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Neuro Meds

Pharmacology: Neurological Agents

TermDefinition
Memory Impairment AND one of the following Aphasia (can’t think of the word), apraxia (don’t recognize feel of holding something), agnosia (don’t recognize something), or impaired executive functioning (24/7)
Neuritic plaques extracellular - abnormal insoluble amyloid protein fragments
Neurofibrillary tangles intracellular - disturbed tau-microtubule complexes (hyperphosphorylated tau)
3 Pathophysiological mechanisms of Alzheimers 1) Neuritic plaques 2) Neurofibrillary tangles 3) Cholinergic system degeneration (with loss of neurons beginning in enterorhinal cortex progressing to other limbic structures.
Describe neurofibrillary tangle process Tau proteins (usually stabilize microtubules) undergo abnormal chemical changes becoming helical -> creating tangles that disrupt cell functions -> cell death
What one problem warrants the most attention in Alzheimers initially? What others? Depression can lead to self harm (SSRI/tricyclics) Psychosis, emotional lability (happy to crying in minutes; divalproex), agitation (can't sedate)
Idea, and Tx approach of the Cholinergic Hypothesis Cholinergic deficiency contributes to cognitive decline in Alzheimers. Tx: acetycholinersterase inhibitors. (allowing more Ach to be retained.
Part of brain depleted of Ach-containing neurons in Alzheimers Basal nucleus of Meyner (basal forebrain)
Does anticholinesterase therapy interrupt the disease process? Why? No, but it can delay need for nursing home placement for up to 12 months
Tacrine Ach inhibitor, dosed 4x/day; associated w/hepatotoxicity; adverse GI effects alleviated w/food intake; LFTs and monitoring required; no longer marketed
Donepezil good starter of Ach inhibitors; dosed 1x/day; higher doses associated w/ cholinergic side effects (too much Ach in body). Maintained up to 50 weeks. Adverse: N/V diarrhea.
Rivastigmine tolerated better than Donepezil; not metabolized by cytochrome P450; GI adverse common but avoided w/ time-release patch. Food avoids adverse: Best if you eat, take, eat more.
Galantamine: What it is/improves, MOA, Adverse, Use Alzheimers cognition, behavior, fn. MOA: 1) Competitive inhibition of acetylcholinesterase 2) allosteric binding to nicotinic receptors to increase Ach sensitivity. Adverse: Enhance heart block, transient nausea. Used when less response to Donepezil
4 Counseling points for all Anticholinesterase agents 1) does not stop or cure disease 2) stabilizes/slows cognition decline for 6-12 months 3) May improve independence/self care 4) Adverse: GI, HA, Bradycardia
Glutamate: what it is, dementia hypothesis principal excitatory NT in brain regions associated with cognition and memory (i.e. it stimulates cholinergic neurons). In dementia: overactivation of neurons -> excitatoxic damage to brain areas (allow Ca2+ to continously leak in -> cell death
T/F Excess glutamate causes problems of dementia F: excitable cells cause the problem, not the glutamate...no way to down-regulate it so we still attack glutamate release
Memantine: what is it? MOA? Use? noncompetitive NMDA (glutamate) receptor antagonist has a moderate effect on preventing glutamate release (preventing excitotoxic rxns and cell death). Slows decline in overall fn and ADLs. Used as adjunctive Tx w/Ach inhibitors.
Memantine: Dosing? Elimination? Adverse? Gradually increase dose over several weeks. Renal elimination. Adverse: agitation, diarrhea, insomnia, hallucinations. D/C prior to surgery: effects anesthetics.
Beta Secretase Inhibitors: MOA? Use? Inhibit cleavage of amyloid precursor protein -> preventing amyloid accumulation -> preventing Alzheimers neuritic plaques from forming -> preventing degenerative changes in the brain. None on the market yet. Work in animal studies.
