Drugs for Parkinson's Disease - Ch. 24

Question 1

What is Parkinson’s Disease (PD)?

Answer 1

Chronic, progressive, degenerative neurological disorder
-affects control of body movements

Question 2

What are the motor symptoms of Parkinson’s?

Answer 2

Bradykinesia
Rigidity
Rest tremor
Postural instability
Gait disturbances
Mask-like, expressionless face
Dystonias

Question 3

What other symptoms are associated with Parkinson’s?

Answer 3

Sleep disturbances
Depression
Psychosis
Dementia
Loss of smell
Apathy
Antonomic dysfunction (orthostatic hypotension, urinary urgency, constipation)

Question 4

What in the brain is affected by Parkinson’s disease?

Answer 4

Dopamine-producing neurons in the brain

Question 5

What are Parkinson’s symptoms caused by?

Answer 5

Imbalance of neurotransmitters:
Dopamine (DA)
Acetylcholine (ACh)

Question 6

When do Parkinson’s disease symptoms occur?

Answer 6

When there is a loss of ~70-80% of dopamine neurons in the substantial nigra of the basal ganglia

Question 7

What are treatments/interventions for PD?

Answer 7

Drugs for movement abnormalities
deep brain stimulation (drug resistant PD)
exercise
socialization

Question 8

What is most PD drug therapy focused on?

Answer 8

DA pathway

Question 9

What are the groups of drugs affecting DA system?

Answer 9

Direct -DA receptor agonists
Indirect -precursor, MAOI

Question 10

What is a precursor drug for PD?

Answer 10

Levodopa-carbidopa

Question 11

What drugs prevent DA metabolism?

Answer 11

MAOIs

Question 12

What anticholinergic agents are used for PD?

Answer 12

Benztropine
Diphenhydramine

Question 13

What is levodopa?

Answer 13

Precursor of dopamine

Question 14

How does Levodopa work?

Answer 14

The BBB does not allow exogenously supplied dopamine to enter but levodopa can so it is taken up by dopaminergic terminals, converted into dopamine then released

Question 15

What does levodopa therapy do?

Answer 15

Increases dopamine release from surviving DA neurones
Balances effects of cholinergic pathways of muscle control
Maintains functional mobility for years

Question 16

Where is Levodopa metabolised outside the CNS?

Answer 16

Liver
GI

Question 17

What drugs are given in combination with Levodopa?

Answer 17

Carbidopa
-benserazide as alternative

COMT inhibitors

Question 18

What does Carbidopa prevent?

Answer 18

Prevents levodopa breakdown in periphery

Question 19

Can carbidopa cross the BBB?

Answer 19

No

Question 20

What else can metabolise Levodopa?

Answer 20

Enzyme COMT
-Use COMT inhibitors to prevent this

Question 21

Examples of COMT inhibitors?

Answer 21

Entacapone, opicapone

Question 22

What is the “wearing-off” effect associated with Levodopa?

Answer 22

Gradual loss
-subtherapeutic levels end of dosing interval

Question 23

What is the “on-off” phenomenon associated with Levodopa?

Answer 23

Abrupt loss of drug effect even at high drug levels
lasts minutes to hours
unknown reason

Question 24

What adverse effects are associated with Levodopa?

Answer 24

Nausea and vomiting (reduced by carbidopa)
Dyskinesia (involuntary muscle movements) LOLLL
Hypotension, dysrhythmias
Psychosis; hallucinations, paranoid ideation

Question 25

What drugs prevent DA metabolism?

Answer 25

MAO-B inhibitors (inhibits DA breakdown in neurons)

Question 26

Examples of MAO-B inhibitors? MAOIs

Answer 26

Selegiline, rasagiline

Question 27

What does Amantadine do?

Answer 27

Promotes DA release from storage sites at nerve endings Blocks reuptake of dopamine into nerve endings Does not stimulate dopamine receptors directly May help with levodopa dyskinesias

Question 28

What is Selegiline?

Answer 28

Irreversible MAOI that selectively inhibits MAO-B Increases dopaminergic stimulation levels in CNS -No cheese effect

Question 29

Why does Selegiline have no effect on NE, 5-HT breakdown

Answer 29

NE, 5-HT breakdown is done by MAO-A Selegiline is a MAO-B inhibitor

Question 30

When is Selegiline used?

Answer 30

Milder symptoms (early in PD)

Question 31

What verse effects are associated with Selegiline?

Answer 31

Usually mild AE: nausea, abdominal pain, dry mouth lightheadedness, dizziness, insomnia, confusions doses higher than 10mg/day may cause more severe AE

Question 32

What is the 1st line treatment for PD in younger pt, mild symptoms of PD?

Answer 32

Direct acting- DA receptor agonists

Question 33

What can DA receptor agonists reduce?

Answer 33

Wearing off effect of levodopa

Question 34

What is an older DA receptor agonists?

Answer 34

Bromocriptine

Question 35

What are newer DA receptor agonists?

Answer 35

Pramipexole Ropinirole Rotigotine (transdermal patch)

Question 36

What DA receptor agonist is administered with a pen injection?

Answer 36

Apomorphine (not an opioid)

Question 37

What are the pros of DA receptor agonists?

Answer 37

No conversion required No dietary protein restrictions less dyskinesias

Question 38

What are the cons of DA receptor agonists?

Answer 38

Halluciantions, postural hypotension, drowsiness Impulse control disorders; gambling, shopping, hypersexuality

Question 39

What should clients taking Levodopa avoid?

Answer 39

High protein diets -amino acids reduce GI absorption and transport across BBB

Question 40

Taking levodopa with what can cause hypertensive crisis?

Answer 40

non-selective MAOIs

Question 41

Levodopa may activate what?

Answer 41

Malignant melanoma

Question 42

Levodopa can darken what?

Answer 42

Urine and sweat

Question 43

What does anticholinergic therapy have greater influence on?

Answer 43

Muscle control -Muscle tremors -Cogwheel rigidity -Pin-rolling movement of fingers and head bobbing while at rest

Question 44

What do anticholinergics do?

Answer 44

Block the effects of ACh

Question 45

Examples of anticholinergics?

Answer 45

Benztropine (Cogentin) trihexyphenidyl ethopropazine diphenhydramine

Question 46

What else are anticholinergics used to treat (muscle related)?

Answer 46

Drug-induced extrapyramidal symptoms (EPS)

Question 47

Adverse effects associated with anticholinergics?

Answer 47

Drowsiness, confusion Constipation, N&V Urinary retention Blurred vision, dilated pupils Dry skin, fever Dry mouth