Parkinson’s Parkinson’s diseasedisease

Dr. Osman Sadig BukhariDr. Osman Sadig Bukhari

Parkinson’s disease is an idiopathicParkinson’s disease is an idiopathic

progressive degenerative disease of progressive degenerative disease of thethe

dopaminergic neurones in za dopaminergic neurones in za substantiasubstantia

nigra resulting innigra resulting in::

11 - -Bradykinesia or akinesiaBradykinesia or akinesia

22 - -Resting tremorsResting tremors

33 - -Muscle rigidity causing restrictedMuscle rigidity causing restricted

mobilitymobility

PrevalencePrevalence - - world wideworld wide

- - 11 : :10001000 general population increasing sharplygeneral population increasing sharply over the age of 60over the age of 60..

- - M> FM> F AetiologyAetiology

- - unknownunknown - - no infective agentno infective agent

- - no enviromental factor ( dis world wide)no enviromental factor ( dis world wide) ? - ? - Less in tobacco smokers (nicotine)Less in tobacco smokers (nicotine)

? - ? - MPTP, a pyridine cpd cause similar syndromeMPTP, a pyridine cpd cause similar syndrome ) ) enviromental MPTP like herbicideenviromental MPTP like herbicide (? (?

? - ? - Genetic factors, clusters of early onset Genetic factors, clusters of early onset Parkinson’sParkinson’s

in some families ? Mutation in parkin gene onin some families ? Mutation in parkin gene on chromosome 6chromosome 6

PathologyPathology - - progressive degeneration with progressive degeneration with

eosinophiliceosinophilic

inclusion bodies ( Lewy bodies) in za inclusion bodies ( Lewy bodies) in za neuronesneurones

of substantia nigra & other basal ganglia of substantia nigra & other basal ganglia nucleinuclei

- - loss of melanin & dopamine that loss of melanin & dopamine that correlate with the degree of akinesiacorrelate with the degree of akinesia

- - imbalance between dopaminergic & imbalance between dopaminergic & cholinergiccholinergic

neurotransmittersneurotransmitters . .

Clinical featuresClinical features - - Symptoms develop over moths & several yearsSymptoms develop over moths & several years

11--Pill rolling tremors of za hands, often unilateral, Pill rolling tremors of za hands, often unilateral, is the most common initial feature. It is is the most common initial feature. It is eventually becomes bilateral involving the UL, eventually becomes bilateral involving the UL, LL & jaw. It diminishes on voluntary LL & jaw. It diminishes on voluntary

movement an increases by emotionmovement an increases by emotion . .

22 - -Slowness of movement or bradykinesia isSlowness of movement or bradykinesia is

usually by za family. There is difficulty inusually by za family. There is difficulty in

initiating movements including fine finger moveinitiating movements including fine finger move

33 - -Rigidity causes stiffness . It is lead pipe andRigidity causes stiffness . It is lead pipe and

cogwheel rigiditycogwheel rigidity..

44 - -Stooping posture, festinant & shufflingStooping posture, festinant & shuffling gait wz reduced limb swinginggait wz reduced limb swinging

Propulsion & retropulsion are characteriPropulsion & retropulsion are characteri There is postural instability & fallsThere is postural instability & falls..

55 - -Masked expressionless face wz reducedMasked expressionless face wz reduced blinkingblinking..

66 - -Monotonous speech progressing toMonotonous speech progressing to slurring & eventually lostslurring & eventually lost..

77 - -MicrographiaMicrographia 88 - -Drooling of saliva, dysphagia, constipatiDrooling of saliva, dysphagia, constipati

urinary troublesurinary troubles 99 - -Excessive sweating & greasy skinExcessive sweating & greasy skin..

1010 - -Power remains normal, reflexes mayPower remains normal, reflexes may

be increased, planters remain flexorbe increased, planters remain flexor

and sensations are normaland sensations are normal..

1111 - -Cognitive fns preserved at least earlyCognitive fns preserved at least early,,

dementia develops in late stagesdementia develops in late stages,,

anxiety & depression are commonanxiety & depression are common

1212 - -No remission & za rate of progressionNo remission & za rate of progression

is variable wz death resulting fromis variable wz death resulting from

chest infection, UTI & bed soreschest infection, UTI & bed sores

DiagnosisDiagnosis - - characteristic clinical picturecharacteristic clinical picture

- - careful history & examination to exclude othercareful history & examination to exclude other causes of Akinetic – rigid syndromes i.ecauses of Akinetic – rigid syndromes i.e..

secondary causes of parkinsonismsecondary causes of parkinsonism 11 - -Drug induced parkinsonism e.g neurolepticsDrug induced parkinsonism e.g neuroleptics,, reserpine, methyldopa, tricyclic antidepressantsreserpine, methyldopa, tricyclic antidepressants mainly cause slowness & rigidity wz little tremormainly cause slowness & rigidity wz little tremor