Reversal strategy: Vaccination Strategy AN-1792 vaccine was in testing. This is an amyloid B protein fragment which can induce antibodies that bind to plaques and activate microglial destruction process. Trial halted due to CNS inflammation and dysfunction (menigoencephalopathies)
Tramiprosate: MOA? binds to soluble amyloid-beta peptide (Abeta) and inhibits the formation of neurotoxic aggregates that lead to amyloid plaque deposition in the brain prevents Amyloid B fragments from forming fibrils. Reversal Strategy for AD
Clioquinol: MOA? A metal-protein-attenuating compound (MPAC) that inhibits zinc and copper ions from binding to beta-amyloid, helping to dissolve it and prevent it from accumulating. Reversal strategy for AD
Vitamin E shown to slow progression at similar rate to monoamine oxidase inhibitors (still minimal effect). Study: No difference from placebo in preventing progression from mild impairment -> AD over 3 years. Works better with Vit C. May be benefit w/ A, E, C.
Estrogen Hormone replacement therapy (HRT) is questionably effective in slowing the onset of AD in some women. Tacrine may be enhanced by estrogen, not shown w/Ach inhibitors
Statins May prevent aggregation of beta-amyloid in the brain by preventing cholesterol build up. Some slowing of amyloid build-up short term (6 months). Bottom line – Mechanism is not clear but some studies showed slowing of progression
Name of study prematurely terminated due sterile meningoencephalitis in 18/300 receiving AN1792? Elan Phase II clinical trial for active immunization
Long-term follow up on Elan Phase II clinical trial active immunization results? Those that succeeded in creating anti-AN1792 antibodies had less decreases in whole brain volume, ventricular enlargement, slower rates of cognitive and functional decline, reduced Tau protein concentration in CSF.
Passive Immunization: Bapineuzumab humanized monoclonal antibody to N-terminus of B amyloid in phase III development
Passive Immunization Monoclonal antibodies in development are designed to target 1 of 3 domains of the β amyloid protein: the n-terminus, the middle portion, or the c-terminus. Similar to inflammatory disease like Crohn’s. Antibodies against amyloids that will destroy them.
Managing anxiety in dementia Don't ignore. Distract, simplify environment, use meds as short term as possible as early as possible, Benzodiazepine discouraged, Trazodone effective agent for anxiety/insomnia
Antipsychotic agents Effective for acute aggressive episodes, benefits seen for delusions/hallucinations, bedtime dose (orthostatic hypo common) Adverse: ^ risk of stroke, weight gain, increased mortality. Never first-line, lowest amount for shortest time possible.
Depression and Alzheimer's 40-50% incidence early in illness. SSRIs first-line. ECT can be helpful for depression but harmful for cognition. Allow pt choices/control; ID pleasurable activities. Cognitive enhancers may help.
Tx of Insomnia Sleep hygiene, Tx psych/medical disorders, melatonin/warm milk/lavendar, meds (benedryl, benzos), light therapy
3 components of full anesthesia 1) analgesia (pain relief) 2) amnesia (loss of memory) 3) Immobilization (lack of response to external stimuli)
Local anesthetics produce loss of sensation to pain and, depending on dose and route, mobility in a specific area of the body w/o loss of consciousness. Require adequate pain control when local wears off
Cocaine comes from leaves of a plant of genus Erythroxylum called coca -> isolated active alkaloid naming it cocaine. Many champions of cocaine became addicted to it.
Karl Koller ophthalmologist used cocaine as a local on mucous membranes and eye
"Bier block" IV regional anesthesia for use in extremity. Tourniquet around the shoulder -> inject into arm -> hold arm up for distribution of anesthesia -> regiional anesthesia. Created in 1898.
Coca cola Kola nut and cocaine used to cure morphine/opium addiction. Caffeine enhanced cocaines potency. Decocainized leaves implemented in 1906
MOA of anesthetics Block influx of Na through fast channels: wide ranging effects on entire body, decreasing rate of depolarization and repolarization of excitable membranes. Nerves unable to generate action potential/carry a signal. Shuts down neurons, takes time.
