acid tyramine. If not they may have complications such as heart attack and headaches. If you want to eat those foods you can take them a few hours after taking the medicine. However, it is better to consult a doctor.

Tyramine Foods

1. Chronic Stored Protein Foods (eg) Cheesecake, Meat

2.Chocolate

3. Citrus fruits, stored avocado (elephant guava), bananas, fruits such as raisins.

4.Pickles

5.Wine made from soaked grapes.

Sweets such as chocolate contain not only tyramine but also norepinephrine and serotonin. Taking all of these in combination with MAOI drugs can lead to a dangerous condition called 'Adrenergic or Hypertensive Crisis'.

MAO enzymes generally react and express their effects as follows.

     1             2      3             1A        2A       3A 

RCH2NH2+O2+H2O⟶RCHO+NH3↑+H2O2

                    MAOs  ↑

The above chemical equation can be explained as follows.

1.A monoamine

2.Oxygen.

3.Water

After MAO ↑ oxidation ()

1A. An aldehyde (toxic)

2A. Ammonia (toxic)

3.A. hydrogen peroxide (toxic)

All of the above toxins are caused by MAO oxidation. This condition can be caused by a number of illnesses, including depression. Under normal health, our body decomposes, detoxify and excrete these aldehyde and hydrogen peroxide toxins further by enzymes such as aldehyde dehydrogenase, catalase, and superoxide dismutase.

But this structure often collapses when subjected to frequent mental stresses, leading to Parkinson's and depressive disorders.

MAO Inhibitors (MAOIs) for Depression

These monoamine oxidase enzymes are classified as MAO-A and MAO-B. MAO-A can cause depression. It often targets neurotransmitters such as norepinephrine, adrenaline, and serotonin, that cause depression. The following medications disable this enzyme and relieve depression. But these should not be taken without a doctor's prescription. They are,

1.Isocarboxazid- (Marplan)-Nonselective &    Irreversible

2.Phenelzine     - (Nardil)--        do-

3.Selegiline      - (Selgin)-Irreversible & MAO-B-I

4.Rasagiline     -                            -do-

5.Safinamide    -              -Reversible & MAO-B-

6.Moclobemide -             -Reversible & MAO-A -

Of the drugs mentioned above, those labeled as Nonselective and  Irreversible have the potential to cause irreversible inaction of both the enzymes. They are very strong in action but have more side effects. So doctors do not recommend this much.

Those labeled as Selective and Irreversible have the ability to disable selectively and irreversibly either MAO-A or MAO-B. These are somewhat safer than the other. These include selegiline and rasagiline. These are used for Parkinson's disease.

Those labeled as Selective and Reversible have the ability to inactivate selectively and reversibly MAO-A or MAO-B.

These are safe but less effective. The new drugs in this category are safinamide and moclobemide. Of which safinamide is beneficial for Parkinson's disease and others for depressions.

MAO-B inhibitors are commonly used for Parkinson's disease. The reason is that MAO-B is the one that most often breaks down dopamine.

Parkinson's Disease and Dopamine: -

Fig-1
Dopamine Vs GABA

The basis of Parkinson's disease is the basal ganglia, the basic brain nucleus located at the center of the brain, the location of our intelligence and memory stability. Diseases such as Parkinson's and Alzheimer's occur when this area is affected (Fig-1).

In the picture above, is the basal ganglia and some of its parts mainly the striatum gland and the substantia nigra are shown. This has been where man's stability, organized movements, for example standing, sitting, responding to others with a moving facial expression, memory, intelligence, intellectual abilities, etc. are embedded.

Especially in this part of the human brain is being the rational wisdom and intelligence embedded.

All of the above will be jeopardized if this place is affected.

For example, if it is affected by high dopamine secretion, it can lead to Schizophrenia. Decreased dopamine secretion can lead to Parkinson's disease (see pictures above)

As you can see in the pictures above, dopamine flows from the substantia nigra to the striatum gland. In the picture, it is shown with a green curved arrow. Once it gets the dopamine it needs, the striatum gland secretes GABA to control the dopamine low. This is a continued cyclic process by nature.

Click here to read more about Parkinson's disease.

Parkinson's Disease -Continuity -Disease Symptoms, Treatment, and Warnings

 Symptoms, Treatment, and Warnings

BASAL GANGLIA (STRIATUM)
(DIAGRAMMATIC)

Parkinson's disease is a degenerative disorder of specific areas of the brain. It is characterized by muscle relaxation (tremor relaxation), increased muscle tone (stiffness), sluggishness of voluntary movements, and difficulty maintaining balance (post-instability). For many people, thinking becomes impaired, or senility develops.

