1. Presented by Abdulaziz .M. Al-Saad
Parkinson's disease
CNS drugs act on brain and spinal cord in medical use (treatment of mental illness, suppression of seizures, relief of pain, and production of anesthesia) and nonmedical uses ( stimulants, depressants, euphoriants, and other mind altering uses.
Presented by
Abdulaziz .M. Al-Saad

2. Contents Definition & Pathophysiology . Static & Facts .
Causes & Stages .
Strategy of treatment .
Drug therapy .
Surgical approach .
The future .

3. What is Parkinson's disease ?
Parkinson’s disease is a disorder of the extrapyramidal system . Characterized by…
It is progressive disease ??
Imbalance between the excitatory neurotransmitter Acetylcholine and inhibitory neurotransmitter Dopamine in the Basal Ganglia : DA
ACh

4. Nonmotor symptoms
Cognitive impairment, dementia** Psychiatric symptoms, particularly depression** Autonomic disturbances**
Urinary urgency and frequency
Constipation
Hypotension with orthostasis
Sweating disorders
Sexual dysfunction
Sleep disturbances**

5. Static and Facts
Age at onset variable ( 50 – 80 years ) . Mean age 55 years
Man and Woman are equally affected.
Prevalence case Per Population .
Incidence case Per People annually.

6. Static and Facts Progression highly variable. Within 10 – 20 years.
Patient age at onset affect progression . ( high rate in older )
Mortality not caused by disease itself , but, due to complications related to immobility . Complication such as ( Aspiration Pneumonia , cardiovascular and cerebrovascular disease (

7. Causes : Drug induce PD : What is MPTP ?
Idiopathic due to exposure to :
Neurotoxins.
Oxidative reactions.
Genetic factors may be important.
Others :
Dopaminergic receptor antagonist ( Antipsychotic ) .
Destruction of dopaminergic neurons ( MPTP ) .
Drug induce PD :
Reserpine depletion of dopamine storage.
Halloperidole, phenothiazin , MPTP.
What is MPTP ?

8. Stages of PD Stage 1 : Unilateral involvement
Minimal or no functional impairment.
Stage 2 : Bilateral involvement
Without impairment of balance
Stage 3 : Postural imbalance
Some restriction of activity
Mild – Moderate disability
Stage 4 : Severely disable
Cannot walk and stand
Stage 5 : Restricted to the bed

9. Treatment of Parkinson’s Disease

10. Classification of Drug Therapy for Parkinson’s Disease
Two major categories
Dopaminergic agents :
Promote activation of dopamine receptors
Levodopa (Dopar)
Anticholinergic agents :
Prevent activation of cholinergic receptors
Benztropine (Cogentin)

11. Blockade of muscarinic cholinergic receptors in the striatum
Dopaminergic Agents
Mechanism of Action
Promotion of dopamine synthesis
Prevention of dopamine degradation
Promotion of dopamine release
Direct activation of dopamine receptors
Anticholinergic Agents
Mechanism of action
Blockade of muscarinic cholinergic receptors in the striatum

12. Levo- dopa Side Effects Immediate metabolic precursor of dopamine
Dopamine not cross BBB.
Levodopa cross BBB.
After it cross BBB, decarboxylated to dopamine.
Peripheral decarboxylation can be prevented by : Carbidopa
This leads to decrease dose by 75 %
Dose Sinemet ( 25 mg / 100 mg ) OR ( 25/ 250 ) OR Controlled release.
Side Effects
GIT .
Cardiac abnormalities .
CNS .
Eye.
Behavior changes.
Fluctuations Drug Holiday
Wearing off Treatment

13. Ergot Derivative Contraindications : Drug Interactions
Psychotic Patients .
Cardiac disease .
Glaucoma .
Peptic ulcer .
Drug Interactions
Pyridoxine ( Vit. B6 ) Increase Periphral decarboxylations.
MAOIs type A Hypertensive crisis.
Ergot Derivative
1- Bromocriptin :
D2 agonist , widely used in PD.
2- Pergolide :
- D1, D2 agonist , widely used in PD .