22 - -Post encephalitis lethargicaPost encephalitis lethargica 33 - -Toxins e.g MPTP, CO, MnToxins e.g MPTP, CO, Mn

44 - -CVAs, hypoparathyroidism, trauma & SOLCVAs, hypoparathyroidism, trauma & SOL 55 - -Wilson’s disease & athetoid C. palsy in childrWilson’s disease & athetoid C. palsy in childr

66 - -Progressive supranuclear palsyProgressive supranuclear palsy

77 - -Multiple system atrophiesMultiple system atrophies::

- - Olivo – ponto – cerebellar Olivo – ponto – cerebellar degenerationdegeneration

- - Pry autonomic failure ( Shy Drager Pry autonomic failure ( Shy Drager syndr)syndr)

88 - -Alzeheimer diseaseAlzeheimer disease

99 - -Huntington's choreaHuntington's chorea

Management of Parkinson’s Management of Parkinson’s diseasedisease

A- identify 2ry causes of parkinsonism & TRA- identify 2ry causes of parkinsonism & TR

e.g withdrawal of neuroleptics, e.g withdrawal of neuroleptics, penicillaminepenicillamine

for Wilson’sfor Wilson’s..

B- Drug therapy to restore dopaminergicB- Drug therapy to restore dopaminergic//

cholinergic balance, butcholinergic balance, but

- - not curativenot curative

- - greatly improve za quality of lifegreatly improve za quality of life

- - should only be started when za functionalshould only be started when za functional

disability interferes wz lifedisability interferes wz life..

11 - -Dopaminergic drugs act throughDopaminergic drugs act through - - replacement of neuronal dopamine e.greplacement of neuronal dopamine e.g L dopa which is za natural precursor ofL dopa which is za natural precursor of

dopamine & crosses BBB ( dopamine not)dopamine & crosses BBB ( dopamine not) - - releasing dopamine from its stores andreleasing dopamine from its stores and inhibiting its re uptake e.g amantadineinhibiting its re uptake e.g amantadine

- - prolonging za action of dopamine by prolonging za action of dopamine by selectivselectiv

inhibition of its metabolism e.g seleglineinhibition of its metabolism e.g selegline - - dopamine receptor agonists e.g dopamine receptor agonists e.g

bromocriptinebromocriptine 22 - -Anti muscarinic anti cholinergics reduceAnti muscarinic anti cholinergics reduce

cholinergic activity by inhibiting acetyl cholinergic activity by inhibiting acetyl cholinecholine

esterase e.g benzhexolesterase e.g benzhexol..

** **drug induced parkinsonism is best treated by drug induced parkinsonism is best treated by anti muscarinic drugs & not by L dopa since anti muscarinic drugs & not by L dopa since

neuroleptic drugs block dopamine receptorsneuroleptic drugs block dopamine receptors.. Individual drugsIndividual drugs

11 - -Levodopa (L dopaLevodopa (L dopa)) - - a a precursor of dopamine wz short ½ life 1,5ha a precursor of dopamine wz short ½ life 1,5h

- - dopamine can not be used as it is rapidlydopamine can not be used as it is rapidly destroyed peripherally (gut, liver & blood) bydestroyed peripherally (gut, liver & blood) by

MAO inhibitor & catechol O –methyl transferaseMAO inhibitor & catechol O –methyl transferase and does not cross BBBand does not cross BBB..

- - peripheral dopa decarboxylase inhibitors whichperipheral dopa decarboxylase inhibitors which do not cross BBB are combined with L dopa indo not cross BBB are combined with L dopa in

therapeutic doses to avoid large doses of L dopatherapeutic doses to avoid large doses of L dopa e.g Sinemet ( cabidopa + L dopa 1 : 10)e.g Sinemet ( cabidopa + L dopa 1 : 10): :

110110 , ,250mg. OR Madopar ( benserazide + L dop250mg. OR Madopar ( benserazide + L dop 1:41:4 : :65.565.5 , ,125125 , ,250mg250mg..

- - With combination low doses of L dopa are With combination low doses of L dopa are usedused

and side effects are reducedand side effects are reduced::) ) N, V, post hypotension, arrhythmias, dyskinN, V, post hypotension, arrhythmias, dyskin confusion, agitation, hallucination, depressioconfusion, agitation, hallucination, depressio

long term problems of end of dose deteriorlong term problems of end of dose deterior and on off swingsand on off swings ( (

- - L dopa interaction wz non selective MAO-IL dopa interaction wz non selective MAO-I causes hypertensive crisis. In this situation L causes hypertensive crisis. In this situation L

dopa dopamine Noradrenaline HT dopa dopamine Noradrenaline HT..

