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70 Cards in this Set
- Front
- Back
Dentothalamic Tract
|
Fibers ext dentate medially
=> SCP |
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Vestibulocerebellar System
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Vestibulocerebellum => Vestibular nuclei & ICP.
ICP => flocculonodular lobe => ICP => Vestibular nuclei All Ipsi |
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Olivocerebellar System
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Cerebral cortex => ipsilateral olivary nucleus => ICP => entire contralateral cerebellum
|
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Pontocerebellar Tract
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Fine, voluntary motor control.
All lobes of the cortex. Frontopontin in ALIC & lateral crus. Parieto-, occipito & Tempopontine in medial crus & PLIC (w/ corticospinal). => pontine nuclei => MCP => ipsicerebellum => dentate nucleus => SCP => red nucleus (dentatorubral) & VL thalamus (dentatothalamic). VL thalamus => cortex. |
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Spinocerebellar Tract
|
Ipsi dorsal spino- & cuneocerebellar tracts => ICP => vermis & paravermis.
Vermis => fastigial nucleus => ICP => vestibular nucleus. Paravermis => interpostis nucleus => SCP => red nucleus & VL thalamus |
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Causes of Parkinsonism
|
1. Idiopathic (75%), due to genetic factor, oxidative distress, or neurotoxins.
2. Infections (enchephalitis) 3. Traumu (head Injury) 4. Endocrine (hypothyroidism, Wilson's Disease) 5. Drugs |
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Drugs that can cause Parkinsonism
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1. Neuroleptics (haloperidol)
2. Metoclopramide (DA antagonist) 3. Reserpine (Depletes DA, NE) 4. Carbamazepine (antiepileptic) 5. MPTP (neurotoxin, analog of meperidine, converted to 1-MPP) |
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4 cardinal features of Parkinson's Disease
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1. Tremor
2. Rigidity 3. Bradykinesia & Akinesia 4. Disorders of gait & posture |
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Surgical Therapies for Parkinson's Disease
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Pallidotomy, thalamotomy.
Deep Brain Stimulation. Fetal nigral transplantation |
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Levodopa
Chemistry & Parmacokinetics |
Dopamine is polar (does not cross BBB). Levodopa is a DA precursor that can cross the BB.
Rapidly absorbed from SI by active transport. Rate depends upon pH of gastric contents. Food decreases absorption; neutral aa compete. First pass metabolism in GI mucosa & liver (decarboxylated to DA). Only 1% enters CNS. Short half-life (1-3 hours). Major metabolites are DOPAC & HVA. It is rapidly excreted in urine. Prodrug. Converted to DA => interacts with dopamine D-2 receptors on neurons in striatum & presynaptic terminals of DA nigrostriatal axons. Improves all major signs & Sx of parkinsonism. Esp bradykinesia & rigidity. |
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Levodopa
Adverse Reactions |
Dose-dependent & reversible.
GI: Anorexia & NV (80%). DA acts on CTZ. Tolerance gradually increases, so start with low doses. Carbidopa decreases. CV: Tachycardia & arrhythmias. Postural hypotension. Dyskinesia: Orofacial tics. Time related (80% of prolonged pts). Carbidopa increases incidence. Behavioral disturbances: Hallucinations, anxiety, depression, vivid dreams. Carbidopa increases. |
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Levodopa
Fluctuations in Response |
Wearing-off effect or end-of-dose akinesia. Relate to time of intake.
On-off phenomenon. Unpredictable, marked dyskinesia during on. Diet may affect. May result from DA-R changes to plasma drug levels. May be decreased by taking med more frequently in smaller doses. Wearing off decreased with COMT Inhibitors or Stalevo. |
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Levodopa
Clinical Uses |
Best results obtained in first 3-4 years of Tx. After that refractoriness or increased SE. Suggested it is reserved for advanced cases.
Gradual withdrawal. Abrupt => severe akinesia. |
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Sinemet
|
Combination of Levodopa with Carbidopa (a peripheral inhibitor of dopa decarboxylase).
