Pharmacology

1. N.MEGHANA
B-PHARM FINAL YEAR STUDENT
14Z31R0032
BNPCW

2. BRAIN
NEURONAL TRANSMISSION
PARKINSONISM
DIFFERENCE BETWEEN PARKINSONS DISEASE AND PARKINSONISM
DIAGNOSIS
TREATMENT
PARKINSONIAL PLUS
CLINICAL CLUES
DIAGNOSIS
TREATMENT FOR THE PARKINSONIAL PLUS
CLINICAL PEARLS
REFERENCES.
CONTENTS:

3. BRAIN:
◊ Brain is the most complex and highly organised organ of the
body.
◊ The brain produces electrical signals, which together with
chemical reactions communicate with other parts of the body
through nerves.
◊ Neurons are the structural and functional units of brain and
there are about 100 billion in number.
◊ Mr. Brain thus helps in
feeling,sensing,thinking,moving,analysing,writing and reading.
◊ Different parts of brain are Forebrain,Mid brain and Hind
brain.
◊ Substantia nigra is a basal ganglia structure located in
the midbrain that plays an important role
in reward and movement. The parts of the substantia nigra
appear darker than neighboring areas due to high levels
of neuromelanin in dopaminergic neurons.

4. Neuronal Transmission:

5. PARKINSONISM
• A disorder of the central nervous
system that affects movement, often
including tremors.
• Parkinsonism is a
clinical syndrome characterized
by tremor, bradykinesia, rigidity,
and postural instability. Parkinsonism
is found in Parkinson's disease (after
which it is named), however a wide
range of other causes may lead to this
set of symptoms, including
some toxins, a few metabolic
diseases, and a handful of
neurological conditions other than
Parkinson's disease.

6. Parkinsons Disease Vs Parkinsonism:
• Parkinson's disease (PD) is a long-term degenerative disorder of the central
nervous system that mainly affects the motor system. The symptoms generally
come on slowly over time. Early in the disease, the most obvious are shaking,
rigidity, slowness of movement, and difficulty with walking. Thinking and
behavioural problems may also occur. Dementia becomes common in the
advanced stages of the disease. Depression and anxiety are also common
occurring in more than a one third of people with PD. Other symptoms include
sensory, sleep, and emotional problems. The main motor symptoms are
collectively called "parkinsonism", or a "parkinsonian syndrome"

7. Clinical features
• Resting tremor
• Writing smaller; harder to do buttons
• Slowness, “weakness”, limb not
working well
• Stiff or achy limb
• Stoop, shuffle-walk, “dragging” leg(s)
• Trouble getting out of chairs or turning
in bed
• Low or soft voice
• Non-motor: anosmia, dream
enactment, constipation, anxiety,
depression, “passiveness”

8. Symptoms:
Bradykinesia
Tremor
Rigidity
Postutal Changes
Depletion of pigmented
dopaminergic neurons in SN
Reduced
dopaminergic
output from SN
Inclusion bodies
(Lewy bodies)
develop in nigral
cells
Neurons in subthalamic nucleus become more active
than usual in inhibiting activation of the cortex
Bradykinesia
Degeneration in
other basal
ganglia nuclei
MECHANISM OF ACTION:

10. Levodopa
• Most effective overall for motor symptoms
• A fine option for initial therapy of PD
• By mid to late disease it is almost always needed
• Non-motor side effects include nausea, orthostasis, sleepiness, hallucinations;
but not as much as other PD drugs
How levodopa works
• Levodopa works by being converted to dopamine, a chemical messenger that
is needed to control the movement through transmission of signals in the
brain.
Common side effects of levodopa
• Nausea, Vomiting, Dizziness, Loss of appetite, Orthostatic hypotension
(sudden lowering of blood pressure on standing), Movement disorder

11. CARBIDOPA
Carbidopa uses
• Carbidopa is used in the treatment of parkinson's disease.
How carbidopa works
• Carbidopa is always given with levodopa. It works by preventing levodopa from
being broken down before it reaches the brain. This allows for a lower dose of
levodopa, which causes less nausea and vomiting.
Common side effects of carbidopa
• Nausea, Neuroleptic malignant syndrome, Panic attacks, Altered behaviour,
Mood changes, Altered sleep, Burning sensation of tongue, Confusion,
Convulsion, Dizziness, Drowsiness, Fever, Frequent dreams, Hallucination,
Increased sweating, Tachycardia, Irregular heart rate, Tremor, Vomiting,
Worsening of tremor, Muscle stiffness

12. Dopamine agonists
(ropinirole, pramipexole, rotigotine)
• Can be monotherapy in early disease; need L-dopa in mid to late disease
• Can add to L-dopa to reduce OFF time
• Frequent side effects! Nausea, sleep attacks, hypotension, compulsive
behaviors, LE edema 
• More prone than L-dopa to causing hallucinations and confusion. Caution in
older or demented patients! 

