Transcript for:
Seizures and Neurodegenerative Disorders Overview

Seizures P: Sudden excessive, uncontrolled discharge of neurons in the brain • Potential causes: idiopathic, PTSD, hypoglycemia, drug withdrawal, febrile, tumor, electrolyte imbalances, state of alkalosis, possibly family history; triggers (bright flashing lights, loud noises, stress) • Several types that are classified by where they occur in the brain A: **need to monitor “ABCs” during seizure as can lead to hypoxia; LOC; VS, labs o Respirations are affected; airway has risk of being obstructed due to tongue, or even saliva o Increased demand of O2 during seizure o Acidosis possible due to increased CO2 and lactic acid in the body T: EEG, MRI (to detect structural abnormalities) T: maintaining seizure precautions, provide a quiet, dim room, assess vital signs and electrolytes; during seizure- roll pt on their side, do NOT put anything in their mouth, administer ordered medications, TIME THE SEIZURE and note how the pt is presenting/what type of seizure they are having; if seizures are persisting, contact MD ASAP • Benzodiazepines (module 10) can be used for seizures as well • Anticonvulsant (aka antiepileptic) meds: Phenytoin, Phenobarbital, Levetiracetam, Pregabalin, Valproic acid, etc. E: Educate on seizure precautions (see picture); educate on compliance with medications; educate on identifying possible triggers and how to avoid them; educate to keep a journal on seizure activity; safety! Generalized: multiple origins in deep structures of both cerebral hemispheres and the brain stem; causes loss of consciousness • Partial: single origin, often in the cerebral cortex; may or may not involve altered consciousness Types of Seizures Myoclonic Generalized • Muscle jerking movements that last about 1-2 seconds Tonic-Clonic (grand-mal) Generalized • Tonic: strong muscle contraction and flexion, followed by limb extension and rigidity • Clonic: repetitive muscle jerking movements of whole body lasting about 1-2 minutes • Prodromal, aura, post ictal phases Atonic Generalized • Sudden stiffness of limbs leading patient to fall Absence (Petit mal) Generalized • Brief loss of awareness; “spacing out”, “staring into space” usually do not realize it; may have facial twitching Simple partial (focal) • Repeated motor activity o Jerking, turning head; tingling in a limb • Remain conscious, reduced awareness • May experience auditory/visual experiences (tinnitus) Complex partial • Bizarre behavior that may be repetitive o Clapping or waving hands o Hallucinating ▪ May have “déjà vu” sensations • Unresponsive to people/activities and usually amnesic/drowsy postictal Epilepsy • Chronic disorder of recurrent pattern of seizures o Syndrome of CNS dysfunction • Most common chronic neurologic illness • Results from excessive electrical activity of neurons located in superficial area of brain (gray matter) • Therapy goals: controlling seizures, avoid side effects from medication, maintain or restore quality of life Antiepileptic meds (anticonvulsants) • Ex: Phenytoin, phenobarbital, carbamazepine, primidone, valproic acid, ethosuximide, levetiracetam, lamotrigine, topiramate, etc. o Sub-classes ▪ Barbiturates, Hydantoins, Iminostilbenes, Valproate, Second- and third-generation antiepileptics • Goal is to control or prevent seizures • Not recommended after only one seizure episode • May also be used for migraines, psychiatric disorders, neuropathy • Start with one medication until max dose before adding additional • Maintain serum drug levels (not indicated for levetiracetam or lamotrigine) • Primidone gets metabolized into phenobarbital in the liver • Common adverse effects: suicidal thoughts o Phenytoin- gingival hyperplasia • Precautions for IV Phenytoin administration