AntiParkinsonism ! Flashcards
بسم الله الرحمن الرحيم وبه نستعين
exxplain pathophysiology of parkinsoinsm disease
Basal ganaglia is responsible for:
inhibition of muscle tone
Intation and modulation of Movements
This Needs balacne of Ach and Dopanmine
And dopamine is syntheisd within it in the subsatnia Nigra and reache s corpus striatum throuh dopaminergic NigroStriatal Fibers
In parkinsonism NigroStiratal are degenrated so no dopaimine in the straitum Casuing Dominiance of Cholinergic Systems :
1-Dyskinesa
2-Tremors
3-RIgidity
Classify antiparkonisan drugs !
1-increasing dopaminergic activity :
CMN DO[PA
DOPA agonists : Ergot and non
Ergot bromocrotpine
Non: Pareximole
LevoDopa carbidopa
COMT inhibtior Entacapone
MAOB inhibitor sergelline raselligne
NMDA-R-Inhibiotr? Amantidine
Sinemet = …+… why?
Levodopa + carbidopa
levodopa crossing BB
Caribdoa inhibiting the peripheral decaroxylase to incerses portion of levodopa to CNS
The most efficent drug for improving feature of parkinsonism
Ldopa but better to be reserved when symptoms become Turbelosome
Mention Adverse effects of L dopa
1-Central : Hallucination +psychosis
Dyskinesia choreoathetosis
2-Peripheral : CI in PU dut vomiting and Nauses
CVS : Postural hypotenison+Arryhthmia
3-Fluctations in responce
On - Off effect: sudden change from mboility to dyskinsea
End of dose akinesia : truning into dyskinestic before next dose
What is the best anti nasuse and antiemetic in parkinsoism ?
Domperidone Blcoking D2 peripherally in CTZ ALSO
Not interferred with Central D2 in basal ganglia so not interfere with antiparkinsoinan effect of l dopa
What is the best anti nasuse and antiemetic in parkinsoism ?
Domperidone Blcoking D2 peripherally in CTZ ALSO
Not interferred with Central D2 in basal ganglia so not interfere with antiparkinsoinan effect of l dopa
L dopa casue psycosis ?
Yes due to incrasing dopaime in mesolimbic tract
Atypical anipsychotics used in ?
l dopa induced psychosis
selecvitve for D2 of Mesolimbic
Dyskinesa casues in l dopa/treat
-Dut to extereme high level of dopamine in basal ganglia
-Fulucations in dopamine level in blood so in Basal ganglia
-Fluctations casue pulsatile stimulation NMDA Rs realsing glutamte in basal gagnlia
_______________
lowering sinemet dose and giving XR dose to prevent fluctations
Anti dyskineas action !
Amantatdine
NMDA R BLOCKERS
Anti parkisonian :
+dopaminergic
anti cholinergic
Motro flucutations is for?
Short t1/2
fLUCTUATING L DOPA LEVEL
:
1-peripheral due to
Gastric paresis
antagoism of protein
short t1/2
________________
2-centrla
pulsatattile deilvert to straitla DA receptros
Impaited storage
Alteration of DA receptor
HOow to treat motor fluctuations?
Decrasing interval between doses of sinemet
SINemet sr
Sinemet+ sillgelline
sinemet +entacapone exntednign
Interactions with l dopa ?
1-Vitb6 = pariphela dopa decarobxylase
2-MAO I increasing dopamine periophelalyy and HTN cirsis occur2
3-Antipsychotic halopridol blocking D2 in nigroStriatal
pHARMACO kinetic of levodopa ?
Ansorbed rapidly from small intestine
Short hald life 1-2h
protein interfers with its absorptions @ so must be taken 30 mintues before meal or after 1.5 h of meal
Nutrition care in PD ?
1-avoid Vit b6
2-lessen Protein
taken 30 minutes before diet
Fibers +fluids for constipations effect of PARKISNONISNM
Ergot problem ?
Vasospam
Fibrosis Pulmonary and Pericardial
young + mild first line antiparkinson ?
Dopamina agonists
less effective but! less dyskinesia
less flutcuations due to rapid absorption and long t1/2
Less dyskinesia in D2 AGONISTS WHY ?
less dyskinesia
less flutcuations due to rapid absorption and long t1/2
Functions of DA agonists?
Stop Fluctations occuring with Sinemet
Referactory to DA we give Siemet
Charatreicsitc adveres effect oPramipexole :
Pramipexole :
Impulse control disorder
Impulse control disorder
Impulse control disorder
Mention Adverese effects of dopamine agonists ?
Day time sleepleness
Like ldopa in /
Haluucination dyskinesia
Nause vomitting- Postural hypotension
Impusle contorl disorder
Vasospam
Pulmonart and pericardial fibrosis
Rescue therapy or drug for Sever off periods of akinesia in parkinsoinsm ?
Apomorphine
Rapid and more effective than l dopa and need antiemetic and it is potetne DA ?
apoMorphiiine
Amantidine
Antidyskinsisa why?
blckin NMDA-R
Dopamierc
anticholinergic
in mild cases
Amantadine side effects mention ?
HALTI
Hallucinations
Ankllllllle Edema
LividoReticularis
Tolerance rapied
Insomnia
Amantadine side effects mention ?
HALTI
Hallucinations
Ankllllllle Edema
LividoReticularis
Tolerance rapied
Insomnia
MAOB I Explian
sellgiline rasergiline
Neuroprotective
Extedning duration of dopamine work
Prevents accumulation of toxic degerative metabolites
in mild cases
Used with siemet to extedning its action preventing fluctuations
MAOB I adverse effects mention
HI
Hallucination -isnmoina
cheese reaction to tyramine dut to imhibitng MAOA MAOB in high doses
Selegilline and Raegiline compare
selegilline : Insmonia but rase no ampetamine like insomnia
Resgelline Once daily less side effects neruoprotectv MAOBI
cOMT II role in therapy
?
Prevent break down of l dopa into 3OMD
increasing l dopa to CNS
dECREASING Antagonism at its receptor to cns
Extending action of dopamine l dopa and decrasing Fluctuation Decrasing waring off and on -off
Other drug can be added to siemet ?q
Entacapone COMT I
orange urine occue int ?
eNTACOPNE
Entacapone adverses ?
as L dopa as dopa antagonists
Hallucination
dyskinesa
nasue postural hypotenison
Orange urin
Indicatiosn of Anticholinergics?
Parknison disease mono in mild and with DA in tremors and droppling sialoherrea
Drug induced Parkinsonism as ?
Halopridol why?
Why antichilinergic in Antipyschotic taking patients ?
Beacuse L dopa cannot attach to blocker receptor by antipsycho
Becasue If dopamine rised will aggravate anipsycotic
Adveerse of anticholinergic ?
Halucination\
memory loss
Urine Retenrion BPH
paresis causing l dopa fluctations
tREMORS can also traeted by ?
Inderal
propranolo blocking b receptors
monitor HR BP
SIALORRHEA
Botox
Sublingual atropine
guidlline ofor parkinsonism
If Drug induced = remove offednidng+ non pharma
If idipathic non phaerma +phaema
ANTICHOLINERGICS + COM I
+
1-cARBIDOPA - LEVODOPA if complications give
vomiting domepridone
P HTN midofdrine
Motor : Wearing off : extenders +DA agonists + sinemet if complications go complications path
Pshyc: depression TCA SSRI
Hallucinton clozpaine quuetapine
______________________
2-DA agonists <65 young
Dopamine agonist + carvidopa livdoppa
الحمدلله رب العالمين