Symptoms: -

The symptoms are rough and rhythmic.

1. Tremor when the hand is at rest (resting tremor)

2. Often the hand moves as it spins small objects (called tablet-rolls).

3. Decreases when the hand is intentionally moved and disappears completely during sleep

4. Emotional awakening may worsen due to stress or fatigue

Eventually next, switch to arms and legs

5. The most obvious symptom is a tremor that occurs when the muscles are relaxed.

6. Muscles become stiff, movements become slow and uncoordinated, balance is easily lost.

Parkinson's disease is the second most degenerative disorder of the central nervous system after Alzheimer's disease

Often the first sign of tremors is hand tremors. These tremors can be classified as follows: -

-Rough and rhythmic

Usually occurs in one hand when the hand is at rest (resting tremor)

-The hand moves as it often spins small objects (called tablet-rolls).

-Decreases when the hand is intentionally moved and disappears completely during sleep

-Emotional aggravation may be due to stress or fatigue

-Finally, this tremor may progress from one side to the arms and legs.

-It can affect the jaws, tongue, forehead, and eyelids, and to a lesser extent, it can affect the voice too.

It often affects the following People:-

1. 1 in 250 people over 40 years of age

2. 1 in 100 people aged 65 or over

3. 1 in 10 people aged 80 or over

Parkinson's disease usually begins between the ages of 50 and 79. Rarely, it occurs in children or adolescents.

Parkinsonism has symptoms similar to Parkinson's disease, but it can be caused by a variety of conditions, such as multiple organ degeneration of the body, progressive neuronal arthritis, stroke, head injury, or certain medications.

Stiffness:

Muscles stiffen and make movement difficult. When a doctor tries to bend or straighten the person's forearm or wrist, the hand resists moving, and when it moves, it starts and stops, as it is squeezed (called a cake wheel stiffness).

Slow movements:

The movements become slower and smaller and harder to start. Thus, people tend to move slowly. When they move slowly, it becomes difficult to move and it is very difficult to move as the joints and muscles weaken.

Difficulty maintaining balance and posture:

The posture is bent and it is difficult to maintain balance. Thus, the patient tends to invert forward or backward. Because the movements are slow, the patient is often unable to move their arms quickly to prevent them from falling down. These problems then develop into diseases.

Walking becomes difficult: -

 The patient will often retreat, especially after starting the first step. So he will take short steps. He bends his arms at the waist or dips his arms a little. While walking, some people have difficulty stopping or turning. As the disease progresses, some people will suddenly stop walking because they will feel like their feet are sticking to the ground (called frostbite). Others will accidentally and gradually accelerate their actions and enter the stumbling block.

Insomnia: -

Sleep problems, including insomnia, are common because people often have to urinate or have difficulty getting back to bed at night as symptoms worsen. Rapid-eye-movement (REM) sleep disorder usually develops. In this disorder, limbs that do not normally move during REM sleep can move suddenly and violently because people express their dreams, sometimes injuring the person lying next to them.

Insomnia can cause depression, weak thinking, and dizziness during the day.

Urinary problem: -

Problems with urination can occur. Urination can be difficult to begin and maintain (called urinary delay). People may have a compelling need to urinate (urgently). Disability is common.

Digestive system

Difficulty in swallowing may develop as the esophagus may move its contents too slowly. As a result, people may inhale oral secretions and/or the food they eat or the fluids they drink into the respiratory tract, which can cause pneumonia.

Constipation: - 

Because the intestine may move its contents slowly. Inactivity and levodopa, the main drug used to treat Parkinson's disease, can worsen constipation.

Orthostatic Hypotension: -

Sudden onset of hypotension when changing the posture from sitting to standing position (orthostatic hypotension)

Scales (seborrheic dermatitis): -

Most often develops on the scalp and face and occasionally on other areas.

Loss of smell (anosmia): - 

It is common, but people may not notice it.

Confusion :-( Dementia)

One-third of people with Parkinson's disease develop dementia, usually later in life. In many more, the thinking is weakened, but people may not recognize it.

Depression: -

 Sometimes people have problems with movements. Depression worsens as Parkinson's disease worsens. Depression can also make movement problems worse.

Hallucination

Hallucinations, delusions, and paranoia can occur, especially if dementia develops. People can see or hear things (illusions) that do not exist or hold firmly (illusions) despite clear evidence that contradicts certain beliefs. They may become hopeless and think that others are harming them (paranoia). These symptoms are considered psychiatric symptoms because they mean losing contact with reality.