Procaine Novacaine; first synthetic local anesthetic. Blocks Na channels like cocaine but doesn't release NTs. Not as potent as cocaine, took too long to set, wore off quickly.
Lidocaine Xylocaine; causes minimal allergenic rxn. Sets quickly, produces desirable level of anesthesia for several hours. We can predict fairly accurately how long it will last. Local DOC in US.
Anesthetic classes: AmIdes Fewer allergies; LIdocaine, BupIvacaine, MepIvacaine, PrIlocaine; toxicity is dose related and may be delayed by minutes or even hours from time of dose.
Anesthetic classes: Esters More allergies; Procaine, Chloroprocaine, Tetracaine, Benzocaine, Cocaine. Toxicity is dose related, allergy related to PABA (sunscreen ingredient)
Environmental factors affecting Local anesthetics: Lipid solubility MOA Increasing the lipid solubility by preventing ionization leads to faster nerve penetration, blockade of sodium channels, and increased speed of onset. Cross nerve bases when they are not ionized, more slowly when ionized.
Environmental factors affecting Local anesthetics: pH influence MOA Locals are weak bases. Decrease in pH shifts equilibrium toward the ionized form, delaying the onset action. Infx/necrosis are more acidic, slowing onset. Mixing bicarb solution promotes rapid onset for intact and traumatized tissue.
Easier blocked: Small diameter nerves or big? Myelinated or unmyelinated? Smaller nerves and myelinated nerves are blocked easier.
T/F: Nerves that are firing frequently will be preferentially blocked. True, Nerves that may be inflammed or injured will be blocked first. Ex: finger that is burned will be blocked faster and more effectively than another finger that isn't burned.
Effects of vasodilation/constriction on local anesthetics Vasodilation speeds movement of the local anesthetic away from tissues at the site of action, therefore vasoconstrictors are combined with many anesthetics to prolong action of drug; chiefly epinephrine.
CNS Toxicity Most commonly Lidocaine; Tinnitus, dizziness, lightheadedness -> anxiety -> disorientation -> loss of consciousness -> seizures -> respiratory arrest
Cardiac Toxicity Most commonly Bupivacaine; Hypotension, rhythmic disturbances manifested by multifocal VT -> V Fib or bradycardia -> asystole
Treatment of local anesthetic toxicity 1) Airway- 100% O2, low threshold for intubation. 2) CNS- break seizure w/benzodiazepine. 3) Cardiovascular- amiodarone for arrythmias (not lidocaine---would exacerbate obviously); resuscitation is difficult w/bupivacaine toxicity
T/F: Muscle relaxants are considered safe during pregnancy and lactation. F: NO! None of them are considered safe during pregnancy.
Muscle spasm sudden, involuntary muscle contraction. Occurs with musculoskeletal trauma. Spasms may be tonic (sustained) or clonic (alternating) (muscle or peripheral nerve issue)
Spasticity increased muscle tone or contraction, stiff, awkward movements. Caused by nerve damage in spinal cord and brain
Diazepam: Use, MOA, Effects, Adverse Benzodiazepine; massive muscle spasms MOA: enhance GABAa activity. Effects: decreased resistance to passive ROM & hyperreflexia, reduced painful spasms, sedation, reduced anxiety. Adverse: sig. cognitive impairment, dependency, withdrawal, tolerance.
Lioresal MOA: GABAb agonist. Effects: eases resistance to passive ROM, hyperreflexia, painful spasms, anxiety. Adverse: weakness, sedation, hypotonia, ataxia, liver toxicity, "flaccid", withdrawal.
