1 / 50

CNS Disorders & Misc Neurological Disorders

CNS Disorders & Misc Neurological Disorders. Week 8. CVA Peripheral Multiple Sclerosis Guillain-Barre Syndrome Amyotrophic Lateral Sclerosis. Diseases du jour. Parkinson's Alzheimer's Epilepsy Muscle Spasm Brain Trauma Meningitis, Encephalitis. CNS Pharmacology.

zaviera
Download Presentation

CNS Disorders & Misc Neurological Disorders

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. CNS Disorders &Misc Neurological Disorders Week 8

  2. CVA Peripheral Multiple Sclerosis Guillain-Barre Syndrome Amyotrophic Lateral Sclerosis Diseases du jour • Parkinson's • Alzheimer's • Epilepsy • Muscle Spasm • Brain Trauma • Meningitis, Encephalitis

  3. CNS Pharmacology • Peripheral neurotransmitters = 3 • CNS neurotransmitters = at least 12 • Exact actions may be unknown • Areas of brain with no known transmitter • Blood-brain barrier • Pharmacologic considerations • Delayed full effect • Tolerance, decreased side effects • Physical dependence

  4. Parkinson's Disease • Extrapyramidal system • Neuronal network responsible for regulation of movement • Dyskinesias • Tremor, Mask • Postural instability • Bradykinesia, akathisia • Psychologic disturbance • Dementia, depression, impaired memory

  5. Parkinson's Disease • Balance Neurotransmitters in EPS striatum • Acetylcholine (excitatory) • Dopamine (inhibitory) • Supplied by neurons in substantia nigra • 70-80% of dopamine supplying neurons must be lost before Parkinson's symptoms appear

  6. Parkinson's Treatment • Currently unable to reverse degeneration • Drugs improve dyskinesias, but not tremor and rigidity • Drug Strategies • Increase dopamine (Dopaminergic) • Inhibit acetylcholine (Anticholinergic)

  7. Dopaminergic Drugs • Promote dopamine synthesis • Stimulate dopamine receptors • Inhibit dopamine breakdown • Promote dopamine release • Block dopamine reuptake • Anticholinergics: all block muscarinic receptors

  8. Drug Selection • Mainstay • Levodopa: most effective, long term side effects • Dopamine agonists: less effective, fewer side effects • Combination

  9. Levodopa • Promotes dopamine synthesis in surviving neurons • Highly effective, but fades over time (5 years) • Adverse effects: long term dyskinesias • Acute loss of effect • Gradual “Wearing off” • Abrupt “on-off”

  10. Levodopa • Kinetics • Well absorbed PO, delayed by food, esp protein • Most levodopa metabolized in periphery • Small amount crosses BBB • Adverse effects (most dose dependent) • NV (take on empty stomach) • Dyskinesias (80%) • CV: postural hypotension • Psychosis (20%), neurotoxicity

  11. Levodopa • Drug holiday • Drug Interactions • Conventional antipsychotics • MAO inhibitors • Anticholinergic Drugs • Food Interactions

  12. Levodopa plus Carbidopa • Brand: Sinemet • Most effective PD drug we have • Carbidopa enhances levodopa action • Inhibits peripheral metabolism • Reduces NV, CV effects

  13. Dopamine Agonists • Four drugs • 2 ergot derivatives (bromocriptine and pergolide) • 2 nonergot (pramipexole and ropinirole) • Ergots have more side effects • Nonselective • Also stimulare alpha and serotonin receptors • Nonergot adverse effects: • Nausea, dizziness, day somnolence, insomnia, constipation, hallucinations

  14. Other Parkinson's Drugs • COMT inhibitors • Selegine (MAO-B inhibitor) • Amantidine • Anti-viral • Promotes release of dopamine • May block reuptake • Anticholinergics: reduce tremor, not bradykinesia • Better tolerated, less effective

  15. Alzheimer's Disease • Progressive memory loss and decreased cognitive function • Pathophysiology • Neuronal degeneration • Reduced Cholinergic Transmission • Characteristic morphology • Amyloid plaques • Neurofibrillary tangles • Apo E4, ER-assoc binding protein, homocysteine

  16. Risk Factors • Age • 90% older than 65 • Rises exponentially thereafter • Early Symptoms • Memory Loss!!! • Disorientation • Changes in personality and judgment

  17. Symptoms Cont • Moderate symptoms • Difficulty with ADLs • Anxiety, suspiciousness, lack of recognition • Sleep disturbance • Wandering, pacing • Severe symptoms • Loss of speech • Loss of appetite • Loss of bladder and bowel control

  18. Evaluation and Treatment • Diagnosis: exclusion • Treatment • Typically die 4-8 years after diagnosis • Delay progression of symptoms long enough for them to die of something else. • The cardiologists are winning • Drug therapy • Cholinesterase inhibitors • Calcium channel stabilizer