Controlled release preparation is also available. Considered one of the most effective drug therapies for Parkinson's. |
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Sinemet
Benefits to Levodopa alone |
Decrease levodopa dose by 75%.
NV much less frequent (2-5%) Less tachycardia. Greater efficacy with smoother control. CR = less fluctuation. Pyridoxine no longer antagonizes L-DOPA effect (increases L-DOPA metabolism). |
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Sinemet
SEs, Cautions & Contraindications. |
Dyskinesia & psychiatric disturbances develop earlier, may be more severe.
Caution for pts with peptic ulcer, cardiac disease, open-angle glaucoma or mydriasis. Contraindications: angle-closure glaucoma, psychosis, malignant melanoma. |
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Sinemet
Drug Interactions |
Pyridoxine (increases L-DOPA metabolism)
Antipsychotic Drugs Anticholinergics (glaucoma) Non-selective MAO inhibitors (hypertensive crisis, decreases catechol metabolism). Other dopamine agonists |
|
Bromocriptine
|
Dopaminergic Agonist
An ergoline. Used to treat hyper-prolactinemia. Binds D2-R (weak at D1-R) & decreases prolactin & galactorrhea release in pituitary. |
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Bromocriptine
Clinical Uses |
Combined with Sinemet in pts experiencing on-off phenomena or becoming refractory.
Oral: Start with low doses. Increase dose gradually. |
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Bromocriptine
Adverse Rxns |
GI: Anorexia, NV, constipation
CV: Orthostatic hypotension; more arrhythmias than levodopa. Dyskinesia (less than levodopa) Mental disturbances: Confusion, hallucinations, delusions, nightmares (esp elderly). Headache, nasal congestion, erythromelalgia. |
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Bromocriptine
Cautions & Contraindications |
History of mental illness
Cardiovascular disease Pregnancy |
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Nonergot dopamine agonists
|
Pramipexole - Tabs
Ropinirole - Tabs Rotigotine - Transdermal (patch, every 24 hours) |
|
Nonergot dopamine agonists
MOA Pharmacokinetics |
Selective D2-R Agonists. Pramipexole & rotigotine also activate D3-R.
Pramipexole is rapidly absorbed & excreted unchanged in urine. Ropinirole is metabolized by CYP1A2; |
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Nonergot DA Agonists
Clinical Uses |
Alone for Mild disease (1st line)
Combination w/ levodopa for advanced disease. Restless Leg Syndrome (GLS) |
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Nonergot DA Agonists
Adverse Effects |
Nausea, fatigue, hallucinations, dizziness, confusion, postural hypotension.
Sudden sleep attacks - during daytime activity; uncommon. |
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Apomorphine (Apokyn)
|
Potent lipophilic DA agonist.
Rapidly absorbed after SC injection; rapid onset, duration ~60 min. |
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Apomorphine
Clinical Uses |
Intermittent SC Tx of hypoactivity ("off" episodes) in advanced Parkinson's Disease.
|
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Apomorphine
Adverse Effects |
Injection site rxns - common
NV, yawning, drowsiness, dyskinesia. Orthostatic hypotension, syncope, confusion, hallucinations. |
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Monoamine Oxidase (MAO) Inhibitors
|
Selegiline
Rasagiline (Selective MAO-B Inhibitors) |
|
MAO Inhibitor
Mechanism of Action |
2 MAO in the body
Type A - primarily for NE & serotonin (peripheral). Type B - predominant in brain; metabolizes DA. Selegiline: Decreases MAO-B (irreversibly) => decreases DA metabolism & increases DA levels. |
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Selegiline
Benefit |
Lack undesirable effects of nonselective MAO inhibitors (eg. hypertension).
May have neuroprotective & anti-apoptotic effects - antioxidant effects => decreases Dx progression. |
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Selegiline
Clinical Uses |
Alone for early disease (less than L-DOPA).
Adjunctive therapy w/ Levodopa for advanced disease. May prolong effect of levodopa & decreases mild on-off or wearing off akinesia. Decrease dose 20-30%. |
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Selegiline
Adverse Reactions |
Dyskinesias & mental disturbances from levodopa (increases incidence & intensity).