Intrathecal Administration: One time dose? Long term administration? One time: spinal tap to administer. Long term: insert intrathecal catheter w/pump implanted under the abdominal skin
Dantrolene Sodium: Use, MOA, Effects, Adverse Minimal use; Used for spasticity and minimal use for muscle spasms/low back pain; MOA: reduces Ca2+ release from SR, uncoupling excitation/contraction of muscle. Effects: Lowers resistance to passive ROM/hyperreflexia etc. Adverse: liver toxicity
Tizanidine and Clonidine: Use, MOA, Effects, Adverse Use: cuts down on episodic spasms. MOA: alpha-2 adrenergic receptor agonist. Effects: reduced tone, contraction and hyperreflexia. Adverse: drowsiness, dizziness, orthostatic hypotension, rebound hypertension w/rapid withdrawal.
Cyclobenzaprine: Use/MOA, Adverse Use/MOA: firstline; acts on alpha motor neurons in spinal cord to suppress spinal reflexes & have mild analgesic effects. Adverse: drowsiness, blurred vision, dry mouth, QT prolongation, serotonin syndrome. Nighttime- medication. Not effective spastic Tx
Metaxalone Use/MOA: 2nd line; thought to reduce skeletal muscle spasm though CNS depression but exact mechanism unknown. DOC in elderly. Adverse: RARE: N/V, drowsiness, nervousness, HA, CONTRA w/impaired liver fn; not as sedating as cyclobenzaprine but as relaxing
T/F: always give pain meds w/complete skeletal muscle relaxants. T/F: complete skeletal muscle relaxants pass through the BBB and placenta. T/F: Complete skeletal muscle relaxants administered IV. T: always give pain meds, pts can still feel. F: relaxants DON'T pass through BBB or placenta. T: these are given IV; too large to be given orally.
Non-depolarizing agents Rocuronium, vecuronium: Use: neuromuscular blocking agents MOA: affinity for nicotinic (neuromuscular) receptors and block out Ach, which can overwhelm it w/ numbers. Does not depolarize, just prevents Ach from doing so.
Succinylcholine: Use/MOA Use/MOA: a depolarizing blockade of Ach from the motor end plate, causing twitching and fasciculation, not rapidly dissociated w/ receptors -> adverse effects. Causes "sub-maximal intrinsic activity" at neuromuscular receptors.
Succinycholine: Adverse Adverse: muscle pain, hyperkalemia -> malignant hyperthermia, hyperstimulation -> inactivation (overstimulated receptors) of sodium channels -> paralysis. Anywhere Ach effects, Succinylcholine will effect -> increased or decreased BP & HR esp in child
Parkinson's Disease (PD) a neurodegenerative disorder affecting the basal ganglia and is associated with loss of dopaminergic neurons in the substantia nigra and degeneration of nerve terminals in the striate nucleus
Parkinson's Syndrome an adverse effect of medications (particularly antipsychotic agents) arising from d2-receptor blockade in the basal ganglia
Parkinson's Disease: MOA MPTP -> MPP+ in glial cell -> MPP+ into cell w/enhanced dopamine transporter -> inhibits oxidative metabolism in mitochondria -> cell death
Levodopa (L-DOPA): Use, MOA Use: first-line in PD, 80% improve rigiditiy & hypokinesia (not cognitive decline or dysphagia. MOA: crosses BBB easily where it converts to dopamine.
Carbidopa DOPA decarboxylase inhibitor that doesn't cross the BBB preventing LDOPA from having peripheral effects.
Levodopa (L-DOPA): Adverse Adverse: some LDOPA metabolized peripherally w/effects -> give w/ carbidopa; dyskinesia (involuntary writhing), On-off effect (hypokinesia and rigidity worsen than improve), nausea, hypotension, Schizophrenia-like syndrome, loss of impulse control.
Monoamine Oxidase - B Inhibitors (MAO-B inhibitors): Selegiline & Rasagiline: MOA 2ndary Txs; prolong life of dopamine (prevents MAO-B from breaking dopamine down). Adverse: Hypertensive crisis, cardiac arrhythmias at high doses, compulsive behaviors (these all higher when combined w/ LDOPA)
Rasagiline: Use, Adverse irreversible MAO-B inhibitor allowing L-DOPA to last longer. More selective than selegiline, amount of "off" time significantly reduced. Adverse: less effects but still has potential for hypertensive crisis, no amphetamine-like effects.