Diagnosis of PD

-A physician's evaluation

-Sometimes computed tomography (CT scan) or magnetic resonance imaging (MRI) studies.

-Sometimes predicting whether levodopa is working properly.

People are more likely to develop Parkinson's disease if they have the following:

- Less, slower movements

- Tremor with a specific characteristic

- Muscle stiffness

-Clear and long-term (lasting) improvement in the effects of levodopa use

It is difficult for doctors to diagnose a mild, early disease because it usually begins with a technique. Diagnosis is especially difficult for the elderly.

Physical examination: -

During the physical examination, the doctor will ask the patient to perform certain movements, which will help confirm the diagnosis. For example, in people with Parkinson's disease, tremors disappear or subside when doctors ask them to touch the nose with their fingers. 

Also, sufferers find it difficult to make quick alternate movements such as placing their hands on their thighs and then quickly turning their hands back and forth several times.

Tests: -

No tests or imaging procedures can directly confirm the diagnosis. However, computed tomography (CT Scan) and magnetic resonance imaging (MRI Scan) can be done to diagnose a structural disorder that can cause symptoms. Common brain disorders of the disease can be detected by single-photon emission computed tomography (SPECT) and positron emission tomography (PET).

However, SPECT and PET are currently only used at the research level, and they do not distinguish Parkinson's disease from other disorders.

PD Treatments: -

-Common measures for managing symptoms

-Physical and occupational therapy

-Levodopa/carbidopa and other drugs

-Sometimes surgery (including deep brain stimulation)

-Common measures used to treat Parkinson's disease can help patients function better.

Many medications facilitate movement and help patients function effectively for many years to come.

Key features of treatment for Parkinson's disease: -

-Levodopa plus Carbidopa

-Other drugs are generally less effective than levodopa, but they may be beneficial for some people, especially when levodopa is ineffective or inadequate.

-However, no drug can cure the disease.

Two or more medications may be needed. For the elderly, doses are often reduced. Medications that cause or worsen symptoms, especially antipsychotic drugs, are avoided.

Medications used to treat Parkinson's disease can cause troublesome side effects. If people notice any abnormalities (such as difficulty or confusion in controlling the stimuli), they should report them to their doctor. They should not stop taking the medication until the doctor tells them to do so.

Deep Brain Stimulation: -

It is a surgical procedure that is only recommended if the patient has an advanced acute illness, but this treatment is not only ineffective for dementia or psychiatric symptoms and injuries caused by the use of certain psychiatric medications but can also cause serious side effects.

General Activities: -

-A variety of simple measures to help people with Parkinson's disease maintain mobility and independence:

-Continue daily activities as much as possible

-Regular exercise should be done regularly

-Facilitate daily tasks such as using fasteners or zippers in clothing and shoes.

Simple changes around the house can be safe for people with Parkinson's disease:

-Remove rugs to avoid stumble walking

-Install handrails in bathrooms and rails in hallways and other places to reduce the risk of falls.

-For constipation, the following may help:

-Eating high-fiber foods such as prunes and fruit juices

-Exercise

-Drinking plenty of fluids

-Using laxatives (such as senna, psyllium) or stimulant laxatives to keep bowel movements regular (such as oral bisacodyl)

-Difficulty in swallowing, can reduce food intake, so the food should be nutritious.

Doing more deep breathing exercises will improve the ability to smell and increase appetite.

Levodopa / Carbidopa

Traditionally, levodopa, given in combination with carbidopa, was the first drug used to treat Parkinson's disease. These medications, which can be taken orally, are an important part of the treatment for Parkinson's disease.

There is no truth in the claim that chronic levodopa use can exacerbate side effects and reduce its effectiveness. However, over time, Parkinson's disease can worsen in some people beyond levodopa usage.

Other medications that doctors may use include amantadine and dopamine agonists (drugs that stimulate dopamine receptors). Such drugs are used to increase dopamine production as it decreases in Parkinson's disease.

Levodopa reduces muscle stiffness, improves mobility, and significantly reduces tremors. Taking levodopa makes dramatic improvement for people with Parkinson's disease. This drug helps many people with mild illnesses to return to almost normal and some people who have been confined to bed can walk again.

Risk factors:-

-Brain damage caused by trauma in the past

-Injuries to the head from sports may increase the risk of this condition.

-Toxic exposure: Pesticides, solvents, metals, and other contaminants.

-Sex:-

 Men are 50% more likely to develop this condition than women, although a 2016 study suggests that the risk for women may also increase with age.

And this condition often appears from the age of 60s.