Drugs for Parkinson's, Myasthenia Gravis, Dementia

Question 1

Name 6 drugs/drug classes which are used in the treatment of Parkinson’s. Give an example where relevant

Answer 1

1) Levodopa
2) Dopamine receptor agonists - e.g. Apomorphine
3) Monoamine oxidase type B inhibitors - e.g. Selegiline
4) Cathechol-O-methyl transferase (COMT) inhibitors - e.g. Entacapone
5) Anticholinergics - e.g. Procyclidine
6) Amantidine

Question 2

Why do you not give dopamine as a treatment for Parkinson’s?

Answer 2

Cannot cross the blood-brain barrier

Question 3

Why do you give levodopa alongside a decarboxylase inhibitor?
Name one

Answer 3

Inhibits peripheral aromatic amino acid decarboxylase, meaning the levodopa you give cannot be converted to dopamine before it has crossed the BBB.
Carbidopa

Question 4

How does Levodopa cross the BBB?

Answer 4

Via a large neutral amino acid transporter

Question 5

Why does the effect of Levodopa decrease as Parkinson’s disease progresses?

Answer 5

Can only be converted to dopamine inside dopaminergic neurones of the substantia nigra - hence requires some to still be present. Therefore cannot work when most have been destroyed

Question 6

What is the mechanism of action of Levodopa?

Answer 6

Increases dopamine concentration in the brain - hence reduces inhibition on the thalamus, which in turn increases excitation of motor cortex.

Question 7

What is a major problem with Levodopa administration?

Answer 7

Vast majority deactivated in the gut/periphery - only around 1% reaches CNS

Question 8

Give 4 ADRs of Levodopa

Answer 8

Nausea
Drowsiness
Confusion
Hypotension

Question 9

What is the “on-off effect” of Levodopa?

Answer 9

• Patient’s symptoms get worse towards end of dosing interval, so you give higher dose
  BUT
• This results in dyskinesias (i.e. excessive involuntary movements) at the beginning of the dosing period

Question 10

List 3 drug interactions associated with Levodopa

Answer 10

• Vit B6 increases peripheral breakdown
• MAOIs risk hypertensive crisis
• Antipsychotic drugs block dopamine receptors, so produce Parkinsonism

Question 11

Give 3 examples of Dopamine receptor agonists

Answer 11

Apomorphine
Bromocriptine
Ropinirole

Question 12

When are dopamine receptor agonists used over levodopa?

Answer 12

In earlier stage Parkinson’s

Question 13

How are Ropinirole and Apomorphine administered?

Answer 13

Ropinirole - oral

Apomorphine - SC injection

Question 14

What is one unusual side effect of the dopamine receptor agonists?

Answer 14

Impulse control disorders - e.g. gambling

Question 15

Compare the benefits/risks of levodopa vs dopamine receptor agonists

Answer 15

DRAs have relatively fewer ADRs, especially motor ones, but lower efficacy and expensive

Question 16

Name a monoamine oxidase type B inhibitor

Answer 16

Selegiline

Question 17

What is the mechanism of action of MAOIs?

Answer 17

MAO metabolises dopamine in the gut and brain, hence by inhibiting this enzyme you increase the amount of dopamine reaching the brain

Question 18

What are the benefits and disadvantages of using MAOIs alongside levodopa?

Answer 18

• Good because increases effects of Levodopa and means lower dose can be used
  BUT
• May lead to hypertension due to increased catecholamines and hence symp. drive

Question 19

What sort of drug is Entacapone?

Answer 19

COMT inhibitor

Question 20

How are COMT inhibitors used?

Answer 20

Only alongside levodopa

Question 21

What is the mechanism of action of COMT inhibitors?

Answer 21

• Inhibits the COMT pathway of dopamine breakdown

- Therefore increases central uptake of levodopa, and decreases levodopa dose needed

Question 22

Give 4 ADRs of COMT inhibitors

Answer 22

• Diarrhoea
• Postural hypotension
• Nausea
• Hallucinations

Question 23

Give an example of an anticholinergic drug used in Parkinson’s

Answer 23

Procyclidine

Question 24

What is the mechanism behind anticholinergic use in Parkinson’s?

Answer 24

• Query usefulness, but thought that ratio between ACh and dopamine must be maintained - decreasing ACh increases dopamine transmission

Question 25

List some ADRs of anticholinergic drugs

Answer 25

Think "SLUDGE" - Salivation - Lacrimation - Urination - Defaecation - GI cramps - Emesis

Question 26

List some drugs which may exacerbate myasthenia gravis

Answer 26

- Aminoglycosides - B blockers - Succinylcholine - ACE inhibitors

Question 27

Give 2 broad mechanisms by which myasthenia gravis is treated

Answer 27

- Immunosuppression | - Acetylcholinesterase inhibitors

Question 28

Give 2 examples of acetylcholinesterase inhibitors used in myasthenia gravis

Answer 28

Pyridostigmine | Neostigmine

Question 29

Which other condition are AChE inhibitors used to treat? | Name some examples relevant to this condition

Answer 29

Dementia | Donepezil, Galantamine

Question 30

Give some ADRs of AChE inhibitors

Answer 30

- Anticholinergic such as SLUDGE - Bradycardia --> falls - Peptic ulcers - Worsening of COPD

Question 31

What is the class/mechanism of action of Memantine?

Answer 31

NMDA antagonist

Question 32

Give some ADRs of Memantine

Answer 32

- Hypertension - Dyspnoea - Headache - Dizziness