Bromocriptine Mesylate D1,D2 agonist - relatively nonspecific (can be used in pregnant women with Parkinson’s that aren’t breast feeding to prevent that physiology). Delays need for L-DOPA therapy in young for a while. Adverse: impulse loss, N/V, orthostatic hypo, nightmares
Entacapone, tolcapone (Catechol-O-Methyltransferase [COMT] Inhibitors) impede peripheral metabolism of L-DOPA decreasing metabolism of drug (making it last longer). Adverse: exacerbates L-DOPA adverse, rhabdomyolysis; Tolca: fulminant hepatic failure (BLACK BOX WARNING)
Rhabdomyolysis break down of muscle fibers (causing renal effects)
Amantadine Mechanism unknown but thought to block dopamine reuptake/stimulate release of dopamine from substantia nigra. Slow onset. Adverse: hallucinations, nightmares, livedo reticularis, N, CNS sx, peripheral edema, bad in renal failure pts; good in hepatic pts
Livedo Reticularis red/purple lace pattern on skin, particularly lower extremities. Caused by uncontrolled capillary dilation. Can occur w/use of Parkinson's med: Amantadine.
Trihexyphenidyl HCl, Benztropine Mesylate: Category, Use/MOA, Adverse Anticholinergics; Use/MOA: old predopaminergic therapy limiting Ach. Most effective for reducing tremor by controlling Ach. May inhibit dopamine reuptake. Adverse: atropine-like effects.
Multiple Sclerosis (MS) Progressive autoimmune disease where body attacks and destroys myelin. If damage is severe enough, nerve can also be destroyed. MOA: Inflammatory plaques in white matter of CNS, blocking impulses. "Disease of time and space"
Tx and management for MS 1) Drug therapy that treat exacerbations and slow or prevent disease progression. 2) Physical therapy 3) Psychosocial support
Glatiramer acetate: Use, MOA, Adverse Combo of synthetic polypeptides containing amino acids, mimicking myelin basic protein. MOA: unknown but thought to act as an alt. susbstrate for T-Cells activated to destroy myelin. Also suppresses T-Cell activation. Injection site effects common.
Beta interferon: Use/MOA, Adverse Reduces frequency of exacerbations and improves measures of disease activity in brain. MOA: Immunomodulation, increasing NK cell cytotoxicity, macrophage activity, decrease production of gamma interferon (key compound in MS Sx). Takes 72 hrs to recover.
Natalizumab: Use/MOA, Adverse monoclonal antibody product for MS interfering w/leukocyte adhesion/passage through BBB (also used in Crohn's). Adverse: multifocal encephalopathy: rare/fatal CNS viral infx (left/returned to market), fatigue, allergic rxn
Dalfampridine: Use/MOA, Adverse Use/MOA: K+ channel blockade to improve walking in pts w/ MS (increase fn of skeletal muscles). Adverse: crosses into CNS causing effects: insomnia, dizziness, HA, burn/tingle/itch of skin, balance disorders, nausea, C&D
Mitoxantrone: Use/MOA, Adverse Use/MOA: chemo agent disrupting DNA synthesis and repair used to slow secondary progressive MS. Adverse: cardiotoxic, pts develop HF during Tx or months-years after completion so cardiac assessment pivotal; reevaluation of LV fn.
Fingolimod: Use/MOA, Adverse Use/MOA: blocks egression of lymphocytes from lymph nodes into circulation/CNS reducing lesions on brain MRI. Adverse: ^ liver enzymes, initial major reduction of HR common (some deaths occurred). If HR drops, admit and monitor for 72 hrs
Cladribine: Use/MOA, Adverse Use/MOA: last line for MS, lymphocyte depleting properties also used in leukemia Tx, disrupts cellular metabolism inhibiting DNA repair ->cell death. Suppresses lesions/plaques after receiving it for 12 months. Adverse: lymphopenia, nephrotoxicity.