  19. Cholinesterase inhibitor • In Alzheimer's, acetylcholine transmission in brain is 90% lower than with normal aging • Acetylcholine essential for forming memories • Inhibitors help ~30% mild-moderate patients • Three agents • Donezepil (Aricept) • Rivastigmine (Exelon) • Galantamine (Razadyne)

  20. Calcium Channel Stabilizer • Amyloid plaques may cause excess influx of calcium into neurons • Memantine (only CCS) • Downregulates calcium channel • “filters out the noise” • Moderate to severe dementia

  21. Epilepsy • Group of related disorders • Excessive neuron excitability in CNS • Seizure • Unconsciousness • Mild Twitching • Convulsions • 100,000 new cases/year – most in elderly • 300,000 peds cases in U.S.

  22. Seizures • Focus: group of hyperexcitable neurons • Causes • Congenital defects • Hypoxia at birth • Head Trauma • Cancer • Seizure • Synchronous, high frequency depolarization of a focus that spreads to other parts of the brain • Manifestations depend on location of focus and recruitment of other parts of the brain

  23. Seizure Types • Partial: only part of the brain • Simple • Complex • Generalized: throughout brain • Tonic-clonic (Grand mal) • Absence (Petit mal) • Atonic (head drop, drop attack) • Myoclonic • Status Epilepticus • Febrile: not associated with epilepsy

  24. Seizures • Stages • Aura • Seizure • Post-ictal • Confusion • Disorientation • Weakness • Hypoglycemia • Status Epilepticus • Seizure that lasts >30 minutes

  25. Anti-Epileptic Drugs • Suppress discharge of neurons in a focus • Suppress propagation of of seizure • Three basic mechanisms • Suppression of Sodium influx • Suppression of Calcium influx • Potentiation of GABA • Therapeutic Goal • Reduce seizures to extent that patients live a normal life; 60 – 70% controlled on therapy • Seizure control vs. tolerability of side effects

  26. Therapy • Non-drug therapy • Surgery • Vagal nerve stimulation • Ketogenic diet • Drug selection • Drug must be matched to seizure type • Evaluation • Hx: Symptoms and precipitating events • Neurologic examination • EEG, CT, PET, MRI

  27. Drug Therapy • Acute Seizure: benzo (diazepam, lorazepam) • Trial Period – establish effectiveness • No driving, operating heavy machinery, swimming must be supervised, etc. • May need to switch agents or add a second • Evaluation • Drug levels • Frequency chart • Promoting Compliance • Undertreatment causes ~50% of all seizures • Withdrawing therapy: slowly (6 months)

  28. Anti-Seizure Medications • Conventional (pre-1990) • Carbamazepine (Tegretol) • Ethosuximide (Zarontin) • Phenobarbital • Phenytoin (Dilantin) • Valproic acid (Depakote) • Newer (post-1990) • Oxcarbazepine • Gabapentin (Neurontin) • Topiramate (Topamax)

  29. Phenytoin • Oldest selective seizure med • Seizure activity • Partial • Generalized tonic-clonic • Mechanism of Action • Slows sodium channel recovery • Does not affect non-excitable neurons

  30. Phenytoin Kinetics • Absoprtion • Varies greatly with individual • Instant vs. sustained release • Can be given IV (cautions) • Metabolism • Liver has very limited capability to metabolize • Saturation kinetics • Exponential vs. linear • Must carefully monitor

  31. Phenytoin Adverse Effects • CNS • Mild sedation at therapeutic levels (10 – 20) • Toxic levels (>20): nystagmus, sedation, ataxia, diplopia, cognitive impairment • Gingival hyperplasia (20%): hygiene!!! • Rash • Pregnancy: cleft palate, heart malformation, and other sundry badnesses

  32. Phenytoin Interactions • Decreases effects of: OCs, warfarin, steroids • Increased by: diazepam, cimetidine, acute ETOH, valproic acid • Decreased by: carbamazpine, phenobarbital, chronic ETOH • Synergy: Other CNS depressants

  33. Carbamazepine • Seizure acitvity: partial, tonic-clonic • Mechanism: same as phenytoin • Preferred in children • Also: Bipolar d/o & neuralgias • Adverse effects • Visual disturbance, vertigo, unsteadiness, headache • Bone marrow suprression, rarely aplastic anemia • Birth defects • Interactions: Ocs, Warfarin, Dilantin, Phenobarb, Grapefruit juice

  34. Valproic Acid • Seizure activity: Unique, can treat all types • Mechanism: Sodium & Calcium channels, and GABA • Uses: Seizures, Bipolar, Migraine • Kinetics • Readily absorbed • Widely distributed • Hepatic metab • Renal excretion

  35. Valproic Acid • Adverse effects: • Nausea • Fatal hepatotoxicity • Don't use in conjunction with other drugs <3 yrs • Don't use in pre-existing liver conditions • Check a baseline LFT • Educate on symptoms: Reduced appetite, malaise, ABD pain, jaundice • Pancreatitis • Neural tube defects

