drugs for parkinson disease

Question 1

what is parkinson’s disease

Answer 1

chronic, progressive, degenerative neurological disorder
- affects the control of body movements

Question 2

motor symptoms of PD

Answer 2

• bradykinesia
• hypokinesia
• rigidity
• rest tremor
• postural instability
• gait disturbances
• expressionless face
• dystonias (lower back)

Question 3

other symptoms of PD

Answer 3

• sleep disturbances
• depression
• psychosis
• dementia
• loss of smell
• apathy
• autonomic dysfunction

Question 4

PD symptoms are caused by imbalance of which two neurotransmitters

Answer 4

• dopamine (DA)
• acetylcholine (ACh)

affects dopamine producing neurons in the brain (in striatum which gives skeletal muscle motor control)

DA is inhibitory and ACh excitatory, when DA not produced encough there is uncontrolled movement

Question 5

when do symptoms occur in PD

Answer 5

when loss of ~70-80% of DA neurons in substantia nigra of the basal ganglia

Question 6

treatments and interventions of PD

Answer 6

• drugs for movement abnormalities
• deep brain stimulation (used when drug resistant)
• exercise (balance, mobility, depression, constipation)
• socialization

Question 7

drug therapy for PD

Answer 7

focusses on DA pathway
- replacement (precursor) drugs
- prevent DA metabolism
- DA receptor agonists

(needs to be DA neurons that still work for the drug to work)

Question 8

direct DA pathway drugs

Answer 8

DA receptor agonists

Question 9

indirect action drugs

Answer 9

• levodopa-carbidopa
• selegiline (MAOI - add on therapy)
• amantadine

Question 10

dopamine system drugs

Answer 10

• precursor: levodopa-carbidopa (best choice)
• prevent DA metabolism: MAOIs
• Da receptor agonists: pramipexole, ropinirole

Question 11

anticholinergic agents for PD examples

Answer 11

• benztropine (good access to CNS)
• diphenhydramine

Question 12

dopamine precursor - levodopa therapy (indirect)

Answer 12

• levodopa is precursor of dopamine
• BBB does not allow exogenously supplied dopamine to enter, but it does allow levodopa
• levodopa taken up by dopaminergic terminal, converted to domaine, then released
• increased dopamine release from surviving DA neurons
• balances effects of cholinergic pathways on muscle control

Question 13

levodopa therapy on disease progression

Answer 13

therapy maintains functional mobility
- prolongs quality of life
- prolongs life expectancy

full therapeutic response may take several months to develop
- therapy does not cure or stop progression of disease
- as PD progresses its harder to control symptoms with levodopa
- DBS alternative

Question 14

levodopa therapy and metabolism

Answer 14

levodopa metabolism happens outside the CNS: liver, GI
- levodopa given in combination to reduce peripheral metabolism
- carbidopa

Question 15

levodopa-carbidopa therapy

Answer 15

• carbidopa doesn’t cross BBB but prevents levodopa breakdown in periphery
• works on enzymes with turn levodopa into DA
• leaves more levodopa in circulation to get to brain and work there
• lower dosage to achieve desired effects: reduced N&V

Question 16

levodopa and COMT inhibitors

Answer 16

• levodopa can be metabolized into inactive substances by enzyme COMT
• use COMT inhibitors to stop this
• levodopa conserved to be made to DA
• entacapone, opicapone

Question 17

wearing off effect levodopa therapy

Answer 17

• gradual loss: subtherapeutic levels near end of dosing interval (reemergence of symptoms)

Question 18

on-off phenomenon levodopa therapy

Answer 18

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

Question 19

levodopa therapy adverse effects

Answer 19

• N&V: CTZ stimulation (reduced by carbidopa)
• dyskinesia: involuntary muscle movements (chewing, flinging of limbs - must adjust dose)
• CV: hypotension, dysrhythmias
• psychosis: hallucinations, paranoid ideation

Question 20

direct dopaminergic therapy

Answer 20

• DA receptor agonists
• directly stimulate dopamine receptors
• 1st line treatment in younger patients (early onset), mild symptoms
• reduce wearing off effect of levodopa
• less effective
• may move to levodopa as disease progresses

Question 21

client care implications

Answer 21

• do not take other meds with PD drugs before checking with prescriber
• potential for dizziness and hypotension with dopaminergic agents

Question 22

levodopa client care implications

Answer 22

• avoid high protein diets: its absorbed by amino acid transportes but protein competes for these transporters so less drug is absorbed and transported across BBB
• taking levodopa with non-selective MAOIs may result in hypertensive crisis
• may activate malignant melanoma (skin assessments)
• may darken urine and sweat (harmless)

Question 23

anticholinergic agents help which symptoms

Answer 23

• muscle tremors
• cogwheel rigidity
• pin rolling movement of fingers and head bobbing while at rest

greater influence of cholinergic excitatory pathways on muscle control
- not first line treatment

Question 24

anticholinergic therapy moa

Answer 24

block effects of ACh
- used to treat muscle tremors and muscle rigidity associated with PD (caused by excessive cholinergic influence when DA is reduced)
- drugs do not relieve bradykinesia

Question 25

other indications for anticholinergic therapy

Answer 25

treat drug induced extrapyramidal symptoms

Question 26

anticholinergic therapy AE

Answer 26

• drowsiness, confusion, disorientation
• constipation, nausea, vomiting
• urinary retention, painful urination
• blurred vision, dilated pupils, photophobia
• dry skin, fever
• decreased salivation = dry mouth