Insomnia, anxiety, nausea, hypotension. |
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Selegiline
Drug Interactions |
SSRIs, Tricyclic antidepressants = increase risk of serotonin syndrome (hypertension, tremors, rigidity, agitation, hyperthermia).
Meperidine = rigidity, agitation, delirium, tremors. |
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Tolcapone
|
Catechol-O-Methyltransferase (COMT) Inhibitor
Rapidly absorbed, bound to plasma protein & metabolized prior to excretion. Given 2-3x/day. COMT blocks primarily peripheral conversion of L-DOPA to 2-O-Methyl-DOPA. Thus, Tolcapone increases L-DOPA. |
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Tolcapone
Clinical Uses |
Adjunct to levodopa/carbidopa in pts experiencing on-off phenomenon.
Produces a smooth response & prolong "on" time. |
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Tolcapone
Adverse Rxns |
ND, Hypotension, Orthostatic hypotension, Vivid dreams, Hallucinations.
Hepatotoxicity (BBW, severe). Monitor liver enzymes, can lead to fatal hepatitis. |
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Amantadine
|
Antiviral drug for Type A influenza. Unexpectedly found to cause symptomatic improvement in pts with parkinson's. No longer used for flu.
Increases DA release from neurons. Blocks DA reuptake. Blocks NMDA-Glutamate R. |
|
Amantadine
Clinical Uses |
Mild cases- alone (less effected than L-DOPA)
Severe cases: Adjuctive therapy w/ levodopa & anticholinergic drugs. Start with low dose & increase gradually to 100 mg 2x/day. |
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Amantadine
Adverse Rxns |
Mild, reversible.
CNS: Dizziness, confusion, insomnia, anxiety, excitement, hallucinations. Livedo reticularis- due to local release of catecholamines. Vasospastic Disease, Fishnet appearance (reddish, bluish discoloration in legs/arms). Edema; orthostatic hypotension. |
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Central Anticholinergic drugs
|
Trihexyphenidyl (Prototype)
Benztropine mesylate. |
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Central Anticholinergic Drugs
Mechanism of Action |
Blocks Central M1 R.
Decreases excitatory cholinergic activity from striatal neurons. |
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Anticholinergic
Adverse Rxns |
CNS: Sedation, drowsiness, confusion, delirium, hallucinations (esp in elderly).
Peripheral: Anti-SLUD (dry mouth, cycloplegia, constipation, urinary retention) |
|
Anticholinergic
Clinical Uses |
Less effective than levodopa. Recommended in younger pts with mild (early) disease & pts with drug-induced parkinsons.
Adjunctive therapy with levodopa. Tremor & rigidity are most improved. Bradykinesia less so. |
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Cocaine
|
Ester type local anesthetic.
A plant alkaloid; 1st LA discovered. Has both LA & CNS stimulant effects. The only LA with sympathomimetic effects => vasoconstriction & tachycardia. Applied topically to decrease bleeding after nasal surgery & ENT procedures. A schedule II controlled substnace with abuse potential due to its euphoric effect. |
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Procaine (Novocaine)
|
Ester-Type local anesthetic.
Low potency and short duration (15-30 min). Given parenterally, metabolized to PABA- may cause allergic reactions. |
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Tetracaine
|
Ester type local anesthetic.
Potent, long duration (2-3 hrs). Used parenterally for spinal, epidural anesthesia. |
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Benzocaine
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Ester type local anesthetic. OTC.
Available topically as cream, lotion, ointment & spray for sunburn, pruritis & other skin conditions. Also in cough lozenges & spray to decrease coughing. |
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Lidocaine
|
Amide type local anesthetic.
Prototype amide. Has intermediate duration of 30-60 min for short duration prodedures (infiltration blocks, epidural and spinal anesthesia). Available as topical creams, lotions, ointment & patch. An effective anti-arrhythmic agent. |
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EMLA
|
A mixture of local anesthetics. Lidocaine & prolocaine.
