Drugs to treat pd

Levodopa (also called L-dopa) is the most commonly prescribed and most effective medicine
for controlling the symptoms of PD, particularly bradykinesia and rigidity. Levodopa is a
chemical found naturally in our brains. When given as a medicine, it is transported to the nerve
cells in the brain that produce dopamine

Levodopa, the most effective Parkinson's disease medication, is a natural chemical that

passes into your brain and is converted to dopamine. Levodopa is combined with carbidopa
(Lodosyn), which protects levodopa from early conversion to dopamine outside your brain. This
prevents or lessens side effects such as nausea.

Primary parkinsonism
Most patients (about 80–85%) diagnosed with Parkinson’s disease have what
is called primary parkinsonism or idiopathic Parkinson’s disease (meaning
that the disease has no known cause). This type tends to respond well to
drugs that work by increasing or substituting dopamine molecules in the
brain.

Secondary parkinsonism -
Fortunately, levodopa can cross the blood brain barrier
and, as it is a 'precursor' to dopamine, the body can
turn it into dopamine. When someone takes tablet
of levodopa, the idea is that it travels to the brain
where cells can turn it into dopamine.
secondary parkinsonism is when symptoms similar to Parkinson
disease are caused by certain medicines, a different nervous system
disorder, or another illness. Parkinsonism refers to any condition that
involves the types of movement problems seen in Parkinson disease.

Peripherally administered (outside of the central nervous

system) dopamine is not effective because it cannot cross the blood
brain barrier. 4 The reason for its inability to cross the blood brain
barrier has to do with at least two influencing factors.

The first is that dopamine is a hydrophilic molecule that has a

greater degree of difficulty in crossing cell membranes.  The
second is the absence of a transporter for dopamine to get past
the blood brain barrier and into the brain.6  Since the increase
in dopamine concentrations are needed in the brain and the
peripheral administration of dopamine cannot get into the
brain, it does not work in the management of symptoms seen in
Parkinson's disease.

In these cases, the cause of the disease is generally known and although it is
very difficult to differentiate idiopathic Parkinson’s disease and secondary
parkinsonism, a key difference is that patients with secondary parkinsonism
do not respond well to dopaminergic medications such as levodopa.

Drug-induced parkinsonism - Any drug that blocks the action of

dopamine (referred to as a dopamine antagonist) is likely to cause parkinsonism.

Drug-induced parkinsonism may be difficult to distinguish from Parkinson’s disease,

but the symptoms of tremors and postural instability will generally improve in the
weeks or months after use of the medication has stopped.

Vascular parkinsonism - As its name implies, vascular parkinsonism is

often due to problems with the vessels in the brain regions that control movement and
small strokes are the primary cause.

Also called cerebrovascular disease, this type of parkinsonism is caused by a series of

small strokes, resulting in the death of parts of the brain, leading to the Parkinson’s
disease-like symptoms. The condition often only displays symptoms in the lower half
of the body (walking difficulties and urinary incontinence) and memory loss. It tends
to be less responsive to typical Parkinson’s disease medication especially as it
progresses. Vascular parkinsonism becomes more common with age, especially in
people with diabetes.
Normal pressure hydrocephalus (NSA) - In some cases, normal
pressure hydrocephalus is caused by other brain disorders such as a tumor, head
injury, hemorrhage, infection or inflammation. But in most cases, the cause of the fluid
buildup remains unknown.

The symptoms of NSA are very similar to those seen in vascular parkinsonism. The
condition can be treated by removing spinal fluid in the short term or by lumbar
puncture to permanently divert the spinal fluid as a long-term treatment.
Corticobasal degeneration (CBD) - The causes of corticobasal
degeneration are unknown, but research suggests that a protein in the brain called tau
may play a role in the disease. A buildup of tau in brain cells may lead to their
deterioration and the symptoms of corticobasal degeneration

CBD is caused by a build-up of proteins called tau, which damage parts of the brain.
The condition tends to start on one side of the body and slowly spread to other areas
over time. This is the least common of the atypical parkinsonisms.

(the tau protein is predominantly found in brain cells (neurons). Among tau's multiple

functions in healthy brain cells, a very important one is stabilization of the internal
microtubules.)

