Part 39 Flashcards
Principles of treatment for parkinson’s disease (2)
- reduce incidence and severity of symptoms
- delay progression of symptoms and complications
Surgical approach to treatment for Parkinson’s
Last resort therapy particularly when drug treatment loses effectiveness, deep brain stimulation of the subthalamic nucleus or globus pallidus with high frequency electrical stimuli from implanted electrodes is a treatment of choice
Levodopa (dopar) function, ADR’s (3), mech of action, drug interactions (1)
- drug of choice for parkinson’s disease at controlling tremor, bradykinesia, and rigidity
- limited duration of efficacy that diminishes over years (on-off effect), acceleration of disease process, cannot stop suddenly
- Promotes synthesis of dopamine in the striatum after being taken across blood brain barrier, is then converted to dopamine by dopa decarboxylase, (dopamine cannot get across BBB on own and has too short half life)
- 1st generation antipsychotics directly decrease therapeutic action
Reasons patients have declined response to levodopa after years of therapy
- progressing disease
- decreased sensitivity of post synaptic receptors to dopamine
2 patterns of acute loss of effect of levadopa
1) gradual loss “wearing off” at end of dosing interval
2) “on-off” phenomenon that can happen any time during dosing interval with off periods lasting minutes to hours and suddenly changing from mobility to immobility
Drug holidays
May benefit some patients taking levodopa, brief 10 day interruption of treatment, when successful, beneficial effects are achieved with lower doses but will not correct “on=-off” phenomenon, must be done in hospital as patient may become immobilized
Carbidopa + levodopa (sinemet) function, mech of action
- Most effective therapy for parkinson disease, more effective than levodopa alone
- Carbidopa which has no therapuetic effects on its own enhances actions of levodopa by inhibitng decarboxylases in periphery making more levodopa available to CNS but carbidopa cannot cross BBB so doesn’t affect it in the CNS (recall only 2% levadopa normally reaches brain, goes up to 10%)
MAO-B inhibitors (selegiline) function
-Selective inhibitors of enzyme that metabolizes dopamine in the brain increasing amount of dopamine that can produce therapeutic effect when used adjunct to levodopa, unfortunately resistance quickly builds within 12-14 months, can delay early progression of parkinson disease when used alone
Recent studies indicate selegiline (MAO-B inhibitor) may actually…
….cause more death than benefit
Amantadine (symmetrel) mech of action, function, ADR (1 big one)
- Developed as antiviral that may be employed alone in early parkinsons disease or in combo with other drugs to improve symptoms modestly and decrease levodopa induced dyskinesias
- improves symptoms in 20-50% of patients but rarely lasts more than 6 months
- Livedo reticularis (rose colored to purple mottling of skin and legs, nonharmful)
Anticholinergics for parkinson disesase and 2 examples
- Can be useful in control of symptoms of PD by blocking ability of acetycholine to reach receptors thereby improving balance between dopamine and Ach
- benztropine and trihexphenidyl
Dopamine receptor agonists for Parkinson’s disease, mech of action, ADR’s (3)
- Effective monotherapy in early mild disease but in few years often require addition of levodopa
- Stimulate effects of dopamine by binding postsynaptic receptors, do not undergo conversion process
- Nausea, confusion, psychosis
What kind of dopamine agonists do we use today?
