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Semester 3 > Case 7 - medications and treatment > Flashcards

Case 7 - medications and treatment Flashcards

1
Q

what is the traditional first line of treatment in PD

A

levodopa - L-dopa

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2
Q

what is the mechanism of levodopa

A

dopamine itself cannot cross the BBB
L dopa can and once it has, it is converted into dopamine by DOPA carboxylase.
it is also concerted to dopamine once it is inside the pNS, and it is thought that this may be responsibke for some of the side effects of this drug
it is thought that dopamine essentially floods the synapses, and this combined with the reduced amount of endogenous dopamine is enough to reduce the clinical consequences of PD

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3
Q

what does Levodopa increase

A

the amount of free dopamine in the brain, and compensate for the usual loss of dopamine

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4
Q

what is the problem with levodopa

A

their efficacy tends to decrease over time, thus you should only give it to them when you feel the PD is adversely affecting life to great enough extent

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5
Q

when is Levodopa usually given

A

12 months after diagnosis

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6
Q

what is the normal dosage of L-dopa

A

naturally very short acting
taken with food to avoid nausea and vomiting
usually doses are sound 800mg /24 hr in divided doses, but get up to this level gradually

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7
Q

what is levodopa usually given with

A

carbidopa, entacapone or benserazide

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8
Q

why is it given with something else

A

decrease L-dopa metabolism and thus prolong the half life of L-dopa

these also reduce the dose needed by about 90&

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9
Q

what are the side effects of levodopa

A

nausea
Dyskinesias - these usually occur in the face and limbs, and usually occur at the peak therapeutic effect, this the link between therapeutic and high dose is fine
Hypotension
Arrhythmia
Psychosis - increased dopamine levels in the brain
Compulsive behaviour
Gambling
Spending
Inappropriate sexual behaviour

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10
Q

what is the on-off effect

A

this is related to the fluctuating plasma concentration of Ldopa. the effect is seen more often the longer the drug has been used. it is also seen in untreated patients. this usually occurs at the ‘end of dose’. you can reduce the on-odd effect with slow release L-dopa. often the on-off effect can never be eliminated once to has occured

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11
Q

how much of a levodopa dose actually crosses the BBB

A

10%

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12
Q

what happens to the remaining levodopa

A

susceptible to conversion to dopamine In the periphery leading to side effects

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13
Q

how do you counteract the conversion of levodopa in the pNS

A

inhibitors that reduce the breakdown of dopamine in the PNS, called peripheral dopa decaerboxylase inhibitors (carbidopa and benserazide) are given. in combination with levodopa to reduce peripheral conversion that would otherwise devour most of the dose given

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14
Q

what does the addition of dopa decarboxylase do

A

maximises the bioavailability of dopamine in the brain, decreases side effects, and allows a lower dose of levodopa to be used

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15
Q

what two enzymes break down dopamine

A

MAO
COMT

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16
Q

what is another therapeutic strategy to do with MAO

A

introduce an MAO inhibitor in too the synapse, which interrupts the action of the MAO enzyme and prevents the breakdown of dopamine in the synapse.

this allows more dopamine to remain in the synapse and increases the likelihood that it will bind to the postsynaptic membrane

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17
Q

what features of PD respond best to levodopa

A

bradykinesia and rigidity.

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18
Q

what is the loss of dopamine due to

A

protein misfolding, aggregation and toxicity

defective proteolysis

mitochondrial dysfunction

oxidative stress

19
Q

how does L-dopa lead to dyskinesias

A

at the disease progresses and dopaminergic neurones continue to be lost in the substantia nigra, l-dopa becomes ineffective for treating the motor symptoms

as medication becomes less effective, off periods may occur when the levodopa dose has worn off and movement is again difficult until another dose is given

20
Q

what are ropinirole and pramipexole

A

selective D3 agonists

they have decreased risk of dyskinesias, and they appear to not exhibit the long term diminished effectiveness as seen with L dopa