One of the hallmarks of Alzheimer's disease is the so-called tau tangles. Tau is a

protein contained within the axons of the nerve cells. More specifically, tau helps form
microtubules — essential structures that transport nutrients within nerve cells.

the main hallmarks of Alzheimer's disease are: Progressive accumulation of beta-

amyloid (Aβ peptide in so called neuritic plaques) outside neurons, interfering with the
neuron-to-neuron communication at synapses and possibly contributing to cell death.

Progressive supranuclear palsy (PSP) - in which abnormal

phosphorylation of the protein tau leads to destruction of vital protein filaments in nerve
cells, causing their death. Recent work suggests that the disease is at least partly
genetic.

PSP is one of the more common forms of secondary parkinsonism. As with idiopathic
Parkinson’s disease, progressive supranuclear palsy has a late age of onset, but the
symptoms tend to progress far more rapidly once they appear.
Multiple system atrophy (MSA) - The cause of MSA is unknown. The
vast majority of cases are sporadic, meaning they occur at random. A distinguishing
feature of MSA is the accumulation of the protein alpha-synuclein in glia, the cells that
support nerve cells in the brain.

α-Synuclein may contribute to PD pathogenesis in a number of ways, but it is generally thought

that its aberrant soluble oligomeric conformations, termed protofibrils, are the toxic species that
mediate disruption of cellular homeostasis and neuronal death, through effects on various
intracellular targets

 An elongated cluster of cells that grows into a fibril.

MSA is caused by an overproduction of a protein called alpha-synuclein in the brain,

leading to damage in multiple areas of the brain. This results in symptoms that are
similar to idiopathic Parkinson’s disease, but with a much faster progression.

There are also several conditions associated with Parkinson’s disease. One
such condition is dementia with Lewy bodies (DLB), or Lewy Body Dementia
(LBD), which is a particular form of dementia associated with Parkinson’s
disease. DLB is caused by Lewy bodies (clumps of alpha-synuclein protein)
forming in the brain. The condition tends to occur early in the progression of
the disease and leads to a progressive deterioration of cognitive functions
such as thinking, memory, and judgment.

Signs and syptoms :

Movement Symptoms
There is no single test or scan for Parkinson’s, but there are three telltale symptoms
that help doctors make a diagnosis:
 1. Bradykinesia means slowness of movement
2. Tremor shaking movement in one or more parts of your body.
3. Rigidity Muscle stiffness

Additional Movement Symptoms

 Cramping (dystonia): sustained or repetitive twisting or tightening of muscle.
 Drooling (sialorrhea): while not always viewed as a motor symptom,
excessive saliva or drooling may result due to a decrease in normally automatic
actions such as swallowing.
 Dyskinesia: involuntary, erratic writhing movements of the face, arms, legs or
trunk.
 Festination: short, rapid steps taken during walking. May increase risk of
falling and often seen in association with freezing.
 Freezing: gives the appearance of being stuck in place, especially when
initiating a step, turning or navigating through doorways. Potentially serious
problem as it may increase risk of falling.
 Masked face (hypomimia): results from the combination of bradykinesia and
rigidity.
 Micrographia: small, untidy and cramped handwriting due to bradykinesia.
 Shuffling gait: accompanied by short steps and often a stooped posture.
 Soft speech (hypophonia): soft, sometimes hoarse, voice that can occur in PD.

Non-Movement Symptoms
 Cognitive changes: problems with attention, planning, language, memory or
even dementia
 Constipation
 Early satiety: feeling of fullness after eating small amounts
 Excessive sweating, often when wearing off medications
 Fatigue
 Increase in dandruff (seborrheic dermatitis)
 Hallucinations and delusions
 Lightheadedness (orthostatic hypotension): drop in blood pressure when
standing
 Loss of sense of smell or taste
 Mood disorders, such as depression, anxiety, apathy and irritability
 Pain
 Sexual problems, such as erectile dysfunction
 Sleep disorders, such as insomnia, excessive daytime sleepiness (EDS), REM
sleep behavior disorder (RBD), vivid dreams, Restless Legs Syndrome (RLS)
 Urinary urgency, frequency and incontinence
 Vision problems, especially when attempting to read items up close
 Weight loss