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Nervous System > Parkinson's > Flashcards

Parkinson's Flashcards

1
Q

Parkinson’s disease classical motor symptoms

A

Hypokinesia/bradykinesia, rigidity, rest tremor, and postural instability

Alternatively, think of the 4 Rs: Resting tremor, Retarded reflexes (bradykinesia/hypokinesia), Rigidity, no postural Reflexes (postural instability).

The 4 Rs of PaRRRRkinson’s, matey.

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2
Q

Parkinson’s disease non-motor symptoms

A

Dementia, depression, insomnia
Speech, language, and swallowing difficulty
Bladder and bowel dysfunction, and weight loss

He’s got Parkinson’s. He’s depressed. He doesn’t have it in him to eat nor speak, and he’s got awful hygiene (bladder and bowel).

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3
Q

Treatment of motor symptoms of Parkinson’s (early stage)

A

Levodopa with carbidopa

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4
Q

What is levodopa converted into?

A

Dopamine

Love of dopamine, baby.

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5
Q

Why do you give carbidopa with levodopa?

A

Inhibits peripheral conversion of levodopa (via dopa decarboxylase inhibition) therefore allowing levodopa to bypass the BBB before conversion into dopamine

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6
Q

Treatment of Parkinson’s with limited motor symptoms

A

Levodopa OR dopamine receptor agonists (ropinirole, rotigotine, pramipexole) OR monoamine oxidase-B inhibitors (rasagiline and selegiline)

Remember:

monoAMINE - RasaGILINE - SeleGILINE.
Alternatively, think of cats.

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7
Q

What metabolises dopamine and what inhibits this metabolism?

A

Monoamine oxidase-b (MAO-b) - the dopamine destroyer.

MAO-b inhibitors: selegiline and rasagiline

MAO-b as in MEOW. Cats are depressed and they take you down with ‘em, tell that silly rasta (sele-giline, ras(t)a-giline)!

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8
Q

What is the pre-cursor of dopamine?

A

Levodopa, or L-dopa

Levodopa said: I lev you o very much dopa, I’m going to make you -mine.

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9
Q

What metabolises levodopa and what inhibits this metabolism?

A

COMT and dopa decarboxylase

COMT inhibitors: tolcapone and entacapone
Dopa decarboxylase inhibitors: carbidopa

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10
Q

What are examples of dopamine agonists?

A

Ropinirole, rotigotine, pramiprexole (ROTI-ROPI-PRAMI). D3 agonist!

Bromocriptine. D1 agonist!

I’d stick to the D3s first. Never go for your first option.

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11
Q

When do you consider using bromocriptine as an adjunct to levodopa?

A

When symptoms are not controlled with D3 agonists (rotigotine, ropinirole, pramipexole).

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12
Q

What vitamin is required for decarboxylase enzymes?

A

Biotin.

It’s a B-vitamin that decarboxylase enzymes depend on. If you don’t have decarboxylase enzymes, then how you going to make dopamine from levodopa, fool?

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13
Q

What are side effects of dopamine receptor agonists?

A

Psychosis, hallucinations, impulse control disorders, excessive daytime sleepiness and sudden onset of sleep

Weight loss, loss of appetite, nausea and vomiting

That’s just too much dopamine, bro.

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14
Q

If patients develop dyskinesia despite optimal levodopa therapy, what can you do?

A

Add a dopamine receptor agonist (D3) OR a COMT inhibitor (tolcapone or entacapone) OR MAO-b (ropinirole, rotigotine or pramipexole)

If this still doesn’t work, consider amantadine (weak dopamine agonist)

He’s still slow - give that man some more dopamine!

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15
Q

Treatment of nocturnal akinesia in patient’s with Parkinson’s

A

First line: dopamine receptor agonists or levodopa

Second line: rotigotine

He can’t move at night, and you need dope to move, baby.

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16
Q

What neurotransmitter is associated with rigidity?

A

High levels of acetylcholine.

You want to bring acetylcholine down, and that’s why you use acetylcholine antagonists, also known as, muscarinic receptor antagonists. Examples: benztropine and trihexyphenidyl.

Acetylcholine binds to muscarinic receptors. Give your musc-les a break from everything with an musc-arinic antagonist.

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17
Q

What neurotransmitter is associated with dyskinesia, rigidity, tremors?

A

Low levels of dopamine

No dopamine? You are going to be slow!

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18
Q

What are side effects of co-careldopa?

A 
Psychosis, hallucinations, agitation
Hypotension, hypertension
Nausea, vomiting, premature satiety, bloating & pain
Oedema
Impulse control disorders.

Too much dopamine? You go CRAZY.

19
Q

What anti-psychotic can be given to patient’s with Parkinson’s suffering from hallucinations and delusions?

A

Clozapine (D1, D2, 5-HT(2a), alpha-1-adrenoceptor, and muscarinic antagonist). Quetiapine (BNF unlicensed, NICE affirmative!)

Parkinson’s says NO to olanzapine. Phenothiazines and butyrophenones worsen motor features of Parkinson’s.

You need the dopamine to go down! You need to CLOZ the door on that dope-fiend.

20
Q

How do you treat postural hypotension in Parkinson’s?

A

Midodrine hydrochloride.

It’s a sympathomimetic and you give it to people who are in the mid-dle of dying.

21
Q

How do you treat Parkinson’s with dementia?

A

Rivastigmine, an acetylcholinesterase inhibitor.

It’s the enzyme that metabolises acetylcholine. If you inhibit that enzyme, acetylcholine goes up.

Memantine as an alternative if it’s not tolerated but it’s not licensed. It’s an NMDA receptor antagonist.

Just remember, memantine helps people with dementia, re-mem-ber. It’s used in moderate-to-severe Alzheimer’s too, and yes, it is licensed in Alzheimer’s.

