Session 13 Neurologial Disrders

Question 1

Clinical features of Parkinsonism?

Answer 1

Tremor
Rigidity
Bradykinesia
Postural instability

Question 2

Non motor manifestations of Parkinson’s disease?

Answer 2

Mood changes 
Pain 
Cognitive change 
Urinary symptoms 
Sleep disorder 
Sweating

Question 3

Complications (15 years0 of PD)?

Answer 3

Risk of

Dyskinesia (94%)
Falls
Cognitive decline 
Somnolence 
Swallowing difficulty 
Severe speech problems (27%)

Question 4

How would you diagnosed idiopathic Parkinson’s disease?

Answer 4

Clinical features

Exclude other causes of Parkinsonism

Response to treatment

Structural neurological imaging is normal

Functional neurological imaging - SPECT, PET

Question 5

Pathology of IPD?

What would you see

Answer 5

Neurodegeneration

Lewy bodies

Loss of pigment
- increased turnover and unregulate receptor

Reduced dopamine

Question 6

Describe catecholamine synthesis (steps)

Answer 6

L-tyrosine —> L-DOPA
Via tyrosine hydroxylase

L-DOPA —> Dopamine
Via DOPA decarboxylase

Dopamine —> Noradrenaline
Via dopamine-B-hydroxylase

Noradrenaline —> adrenaline
Via phenylethanolamine n-methyltransferase (in cytosol)

Question 7

Describe dopamine degradation

Answer 7

Dopamine can be degraded into;

3,4 - dihydrophenyl acetic acid

OR

3-methoxytyramine (3-MT)

Both broken down into:

Homovanillic acid

Question 8

PK of L-DOPA (levodopa)

Answer 8

Oral administration

Absorbed by active transport

90% inactivated in intestinal wall

Half life is 2 hrs

9% converted to dopamine in peripheral tissues

<1% enters CNs

Question 9

Formulations of L-DOPA?

Answer 9

Used in combination with a peripheral DOPA decarboxylase inhibitor

Co-careldopa - sinemet

Co-beneldopa - madopar

Question 10

Why are formaultions of L-DOPA good to use?

Answer 10

Reduced dose required
Reduced side effects
Increased L-DOPA reaching brain
Tablet formulations

Question 11

Advantages and disadvantages of L-DOPA

Answer 11

Good

• highly efficacious
• low side effects

Bad

• its a precursor so needs enzyme conversion
• long term
• loss of efficacy
• involuntary movements
• motor complications

Question 12

Interactions of L-DOPA?

Answer 12

Pyridoxine (vitamin B6) increases peripheral breakdown of L-DOPA

MAOIs risk hypertensive crisis

Many antipsychotic drugs block dopamine receptor and Parkinsonism is a side effects

Question 13

Advantages and disadvantages of dopamine receptor agonists?

Answer 13

Advantages

• direct acting
• less dyskinesia or motor complications
• Possible neuroprotection

Disadvantages

• less efficacy than L-DOPA
• impulse control disorders
• more psychiatric side effects
• expensive

Question 14

What are 5 examples of impulse control disorders (dopamine dysregulation syndrome)

Answer 14

• pathological gambling
• hyper sexuality
• compulsive shopping
• desire to increase dosage
• punding

Question 15

Side effects of dopamine receptor agonists?

Answer 15

Sedation 
Hallucinations
Confusion 
Nausea
Hypotension

Question 16

What does monoamine oxidase B do?

Answer 16

Metabolises dopamine

Predominates in dopamine containing region of the brain

Question 17

Monoamine oxidase B inhibitors

Drug names

MoA

Answer 17

Drug names

• selegiline
• rasagaline

Prolong action of L-DOPA (enhance dopamine)
Smooths out motor response
Neuroprotective and can be used alone

Question 18

Catechol-O-methyl transferase (COMT) inhibitors

Names of drugs and which ones cross the BBB?

How do they work?

Answer 18

Entacapone - doesn’t cross BBB
Tolcapone - crosses BBB but main effect is peripheral

Both reduce the peripheral breakdown of L-DOPA

No therapeutic effect when used alone
- use combination tablets with L-Dopa and peripheral dopa decarboxylase inhibitor (Stalevo)

Have a L-DOPA sparing effect

Prolongs motor response to L-DOPA
- reduces symptoms of wearing off

Question 19

What effect do anticholinergics have on dopamine?

Answer 19

Acetyl choline may have antagonistic effects to dopamine so blocking ACh will stop the anti effects

Question 20

Advantages and disadvantages of anticholinergics

Answer 20

Advantages

• treat tremor
• not acting via dopamine systems

Disadvantages

• no effect on bradykinesia
• side effects: confusion, drowsiness etc

Question 21

What drugs can exacerbate myasthenia gravis?

Answer 21

Aminoglycosides 
Beta blockers, CCBs, quinidine, procainamide
Chloroquine, penicillamine
Succinylcholine
Magnesium 
ACE inhibitors 

DRUGS THAT AFFECT neuromuscular transmission!

Question 22

How does pyridostigmine work?

Answer 22

Prevents breakdown of ACh in NMJ

ACh more likely to engage with remaining receptors

Question 23

Side effects of pyridostigmine?

Answer 23

Cholinergic side effects

Miosis and the sludge syndrome

Salivating 
Sweating 
Lacrimation 
Urinary incontinence
Diarrhoea
GI upset and hypermotility 
Emesis