Nonergoline
COMT inhibitors function
-approved for adjunctive use with levo/carbidopa in parkinson patients who have end dose wearing off symptoms by prolonging half life of levodopa and decreasing parkinsonian disability, but can increase dyskinesia
Tolcapone (tasmar) drug class and mech of action
- COMT inhibitor
- Adjunct to levodopa/carbidopa that prolongs half life of levodopa increasing amount that can cross the BBB
Principles of migraine headache treatment (2)
- Management at abortive or symptomatic therapy of onset attack
- prevention of attack all together
Drug of choice in mild migraine, moderate, and severe
- nonopiod analgesic (NSAIDs, excedrin migraine (ibuprofen+caffeine)
- triptans
- opioid
Excedrin migraine content, clinical usefulness
- Acetaminophen, aspirin, caffeine
- readily effective in studies
Theories to how NSAIDs alleviate migraine pain (3)
- inhibition of PG synthesis
- blocking platelet aggregation
- reducing serotonin release
Indomethacin has a very specific ADR that should make it avoided in use of migraine patients
AVOID it regarding migraine treatment because it causes headaches
Injectable ketorolac function
highly useful in resolving nausea and vomiting in migraine patients
Serotonin 1B/1D receptor agonists (triptans) function, mech of action, ADR’s (3), drug interactions
- Allow for relief generally 60 minutes after administration
- analogue of serotonin that stimulates receptor subtypes causing vasoconstriciton of intracranial blood vessels
- Chest pain, coronary vasospasm (contraindicated in CAD patients), vertigo
- MAOI’s increase half life, SSRI’s can lead to serotonin syndrome
Ergotamine function, mech of action, ADR’s (2)
- Used to stop an ongoing migraine attack and to treat cluster headaches not to be used on a long term basis (especially not daily)
- Direct vasoconstrictor of smooth muscle in cranial blood vessels and an agonist at serotonin receptors
- Ergotism (headache, NVD, gangrene of fingers and toes), Ischemia resulting in cold limbs and potential gangrene
dihydrogotamine function, contraindications (2)
- Nonsedating serotonin agonist used as DOC for terminating severe refracatory migraine and cluster headaches and provides minimal peripheral vasoconstriction and little physical dependence (unlike ergotamine)
- CAD, peripheral vascular disease
butorphanol nasal spray function, administration, ADR’s (2)
- An opioid agonist-antagonist nasal spray effective for relief of moderate to severe migraine
- One spray in one nostril, another in the other following 60 min, same 2 dose sequence repeated next 3-5 min
- Syncope, respiratory depression
Butterbur definition and use
Extract supplement given prophylactically in migraine patients that has been shown to have a 50% reduction or greater in headaches, can cause mild GI upset as common side effect
Most common type of dementia in patients >65 years old
Alzheimer’s disease
Dementia definition
Syndrome characterized by progressive loss of cognitive functions that interfere with patients daily living as well as anterograde amnesia (cannot learn new things and have difficulty with language, abstract reasoning, judgement, visuospatial processing, etc)
What is NOT affected in dementia but is in delirium? (2 things)
Arousal and alertness
Short term memory is stored in the ___, long term memory is stored in the ___ and acquired via ____. Remote memory (>6 months to years) is stored in the ___, no longer requiring ____ for retrieval
Pre-frontal cortex, hippocampus, rehearsal, neo-cortex, hippocampus
Alzheimer’s disease epidemiology
1 in 9 people age 65 and older, 1/3 age 85 and older, mean survival is 8-10 years from onset without treatment, but 15+ with treatment
Alzheimer’s disease Risk factors, which is the greatest? (4)
- Age (greatest)
- Family and genetics
- Past head trauma
- Lifestyle and heart health
Alzheimer’s disease clinical features (5)
- Anosgnosia (loss of awareness of one’s own deficits)
- memory dysfunction
- personality change
- psychiatric disturbance
- late stage motor involvement
Clinical course of alzheimer’s disease
Mild: memory/orientation
Moderate: activities of daily living
Severe: behavioral disorders, nutrition, hygiene
Alzheimer’s effect on memory
