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67 Cards in this Set
- Front
- Back
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excitatory neurotransmitters
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gluatamate, dopamine, norepi, histamine, substance P, met-enkephalin, acetylcholine
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inhibitory neurotransmitters
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gaba, serotonin, glycine
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motor aspects of parkinson's
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tremors, muscular rigidity, bradykinesia, gait disturbance, akinesia, mask-like face, micrographia
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neuropsychiatric aspects
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sensory deficits: olfactory dysfunction, cognitive difficulties (executive planning), memory deficits, sleep problems, mood problems, psychosis, 6x's more likely to suffer from dementia, autonomic dysfunction
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pathophysiology
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loss of dopaminergic nuerons in substantia nigra allows acetylcholine to be secreted unchecked in the neostriatum, resulting in uncontrolled muscle movements
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A synucleinopathy
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abnormal accumulation of alpha-synculein protein (Lewy Bodies)
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differential diagnosis
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essential tremor, dementia with Lewy Bodies, Multiple system atrophy, progressiver supranuclear palsy, idiopathic basal ganglia calcification, Huntington's disease, Secondary parkinsonism
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Diagnosis is
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largely based on history/clinical impression: presence of major symptoms/signs; response to dopaminergic therapy, diagnostic accuracy is low as 75% using neuro-pathological exam
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aim of biomedical treatment
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targeting neurons in the neostriatum: supporting activity of dopaminergic neurons; inhibiting activity of cholinergic neurons
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current meds only address
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symptoms and not primary neuronal degeneration
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natural med support
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systemic inflammation, oxidative stress, mitochonrial dysfunction, systemic toxicity
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Precursor to dopamine, crosses BB-barrier (which dopamine does not), remaining dopaminergic neurons in basal ganglia are enough to convert _______ to dopamine
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Levodopa/Carbidopa
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Levodopa/Carbidopa
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decrease the rigidity, tremors and symptoms of parkinsons
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characteristics of Levodopa
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effects wear off over time as more neurons are lost with time, very short half life; large proteins in diet may inhibit absorption
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Much of levodopa is _______________ outside the ___________, leading to dopamine effects: nausea, vomiting, hypotension, cardiac arrhythmias
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decarboxylated, brain
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Vitamin B6 increases
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peripheral breakdown of levodopa
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MAO inhibitors may precipitate
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hypertensive crisis
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Carbidopa blocks the decarboxylation of levodopa in the _______________, thus _________________ and minimizing side effects
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periphery/GI tract, increasing the amount available to the brain
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Levodopa/Carbidopa is very effective for first years but begins to decline by
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3rd to 5th year of treatment
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Selective MOA inhibitors
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Selegiline
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Selegiline works to
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MOA B: metabolizes dopamine; MOA A: metabolizes NE and serotonin; usually administered with Levodopa; enhances effects
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COMT inhibitors
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selectively and reversibly inhibit COMT, inhibit the breakdown of Levodopa by COMT in the peripheral tissues, reduces wearing off phenomena in patients in Levodopa/carbidopa combo
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Tolcanpone
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may result in fulminating hepatic necrosis
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Dopamine receptor agonists
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Bromocriptine - ergot alkaloid derivatives; act similarly to levodopa but have vasocontrictor properties as well
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Bromocriptine is also used
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to treat pituitary tumors and suppress lactation
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Adverse effects of Bromocriptine
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hallucinations, confusion, nausea, hypotension
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Pergolide is associated with
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cardiac fibrosis; withdrawn from U.S. market by USDA
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Dopamine receptor agonist/ weak anticholinergic
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Amantadine
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Amantadine side effects
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restlessness, agitation, confusion, hallucinations, psychosis, orthostatic hypotension, urinary retention, peripheral edema, dry mouth (still fewer side effects than Levodopa)
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Antimuscarinic Agents
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Benztropine
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pathophysiology of Alzheimer's
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Neuronal and synaptic loss (esp ACh secreting neurons in temporal, parietal lobes, prefrontal cortex & cingulate gyrus; beta-amyloid peptide depostion; neurofibrillary tangles; excitotoxicity
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Differential diagnosis
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vascular dementia, dementia with Lewy bodies, frontotemporal dementia
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Diagnosis of Alzheimer's
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definitive diagnosis requires histopathological exam: rarely done in life
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Cognitive exam giving to diagnose Alzheimer's
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Mini Mental State Exam, diagnosis if scoring less than 26
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Other diagnostic procedures for Alzheimer's
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detailed neurological exam, clinical criteria, neuroimaging, thyroid and B12 levels useful
