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69 Cards in this Set

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Define dementia
1. Memory impairment
2. At least one: aphasia, apraxia, agnosia, executive dysfunction
Onset of:
Alzheimer's disease
Vascular dementia
Alzheimer's - Gradual
Vascular dementia - Acute
Major symptoms of Dementia with Lewy bodies
1. Fluctuating cognition with pronounced variations in attention and alertness
2. Recurrent visual hallucinations
3. Spontaneous motor features of Parkinsonism
3 Reversible causes of dementia
1. Normal pressure hydrocephalus
2. Vitamin B-12 deficiency
3. Brain tumor (if operable)
The Components of the Confusion Assessment Method (for delirium diagnosis)
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
7 Drugs that commonly precipitate delirium
1. Sedative hypnotics
2. Antidepressants
3. Anticholinergics
4. Opioids
5. Anticonvulsants
6. Antiparkinsonian drugs
7. H-2 blockers
MMSE scores
Mini-Mental Status Exam is based on a 30 point scale, scores below 24 are suggestive of dementia
Definite Risk factors of Alzheimer's Disease
1. Age
2. Family history
3. Identified apo E mutations/polymorphisms
4. Head trauma
5. Downs syndrome
Brain autopsy of:
Alzheimer's Disease
Vascular Dementia
Dementia with Lewy Bodies
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
2 drug classes that should be eliminated in elderly patients at risk for dementia
1. Antichoinergics
2. Benzodiazepines
Drugs which need to be evaluated in the elderly
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
What 4 classes of drugs are used as general strategies to treat dementia?
1. Antiplatelet drugs
2. Statins
3. Anticoagulation
4. Antihypertensives
Name the Cholinesterase inhibitors.
1. Aricept - donepezil
2. Exelon - rivastigmine
3. Razadyne - galantamine
Dosing scheme of donepezil (Aricept)
Initial 5 mg daily, increase to 10 mg daily in 4-6 weeks
Dosing scheme for Exelon (rivastigmine)
Initial 1.5 mg BID with food, increase by 1.5 mg every 2-4 weeks to 6 mg total daily dose
Dosing scheme for Exelon Patch (rivastigmine)
Apply 4.6 mg patch daily, increase to 9.5 mg after 4 weeks
Dosing scheme for Razadyne (galantamine)
4 mg BID with meals (8 mg daily for ER), increase by 8 mg daily every 4 weeks to 24 mg total daily dose
Special info about Cholinesterase inhibitors
Rivastigmine has no hepatic metabolism, unlike the others
Rivastigmine patch has reduced incidence of side effects compared to oral
Galantamine requires renal dosing adjustment
Adverse effects of Cholinesterase inhibitors
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
Dosing scheme for memantine (Namenda)
initial 5 mg daily, increase by 5 mg increments up to the target dose of 10 mg BID or 20 mg daily
Adverse effects of memantine
Renal dosing adjustment is required
Effects include agitation, urinary incontinence, insomnia, diarrhea, confusion
What are some miscellaneous agents used for dementia treatment?
1. vitamin E
2. gingko biloba
3. curcumin
4. amyliod antibodies
5. abatacept (Enbrel)
What are some non-pharmacologic treatment methods for dementia?
1. Environmental manipulation
2. Planned daily acitivities
3. Validation therapy
4. Stimulation therapy
5. Patient-centered care
What are the main drugs used for the treatment of non-cognitive symptoms of dementia?
1. Atypical antipsychotics (too many adverse effects)
2. Cholinesterase inhibitors
3. SSRI's
4. Antiepileptic agents
Treatment of anxiety in dementia patients
Try buspirone or an SSRI/SNRI. Gabapentin has also been useful. Limit benzo's.
Treatment of paranoia in dementia patients
Antipsychotics are indicated for moderate to severe symptoms
Treatment of hallucinations in dementia patients
Risperidone, olanzepine or quetiapine can be used at very low doses
Treatment of insomnia in dementia patients
Start with non-pharmacologic treatment, sleep hygeine techniques. Melatonin at bedtime may help normalize sleep-wake cycles.
Treatment of depression in dementia patients
Use SSRI or mirtazepine
Treament of sundowning in dementia patients
Low doses of atypical antipsychotic agents
Which drugs can cause drug-induced parkinsonism (tardive dyskinesia)?
