#alzheimers #_parkinsonism #_recent_advancement #_treatments

1. RECENT ADVANCEMENT
TREATMENT IN
ALZHEIMER’S AND
PARKINSON DISEASE.
Prepared by:-
J. Ram Gopal
170122887009
DEPT:-pharmacology
G. Pulla reddy college of
pharmacy

2. ALZHIEMERS DISEASE:-
•Neurodegenerative disorder which is irreversiblesort of neurons
damage in brain cells in cortex.
•Caused due to formation of plaques and tangles.
•Which cause demantia loss of memory and difficulty in learning
•Commonly seen in old age people
•Most of the existing treatments only cause symptomatic
solutions.
Symptoms:
-
#Memory loss
#Difficult in thinking
and reasoning
#decline in making
judgments
#decline in personal
ability
#depression
#social withdrawal
#wandering.

3. RISK FACTORS
.

4. ALZHEIMER'S DISEASE
CONFORMATIONAL TESTS
1.Neuronal amyloid plaques
2.neurofibrillatory tangles
3.brain atrophy
HYPOTHESIS
Three types of hypothesis
majorly
1.Amyloid hypothesis.
2.Tau hypothesis.
3.Cholinergic deficit

5. AMYLOID HYPOTHESIS

6. TAU HYPOTHESIS
CHOLINERGIC DEFICIT

7. DRUGS USED FOR ALZHEIMER'S

8. CHOLINERGIC HYPOTHESIS
ROLE- ach acts as imp transmitter in brain
memory
Impact- loss of ach in AD impairment of
memory
Treatment is bases on enhancing cholinergic function.
It may stabilize or improve the function
TACRINE- amino acridine derivative .
Dose dependent effect- 40 – 160 mgkg
Half life – 3-5 hrs
Cyp450 enzyme
Adverse effects-
Hepatotoxicity, nausea vomiting.

9. DONEPEZIL-
HALF LIFE – 70 HRS
DOSE – 5 – 10 mg daily
Not hepatotoxic
ADVERSE EFFECTS
Nausea
Vomit
Fatigue
Muscle cramps
Bradycardia
THIS DRUG IS GENERALLY SAFE AND
WELL TOLERATED
RIVASTIGIMINE-
Inhibits both Ache and Bche
Higher affinity to brain
HALF LIFE – 12 hrs
DOSE- 3-12 mg
Available in patches
GI adverse effects are common and
weight loss
GALANTAMINE
HAS DUAL MOA
Competitive inhibitor of ache
Allosteric modulation of presynaptic
and postsynaptic nicotinic receptors
Improves cognition, behaviour and
function

10. NMDA RECEPTOR ANTAGONIST
•Glutamine is an excitatory
neurotransmitter
•Acts on post synaptic NMDA
receptors
•Its overstimulation may result in
neuronal damage
MEMANTINE-
•Used in moderate to severe AD
•Has low affinity, non competitive
•Interact with mg2 binding site of
channel to prevent excessive
excitation
•Has 100 per BA
• dose 5mg OD
•ADRES –dizziness, headache,
confusion, constipation, and
agitation.

11. RECENT ADVANCE MENT
TREATMENT OF ALZHEIMER'S
1.anti amyloid
2.beta secretase inhibitors
3.alpha secretase inhibitors
4.kinase inhibitor
5.Theraphy for mitochondrial
dysfunction
6.anti cholinergic therapy.

12. ANTI AMYLOID THERAPY
This involves the use of drugs with diff mechanism of action
That enhances the clearance of amyloid beta protein
Prevent the production of A BETA PROTEIN
Inhibits the accumulation of A BETA PROTEIN
Some of the examples are
VACCINES ;- ANDI 792, CAD 106
MONOCLONAL ANTIBODIES ;- Ponezumab, bapineuzumab
GAMA AND BETA SECRETASE INHIBOTORS;- semagestat.

13. GAMMA SECRETASE INHIBITORS
These will be responsible for cleavage of
amyloid precursor protein and include L685
and MRK560
THERAPHY FOR MITOCONDRIAL
DYSFUNCTION;-
It is preserve mitochondrial structure, function
and protect against A beta induced apoptosis
Example are latrepirdine an anti histamine.

