Pharmacology of the Basal Ganglia II Flashcards
Pharmacological management of Parkinson’s disease
Name two drugs that can combined with L-DOPA (aka levodopa) that means it doesn’t get metabolised to dopamine outside the BBB [2]
What is their MOA? [1]
L-DOPA (levodopa) & carbidopa orbenserazide
carbidopa, benserazide are decaboxylase inhibitors: allows L-DOPA to pass BBB where it can then be converted to dopamine
Pharmacological management of Parkinson’s disease
Name 3 dopminergic agonists and describe their MOA
Dopamine agonists:
* ropinirole
* pramipexole
* rotigotine (in BB PBL; transdermal patch)
Dopamine agonists act directly on the dopamine receptors and mimic dopamine’s effect
Which of the following dopamine agonists can be used as a transdermal patch?
bromocriptine,
pramipexole
ropinirole
rotigotine
Apomorphine
Which of the following dopamine agonists can be used as a transdermal patch?
bromocriptine,
pramipexole
ropinirole
rotigotine
Apomorphine
Which of the following dopamine agonists can be used as an infusion for major motor fluctuations?
bromocriptine,
pramipexole
ropinirole
rotigotine
Apomorphine
Which of the following dopamine agonists can be used as an infusion for major motor fluctuations?
bromocriptine,
pramipexole
ropinirole
rotigotine
Apomorphine
Why are dopamine agonists sometimes an advantage if a patient has difficulty swallowing? [1]
Dopamine agonists differ in their pharmacokinetics: longer acting drugs require fewer daily doses and this can be an advantage when there are swallowing difficulties
Pharmacological management of Parkinson’s disease
Name three drugs that are monoamine oxidase inhibitors [3]
Describe their MoA [1]
- rasagiline
- selegiline (in PBL)
- safinamide
MAO-B inhibitors stop Monoamine oxidase type B breaking down dopamine into DOPAC or homovanillic acid
What is the MoA of COMT inhibitors? [1]
Explain why [1]
Which drugs are they used in conjunction with? [1]
COMT is an enzyme involved in the breakdown of dopamine (DOPAC –> homovanillic acid) and hence may be used as an adjunct to levodopa therapy
Pharmacological management of Parkinson’s disease
Name 2 COMT inhibitors [2]
entacapone
tolcapone
Pharmacological management of Parkinson’s disease
Why are anticholinergic (antimuscarininc) compounds used to treat PD? [1]
Dopamine loss leads to hyperactivity of cholinergic cells
Pharmacological management of Parkinson’s disease
Name three anticholinergic compounds [3]
Which symtpom are they particularly good for treating? [1]
orphenadrine, procyclidine, trihexyphenidyl
Block tremors (as block muscarinic receptors on muscles) but also cause dry mouth and constipation
Pharmacological management of Parkinson’s disease
What is the MoA of Amantadine? [1]
inhibits dopamine reuptake, increases dopamine release, also weak antagonist at NMDA glutamate receptors
Name 5 AEs of L-DOPA medication [5]
Adverse effects of L-DOPA:
Nausea/vomiting
Postural hypotension
Psychosis
Impulse-control disorders (more frequent with dopaminergic agonists –e g. gambling)
Excessive day-time sleepiness
On/Off effect
Dyskinesia
Dystonia
What is the difference between tremor and dyskinesia with PD? [2]
Tremor is a symptom of Parkinson’s
* rhythmic in movement
Dyskinesia is a side effect of levodopa
* more unsteady and disorganised.
Describe a common pattern of long term L-DOPA treatment [1]
L-DOPA works well for 5 years then the effect decreases
Then add other drugs
Pharmacological management of PD:
Other treatment approaches
Name two cell based approaches that can use to treat PD [2]
- Striatal graft of embryonic mesencephalic cells: intrastriatal transplant of foetal nigral cells
- Systemic administration of mesenchymal stem cells: Improvement following repeated intravenous injection of adipose tissue-derived cells
What are the pathological changes seen to a HD patient’s brain? [3]
Loss of medium size spiny neurons
cortical atrophy
prominent striatal degeneration