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Biomedical aims for treatment of Alzheimer's
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palliation of symptoms, improve cholinergic transmission in the CNS, prevent excitotoxicity actions of the NMDA glutamate receptors
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Centrally-acting acetylcholinesterase inhibitors
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reversible inhibitors, approved for mild to moderate Alzheimer's disease: Donepezil - provide only modest cognitive, behavioral and functional benefit for 6-12 months at best
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Adverse effects of centrally acting acetylcholinesterase inhibitors
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nausea, diarrhea, vomiting, anorexia, muscle cramps
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Tacrine can cuase
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hepatotoxicity
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NMDA receptor agonist
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new class; overstimulation of NMDA glutamate receptors has excitotoxic effects on neurons, may worsen neurodegenerative process; mechanism of reperfusion injury
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NMDA receptor agonists slow
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rate of memory loss; have few side effects
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diagnosis of depression
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patient health questionaire-9 - score greater than 20 = major depression; Beck Depression Inventory - 7 item scale; 97% sensitivity and 99% specificity for identifying MDD
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to diagnose depression
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establish the presence of 9 basic symptoms of depression
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functional conditions that need to be ruled out as causes
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thyroid, sex hormones, electrolytes, glucose, CB/anemia-infection, ESR/Inflammation, urinalysis, Vitamin D, B-vitamins, zinc magnesium
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Many with depression have a variation in the ______ gene (inherit 2 short alleles)
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serotonin transporter (5HTT)
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Monoamine hypothesis
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postulates that depression is related to CNS imbalances of monoamines
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maintains alterness/energy, as well as anxiety, attention and interest in life
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norepinephrine
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deficiency: related to anxiety, obsessions, compulsions
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serotonin
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maintains attention, motivation, pleasure, reward, interest in life
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dopamine
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challenges to monoamine hypothesis
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deficiencies of monoamines not enough, usually therapeutic response happens over a few weeks (not immediately), changes in depression may be associated with increased brain neurogenesis
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SSRIs
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block reuptake of serotonin, take 2-12 weeks to be beneficial, 40% don't respond after 8 weeks of dosing, don't produce CNS stimulation
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therapeutic uses of SSRIs
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depression, obsessive-compulsive, panic disorder/anxiety, PMDD, bulimia
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Adverse effects of SSRIs
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insomnia, sexual dysfunction, 1/50 children become suicidal, seizures
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serotonin syndrome
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hyperthermia, muscle rigidity, muscle twitching, mental changes--esp occurs if SSRI is used with MAO inhibitor
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Serotonin/Norepinephrine Re-uptake Inhibitors
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block re-uptake of serotonin and NE, useful for neuropathic pain that accompanies depression
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therapeutic uses of SNRIs
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depression, anxiety, bipolar disorder, MDD, GAD, peripheral neuropathy
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adverse effects of SNRIs
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nausea, dry mouth, constipation, insomnia, dizziness, somnolence, sweating, sexual dysfunction
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Atypical Antidepressants
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have actions at several receptor sites, not necessarily any better than SSRIs or tricyclic antidepressants - work with serotonin, dopamine, norepinephrine, nicotinic
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therapeutic uses of atypical antidepressants
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smoking cessation, depression, sexual dysfunction - caused by SSRIs, obesity, ADHD, restless leg syndrome
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adverse effects of atypical antidepressants
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dry mouth, sweating, tremor, seizures (high doses)
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Tricyclic Anti depressants
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block reuptake of serotonin and NE, useful in those not responding to SSRIs, also block alpah adrenergic, histamine, muscarinic receptors
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pharmacokinetics of tricyclic anti depressants
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lipophilic, plasma half life btwn 4-17 hrs, initial trtmnt period betwn 4-8 weeks, liver metabolism via CYP450/glucoronide conjugation, 5-6x's maximum dose may be fatal
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therapeutic uses for Tricyclic anti depressants
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severe major depression, neuropathic pain, especially amitriptyline, panic disorder/anxiety
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adverse effects of tricyclic anti depressants
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blurred vision xerostomia, urinary retention, constipation, aggravation of glaucoma, blockage of alpha andrenergic receptors cause orthostatic hypotension and reflex tachycardia (serious in elderly), sedation, weight gain, sexual dysfunction, may unmask manic behavior in bipolar patients
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Monoamine Oxidase Inhibitors
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cause irreversible inactivation of MAO, which normally breaks down catecholamines, also act on MAO in peripheral tissues, results in a mild, amphetamine-like effect; when discontinuing these drugs must wait two weeks before starting MAO to prevent toxicity
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therapeutic uses of MAO inhibitors
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depression esp. in those unresponsive to other meds, atypical depression--labile mood, rejection sensitivity, appetite disorders
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adverse effects
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high incidence of drug and food interactions, tyramine containing foods (aged cheeses, chicken liver, beer, red wine) may cause toxicity
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