Neurodegenerative diseases

Question 1

Therapy of Parkinsons disease

Answer 1

Increase dopamine levels:
Levadopa, MAO-B inh, Dopamine AG, COMT inhbitiors, amantadine
Decrease Ach:
Centrally acting anticholinergic drugs

Question 2

Levodopa

Answer 2

Precursor of dopamine, can cross the BBB. Given in combination with Carbidopa or Benserazide (DCC inhibitors).
I: Parkinsons disease
SE: acute peripheral: nausea, diarrhea (area pastrami has no BBB), arrhythmias, hypotension. Acute central: depression, psychosis, anxiety. Decreased BP (D Rs stim in kidney), tachycardia (D stim beta1 Rs), Dyskinesia, End of dose phenomena, on-off phenomena
Should be started as late as possible.

Question 3

End of dose phenomena. which drug and why

Answer 3

Levodopa.
After taking the drug - patient can mote. As the effect of levodopa suddenly wears off/stops, akinesia will develop.
if patient moves more - effect is shorter.
Is related to serum level of dopamine

Question 4

On-Off phenomena. Which drug and why

Answer 4

Levodopa
ON: levodopa induced dyskinesia (choreoattatoid dyskinesia)
OFF: akinesia
Alteration btwn on and off phase. Not related to serum levels of dopamine

Question 5

MAO-B inhibitors

Answer 5

Selegiline (Sledgehammer)
Rasagiline
Safinamide

Question 6

Selegiline

Answer 6

irreversible MAO-B inhibitor (CNS)
Used for early treatment of PD. Is also an antioxidant -neuroprotective.
I: PD, alzheimers, depression.
SE: no cheese reaction

Question 7

Resegiline, Safinamide

Answer 7

irreversible MAO-B inhibitors. act in the CNS

Question 8

Dopamine D2 AGs

Answer 8

Ergot derivatives: Bromocryptine, Cabergoline
Non-ergot derivatives: Pramipexole, Ropinirole, Rotigotine, Apomorphine
all act in the CNS

Question 9

Bromocryptine, Cabergoline

Answer 9

Are central D2 R AG

Not used anymore - can cause subendocardial fibrosis

Question 10

Pramipexole, Ropinirole

Answer 10

Ropinorole (rope in a roll), Pramipexole (Big Pecs)
Are both central D2 AG, and are both taken orally. PD treatment.
SE:Nausea, vomiting, dyspepsia, orthostatic hypotension, arrhythmias, dyskinesias, confusion, delusions, impulse control disorders

Question 11

Rotigotine

Answer 11

D2 R AG. Given as a patch. PD treatment.
SE: nausea, vomit, constipation, dyspepsia, orthostatic hypotension, arrhythmias, dyskinesias, impulse controll disorders. etc

Question 12

Apomorphine

Answer 12

D2 R AG - given as injection. PD treatment.
SE: Nausea, vomit, constipation, dyspepsia, orthost. hypotension, arrhythmias, dyskinesias, confusion, hallucinations, impulse controll disorders etc

Question 13

COMT inhibitors

Answer 13

(inTerCOM) - The capone family
Entacapone (Entering al capone gangster)
Opicapone
Tolcapone (Tall al capone ganster)

Question 14

Entacapone, opicapone

Answer 14

Are inhibitors of peripheral COMT - prevent formation of levodopa to 3-methyldopa in periphery.

Question 15

Tolcapone

Answer 15

Central and peripheral COMT inhibitor. prevents formation of levodopa to 3-methyldopa (periphery), and 3-methylTyramine (in CNS).
Always given in combo with levodopa, increases its bioavailability.

Question 16

Amantedine

Answer 16

(Manatee). An antiviral.
Mech of action: NDMA ATG, inhibit D reuptake and stim. D release and synthesis. Adenosine A2A receptor ATG, Anticholinergic effect.
I: Akinetic crisis (patient has lost all movement capacity) - stop levodopa and give amantedine for 1 week.
SE: mental, seizure at high doses, not effective when given orally.

Question 17

centrally Acting cholinergic drugs (Ach M-receptor ATG)

Answer 17

Procyclidine, Benztropine (Benz car)
biperiden, trihexyphenidyl (3 hexagons on car), Orphenadrine, Dexethimide, metixene.
Have good CNS penetration.

Question 18

Procyclidine, benztropine, trihexyphenidyl

Answer 18

Centrally acting anticholinergic drug.
I: drug induced parkinsonism (from antipsychotics), tremor dominated PD only, treatment of early EPS and perioral EPS (a late eps).
SE: atropine like: dry mouth, consitpation, mydriasis, blurred vision. Cognitive dysfunction (dementia like)

Question 19

Treatment of Parkinsons disease, from start to end

Answer 19

1) Selegiline - at diagnosis
2) Amantadine + selegiline
3) Dopamine AG + amantadine + selegiline
4) Levodopa + carbidopa + COMT inhibitors and dopamine AG+amantadine+selegiline

Question 20

Treatment of drug induced psychosis in PD

Answer 20

Clozapine (a 2nd generation antipsychotic drug)

Question 21

Treatment of Alzheimers disease

Answer 21

Increase of Ach.
AchEase inhibitors:
Tacrin, Rivastigmine, Donezepil, Galantamine
NMDA ATG: Memantine
NSAIDs: ibuprofen, indometacine (inhibits gamma-secretase)
other: amyloid vaccination, amyloid ABs, antioxidants

Question 22

Cause of Alzheimer disease

Answer 22

amyloid theory and Tau hypothesis - result is loss of cholinergic neurons.

Question 23

Tacrin

Answer 23

AchEase inhibitor

SE: hepatotoxic, nausea, vomiting, diarrhea, short duration of action

Question 24

Rivastigmine

Answer 24

AchEase inhibitor. longer duration of action

Question 25

Galantamine

Answer 25

AchEase inhibitor + weak nicotine R AG

Question 26

Donezepil

Answer 26

AchEase inhibtor

No hepatotoxicity