13. Differential diagnosis of parkinsonism
• Parkinson disease (idiopathic or genetic)
• Parkinson-plus degenerations (dementia with Lewy bodies, progressive
supranuclear palsy, corticobasal degeneration, multiple system atrophy)
• Drug-induced parkinsonism (anti-dopaminergics)
• Rare but treatable in young people: Wilson disease and Dopa-responsive
dystonia
• Other: “vascular” parkinsonism, brain trauma, CNS infection

14. PARKINSONIAL PLUS
• Parkinson-plus syndromes, also known as disorders of multiple system degeneration,
is a group of neurodegenerative diseases featuring the classical features of
Parkinson's disease (tremor, rigidity, akinesia/bradykinesia, and postural instability)
with additional features that distinguish them from simple idiopathic Parkinson's
disease (PD). Some consider Alzheimer's disease to be in this group. Parkinson-plus
syndromes are either inherited genetically or occur sporadically.
• The atypical parkinsonian or Parkinson-plus syndromes are often difficult to
differentiate from PD and each other. They include multiple system atrophy (MSA),
progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD).
Dementia with Lewy bodies (DLB), may or may not be part of the PD spectrum, but it
is increasingly recognized as the second-most common type of neurodegenerative
dementia after Alzheimer's disease. These disorders are currently lumped into two
groups, the synucleinopathies and the tauopathies. They may coexist with other
pathologies

15. CLINICAL CLUES:
• Early onset of dementia
• Early onset of postural instability
• Early onset of hallucinations or psychosis with low doses of carbidopa/levodopa or
dopamine agonists
• Ocular signs, such as impaired vertical gaze, blinking on saccade, square-wave jerks,
and apraxia of eyelid opening or closure
• Pyramidal tract signs not explained by previous stroke or spinal cord lesions
• Autonomic symptoms such as postural hypotension and urinary incontinence early in
the course of the disease
• Prominent motor apraxia
• Alien-limb phenomenon
• Marked symmetry of signs in early stages of the disease
• Truncal symptoms more prominent than appendicular symptoms
• Absence of structural aetiology such as a normal-pressure hydrocephalus (NPH)

16. Diagnosis:
 Modern immunocytochemical techniques and genetic findings suggest that
Parkinson-plus syndromes can be broadly grouped into 2 types:
 Synucleinopathies
 Tauopathies.
oClinically, however, 5 separate Parkinson-plus syndromes have been identified,
as follows:
• Multiple system atrophy (MSA)
• Progressive supranuclear palsy (PSP)
• Parkinsonism-dementia-amyotrophic lateral sclerosis complex
• Corticobasal ganglionic degeneration (CBD)
• Dementia with Lewy bodies (DLB)

17. TREATMENT:
• Parkinson-plus syndromes are usually more rapidly progressive and less likely
to respond to antiparkinsonian medication than PD. However, the additional
features of the diseases may respond to medications not used in PD.
• Current therapy for Parkinson-plus syndromes is centered around a
multidisciplinary treatment of symptoms.
• These disorders have been linked to pesticide exposure.
• Not fatal but may effect the longevity.
• In addition to lack of response to carbidopa/levodopa (Sinemet) or dopamine
agonists in the early stages of the disease.

18. CLINICAL PEARLS:
Brain the mysterious and highly complicated organ of the body.
Parkinsonism disease is a neuro muscular disorder.
Dopamine is the heart of the game.
Levodopa and Syndopa drugs act as life lines.
Parkinsonial Plus is a collective disorder which includes IPD,AD.
Treatment for PP can be our future scope for study.

19. REFERENCES
• Connolly, Barbara S.; Lang, Anthony E. (23–30 April 2014). "Pharmacological
treatment of Parkinson disease: a review". JAMA. 311 (16): 1670–1683. ISSN
1538-3598. PMID 24756517. doi:10.1001/jama.2014.3654.
• "The non-motor and non-dopaminergic fratures of PD". Parkinson's Disease :
Non-Motor and Non-Dopaminergic Features. Olanow, C. Warren., Stocchi,
Fabrizio., Lang, Anthony E. Wiley-Blackwell. 2011. ISBN 1405191856. OCLC
743205140.
• The National Collaborating Centre for Chronic Conditions, ed. (2006).
"Symptomatic pharmacological therapy in Parkinson's disease". Parkinson's
Disease. London: Royal College of Physicians. pp. 59–100. ISBN 1-86016-283-
5.
• Zhang, Jinglin; Tan, Louis Chew-Seng (2016). "Revisiting the Medical
Management of Parkinson's Disease: Levodopa versus Dopamine Agonist".
Current Neuropharmacology. …..