PARKINSON’S DISEASE

PRESENTED BY-

NAVEEN KADIAN

DEPARTMENT OF PHARMACEUTICAL CHEMISTRY

K.L.E’S COLLEGE OF PHARMACY

BELGAUM-10

CONTENTS

• Introduction• Epidemiology of PD• Causes of Parkinsonism• Risk factors of PD• Clinical features of PD• Treatment• Reference

Definition• Neurodegenerative disease is a condition which affects

brain function. Neurodegenerative diseases result from deterioration of neurons.

• They are divided into two groups: – conditions causing problems with movements – conditions affecting memory and conditions related to

dementia.

– Examples:• Alzheimer’s • Parkinson’s• Huntington’s• Creutzfeldt-Jakob disease• Multiple Sclerosis• Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's

Disease)

Risk Factors• Known

– Certain genetic polymorphisms

– Increasing age

PossibleGenderPoor educationEndocrine conditionsOxidative stressInflammationStrokeHypertensionDiabetesHead traumaDepressionInfectionTumorsVitamin deficienciesImmune and metabolic conditionsChemical exposureSmoking??

PARKINSON`S DISEASE is movement disorder of unknown etiology due to degeneration of neurons in the nigrostrial dopamine system.

History:First described in 1817 by an English physician, James Parkinson, in “An Essay on the Shaking Palsy.”

The famous French neurologist, Charcot, further described the syndrome in the late 1800s.

Epidemiology of PD

The most common movement disorder affecting 1-2 % of the general population over the age of 65 years.

The second most common neurodegenerative disorder after Alzheimer´s disease (AD).

Causes of Parkinsonism• Impaired release of dopamine- Idiopathic

parkinsonism.

• Drug depleting dopamine store-reserpine, tetrabenzine.

• Toxin damaging dopaminergic neuron.

• Viral infection- Encephalitis ,Japanese encephalitis

• Trauma-repeated head injury[punch drunk syndrome]

• Miscellaneus-wilson disease,huntingtion,s disease

Dopamine pathways in human brain

Dopamine synthesis

Risk factors of PD Age - the most important risk factor Positive family history Male gender Environmental exposure: Herbicide and pesticide

exposure, metals (manganese, iron), well water, farming, rural residence, wood pulp mills; and steel alloy industries

Race Life experiences (trauma, emotional stress, personality

traits such as shyness and depressiveness)? An inverse correlation between cigarette smoking and

caffeine intake in case-control studies.

Clinical features of PD

• Three cardinal symptoms:

® resting tremor

® bradykinesia (generalized slowness of

movements)

® muscle rigidity

CLINICAL FEATURE• TREMORS(4-6hz): • tremors[pill rolling] at rest, decreases on action.

Usually first in finger/thumb.• Coarse flexion/extension of finger[pill rolling &

drum beating]• RIGIDITY- • Cog wheel type especially in upper limb

{stiffness in all direction of movement}.• Plastic type {lead type} mostly appreciated in

legs. In trunk rigidity manifest by flexed& stooped posture

Hypokinesis• Charactrized by poverty & slowness of

movement. Slowness in initiating movement. Handwriting micrographia.

• GAIT-patient walk with short step , with a tendency to run{as they are catching their own centre of gravity}-festinating gait

• General-expressionless face with staring look with infrequent blinking. Monotonus speech. Dementia & Depression in advance stage

Drugs used to treat Parkinson’s Disease

TREATMENT• Anticholinergic drug- to relieve tremors.• Dopamine agonist- bromocriptine&

pergolide.• Amantadine-potentiate release of

dopamine.• Selegeline : early stage, neuroprotective, delay

neuronal degeneration.

• Levodopa & carbidopa

Therapy of PD: levodopa

Late 1950s: L-dihydroxyphenylalanine (L-DOPA; levodopa), a precursor of DA that crosses the blood-brain barrier, could restore brain DA levels and motor functions in animals treated with catecholamine depleting drug (reserpine).

First treatment attempts in PD patients with levodopa resulted in dramatic but short-term improvements; took years before it become an established and succesfull treatment.

Still today, levodopa cornerstone of PD treatment; virtually all the patients benefit.

Therapy of PD: limitations of levodopa

Efficacy tends to decrease as the disease progresses.

Chronic treatment associated with adverse events (motor fluctuations, dyskinesias and neuropsychiatric problems).

Inhibition of peripheral COMT by entacapone increases the amount of L-DOPA and dopamine in the brain and improves the alleviation of PD symptoms.

Therapy of PD: limitations of levodopa

Does not prevent the continuous degeneration of nerve cells in the subtantia nigra, the treatment being therefore symptomatic.

Therapy of PD: Other treatmentsDA receptor agonists:

Bromocriptine Pergolide

ropinirolecabergoline

Anticholinergics:

Amantadine

AntiHistamines:

Diphenhydramine Orphenadrine

Selegiline

Antidepressant

Miscellanous:

imipraminenortriptyline

Benzotropineprocyclidine

References BURGER’S Medicinal Chemistry & Drug discovery,6th

Edn,vol-1, Wiley-interscience publication CORWIN HANSCH, Comprehensive Medicinal

Chemistry,vol –IV 2008,Pregamon press Principles of Medicinal Chemistry by William O.Foye Medicinal Pharmacology by K.D Triphati. http:// www.cpharm.ucsf.edu/ kuntz/doct.html http:// www.bmm.icnet.uk/ ftdock/ftdoc.html www. Wikepedia.com www. Google.com www. Ipasp . com

THANK

YOU