o Very irritating to veins, Slow IV directly into a large vein through a large-gauge (20-gauge or larger) venous catheter, diluted in normal saline (NS) for IV infusion, Filter must be used, Saline flush, Numerous IV incompatibilities • Interventions: head-to-toe, VS, weight, labs (liver function, CBC), drug allergies, do not crush/chew/open ER meds Phenobarbital- Barbiturate MOA Uses Adverse effects Contraindications Notes • Potentiates effects of GABA* • Seizure prophylaxis • Epilepsy • Sedation, sleep promotion • PO and IV • Therapeutic effects seen at serum drug levels of 10- 40mcg/mL • Long half-life • 20-320mg/day • Sedation • Paradoxical restlessness • GI upset • Learning impairments • Potential birth defects (regardless of if mother was taking med during pregnancy) • Physical dependence • Allergy • Porphyria • Pregnancy • Liver or renal impairment • Respiratory infection • Interacts with alcohol by enhancing CNS suppression • Altered CYP450 enzyme metabolism in liver and decrease effects of beta blockers, steroids, calcium channel blockers, metronidazole • Can interact with Ca and Vitamin D Phenytoin- Hydantoins MOA Uses Adverse effects Contraindications Notes • Selective inhibition of sodium channels and suppresses impulses • Partial seizures • Tonic-clonic seizures • Potential use for arrythmias • IV, PO (chewable, oral suspension, extended release) • Therapeutic level of 10-20 mcg/mL • 300-400mg/day • Mild sedation • Nystagmus • Cardiac arrythmias and hypotension with IV admin (inject SLOW) • Suicidal thoughts • Thrombocytopenia • Purple hand syndrome (rare) • Gingival hyperplasia • Stevens- Johnson syndrome • Pregnancy • Heart blocks • Interacts with amiodarone, benzodiazepines, PPIs, sulfonamide antibiotics • Interacts with alcohol • Interacts with St John’s wort • Most prescribed drug for seizures • May increase glucose levels (inhibits insulin release) • Monitor oral health closely • Regular lab work to monitor drug levels • Long term use can cause acne, hirsutism, osteoporosis Valproic Acid- Valproate MOA Uses Adverse effects Contraindications Notes • Selective inhibition of sodium channels and suppresses impulses • Suppresses Ca influx through T- type Ca channels • Augments the inhibitory influence of GABA • Epilepsy • Generalized seizures • Bipolar disorder • Migraines • PO • IV • Dizziness • Drowsiness • GI upset • Weight gain • Hepatotoxicity • Pancreatitis • Hepatic impairment • Pregnancy • Pancreatitis • NOT to be given with milk or carbonated drinks (may cause drug to be dissolved too quickly) Levetiracetam- Pyrrolidine MOA Uses Adverse effects Contraindications Notes • Unknown? • Partial seizures • PO, IV • Rapid PO onset • Half-life 12- 59hrs • 500 mg BID to 3000 mg/day • Therapeutic level 12- 46mcg/mL • Dizziness • Drowsiness • Hyperactivity • Hostility • Suicidal ideation • Anxiety • Potential for excessive CNS depression with use of other sedating drugs • Do not need routine serum level monitoring Pregabalin- GABA analogue MOA Uses Adverse effects Contraindications Notes • Binds to alpha2-delta receptor sites which affects Ca channels in CNS • Partial seizures • Neuropathic pain • Postherpetic neuralgia • Fibromyalgia • PO • Dizziness • Drowsiness • Peripheral edema • Blurred vision • Drug allergy • Schedule V controlled substance • Do not need routine serum level monitoring Diazepam- Benzodiazepine MOA Uses Adverse effects Contraindications Notes • inhibits stimulation of the brain • Anxiety • Sedation • Anticonvulsant • Skeletal muscle relaxation • PO, IV, rectal • Headache • Drowsiness • Paradoxical excitement or nervousness • Dizziness or vertigo • Cognitive impairment • Lethargy • Drug allergy • Narrow-angle glaucoma • Pregnancy • Do NOT take with ETOH, CNS depressants • Interacts