1. Antipsychotics (phenothiazines, butyrophenones)
2. Antiemetics (metoclopramide, prochlorperazine)
What are the hallmark features of Parkinson's Disease?
1. Tremor
2. Rigidity
3. Bradykinesia
4. Postural instability
What is the goal of Parkinson drug therapy?
The goal is to restore dopaminergic/cholinergic balance via dopamine stimulus and/or muscarinic cholinergic antagonism
What ratio carbidopa/levodopa should patient be started on? When should this change?
Patient should be started on a 1:4 ratio. Once levodopa requirements exceed 750 mg/day, switch to the 10/100 tablet.
What are the dosing guidelines for carbidopa/levodopa?
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.
What is the ODT form of carbidopa/levodopa?
Parcopa
What are the side effects of carbidopa/levodopa?
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.
What can be done for "wearing off" or "end-of-dose" with levodopa therapy?
Improved by shortening dosing interval, using extended release products, a dopamine agonist, MAO-B inhibitor, or COMT inhibitor.
What can be done for the "on-off" effect of levodopa therapy?
May benefit from increasing carbidopa/levodopa, dopamine agonist, MAO-B inhibitor, or alteration in dietary habits.
What can be done for abnormal involuntary movements with levodopa therapy?
Dose reduction or "smoothing" of levodopa-derived dopaminergic stimulation required.
What is "smoothing" of levodopa therapy? How is this achieved?
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).
What are the major drug interactions with carbidopa/levodopa?
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
Contraindications of carbidopa/levodopa
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
What is the main ergot dopamine agonist?
bromocriptine (Parlodel)
What is the most concerning side effect of bromocriptine?
Valvular heart disease
Others include N/V/anorexia, hallucinations, OH, decreased prolactin
How does bromocriptine work?
stimulates D2 and antagonizes D1
What are the non-ergot dopamine agonists?
ropinirole (Requip)
pramipexole (Mirapex)
How do ropinirole and pramipexole work?
stimulate D2 and D3 receptor sites
How are ropinirole and pramipexole eliminated?
1. ropinirole is eliminated via hepatic metabolism
2. pramipexole is eliminated renally
Dosing schedule for ropinirole
initial 0.25 mg TID, usual dose is 3-24 mg/day divided TID
Dosing schedule for pramipexole
initiate at 0.125 mg TID, usual dose is 1.5-4.5 mg/day divided TID
Pramipexole dosing in renal failure
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
How does rotigotine (Neupro) work?
stimulates D1, D2, and D3 receptors
What are the side effects of rotigotine (Neupro)?
GI: nausea, vomiting
application site reations
fatigue and somnolence
How does apomorphine (Apokyn) work?
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
What are the side effects of apomorphine (Apokyn)?
Due to emetic properties, must start patient on antiemetic at least 3 days before initiating apomorphine. Hypotension is also a risk.
What are the main COMT inhibitors?
1. tolcapone
2. entacapone
How do COMT inhibitors work?
They increase levodopa bioavailability and half-life. They reduce 'off' time of 'wearing-off' phenomena. Levodopa dose needs to be decreased by 30%.
What are the side effects of entacapone?
1. Dopaminergic: dyskinesias, N/V/D/A, OH, HA
2. Increased liver transaminases that requires monitoring, rarely used anymore due to this
How is entacapone metabolized?
Metabolized through glucuronidation (no liver problems makes it the more common COMT inhibitor)
What is the levodopa/carbidopa/entacapone combination?
Stalevo
What are the main MAO Type B inhibitors?
1. Selegiline
2. Rasagiline
How do MAO Type B inhibitors work?
They prevent degradation of dopamine in the brain. Must reduce dose of levodopa by 10-30%.
Drug interactions with selegiline
1. Risk of serotonin syndrome (meperidine is contraindicated)
Drug interactions with rasagiline
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
What is amantadine used for?
Improves tremor, rigidity, bradykinesia; especially tremor
Amantadine dosing
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
Side effects of amantadine
Cardiac: OH, edema, CHF exacerbation
CNS: insomnia, confusion, hallucinations
GI: N/V/D
Not used too often due to these side effects
Anticholinergic use in Parkinson's
Rarely used due to adverse effects in elderly
Improvement in symptoms in 25% of patients; helps mostly with tremors
benztropine