-Immediate and short term are affected first, remote not impaired until disease advances
Apraxia definition
loss or impairment of ability to execute complex coordinated movement usually a later finding of alzheimer’s disease
Sundowning theory
Theorized to be due to remote memory remaining in an alzheimer’s patient despite lack of short term memory causing them to be triggered at certain points later in the day to be confused as to why their routine from their remote memory is interrupted leading to distress
Alzheimer’s disease diagnostic criteria (5)
- progression over 6 months
- anterograde amnesia
- multiple cognitive deficits
- impairment in functioning
- other conditions ruled out
Best diagnostic study for mild cognitive impairment
Montreal cognitive Assessment (MOCA) (better than the mini mental status exam)
Alzheimer’s diagnostic studies (5)
- CBC, electrolytes, TSH, B12 (checking if infection or other cause for symptoms in elderly)
- CT or MRI (rule out)
- EEG (rule out nonconvulsive seizures)
- Lumbar puncture (not routine, rule out metastatic cancer, hydrocephalus, etc)
- Genetic councilor referral (amyloid ligand PET imaging not typically covered by insurance)
There is no ____ for screening for Alzheimer’s
Gold standard
Alzheimer’s disease is a diagnosis of…
…exclusion
MRI findings Alzheimer’s disease (2)
- Diffuse cerebral atrophy in frontal, temporal, and parietal lobes
- Hippocampal atrophy
Microscopic findings of Alzheimer’s disease (3)
- Neurofibrillary tangles in hippocampus
- neuritic plaques containing amyloid in cortical cells
- granular-vacular degernation of neurons especially in hippocampus
Alzheimer’s disease pathophysiology
-Reduced amount of acetycholine and reduced activity in entire cholinergic pathway (basal forebrain to cortex and hippocampus)
Treatment for Alzheimer’s is ____ not ____
palliative (preservative), curative
Drugs to slow progression of Alzheimer’s (2)
- Acetycholine and butylcholine esterase inhibitors
- N-methyl-D-aspartate receptor antagonists (NMDA)
Alzheimer’s disease admission criteria (5)
- acute illness cannot be managed by patient or caregivers at home
- short term admission for eval and adjustment to psychotropic meds
- short term respite care
- long term care facility if cannot be provided at home
- hospice care if <6 months
Mild cognitive impairment in alzheimer’s disease treatment (4)
- pharmacologic treatment not effective!
- exercise
- cognitive interventions
- long term planning
Moderate cognitive impairment in alzheimer’s disease treatment (3)
- cholinesterase inhibitors recommended but benefit is modest
- vit E supplementation
- exercise
Severe cognitive impairment in alzheimer’s disease treatment (4)
- Cholinesterase inhibitors
- Memantine
- antipsychotics to treat severe agitation and psychosis if dangerous
- management of comfort
Alzheimer’s disease medications do not….
….work well for everyone
Vascular dementia definition
Dementia brought on by either multiple or singular (rare) infarcts decreasing adequate blood flow to the brain (ischemia, not necessarily stroke), begins as mild changes and worsens gradually leading to cumulative damage
Vascular dementia epidemiology
2nd most common cause of dementia, prevalence rises steeply with age
Vascular dementia risk factors (4)
- TIA
- Age
- High blood pressure
- High cholesterol
Emotionally labile meaning
Easily fluctuating without warning or transition
Vascular dementia clinical features (5)
- Memory impairment
- language disturbance
- impairment of motor skills
- emotionally labile
- Loss of intellectual skills more abrupt (progress in steps (flat then decline rapidly)
Middle cerebral infarct signs
Aphasia, confusion, anosognosia
Anterior cerebral infarct signs
Frontal lobe syndrome (dis-inhibition, poor planning, lack of initiative)
Posterior cerebral infarct signs
Visual distortions, hallucinations, cortical blindness
Thalamic infarct signs
Global cognitive and psychiatric dysfunction
Vascular dementia studies and which one is diagnostic (3)
- Neurocognitive exam
- Lab tests to rule out other etiologies
- CT and MRI is diagnostic
Treating vascular dementia sees more ___ than other kinds of dementia treatment
Cognitive improvement
Frontotemporal dementia (Pick’s disease)
