A. 34. Drugs used for treatment of neurodegenerative disorders. Nootropic drugs.

Question 1

drugs used in Parkinson’s disease

Answer 1

“Lets Call iT PARkinson’S DisEase Please”

Levodopa
Carbidopa 
Tolcapone  
pramipexole 
Amantadine
Ropinirole 
Selegiline

Diphenhydramine
Entacapone
Procyclidine

Benztropine, Trihexyphenidyl*

Question 2

drugs used in Alzheimer disease

Answer 2

“Mom! Dona Riva dances at the Gala”

Memantine
Donepezil
Rivastigmine
Galantamine

Question 3

what is Piracetam?

Answer 3

Nootropic agent

Question 4

what are Nootropics?

Answer 4

drugs, supplements, and other substances that may improve cognitive function (memory, creativity, motivation) in healthy individuals

Question 5

what is the mechanism of Piracetam?

Answer 5

binds to the protein SV2A on the synaptic vesicle –> interfere with neurotransmitter release

Question 6

what is Piracetam’s therapeutic potential?

Answer 6

cognition enhancer and in the treatment of schizophrenia, depression, ADHD, and Parkinson’s disease.

Question 7

how are the drugs for Alzeheimer given?

Answer 7

orally

Question 8

what are Rivastigmine , Galantamine and Donepezil?

Answer 8

Acetylcholine-esterase inhibitors (centrally-acting)

Question 9

1st line agent for Alzheimer’s disease?

Answer 9

Rivastigmine
Galantamine
Donepezil

*provide a modest reduction in the rate of loss of cognitive function

Question 10

side effects of rivastigmine, galantamine, donepezil

Answer 10

Nausea, vomiting
Diarrhea
bradycardia

Question 11

what is Memantine?

Answer 11

glutamate NMDA receptor blocker

Question 12

side effects for memantine

Answer 12

“car”
confusion
agitation
restlessness

Question 13

why is Levodopa given with Carbidopa?

Answer 13

cause Carbidopa acts as a peripheral dopa decarboxylase inhibitor (does not cross the BBB)

Question 14

what is Levodopa and what does it do?

Answer 14

it’s a dopamine precursor
enters the brain via LAT
converted by DOPA decarboxylase to dopamine –> ↑ dopamine activity in the brain (↓ bradykinesia)

Question 15

how are the drugs for Parkinson’s disease given?

Answer 15

orally

*diphenhydramine also has IV preparation for acute drug-induced parkinsonism (acute dystonia)

Question 16

what is the duration of action of Levodopa?

Answer 16

6-8 hours

Question 17

what is Levodopa+carbidopa for?

Answer 17

Parkinson’s disease

Question 18

side effects of Levodopa+carbidopa

Answer 18

GI distress- nausea, vomiting anorexia
Dyskinesia (on/off phenomenon)
hypotension, arrhythmias (peripheral effect of dopamine)
psychosis, agitation, anxiety, hallucinations (central effect of dopamine)

Question 19

what is the mechanism of action of Selegiline?

Answer 19

selective MAO-B inhibitor–> ↓ metabolism of dopamine –>↑ dopamine activity in the brain (↓ bradykinesia)

Question 20

can we see a “cheese effect” when given Selegiline?

Answer 20

no

there is no tyramine interaction like in non-selective MAO inhibitors.

Question 21

does selegiline have a short T1/2?

Answer 21

no, long

Question 22

what type of metabolism is seen with Selegiline?

Answer 22

hepatic
form: 1. desmethylselegiline (neuroprotective)
and 2. amphetamine (psychostimulant)

Question 23

when is selegiline given?

Answer 23

as monotherapy for Parkinson’s disease (early stage) or in adjunct to levodopa+carbidopa (advanced stage)

Question 24

side effects of selegiline

Answer 24

“Pork DISH”

Psychosis
Dyskinesia 
Insomnia 
Serotonin syndrome (when used with SSRI'S) 
Hypotension

Question 25

name 2 COMT inhibitors

Answer 25

Entacapone | Tolcapone

Question 26

where does Entacapone work?