14. KINASE INHIBITORS
These drugs will decrease the Tan phosphorylation
by decrease the activity of kinase enzyme.
Example include lithium and valproate
BETA SECRETASE INHIBITORS
Thiazolidine derivatives can induce PPAR to inhibit
beta secretase ubiquitination to reduce the amyloid
burden
Its derivatives like pioglitazone, rosiglitazone helps in
proteolysis of A BETA

15. IMMUNO MTHERAPHY
-Many vaccination modalities under current investigation are directed towards
adverse T- cell mediated immune response
-nasal immunization models are also being developed in addition to
transcutaneous administration
CLIOQUINOL- its associate with zinc and unstable plaques
-it can reduce zinc accumulation in neuritic plaques by metal chelation
RESVERATRAOL- it’s a red wine poly phenol which promotes anti
aging effects
-it was found to be effective in slowing down AD development by A
BETA aggregation and by scavenging oxidants and exerting anti
inflammatory activities
NICOTINE- it’s a cholinergic agonist .
-alkaloid derived from leaves of tobacco plant
-it enhances the neuronal survival in respective to a range of

16. RECENT DEVELOPMENT
•Nano particle based treatment
•Ranging from 1-200nm easily cross the BBB
•Transportation will be achieved via both transcellular and paracellular
pathways .
•Examples of nano particles are lipoproteins, micelles, solid np`s,
polymer np`s, dendrimers, nano emulsion, inorganic np`s.

19. PARKINSONI
SM
Chronic, progressive, motor
nerve disorder.
Characterised by rigidity,
tremors, bradykinesia and
postural instability
Seen in above 65 years of aged
people
Imbalance between dopamine
and ach
Mainly seen at substantia nigra
destruction of dopaminergic
neuron.

20. WHAT EXACTLY GOES
WRONG IN
PARKINSONS DISEASE
In parkinson disease
dopaminergic neurons in
sb.nigra gradually die
leads to the mal functions
of the motor
conductance.
Loss of melanin
containing neurons
produces characteristic
changes in
depigmentation
Formation of LEWY
BODIES
Formed by alpha
synuclein,which oligorise
to form fibrils.
Mitocondrial dysfunction
is seen in the PD.
Glial cells surrounded to
neurons leads to release
cytokinins activates
astrocytes cell both
mediate inflammatory
response

21. DRUGS FOR PARKINSON DISEASE

22. MOA

23. RECENT ADVANCEMENT
SAFINAMIDE –
•FDA approved safinamide for treatment
of PD experiencing off episodes
•Acts by inhibiting i.e, reversible of
MOA-B than MOA-A and also by blocking
the glutamate release
•Dose 50 mg OD if needed increased to
100 mg based on tolerability
•Effective only on combination with
levodopa and carbidopa
•B.A is 95 per.
ADVERSE EFFECTS –
1. Falling asleep
during activities
of daily living
2. Dyskinesia
3. Hallucinations
4. Retinal
degeneration and
loss of
photoreceptor
cells

24. ISTRADEFYLLINE
•FDA approved drug for off episodes
•Dose is 20 mg OD
• MOA- by antagonize adenosine
receptor
•Adenosine is functionally linked to
D2 receptor and enhances GABA
release which contributes to over
activity of indirect pathway [which
is underlying mechanism of PD]

25. DUO DOPA
For patients with motor
fluctuations in advanced
PD.
 DOSE – 4.63 mg of
carbidopa and 20 mg of
levodopa per ml in single
use cassette. Each cassette
contains approx. 100ml
suspension
Max recommended dose is
2000mg administered over
16 hrs
At the end of 16 hrs
infusion patient will
disconnect the pump from
the PEG-J and take their
Precautions
If patient is discomfort with
duopa he should be
switched to oral therapy
Cautious in patient taking
non selective moa
inhibitors
ADRES
Falling asleep during
activities
Orthostatic hypotension

26. PEG-J TUBE

27. STEM CELL THERAPY
A break through study from
university in Sweden
Showed that it is possible to get
human embryonic stem cells to
produce a new generation of
dopamine cells that behave like
native dopamine cells when
transplanted in to the brains of
rat
The new cells show the all the
properties and functions of the
dopamine that are lost in PD

28. GENE THERAPY
The treatment called PROSAVIN uses a modified lentivector
technology to deliver the genes responsible for synthesis of-
1.tyrosine hydroxylase
2.glutamate acid decarboxylase
The product is administered locally to the striatum where
dopamine is needed
In early stages of PD levodopa tab are effective
L-DOPA is a pro drug it has to be converted to dopamine.
However the body progressively loses it ability to convert it and
its effectiveness is reduced in long term use
So it is designs to restore local continueos dopamine release
to control symptoms with out fail.

29. DEEP BRAIN STIMULATION
Uses electrical impulses to stimulate the
targeted area in the brain
Preferred treatment for advanced PD
Surgical process