21
Q

who are D3 agonists used in

A

first line treatment in younger patients

22
Q

what are the side effects of ropinirole and pramipexole

A

drowsiness
hallucinations
nausea

23
Q

what is bromocriptine

A

a selective D2 agonist
has a long half life so does not need to be given as often as L dopa

24
Q

what are the side effects of bromocriptine

A

hallucinations
hypotension
nausea
fibrosis
drowsiness

25
Q

what is selegilene

A

inhibits MAO-B selectively
MAO-B metabolises dopamine thus this helps increase the level of dopamine in the brain

26
Q

what may MAO-B inhibitors do in early stage PD

A

may help slow down the progression of the disease

27
Q

why is MAO-B used in conjunction with Ldopa

A

helps to reduce the dose of L dopa which in turn reduces the side effects and increases the long term effectiveness of L dopa

28
Q

what are the side effects of selegilene

A

postural hypotension

29
Q

how do MAO-B inhibitors increase the level of dopamine

A

by blocking its metabolism. they inhibit the MAO-B enzyme responsible for breaking down dopamine. alone can improve motor symptoms and delay the need for levodopa. can be used between the on-off period with levodopa

30
Q

what drug type releases dopamine

A

amantadine

31
Q

what does amantadine do

A

used as an adjunct to Ldopa
it is a weak antagonist of the NMDA type glutamate receptors that increase dopamine release and blocks dopamine re uptake into the synapse

32
Q

what are examples of anticholinergics

A

orphenadrine and atropine

33
Q

what do anticholingergics do

A

many of the motor symptoms of PD are the result of over activity of ACh releasing neurones, because their dopamine inhibition has been lost
anticholinergics can reduce this overactivity and thus reduce the motor signs as seen in PD

34
Q

what do they essentially do to the muscle nerve connections

A

anaesthetise the muscle nerve connections to reduce intend motor symptoms and rigidity

35
Q

what is deep brain stimulation

A

surgical intervention that utilises an implantable pulse generator as a waveform generator and power source. the neurostimulator controls the flow of current to specific brain regions through an attachment to an implantable DBS lead.

each DBS lead has multiple contacts and therefore many possible parameter configurations. the optomisation of possible settings, which may number into the thousands when considering the range of pulse widths, frequencies, amplitudes and configurations of anodes and cathodes, can provide critical determinant for therapeutic success or failure

36
Q

what is involved in the DBS procedure

A

two stage process involved in stereo static frame, with the patient under sedation yet awake for a 30 minute 3D MRI to locate the coordinates of the deep Brain target.

after determining the target in the operating room, a path for the very fine metal electrodes is selected that will reach the target

the DBS electrode is placed, and electrical impulses are sent to see which placement gives the best reduction in tremors, while monitoring for other unwanted side effects in speech or numbness

37
Q

what is the second procedure

A

performed under general anaesthetic to place. small battery pouch containing the stimulator pulse generator under the collar bone. from there, a wire is passed under the skin up the neck and behind the ear where it re emerges and is attached to the stimulator wire in the brain.

observed for several weeks and then it is turned on. depending on the targeted area or the brain, one or more sides may be targeted

38
Q

what is involved in Sinamet

A

carbidopa and levodopa

39
Q

factors of a person with a good sinamet profile

A

shows dramatic improvement in response to sinamet
experiences a dramatic difference between off and on states
appears near normal in the on state
spends most of the day pff

40
Q

what are the symptoms most commonly helped by DBS

A

dyskinesias and tremor

41
Q

what does DBS not help

A

swallowing problems
softness of speech
constipation
drooling
memory difficulties

42
Q

what is benserazide

A

peripherally acting DOPA decarboxylase inhibitor

this is combined with levodopa to reduce peripheral side effects

43
Q

what can benserazide not do

A

cannot cross the BBB and so doesn’t prevent the effects of leopdopa in the brain

Semester 3 (94 decks)

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