22 - -AmantadineAmantadine

- - anti viralanti viral

- - less effective than L dopa but mayless effective than L dopa but may

enhance its effectenhance its effect

- - mainly used in early mild casesmainly used in early mild cases

- - dose: 100-300mg/ddose: 100-300mg/d

- - SE= post hypot, ankle edema & livedoSE= post hypot, ankle edema & livedo

reticularisreticularis..

33 - -BromocriptineBromocriptine

- - dopamine receptor agonistdopamine receptor agonist

½ - ½ - life 5hrs, therefore smoother action life 5hrs, therefore smoother action thanthan

L dopa & no fluctuation in actionL dopa & no fluctuation in action

- - dose: 10-80mg starting wz 1.25mg e.gdose: 10-80mg starting wz 1.25mg e.g

Parlodel (2.5 &10mg)Parlodel (2.5 &10mg)

- - used in long term L dopa problemsused in long term L dopa problems

- - SE= similar to L dopaSE= similar to L dopa..

44 - -SeleglineSelegline - - selective B MAO-Iselective B MAO-I

- - It delays break down of dopamine & prolongsIt delays break down of dopamine & prolongs its actionits action

- - main use in those wz long term L dopamain use in those wz long term L dopa problems e.g end of dose deteriorationproblems e.g end of dose deterioration

- - anti depressant alsoanti depressant also - - e.g eldepryl 5mg X2. SE= similar to L dopae.g eldepryl 5mg X2. SE= similar to L dopa.. - - no hypertensive cheese reaction (tyramine)no hypertensive cheese reaction (tyramine)

which occur wz non selective MAO-I whichwhich occur wz non selective MAO-I which prevent degradation of dietary amines byprevent degradation of dietary amines by

MAO-I. Tyramine is degraded by type A MAO-IMAO-I. Tyramine is degraded by type A MAO-I

55 - -EntacaponeEntacapone - -COMT inhibitorCOMT inhibitor

- - Used to reduce end- of- dose fluctuationUsed to reduce end- of- dose fluctuation in response to L dopain response to L dopa..

66 - -Anti muscarinic anti cholinergicsAnti muscarinic anti cholinergics- - - Act by blocking Ach in za CNS restoring theAct by blocking Ach in za CNS restoring the

- imbalance created by decreased imbalance created by decreased dopaminergidopaminergi

- activityactivity..- - - most effective in drug induced parkinsonism most effective in drug induced parkinsonism

and in mild cases sp. tremor, rigidity and and in mild cases sp. tremor, rigidity and sialorrhMoea. Not used I n > 65, glucoma & sialorrhMoea. Not used I n > 65, glucoma &

BPH. SE= those of anti cholinergics BPH. SE= those of anti cholinergics . .-

- -trihexyphenidyl (benzhexol 2mg), benz trihexyphenidyl (benzhexol 2mg), benz atropinatropin

orphenadrineorphenadrine..

33 - -General management of parkinsonismGeneral management of parkinsonism - - Positive attitude by encouraging physicalPositive attitude by encouraging physical activity, physiotherapy & speech therapyactivity, physiotherapy & speech therapy

- - Early mild cases: anti muscarinic & Early mild cases: anti muscarinic & amantadineamantadine

- - With progression of za disease dose of L dopaWith progression of za disease dose of L dopa needs to be increased wz more SEs which needs to be increased wz more SEs which

maymay be overcome by reducing individual dosesbe overcome by reducing individual doses

and increasing za frequency of administration and increasing za frequency of administration oror

by using bromocriptine & seleglineby using bromocriptine & selegline - - L dopa + carbidopa restore near normalL dopa + carbidopa restore near normal

physical activity in 75%. Ultimately higher physical activity in 75%. Ultimately higher doses are required doses are required . .

- - long term therapy is associated withlong term therapy is associated with : :

11 - -end- of- dose fluctuation= swings end- of- dose fluctuation= swings from early morning akinesia to peakfrom early morning akinesia to peak

dose dyskinesiadose dyskinesia..

22 - -on- off swings= random fluctuationon- off swings= random fluctuation

from mobility to dyskinesia wz peakfrom mobility to dyskinesia wz peak

plasma concplasma conc..

- - Long term problems wz L dopa is treatedLong term problems wz L dopa is treated

by: - gradual & partial substitution ofby: - gradual & partial substitution of

L dopa wz bromocriptine & seleglineL dopa wz bromocriptine & selegline

effective in end- of- dose deteriorationeffective in end- of- dose deterioration

- - decreasing dose of L dopa & shortening za decreasing dose of L dopa & shortening za interval between doses interval between doses . .