Therapeutics Iii Exam 4 - Lectures 13-16 (Dementias And Parkinson's Disease)

Front 1

Define dementia

Back 1

1. Memory impairment
2. At least one: aphasia, apraxia, agnosia, executive dysfunction

Front 2

Onset of:
Alzheimer's disease
Vascular dementia

Back 2

Alzheimer's - Gradual
Vascular dementia - Acute

Front 3

Major symptoms of Dementia with Lewy bodies

Back 3

1. Fluctuating cognition with pronounced variations in attention and alertness
2. Recurrent visual hallucinations
3. Spontaneous motor features of Parkinsonism

Front 4

3 Reversible causes of dementia

Back 4

1. Normal pressure hydrocephalus
2. Vitamin B-12 deficiency
3. Brain tumor (if operable)

Front 5

The Components of the Confusion Assessment Method (for delirium diagnosis)

Back 5

1. Acute onset and fluctuating course
2. Inattention
3. Disorganized thinking
4. Altered level of consciousness
-Must have 1 and 2, then must have either 3 OR 4

Front 6

7 Drugs that commonly precipitate delirium

Back 6

1. Sedative hypnotics
2. Antidepressants
3. Anticholinergics
4. Opioids
5. Anticonvulsants
6. Antiparkinsonian drugs
7. H-2 blockers

Front 7

MMSE scores

Back 7

Mini-Mental Status Exam is based on a 30 point scale, scores below 24 are suggestive of dementia

Front 8

Definite Risk factors of Alzheimer's Disease

Back 8

1. Age
2. Family history
3. Identified apo E mutations/polymorphisms
4. Head trauma
5. Downs syndrome

Front 9

Brain autopsy of:
Alzheimer's Disease
Vascular Dementia
Dementia with Lewy Bodies

Back 9

Alzheimer's brains show plaques and tangles
Vascular dementia brains show multiple CVAs
Dementia with Lewy bodies brains show Lewy bodies in the deep corical layers

Front 10

2 drug classes that should be eliminated in elderly patients at risk for dementia

Back 10

1. Antichoinergics
2. Benzodiazepines

Front 11

Drugs which need to be evaluated in the elderly

Back 11

1. Tricyclic antidepressants
2. H2 blockers
3. Antihistamines
4. Scopolamine
5. Benzodiazepines
6. Phenytoin
7. Phenobarbital
8. Ethanol
9. Bromocriptine
10. Antiarrhythmics
11. Antipsychotics
12. Lithium
13. Beta blockers
14. NSAIDS
15. Digoxin
16. Carbamazepine
17. Antispasmodics
18. Corticosteroids

Front 12

What 4 classes of drugs are used as general strategies to treat dementia?

Back 12

1. Antiplatelet drugs
2. Statins
3. Anticoagulation
4. Antihypertensives

Front 13

Name the Cholinesterase inhibitors.

Back 13

1. Aricept - donepezil
2. Exelon - rivastigmine
3. Razadyne - galantamine

Front 14

Dosing scheme of donepezil (Aricept)

Back 14

Initial 5 mg daily, increase to 10 mg daily in 4-6 weeks

Front 15

Dosing scheme for Exelon (rivastigmine)

Back 15

Initial 1.5 mg BID with food, increase by 1.5 mg every 2-4 weeks to 6 mg total daily dose

Front 16

Dosing scheme for Exelon Patch (rivastigmine)

Back 16

Apply 4.6 mg patch daily, increase to 9.5 mg after 4 weeks

Front 17

Dosing scheme for Razadyne (galantamine)

Back 17

4 mg BID with meals (8 mg daily for ER), increase by 8 mg daily every 4 weeks to 24 mg total daily dose

Front 18

Special info about Cholinesterase inhibitors

Back 18

Rivastigmine has no hepatic metabolism, unlike the others
Rivastigmine patch has reduced incidence of side effects compared to oral
Galantamine requires renal dosing adjustment

Front 19

Adverse effects of Cholinesterase inhibitors

Back 19

1. GI: nausea, vomiting, diarrhea, increase GI bleeding esp if used with NSAIDS
2. CNS: headache, insomnia, dizziness
3. Cardiac: bradycardia, orthostatic hypotension, syncope
4. GU: incontinence

Front 20

Dosing scheme for memantine (Namenda)

Back 20

initial 5 mg daily, increase by 5 mg increments up to the target dose of 10 mg BID or 20 mg daily

Front 21

Adverse effects of memantine

Back 21

Renal dosing adjustment is required
Effects include agitation, urinary incontinence, insomnia, diarrhea, confusion

Front 22

What are some miscellaneous agents used for dementia treatment?

