Parkinson's disease

Question 1

what is the biggest risk factor for PD?

Answer 1

The biggest risk factor for the disease is age, which has major implications for public health as the lifespan of the world’s population increases.

Question 2

what is bradykinesia?

Answer 2

slowness of movement

Question 3

what are the other cardinal features of PD?

Answer 3

The cardinal features of the disease are bradykinesia, tremor when at rest (pill-rolling tremor), postural instability and cogwheel rigidity.

Question 4

what is cogwheel rigidity?

Answer 4

Cogwheel rigidity describes the jerky resistance when limbs are moved.

Question 5

PD presents as asymmetrically or symmetrically?

Answer 5

The disease presents asymmetrically and patients continue to report a ‘bad side’ as the disease progresses, although pure unilateral disease is rare, and usually raises concerns that some other disease process is occurring if this is the case.

Question 6

how postural instability affects in PD?

Answer 6

Postural instability is an important milestone in PD, and typically more than half of patients will reach this stage within 10 years of diagnosis. This problem comprises an impairment of righting reflexes, which leads to impaired gait and increased risk of falling.

Question 7

Features of PD?

Answer 7

Patients typically display a characteristic stooped posture and loss of arm swing when walking, which is often a very helpful early diagnostic sign when seeing patients for the first time.

There is reduced blink frequency and facial expression (hypomimia), which, together with a low-volume (hypophonic), monotonous speech, may lead to significant difficulties in communication. All of this can easily be misdiagnosed as depression.

Writing becomes small (micrographia) and barely legible, with the words falling off the line as the patient continues to write.

Question 8

which antiemetics can induce- Parkinsonism?

Answer 8

Cinnarizine, metoclopramide, prochlorperazine

Question 9

which antipsychotics can induce- Parkinsonism?

Answer 9

Dose-dependent effects; clozapine least associated with abnormal movements

Question 10

which other drugs can induce- Parkinsonism?

Answer 10

Sodium ­valproate, Non-steriodal antiinflammatory drugs, ­amiodarone, ­phenytoin, oral ­contraceptives

Question 11

can lithium induce- Parkinsonism?

Answer 11

Lithium causes postural tremor; reports of Parkinsonism occurring with lithium have usually been in the context of prior exposure to neuroleptics

Question 12

Drug-induced Parkinsonism is more common in which groups?

Answer 12

Drug-induced Parkinsonism is more common in the elderly and in women.

Question 13

what are the clinical features of Drug-induced Parkinsonism?

Answer 13

The clinical features can be indistinguishable from PD, although the signs in drug-induced Parkinsonism are more likely to be bilateral at onset.

Question 14

Drug-induced Parkinsonism is reversible or irreversible?

Answer 14

Withdrawal of the offending agent will lead to improvement and resolution of symptoms and signs in approximately 80% of patients within 8 weeks of discontinuation. Drug-induced Parkinsonism may, however, take up to 18 months to fully resolve in some cases. Further, in other patients, the Parkinsonism may improve after stopping the drug, only to then deteriorate. In this situation, the drug may have unmasked previously latent PD.

Question 15

what is dyskinesia?

Answer 15

Dyskinesias are involuntary, erratic, writhing movements of the face, arms, legs or trunk.

Question 16

co-careldopa or sinemet is formulated with?

Answer 16

carbidopa plus levodopa is known as co-careldopa (Sinemet)

Question 17

co-beneldopa or madopar is formulated with?

Answer 17

benserazide plus levodopa is co-beneldopa (Madopar).

Question 18

what is the drug regimen for immediate release of co-beneldopa?

Answer 18

Immediate-release co-beneldopa is usually commenced in a dosage of 50 mg, typically three times a day.

Question 19

how levodopa affects the absorption?

Answer 19

The patient may be instructed in the early stage of the illness to take the drug with food to minimise nausea. Paradoxically, in more advanced PD, it may be beneficial to take levodopa 30 minutes or so before food, as dietary protein can critically interfere with the absorption of the drug.

Question 20

side effects of levodopa?

Answer 20

Nausea, vomiting and orthostatic hypotension are the most commonly encountered side effects.

Later in the illness, and in common with all anti-Parkinsonian drugs, levodopa may cause vivid dreams, nightmares or even precipitate a confusional state, which tends to indicate that the patient is starting to develop a PD dementia.

Question 21

what are the significant interactions with levodopa?

Answer 21

Levodopa can also enhance the hypotensive effects of antihypertensive agents and may antagonise the action of antipsychotics. The absorption of levodopa may be reduced by concomitant administration of oral iron preparations.

Question 22

what is the bioavailability of immediate and controlled release levodopa formulations?

Answer 22

Levodopa in CR preparations has a bioavailability of 60– 70%, which is less than the 90– 100% obtained from immediate-release formulations. CR preparations have a response duration of 2– 4 hours, compared with 1– 3 hours for immediate release.

Question 23

in what situations controlled release levodopa can be used?

Answer 23

simplifying drug regimens, in relieving nocturnal akinesia, and in co-prescribing with immediate-release levodopa during the day to relieve end-of-dose deterioration.

Question 24

what are the problems associated with controlled release levodopa preparations?

Answer 24

Two commonly encountered problems with CR preparations are, first, changing the patient from all immediate-release to all CR levodopa. This is poorly tolerated, because CR levodopa has a longer latency than immediate-release levodopa to turn the patient ‘on’ (typically 60– 90 vs 30– 50 minutes), and the patient’s perception is that the quality of their ‘on’ period is poorer. Second, CR preparations should not be prescribed more than four times a day, because the levodopa may accumulate, causing unpredictable motor fluctuations and especially leading to dyskinesias later in the day.