22
Q

How do you treat advanced Parkinson’s?

A

With a dopamine agonist, of-course.

It’s called apomorphine hydrochloride. It’s given by subcutaneous injection. That’s going to shoot dopamine up real fast. You want limit nausea and to slow that spike, right? Remember, stimulation of dopaminergic receptors inhibits gastric motility. That’s why you don’t feel hungry.

Start domperidone (a dopamine receptor antagonist -D2) 2 days before. Stop it as soon as possible. It’s bad for the heart but it does increase gastric motility. It also increases acetylcholine. It doesn’t cross the BBB. The big boys at MHRA advise that treatment shouldn’t exceed 1 week.

If you thought it was an opioid, you’d be wrong.
It’s a-poo-morphine for a reason. An unadvanced drug for an advanced disease. Who would have thought?

Oh, and don’t give domperidone to kids under 12. Just don’t, the MHRA said so.

23
Q

What should you assess and monitor before giving domperidone and apomorphine hydrochloride?

A

Cardiac risk factors. Use ECG monitoring.

Remember, domperidone can cause QT interval prolongation (so can atypical anti-psychotics, by the way).

24
Q

What are some peculiar ways of treating advanced Parkinson’s?

A

Using a portable pump to shoot gel directly into the duodenum or upper jejunum, that’s the small intestine, by the way. The horror.

Deep brain stimulation is another way.

25
Q

What are contraindications of domperidone?

A

1) Cardiac disease. Remember, ECG monitoring and QTc prolongation!

Domperidone is associated with cardiac toxicity.

2) GI haemorrhage
3) Prolactinoma. What’s this? Dopamine inhibits prolactin production. Since domperidone (or dopamine antagonists) inhibits dopamine production, it increases prolactin production.

Prolactinoma means too much prolactin. Why is that a problem? Well, it causes infertility.

26
Q

What effect does dopamine have on the intestines?

A

It slows gastric motility.

27
Q

Can you give metoclopramide (a dopamine antagonist) to a person with Parkinson’s?

A

With caution.

It crosses the BBB. It would antagonize levodopa (or other dopamine agonists), but what if that’s what you want because dopamine levels are too high and the patient is nauseous, and say, having a psychotic episode?

28
Q

Between levodopa, dopamine agonists, and MAO-b inhibitors, what has the most improvement on motor symptoms?

A

Levodopa

Wait, isn’t that a contradiction?

29
Q

Between levodopa, dopamine agonists, and MAO-b inhibitors, what has the most motor complications?

A

Levodopa

Wait, isn’t that a contradiction?

30
Q

Between levodopa, dopamine agonists, and MAO-b inhibitors, what has the fewest adverse effects?

A

Levodopa and MAO-b inhibitors have fewer adverse effects than dopamine agonists

31
Q

Why should antiparkinsonian drugs not be withdrawn abruptly?

A

There’s a risk of neuroleptic malignant syndrome.

32
Q

What is an indication for bromocriptine other than for Parkinson’s?

A

Prolactinoma!

Technically, any dopamine agonist would function against prolactinoma, because dopamine inhibits proalctin but the BNF only seems to mention bromocriptine and cabergoline as medications licensed and indicated for prolactinoma.

33
Q

Bromocriptine, cabergoline, pergolide… I summon thy important safety information.

A

Ok…

Pulmonary retroperitoneal and pericardial fibrotic reactions. Monitor for dyspnoea, persistent cough, chest pain, cardiac failure, abdominal pain and tenderness.

34
Q

What foods shouldn’t be eaten whilst taking selegiline?

A

Tyramine-rich foods (e.g. mature cheese, salami, pickled herring, Bovril, Oxo, Marmite, or any similar meat or yeast extract or fermented soya extract, some beers, lagers or wines).

Why? It could cause hypertension.

35
Q

MAO-B inhibitors can lead to severe hypertension when taken with which class of medications?

A

Amfetamines, safinamide, beta-2-agonists, bupropion, methylphenidate, reboxetine, sympathomimetics (inotropic and vasoconstrictor).

36
Q

What medications should be avoided when taking MAO-b inhibitors?

A

Pethidine - an opioid rhymes with selegiline and rasagiline.

With (irreversible) MAO-b inhibitors: isocarboxazid, phenelzine, tranylcypromine. Same class but slightly different MoA and different indication. These are used for depression.

37
Q

Between dopamine agonists, MAO-b inhibitors and COMT inhibitors, which has the most off-time reduction and hallucinations?

A

Dopamine agonists.

It makes sense that it has the most off-time reduction AND the most hallucination. Off-time reduction means more time with more dopamine. More dopamine means more adverse effects associated with dopamine (psychosis, hallucinations, impulse control disorders).

38
Q

What can be used to treat daytime sleepiness in people with Parkinson’s?

A

Modafinil. It’s a sympathomimetic (centrally-acting).

And don’t even think about giving this to pregnant ladies. Unless you want their babies to have brain deformities.

39
Q

How do you manage drooling in Parkinson’s?

A

Glycopyrronium bromide (BNF unlicensed, NICE affirmative)

40
Q

Vitamin D and vitamin E are both appropriate for a person with Parkinson’s.

True or false?

A

False.

Only vitamin D is.

41
Q

Concurrent use of a MAO-b inhibitor and a beta-blocker can increase the risk of?

A

Bradycardia

42
Q

MAO-b inhibitors have the potential to cause hypotension when used concurrently with other agents that cause hypotension (e.g. a CCB).

True or false?

A

True

43
Q

MAO-b inhibitors have the potential to cause serotonin syndrome when used with SSRIs and opioids.

True or false?

A

True

Nervous System (3 decks)

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