Back 22

1. vitamin E
2. gingko biloba
3. curcumin
4. amyliod antibodies
5. abatacept (Enbrel)

Front 23

What are some non-pharmacologic treatment methods for dementia?

Back 23

1. Environmental manipulation
2. Planned daily acitivities
3. Validation therapy
4. Stimulation therapy
5. Patient-centered care

Front 24

What are the main drugs used for the treatment of non-cognitive symptoms of dementia?

Back 24

1. Atypical antipsychotics (too many adverse effects)
2. Cholinesterase inhibitors
3. SSRI's
4. Antiepileptic agents

Front 25

Treatment of anxiety in dementia patients

Back 25

Try buspirone or an SSRI/SNRI. Gabapentin has also been useful. Limit benzo's.

Front 26

Treatment of paranoia in dementia patients

Back 26

Antipsychotics are indicated for moderate to severe symptoms

Front 27

Treatment of hallucinations in dementia patients

Back 27

Risperidone, olanzepine or quetiapine can be used at very low doses

Front 28

Treatment of insomnia in dementia patients

Back 28

Start with non-pharmacologic treatment, sleep hygeine techniques. Melatonin at bedtime may help normalize sleep-wake cycles.

Front 29

Treatment of depression in dementia patients

Back 29

Use SSRI or mirtazepine

Front 30

Treament of sundowning in dementia patients

Back 30

Low doses of atypical antipsychotic agents

Front 31

Which drugs can cause drug-induced parkinsonism (tardive dyskinesia)?

Back 31

1. Antipsychotics (phenothiazines, butyrophenones)
2. Antiemetics (metoclopramide, prochlorperazine)

Front 32

What are the hallmark features of Parkinson's Disease?

Back 32

1. Tremor
2. Rigidity
3. Bradykinesia
4. Postural instability

Front 33

What is the goal of Parkinson drug therapy?

Back 33

The goal is to restore dopaminergic/cholinergic balance via dopamine stimulus and/or muscarinic cholinergic antagonism

Front 34

What ratio carbidopa/levodopa should patient be started on? When should this change?

Back 34

Patient should be started on a 1:4 ratio. Once levodopa requirements exceed 750 mg/day, switch to the 10/100 tablet.

Front 35

What are the dosing guidelines for carbidopa/levodopa?

Back 35

Initiate with 25/100 tablet given 2-3 times per day. Dosage may be increased by one 25/100 tablet daily or QOD as tolerated. Avoid taking with protein.

Front 36

What is the ODT form of carbidopa/levodopa?

Back 36

Parcopa

Front 37

What are the side effects of carbidopa/levodopa?

Back 37

Initial side effects are mostly peripheral. These include N/V, orthostatic hypotension, tachycardia/cardia arrhythmias, PUD
Over time, central effects take hold. These include dyskinesias, response fluctuations (motor complications), psychiatric complications, mental status changes including confusion, hallucinations, and psychosis.

Front 38

What can be done for "wearing off" or "end-of-dose" with levodopa therapy?

Back 38

Improved by shortening dosing interval, using extended release products, a dopamine agonist, MAO-B inhibitor, or COMT inhibitor.

Front 39

What can be done for the "on-off" effect of levodopa therapy?

Back 39

May benefit from increasing carbidopa/levodopa, dopamine agonist, MAO-B inhibitor, or alteration in dietary habits.

Front 40

What can be done for abnormal involuntary movements with levodopa therapy?

Back 40

Dose reduction or "smoothing" of levodopa-derived dopaminergic stimulation required.

Front 41

What is "smoothing" of levodopa therapy? How is this achieved?

Back 41

Smoothing is reducing peak levodopa concentrations and increasing trough concentrations. It is achieved by shortening dosing interval, using CR products, combining IR and CR, and/or adding a COMT inhibitor (with levodopa dose reduction).

Front 42

What are the major drug interactions with carbidopa/levodopa?

Back 42

1. Pyridoxine decreases the effectiveness of levodopa; this effect is reversed when used with carbidopa though.
2. Drugs that possess dopamine antagonist activity (phenothiazines, metoclopramide)
3. Ferrous sulfate forms chelation complex decreasing levodopa absorption
4. Anticholinergics delay gastric emptying.
5. MAO inhibitors cause build up of metabolites

Front 43

Contraindications of carbidopa/levodopa

Back 43

1. history of melanoma
2. concomitant non-specific MAO inhibitor within prior 14 days
3. narrow-angle glaucoma
4. Precautions with MI, arrhythmias, asthma, wide-angle glaucoma, PUD

Front 44

What is the main ergot dopamine agonist?