Answer 26

periphery

Question 27

where does Tolcapone work?

Answer 27

periphery+CNS

Question 28

what is the daily dose of Entacapone?

Answer 28

5 times

Question 29

what is the daily dose of Tolcapone?

Answer 29

3 times

Question 30

side effects of Entacapone and Tolcapone?

Answer 30

sleep disorders | tolcapone: hepatotoxicity

Question 31

when do we use Entacapone or Tolcapone?

Answer 31

Parkinson's disease (adjunct to levodopa/carbidopa)

Question 32

mechanism of COMT inhibitors

Answer 32

periphery: inhibition of COMT enhances levodopa uptake and efficacy CNS: inhibition of COMT enhances dopamine activity

Question 33

what converts Levodopa to 3-OMD (3-O-Methyldopa)?

Answer 33

COMT

Question 34

what does 3-OMD do?

Answer 34

``` partial agonist (antagonist in the presence of a full agonist) competes with levodopa for transport and activity ```

Question 35

name the Dopamine agonists

Answer 35

Ropinirole Pramipexole Bromocriptine Pergolide

Question 36

what is Ropinirole?

Answer 36

D₂ receptor agonist | non-ergot derivative

Question 37

what is pramipexole?

Answer 37

D₃ receptor agonist | non-ergot derivative

Question 38

what type of metabolism does Ropinirole go through?

Answer 38

hepatic

Question 39

what type of metabolism does pramipexole go through?

Answer 39

renal

Question 40

how many times are ropinirole and pramipexole administered?

Answer 40

3 times daily

Question 41

does pramipexole have a short T1/2?

Answer 41

yes

Question 42

what are bromocriptine and pergolide?

Answer 42

partial D₂ receptor agonists | Ergot alkaloid derivatives

Question 43

side effects of dopamine agonists

Answer 43

``` Dyskinesia Psychosis hallucinations anorexia, nausea bromocriptine--> orthostatic hypotension ```

Question 44

indications for Ropinirole AND pramipexole

Answer 44

1. Parkinson's disease -monotherapy/adjunct to levodopa 2. pramipexole: potential antioxidant 3. Restless leg syndrome (RLS)- first-line treatment!

Question 45

indications for bromocriptine and pergolide

Answer 45

1. Parkinson's disease -monotherapy/adjunct to levodopa 2. hyperprolactinemia 3. acromegaly

Question 46

what is the mechanism of action of Amantadine?

Answer 46

1. Antiviral medication 2. enhances the effect of endogenous dopamine (↑ the synthesis and inhibiting its uptake) 3. muscarinic blockade 4. NMDA blockade

Question 47

how is Amantadine eliminated?

Answer 47

by the kidneys

Question 48

when is Amantadine used?

Answer 48

for Parkinson's disease (adjunct to levodopa/carbidopa)

Question 49

side effects of Amantadine

Answer 49

Livedo reticularis Psychosis Gi disturbances Ataxia

Question 50

mechanism of action of antimuscarinics

Answer 50

muscarinic blockade--> ↓ the excitatory activity of cholinergic neurons in the striatum--> improves tremor and rigidity *no effect on bradykinesia

Question 51

names the antimuscarinic agents

Answer 51

``` Procyclidine Diphenhydramine Benztropine Trihexyphenidyl "Tri PARKing my mercedes BENZ" ```

Question 52

is antimuscarinic recommended as monotherapy for early Parkinson's disease?

Answer 52

no

Question 53

what is the other indication for antimuscarinics except for Parkinson's disease?

Answer 53

drug-induced extrapyramidal symptoms

Question 54

side effects of Antimuscarinics

Answer 54

"atropine-like effects": ``` dry mouth urinary retention constipation hyperthermia tachycardia Mydriasis blurred vision toxicity (3 C's)--> cardiotoxicity, convulsions, coma ```

Question 55

contraindications of antimuscarinics

Answer 55

glaucoma | prostatic hyperplasia