with herbal supplements kava, valerian • Interacts with grapefruit • High risk for falls, confusion • Rebound insomnia with withdrawal • Reversal agent: Flumazenil Benzodiazepines • Ex: Diazepam, Lorazepam, Midazolam, Clonazepam, Alprazolam, Zolpidem, etc. • Used for sedation, anxiety, seizure, agitation, anesthesia, ETOH withdrawal • BBW: risk for abuse, physical dependence • MOA: inhibits stimulation of the brain o Works in hypothalamus, the thalamic and limbic systems • Reversal agent: Flumazenil Parkinson’s Disease P: Chronic, progressive, neurodegenerative disorder • 2nd most common neuro disease after Alzheimer’s • Caused by an imbalance of two neurotransmitters: Dopamine and Acetylcholine (ACh) o Balance of these are necessary • Affects dopamine-producing neurons in the brain o Ultimately affects Extrapyramidal system (made up from substantia nigra, basal ganglia, globus pallidus) ▪ This system involves motor function, posture, muscle tone, smooth muscle activity L: bradykinesia, postural instability, rigidity, tremors, shuffled gait T: symptom assessment; r/o of other conditions T: PT/OT/ST; *physical activity*; drug therapy Carbidopa-Levodopa- Dopaminergic MOA Uses Adverse effects Contraindications Notes • Carbidopa: inhibits decarboxylation of levodopa in the intestine and tissues to make levodopa more available in CNS • Stimulate presynaptic dopamine receptors to increase levels • Parkinson’s Disease • PO (do NOT crush) • Immediate release, extended capsule, extended suspension • Cardiac arrhythmias • Hypotension • Chorea • Muscle cramps • GI upset • Angle-closure glaucoma and open-angle glaucoma • Undiagnosed skin condition (due to potential activation of malignant melanoma) • Interferes with pyridoxine and dietary protein; tricyclic antidepressants • Carbidopa cannot cross BBB • Levodopa is precursor to Dopamine • Large levels of Levodopa are required to obtain therapeutic effect (which leads to more adverse effects) “Carbidopa is the car that drops off levodopa in the brain” Amantadine- Dopamine Agonist (also an Antiviral) MOA Uses Adverse effects Contraindications Notes • Releases dopamine and catecholamines from presynaptic fiber storage in basal ganglia • Blocks reuptake of dopamine into nerve fibers • Influenza • Mild-moderate Parkinson’s • PO • Dizziness • Insomnia • nausea • Drug allergy • Interacts with anticholinergics • Monitor for s/s infection • May need to monitor CBC Pramipexole- Dopamine Agonist MOA Uses Adverse effects Contraindications Notes • Stimulates dopamine receptors at striatum of brain • Parkinson’s • Restless leg syndrome • Dizziness • Hallucinations • Weakness • Hypotension • Abnormal dreams • Constipation • Extrapyramidal syndrome • Pregnancy • Renal impairment • Breastfeeding • Monitor for patient safety due to risk of weakness, hallucinations • Monitor for orthostatic hypotension Entacapone- Catechol Ortho-Methyltransferase Inhibitor MOA Uses Adverse effects Contraindications Notes • Block COMT, the enzyme that catalyzes the breakdown of the body’s catecholamines, presynaptically • Parkinson’s • Helps to decrease wearing off effects from Levodopa • PO • Quick onset • GI upset • Urine discoloration • Can worsen dyskinesia • Hallucinations • Somnolence • Do NOT take with MAOIs (increases cardiac event risk) • Taken with Levodopa Selegiline- Monoamine Oxidase Inhibitors (MAOI) MOA Uses Adverse effects Contraindications Notes • Inhibits monoamine oxidase type B to keep dopamine present in brain • Parkinson’s • May be used with depression • Insomnia • Hypertensive crises in higher doses • Increased suicidal thoughts • Drug allergy • Interacts with Meperidine, Abatacept • Avoid foods with tyramine if dose is >10mg/day • Used as monotherapy or used as adjuncts with levodopa