Back 44

bromocriptine (Parlodel)

Front 45

What is the most concerning side effect of bromocriptine?

Back 45

Valvular heart disease
Others include N/V/anorexia, hallucinations, OH, decreased prolactin

Front 46

How does bromocriptine work?

Back 46

stimulates D2 and antagonizes D1

Front 47

What are the non-ergot dopamine agonists?

Back 47

ropinirole (Requip)
pramipexole (Mirapex)

Front 48

How do ropinirole and pramipexole work?

Back 48

stimulate D2 and D3 receptor sites

Front 49

How are ropinirole and pramipexole eliminated?

Back 49

1. ropinirole is eliminated via hepatic metabolism
2. pramipexole is eliminated renally

Front 50

Dosing schedule for ropinirole

Back 50

initial 0.25 mg TID, usual dose is 3-24 mg/day divided TID

Front 51

Dosing schedule for pramipexole

Back 51

initiate at 0.125 mg TID, usual dose is 1.5-4.5 mg/day divided TID

Front 52

Pramipexole dosing in renal failure

Back 52

CrCl over 60 start with 0.125 mg TID with a max dose of 1.5 mg TID
CrCl 35-59 start with 0.125 mg BID with a max dose of 1.5 mg BID
CrCl 15-34 start with 0.125 mg daily with a max dose of 1.5 mg daily

Front 53

How does rotigotine (Neupro) work?

Back 53

stimulates D1, D2, and D3 receptors

Front 54

What are the side effects of rotigotine (Neupro)?

Back 54

GI: nausea, vomiting
application site reations
fatigue and somnolence

Front 55

How does apomorphine (Apokyn) work?

Back 55

It stimulates D2 receptors. It is used to treat acute episodes of hypomobility (the off side of 'on-off') associated with advanced Parkinson's disease

Front 56

What are the side effects of apomorphine (Apokyn)?

Back 56

Due to emetic properties, must start patient on antiemetic at least 3 days before initiating apomorphine. Hypotension is also a risk.

Front 57

What are the main COMT inhibitors?

Back 57

1. tolcapone
2. entacapone

Front 58

How do COMT inhibitors work?

Back 58

They increase levodopa bioavailability and half-life. They reduce 'off' time of 'wearing-off' phenomena. Levodopa dose needs to be decreased by 30%.

Front 59

What are the side effects of entacapone?

Back 59

1. Dopaminergic: dyskinesias, N/V/D/A, OH, HA
2. Increased liver transaminases that requires monitoring, rarely used anymore due to this

Front 60

How is entacapone metabolized?

Back 60

Metabolized through glucuronidation (no liver problems makes it the more common COMT inhibitor)

Front 61

What is the levodopa/carbidopa/entacapone combination?

Back 61

Stalevo

Front 62

What are the main MAO Type B inhibitors?

Back 62

1. Selegiline
2. Rasagiline

Front 63

How do MAO Type B inhibitors work?

Back 63

They prevent degradation of dopamine in the brain. Must reduce dose of levodopa by 10-30%.

Front 64

Drug interactions with selegiline

Back 64

1. Risk of serotonin syndrome (meperidine is contraindicated)

Front 65

Drug interactions with rasagiline

Back 65

1. Metabolism through CYP1A2 is inhibited by many drugs (cimetidine, macrolides, estrogen, ketoconazole, levofloxacin, paroxetine)
2. Serotonin syndrome (meperidine, tramadol, methadone, propoxyphene, mirtazapine, etc.)
3. Contraindicated with MAOI's
4. Watch tyramine over 75 mg/day

Front 66

What is amantadine used for?

Back 66

Improves tremor, rigidity, bradykinesia; especially tremor

Front 67

Amantadine dosing

Back 67

Initiate with 100 mg daily with breakfast, increase to 100 mg BID with breakfast and lunch on day 5 of therapy (early dosing due to insomnia); dosage adjustment with renal impairment

Front 68

Side effects of amantadine

Back 68

Cardiac: OH, edema, CHF exacerbation
CNS: insomnia, confusion, hallucinations
GI: N/V/D
Not used too often due to these side effects

Front 69

Anticholinergic use in Parkinson's

Back 69

Rarely used due to adverse effects in elderly
Improvement in symptoms in 25% of patients; helps mostly with tremors
benztropine