Drugs Used in Neurological Disorders Flashcards
What main 2 neurological disroders can we treat?
Idiopathic parkinson’s disease
Myasthenia Gravis
What is the pathophysiology of IPD?
Neurodegeneration in the substantia nigra in the cells which produce dopamine, leading to reduced number of dopaminergic neurones
How are catecholamines synthesised?
L-tyrosine -> L-DOPA -> Dopamine -> Norepinepherine/NA -> Epinepherine (adrenaline)
How is L-tyrosine converted to L-DOPA?
By tyrosine hydroxylase
How is L-DOPA converted to dopamine?
By DOPA decarboxylase
How is dopamine converted to NA?
By dopamine B-hydroxylase
What 2 enzymes can break down dopamine?
COMT then MAO/aldehyde dehydrogenase
MAO/aldehyde dehydrogenase then COMT
What is the end product of dopamine breakdown?
Homovanillic acid
What are the 3 ways to manage IPD?
Treat symptoms, neuroprotection, and surgery
What should be offered to pts with early IPD to manage motor symptoms (which decrease QoL)?
Levodopa
combined with carbidopa (co-careldopa) or benserazide (co-beneldopa)
If IPD pts aren’t affected (QoL) by motor symptoms, which drugs can pts be offered?
Levodopa
Dopamine receptor agonists
MAO-B inhibitors
How does levodopa work?
Formulation of L-DOPA that crosses the blood brain barrier and is taken up by dopaminergic cells in the SN where it -> dopamine
What is the disadvantage of levodopa?
If there are fewer SN cells (more progressed disease), its effect is lessened as it cannot be converted
How is levodopa administered?
Orally
Describe what happens in absorption of levodopa
Levodopa is absorbed in the gut by active transport (competition with amino acids).
90% is inactivated in the intestinal wall by MAO and dopa decarboxylase
What is the half life of levodopa?
2 hours
What does this half life mean for levodopa dosage and effect?
Short dose interval so blood levels can fluctuate, so symptoms also fluctuate
How much levodopa is converted to dopamine in peripheral tissues?
9%
What does this peripheral conversion of levodopa mean, practically?
It can cause peripheral tissue side effects, such as hypertension
What does the remaining 1% of levodopa compete with to get across the BBB?
Amino acids again
How can levodopa administration and effect be maximised?
Different formulations with a DOPA decarboxylase inhibitor
What are the 2 formulations of levodopa with dopa decarboxylase inhiitors?
Co-careldopa (sinemet)
Co-beneldopa (madopar)
How much L-DOPA reaches the brain in levodopa cobined formulations?
About 10%
What are the advantages of levodopa?
Very effective
Low side effects
What ADRs can be experienced with levodopa?
Nausea/anorexia
Hypotension
Psychosis
Tachycardia
What are the disadvantages of levodopa?
Needs enzymatic conversion
Loss of efficacy long term
Involuntary movements and motor complications
What can increase the breakdown of levodopa?
Pyroxidine/Vit B12 (breakdown in peripheries)
What is a risk with levodopa and MAO inhibitors together?
Hypertensive crisis
Which group of drugs block dopamine receptors?
Antipsychotics
What 4 groups of dopamine receptor agonists are there?
Ergot derived (not used)
Non-ergot derived
Patch
Subcut
What types of non ergot dopamine receptor agonists are there?
Ropinirole
Pramipexole
What dopamine receptor agonist patch is there?
Rotigotine
What subcut dopamine receptor agonist is there?
apomorphine