Question 25

any other levodopa formulations used for PD? except tablets

Answer 25

An intestinal gel preparation of levodopa and carbidopa (Duodopa) is currently available that is administered directly into the small bowel (specifically, the jejunum) via a percutaneous route, using a portable electronic pump. Through continuous delivery in this way, motor fluctua - tions may be significantly reduced.

Question 26

what is mode of action of dopamine agonists?

Answer 26

stimulate dopamine receptors both postand pre-synaptically at D2 receptor.

Question 27

examples of non-ergot dopamine agonists?

Answer 27

Ropinirole and pramipexole, rotigotine are non-ergot derivatives

Question 28

examples of ergot dopamine agonists?

Answer 28

cabergoline

Question 29

side effects of dopamine agonists?

Answer 29

The principal side effects of the dopamine agonists are nausea and vomiting, postural hypotension, hallucinations, confusion and, in some cases, major behavioural problems linked to impulse control disorders.

Question 30

what is the role of apomorphine?

Answer 30

It is the most potent non-selective dopamine agonist available but has a short half-life, a single bolus administration lasting for 45– 60 minutes. It is therefore administered as either a bolus or subcutaneous infusion depending on the purpose.

Question 31

advantages of using apomorphine injections?

Answer 31

A bolus subcutaneous injection of apomorphine is suitable for patients who are optimised on their oral medications but who still suffer from troublesome, typically unpredictable ‘off’ periods or would benefit from rapid early-morning relief until their oral medication takes effect. Alternatively, continuous infusion is a useful therapeutic option in patients who are no longer well controlled by standard oral therapies and in whom apomorphine injections have proven effective.

Question 32

Apomorphine, in conjunction with levodopa can cause what?

Answer 32

Apomorphine, in conjunction with levodopa, may, in rare cases, cause a Coomb’s positive haemolytic anaemia, which is reversible.

Question 33

examples of Inhibitors of the enzyme catecholO -methyl transferase (COMT)

Answer 33

entacapone and tolcapone.

Question 34

tolcapone should be avoided due to what effects?

Answer 34

hepatotoxicity.

Question 35

mode of action of COMT?

Answer 35

tolcapone and entacapone act primarily as peripheral COMT inhibitors and by so doing increase the amount of levodopa that enters the CNS.

Question 36

STALEVO contains which drugs?

Answer 36

Entacapone is also marketed as a compound tablet containing levodopa and carbidopa (Stalevo).

Question 37

COMT side effects?

Answer 37

Other than exacerbation of dyskinesias, COMT inhibitors may also cause diarrhoea, abdominal pain and dryness of the mouth. Urine discolouration is reported in approximately 8% of patients who are taking entacapone.

Question 38

interactions with entacapone?

Answer 38

It is best to avoid non-selective MAO inhibitors or a daily dose of selegiline in excess of 10 mg (which in reality never happens in PD) when using entacapone. In addition, the co-prescribing of venlafaxine and other noradrenaline (norepinephrine) reuptake inhibitors is best avoided. Entacapone may potentiate the action of apomorphine. Patients who are taking iron preparations should be advised to separate this medication and entacapone by at least 2 hours.

Question 39

examples of MAO-B?

Answer 39

The propargylamines selegiline and rasagiline are inhibitors of MAO-B.

Question 40

mode of action of MAO-B?

Answer 40

Inhibition of this enzyme slows the breakdown of dopamine, effectively having a ‘levodopa-sparing’ effect in the striatum. The result of this is both a mild therapeutic effect and a possible delay in the onset of or reduction in existing motor complications.

Question 41

side effects of selegiline?

Answer 41

Selegiline can rarely cause hallucinations and confusion, particularly in moderate-to-advanced disease, typically through enhancing the actions of levodopa centrally. The withdrawal of selegiline may then be associated with significant deterioration in motor function.

Question 42

mode of action of amantadine?

Answer 42

It has a number of possible modes of action, including facilitation of presynaptic dopamine release, blocking dopamine reuptake, an anticholinergic effect (nicotinic antagonist), and also may act as a weak N -methyld -aspartate (NMDA) receptor antagonist.

Question 43

side effects of amantadine?

Answer 43

side effects become much more frequent at higher doses. These side effects include a toxic confusional state and peripheral and corneal oedema. Monitoring is not needed, but attention needs to be paid to patients reporting sudden visual changes. Livedo reticularis, a persistent patchy reddish-blue mottling of the legs, and occasionally the arms, is also a side effect.

Question 44

which drug can cause Livedo reticularis?

Answer 44

amantadine

Question 45

what is Livedo reticularis?

Answer 45

Livedo reticularis is a common skin finding consisting of a mottled reticulated vascular pattern that appears as a lace-like purplish discoloration of the skin. The discoloration is caused by reduction in blood flow through the arterioles that supply the cutaneous capillaries, resulting in deoxygenated blood showing as blue discoloration.

Question 46

which groups of patients can be considered for the surgical treatment?

Answer 46

Careful case selection is essential for all forms of surgical intervention for PD: older and less biologically fit patients, those with active cognitive and/or neuropsychiatric problems, and patients with a suboptimal levodopa response are generally regarded as poor surgical candidates

Question 47

which antipsychotics worsen PD?

Answer 47

risperidone and olanzapine are associated with worsening Parkinsonism and should not be used in cognitively impaired elderly people because of an increased risk of stroke.

Question 48

which antipsychotics can be used in PD?

Answer 48

quetiapine or clozapine