Available topically as a cream for venipuncture, IV cannulation & dental procedures, particularly in children. EPI might be added to increase absorption. |
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Prilocaine
|
Amide type local anesthetic.
Has intermediate duration of 30-60 minutes. May cause methemoglobinemia => metabolized to O-Toluidine that oxidizes Hb to MET-Hb. Can cause cyanosis or decompensation in patients with CV or pulmonary diseases. Treated with IV methylene blue. Limited to topical and infiltration anesthesia. |
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Bupivacaine
Ropivacaine |
Amide type local anesthetics.
Potent with long duration of action (2-3 hrs). Bupivacaine = used for obstetrical anesthesia. May cause cardiac depression & ventricular arrhythmia. Ropivacaine = newer drug that may cause fewer cardiac toxicity. |
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Cerebellum Anterior Lobe Degeneration
|
Seen in chronic alcoholism & malnutrition.
Gait ataxia. "Drunken walking" |
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Pressure in subtentorial space
(such as a tumor) |
Herniates cerebellar tonsils.
Compresses brainstem nuclei => nausea, respiratory distress & ataxia. Pressure causes squeezing through foramen magnum. |
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SCA Occlusion
|
Affected: SCP, Spino- & Cerebro-cerebellar tracts.
Gait, truncal & limb ataxias. |
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Spinocerebellar Lesion
|
Gait & truncal ataxia.
Inability to stand upright (fall towards lesion side). |
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Bergman Astrocytoma
|
2/3 of Pediatric tumors are in subtentorial space (posterior fossa).
This is the most common kind. The cell body of these astrocytes lies in the purkinje layer. |
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AICA Occlusion
|
Affected: MCP & cerebrocerebellar tracts.
Limb ataxia & dysarthria. |
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Pontocerebellar Lesion
|
Problems with voluntary & fine motor control.
Limb ataxia (uncoordinatory skilled voluntary movements). Dysdiadochokinesia (no alternating movements). Dysmetria (inaccurate movement over distance). Laryngeal MM problems. |
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Dentothalamic Tract
|
Fibers exit dentate mediall
=> SCP |
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Vestibulocerebellar Lesion
|
Unsteady gait, swaying (fall towards lesion side).
Oculomotor uncoordination with head movements. |
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Midline Cerebellar Lesion
|
Eye MM problems.
|
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Parkinson's
|
Hypokinesia caused by dopamine depletion (lose cells in the SNpc).
Loss of excitation of direct pathway (movement promoting) and loss of inhibition of indirect pathway (movement inhibition). Resting tremor, brady- & akinesia. SNpc will not appear dark (no melanin). May use low frequency ultrasound to diagnose. |
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Huntington's
|
Hyperkinesia caused by the loss of medium spiny neurons in the caudate putamen.
Leads to uncoordinated disinhibition of the thalamus. Causes increased, abnormal movements. The reduced volume of the caudate putamen leads to increased ventricle size (ant horn). |
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Hemiballismus
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Hyperkinesia due to subthalamic lesion.
ST is a major player in movement inhibition (Indirect pathway). Leads to wild uncontrolled movements. |
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Recurrent Artery of Heubner infarction
|
Causes motor deficits.
|
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Vestibulo-ocular reflex
|
When you turn the head to the left, both eyes reflexively turn right. CN III towards turn side is excited, CN IV is inhibited.
This can be tested in comatose patients letting you know if the vestibular part of the brainstem is functioning. Move head and see if eyes move or remain fixed in socket => Doll's eye phenomenon. |
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Testing vestibular function
|
Tilt head back 60% => horizontal canal is now verticle.
Cool or heat ECM. COWS. Warm => utriculopetal (towards); cool => utriculofugal (away). => Fast phase of nystagmus. |
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Ipsilateral loss of macular function
|
Fall towards lesion side.
|
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Meniere's Disease
|
Hydrops = increased endolymph pressure.
=> expands/distorts membraneous labyrinth => hearing and balance Sx. |