S12.2 Drugs used in neurological disorders

Question 1

Describe the presentation of Idiopathic Parkinson’s disease (IPD)

Answer 1

Motor: Tremor, Rigidity, Bradykinesia

Non-motor: Mood changes, pain, REM sleep disorder

Question 2

Outline the pathophysiology of IDP

Answer 2

Loss of dopaminergic neurons in substantia nigra results in reduced stimulation of the cortex and so slow movements

Question 3

What are the features of Parkinson’s Plus Syndromes?

Answer 3

Parkinson’s Plus Syndromes respond poorly to Parkinson treatment, clinical features include early onset hallucinations and dementia

Question 4

Outline the synthesis of dopamine from L-tyrosine

Answer 4

L-tyrosine; L-DOPA; Dopamine (; NA; Adrenaline)

Question 5

How can dopamine be targeted for IPD treatment?

Answer 5

DOPA degradation into homovanilic acid involves either a Monamine Oxidase (MAO) enzyme or a Catechol-O-Methyl Transferase (COMT) enzyme, and both these enzymes can be targeted to treat IPD

Question 6

Describe the mechanism of levodopa

Answer 6

We use L-DOPA as dopamine can’t cross BBB.

L-DOPA is be taken up by dopaminergic cells in the Substantia Nigra and converted to dopamine

Question 7

Outline the pharmacokinetics of L-DOPA and the use of carbidopa

Answer 7

Oral
90% inactivated in intestinal wall by DOPA decarboxylase (L-DOPA into DOPA) and monoamine oxidase.
Therefore need to give carbidopa, a DOPA decarboxylase inhibitor, which allows more L-DOPA to reach the BBB

Question 8

Give some disadvantages of L-DOPA

Answer 8

Needs enzyme conversion, long term loss of efficacy, involuntary movements, motor complications

Question 9

Describe dopamine receptor agonists

Answer 9

E.g Apomorphine, Ropinirole
Advantages: direct acting, show less motor complications/dyskinesia then L-DOPA
Disadvantages: less efficacy than L-DOPA, expensive, side effects (hallucinations, confusion).

Question 10

Describe MAO B inhibitors

Answer 10

Eg selegiline
Prevents dopa metabolism.
Prolongs action of L-DOPA

Question 11

Describe COMT inhibitors

Answer 11

E.g entacapone

Doesn’t cross BBB. Prevents breakdown of L-DOPA, therefore prolonging its effects

Question 12

Describe anticholinergics

Answer 12

E.g procyclidine, orphenadrine.
May have an antagonistic effect to dopamine, so can have a minor role in the treatment of IPD esp for a tremor.
However, no effect on bradykinesia and have side effects of confusion, drowsiness, and anti-cholinergic side-effects (e.g. dry mouth, urinary retention etc.)

Question 13

Describe amantadine

Answer 13

May enhance dopamine release and inhibit NMDA

Question 14

What is myasthenia gravis?

Answer 14

Autoimmune condition that causes blockage (IgG) and/or degradation of the nAChRs at the NMJ, so less synaptic transmission.

Question 15

What is the presentation of myasthenia gravis?

Answer 15

Results in Fluctuating, fatigable weakness in skeletal muscle. Commonly the extraocular muscles (diplopia/ptosis), but also bulbar and limb involvement

Question 16

What is the treatment for myasthenia gravis?

Answer 16

Acetylcholinesterase inhibitors
E.g Pyridostigmine or neostigmine (oral)
More Ach left in cleft to bind to receptors

Question 17

What are some ADRs of acetylcholinesterase inhibitors?

Answer 17

Acute exacerbation can cause a Myasthenic crisis (drooping face).
Over treatment of the condition can lead to cholinergic crisis (flaccid paralysis and respiratory failure).
ADRs: SSLUDGE (Salivation, Sweating, Lacrimation, Urinary incontinence, Diarrhoea, GI hypermobility, and Emesis).