14. SE: ( fatiguge , insomnia , dyskinisia , confusion )
Non-Ergot Derivative
Advantage :
1- Newer Agents
2- Effective against PD.
3- Approved by FDA.
4- Lower SE Than old group.
1- Ramipexole :
D3 receptor
Effective as monotherapy in mild cases
Adjunctive + LD decrease dose and fluctuation with LD.
2- Roprinil :
D2 receptor
SE: ( fatiguge , insomnia , dyskinisia , confusion )

15. Mechanism of action ( Selegiline) :
Selective inhibitor of Monoamine Oxidase type B .
( what do you think about non-selective ? ) .
Too much- anxiety, panic anorexia, excitability, insomnia
Too Little- Depression, ADD/ADHD
2. Too much- Psychoses, Tourettes/Tics, chorea
Too little- Parkinson’s ADD/ADHD, depression
3. Too much-delirium, confusion, psychoses
Too little-Alzheimers
4. Too much- Sleep, Hallucinations,Decreased appetite, anxiety
Too little- Depression, OCD, pain sensitivity
5. Too much- CNS depression, Resp. depression, Sedation
Too little- Seizures, Movement disorders
Too much- Seizures, neuronal degeneration
Too little-schizophrenia, depression, cognitive impairment
MAO B
L -dopa
Dopamine
Reuptake
COMT

16. Advantages of Selegiline :
Enhance and prolongs the anti-parkinsonism effect of Levo – dopa .
Reduce the dose of Levo – dopa .
Dose : ( 5 mg at break fast ) ( 5 mg at lunch )
SE : increase insomnia with LD.
Not used with TCAs.
L - dopa
The blood brain barrier- impedes entry of drugs into the brain, limited to lipid soluble agents or drugs by specific transport systems in an intact barrier, this is positive (protection from toxic substances), and negative (obstacle to therapeutics) not fully developed at birth.
70 %
29 %
GIT
1 – 3 %
Prephral tissues
Brain

17. Effect of adding selegiline to levodopa in early, mild Parkinson’s disease 4
Evidence is insufficient to show that combined treatment increases mortality .
Proportions of deaths and overall mortality in 11 clinical studies of treatment of Parkinson’s disease with selegiline :
Study
Selegiline
No selegiline
Olanow et al 1998
14/297
17/292
Caraceni et al 1997
25/155
25/156
Di Rocco et al 1996
30/109
40/67
Rinne et al1-151
3/30
10/30
Parkinson’s Study Group 1998
70/399
67/401
Birkmayer et al 1985
118/564
114/377
Ben-Shlomo et al 1998
103/271
73/249
Total
363/1825 (19.9%)
346/1572 (22%)

18. Catichol-O-Methyltransferase Inhibitor
( COMT )
1- Tolcapone & entacapone
Prolong duration of action of LD.
SE : Similar to LD .
2- Amantadine
Antiviral agents.
Potentiate action of DA by increase synthesis ,release and decrease reuptake.
Therapeutic effect short – lived.
SE :
Restlessnes, agitation, depression , irritability ( CNS se )
Is a degenerative disorder of the CNS caused by death of neurons that produce the brain neurotransmitter dopamine. It is the most common degenerative disease of the nerves. sym

19. Experimental approach to treat PD
Acetyl choline- blocking agents :
Antimuscarinc Agents:
Bnzotropine , biperiden, orphenadrin.
Effective against PD .
SE :
Drowsiness, hallucination , restlessness, depression
Other : dry mouth , Mydriasis, urinary retention .
Experimental approach to treat PD
Vitamin E: Free radical scavenger.
Neurotropfic factor e.g. Glial –derived neurotropfic factor
Explanation of symptoms- A disruption of neurotransmission within the striatum (proper function requires balance between dopamine and acetylcholine.

20. Surgical Procedure :
Used in poorly responsive PD patients to pharmacotherapy ..
High Frequency Deep Brain Stimulation ( Thalamic Stimulation ).
Transplantation of Dopaminergic tissue

21. Conclusion
Patients with Parkinson's disease have a constellation of clinical symptoms that evolve over the course of the condition.
Patient management involves the accurate clinical diagnosis of the disease, multidisciplinary management of clinical problems and the use of a number of therapeutic options.
Until disease-modifying drugs become available, we must focus on reducing the burden of Parkinson's disease by treating the symptoms and helping our patients cope with their disability by improving their quality of life.

22. The end
Treatment strategy- Restore balance between DA and ACH by activating DA receptors or blocking ACH receptors.

23. Pain Management in Patients with CA
CNS Pharmacology

24. Pain Management
Pain
Unpleasant sensory and emotional experience associated with tissue damage
Patient’s pain description is the cornerstone of pain assessment

25. Types of Pain Nociceptive pain Results from injury to tissues
Called somatic or visceral pain
Neuropathic pain
Results from injury to peripheral nerves
Responds poorly to opiods

26. Clinical Approach to Pain Management
A- Ask and assess
B- Believe
C- Choose
D- Deliver
E- Empower and enable

27. Pain Assessment Assessment parameters of pain
Onset and temporal patterns
Location
Quality
Intensity
Modulating Factors
Previous treatment
Impact

28. WHO Analgesic Ladder Step 1- Mild to moderate pain
Nonopiod analgesic
Step 2- More severe pain
Add opioid analgesic
Step 3- Severe pain
Substitute opioid-morphine