  36. Ethosuximide & Phenobarbital • Ethosuximide • Seizure activity: absence • Mechanism: Calcium channels • Adverse effects: drowsiness, dizziness • Phenobarbital • Barbiturate, but can reduce seizures without causing sedation • Usually used adjunct • Persistent Status epilepticus (Barbiturate coma)

  37. Newer Anti-Epileptics • Generally used if do not respons to older drugs • Exception: Oxcarbazepine • Carbamazepine derivative • As effective, fewer side effects, more expensive • Gabapentin (Neurontin) • Seizures: Used only as adjunct for partial seizures • PHN, Invest: bipolar, neuropathic pain, migraine, leg cramps • Topiramate (Topamax) • Seizures: Used only as adjunct for partial seizures • Bipolar, cluster headaches, migraines

  38. Brain Trauma • Most common causes • MVC • Falls • Sports • Violence • Coup vs Contrecoup • Focal Brain Injury: contusions, epidural hemorrhage, subdural hematoma • Diffuse brain injury

  39. Concussion • Mild • Grade I: Confusion, disorientation, moment amnesia • Grade II: retrograde amnesia develops 5-10 min post • Grade III: Retrograde amnesia at moment 5-30 min • Moderate (Classic) • Grade IV: LOC less than 6 hours; retrograde and anterograde amnesia (no axonal damage) • Moderate Diffuse Axonal Injury • Severe Diffuse Axonal Injury

  40. Cerebrovascular Diseases • >50% patients admitted with neuro symptoms have cerebrovascular diseases • Ischemia with or without infarction • Cerebrovacular Accident (CVA, Stroke Syndrome) • Vascular dementia • Hemorrhage

  41. CVA • 500,000 people/year • 3rd leading cause of death in U.S. • Leading cause of disability in U.S. • 70% in persons >65 years • Types • Thrombotic Stroke • TIA (symptoms clear within 24 hours) • Embolic stroke • Hemorrhagic stroke • Lacunar infarct

  42. CVA Manifestations • Cerebral edema peak 72 hours, lasts 2 weeks • Cerebral edema is usually cause of death • Basilar infarcts of brain stem usually fatal • Symptoms vary widely depending on location • Sensation, Cognitive, Motor, Expressive or receptive aphasia, dysphagia, loss of vision, etc. • Intracranial hemorrhage • Onset of Excruciating headache becoming unresponsive • Headache with consciousness • Sudden lapse of consciousness

  43. CVA Eval and TX • Time is Brain • Treatment should begin < 6 hours • Hx, physical, MRA, CT, PET • Thrombotic • Anticoagulation • Thrombolytics • Vasodilation, Antioxidant therapy • Hemorrhagic • Stop bleeding • Reduce/Tx ICP

  44. Meningitis & Encephalitis • Meningitis: infectious or toxic • Viral usually benign and self-limiting • Bacterial: life threatening, may cause retardation in children • Manifestations: sudden fever, headache, nucchal rigidity; also malaise, nausea, vomiting, malaise • Encephalitis: inflammation of parenchyma • Usually viral • Manifestations: mengingeal, decreased LOC, seizures, focal symptoms

  45. Multiple Sclerosis • Central patchy destruction of myelin • Attack and remission  progressive deterioration • Manifestations • Sensory: paresthesias, proprioception, dizziness • Visual: diplopias, blurred • Spastic weakness of limbs • Cerebellar: nystagmus, ataxia • Bladder: hesitancy, frequency, retention • Mood: euphoria, memory loss

  46. Multiple Sclerosis • Tx • Usually aimed at symptoms • Episodic nature makes evaluation of treatment difficult • Most drugs anti-inflammatory or anti-immune • Steroids • Immunosuppressants • Diet therapy

  47. Misc D/Os • Guillain-Barre symptoms • Acute ascending, progressive demyelinization • Precipitating events (1-3 weeks prior) • Mild viral or bacterial illness • Surgery • Immunizations • Most frequent: Campylobacter jejuni • Negative symptoms: muscle weakness/paralysis, decreased DTRs, loss of sensation • Positive symptoms: pain and paresthesias

  48. Misc D/Os • Guillain-Barre • Usually self limiting • Severity peaks at 2 weeks • Recovery 6 weeks to several years • If paralysis is severe, may require mechanical ventilation • Tx • Plasmapheresis decreases severity

  49. Misc D/Os • Huntington’s Disease (aka Huntington’s Chorea) • Autosomal Dominant • Onset of disease usually late 40s – early 50s • Insidious onset: chorea & cognitive loss • Amyotrophic Lateral Sclerosis (ALS) • Progressive degeneration of motor neurons • Fine coordination  gross movement  breathing • 2 – 6 year average lifespan after dx

More Related