Clinical syndrome associated with shrinking of the frontal and temporal anterior lobes of the brain
Frontotemporal dementia 2 clinical categories
- Changes in behavior
- Problems with language
Behavioral changes in frontotemporal dementia (4)
- Inappropriate social behavior (sexually)
- lack of empathy
- agitation or blunting emotions
- repetitive or compulsive behavior
Language changes in frontotemporal dementia (2)
- Difficulty making or understanding speech
- spatial skills and memory remain intact
Frontotemporal dementia epidemiology
-Mean onset is 58 years old, 10-15% of all dementia, highly heritable
Frontotemporal dementia diagnostic studies (2)
- Clinical
- PET and MRI***
Frontotemporal dementia treatment options (2)
- management of symptoms
- off label use of antidepressants or antipsychotics
Key differences between alzheimer’s disease and frontotemporal dementia (4)
- Age at diagnosis is clue
- Memory loss more prominent in early alzheimer’s
- Spatial orientation more common in alzheimer’s
- speech changes differ
Dementia with lewy bodies definition
Progressive dementia that leads to decline in thinking, reasoning, and independent function due to abnormal microscpic protein deposits (alpha synuclein protein) that damage brain cells over time
Dementia with lewy bodies epidemiology
-3rd most common cause of dementia
Dementia with lewy bodies symptoms (4)
- Parkinson’s symptoms (closely related)
- REM sleep disorder
- visual hallucinations
- less memory loss than other dementias
Dementia with lewy bodies is a….
…clinical diagnosis
Hallmark finding of parkinson’s disease dementia
-hallucinations
Antipsychotic drugs need to be used with extreme caution in what type of dementia?
Dementia with lewy bodies (may impair swallowing, cause acute episodes of hallucinations, or worsen parkinson’s symptoms)
Key differences between dementia with lewy bodies and alzheimer’s (2)
- Memory loss is more prominent in early alzheimer’s
- Hallucinations and REM sleep disorder normal to see in early stage DLB than alzheimer’s
Normal pressure hydrocephalus definition
Brain disorder which excess CSF accumulates in brain ventricles but pressure level normalizes because brain becomes compressed resulting in thinking and reasoning problems, difficulty walking, and loss of bladder control
Normal pressure hydrocephalus epidemiology
-Idiopathic and secondary occur equal proportions, idiopathic most common in adultts >60
Normal pressure hydrocephalus triad of symptoms
- Gait apraxia (shuffling along, feet glued to deck)
- decline in thinking (dementia)
- Bladder incontinence (late stage, does not improve)
Diagnosis for normal pressure hydrocephalus (2)
- MRI detecting enlargement of ventricles
- CSF tap and removal to see if symptoms improve
Normal pressure hydrocephalus treatment (1)
-Shunt of CSF to peritoneum
Huntington’s disease
Progressive brain disorder caused by single defective dominant gene on chromosome 4 in which certain areas of brain start to break down causing emotional disturbances, loss of intellectual abilities, and uncontrolled movements (chorea)
Huntington’s disease epidemiology
Age of onset ranges from childhood to 8th decade, most often in mid life
Huntington’s disease symptoms (3)
- Uncontrolled movement of arms, legs, head, face, upper body (chorea)
- progressive decline in thinking and reasoning skills
- OCD often
Huntington’s disease treatment (1)
-Management of symptoms
Creutzfedlt-Jakob and other prion disease definition
-Class of dementias caused by abnormal form of proteins in brain known as prions, characterized by spongy appearance of brain tissue leading to classification as transmissible spongiform encephalopathies (TSE’s)
Creutzfedlt-Jakob and other prion disease symptoms (3)
- Psychiatric symptoms
- rapid cognitive decline
- abnormalities in walking and balance
Creutzfedlt-Jakob and other prion disease diagnostic studies (3)
- CSF analysis
- Electroencephalogram
- MRI
Creutzfedlt-Jakob and other prion disease treatment and prognosis
- No cure, management of symptoms
- 2 year fatality
What kind of changes in the brain are hallmarks of alzheimer’s?
-Amyloid plaques and neurofibratory tangles
What type of dementia is associated with chronic alcoholism
Korsakoff syndrome