Teriflunomide: Use/MOA, Adverse Use/MOA: inhibits activation/proliferation of T/B cells in CNS significantly reducing number of active new lesions on brain MRI. Adverse: Well tolerated, URI and HA most common effects. Also treats RA. "Changes immune system from pro->anti inflammatory"
Dimethyl Fumarate: Use/MOA, Adverse Best long term; suppresses inflammation (decreases production of cytokines and helper-T cells) and globally lowers oxidative stress responses lowering lesions by 69% vs placebo. Favorable safety profile. Adverse: minimal: liver enzymes transiently up.
Myasthenia Gravis autoimmune disease characterized by antibodies attacking and destroying Ach receptors. Since there are fewer receptors, end plate potentials (EPPs) are smaller. Less chance post-synaptic fibers will be activated.
Myasthenia Gravis Tx 1) Immunosuppressants: Steroids at first, azathioprine/cyclosporine. 2) Plasmaphaeresis/IV Immunoglobulin combo can give rapid improvement lasting weeks. 3) Thymectomy- won't get full response, but def improvement. 4) anticholinesterasae drugs
Important part of Rx: Anticholinesterase: Use, Adverse Pyridostigmine; need varies day to day; Adverse: Excessive use -> cholinergic crisis (all effects of overstimulation of Ach: salivation, lacrimation, urination, defecation, bronchospasm etc) Tx of crisis: Atropine/mechanical ventilation.
Prednisone: Use, Effects marked improvement or complete relief of Sx occurs in 75%, but there is a time lag. Improvement in 6 weeks, but total remission possible over months. Thymoma pts have excellent response before or after thymectomy. Not long term tx.
Steroid use in pregnant patients Prednisone has minimal placental transfer and is DOC. Dexamethasone and betamethasone DO cross placenta. Adverse: increased risk of oral cleft.
Inhibition of hypothalmic-pituitary-adrenal axis If you stop prednisone abruptly, pts won't have any cortisol and will show signs of Addison's
Extra-pyramidal area of brain Basal Ganglia
8 Factors precipitating seizures 1) hyperventilation 2) electrolyte changes 3) sleep deprivations 4) sensory stimuli 5) hypoglycemia 6) stress 7) hormonal changes 8) trauma
GABA Opening chloride or potassium channels for inhibitory effect lowering any magnitude of response if stimulation were to occur.
Glutamate Opening sodium or calcium channels for excitatory effect increasing magnitude of response to stimulation.
Process of emergent Tx of seizures lasting more than 5 min 1) protect patient and airway 2) start IV infusion giving glucose and thiamine. 3) start lorazepam (ativan).
What severe adverse risk do AEDs increase? Suicidal ideation or behavior; they should all be monitored for this.
Phenytoin: Use/MOA, Non-seizure use first line for partial and generalized (except absence and myoclonic), including s. epilepticus. MOA: stabilizes Na channels in the resting state reducing propagation of impulses. (ALSO A CARDIAC ANTIARRTHYMIC (Class 1B)
Myoclonic seizures sudden, brief muscle contractions that may involve one part or entire body. Isolated or rapidly repetitive.
Atonic seizures sudden loss of muscle tone, short loss of consciousness. Often present as head drop, limb drop, or slumping to ground. May require protective head gear.
Phenytoin: Characteristics Slow oral absorption, ^protein bound allowing 1 dose. Logarithmic pharmacokinetics.
Logarithmic pharmacokinetics small increases in dose can result in large increases in plasma concentrations (toxic levels) Ex: if you double dose, will have strong adverse quickly
Phenytoin: Adverse Concentration related: 1) Nystagmus 2) ataxia 3) lethargy 4) cog. impairment. Chronic effects: gingival hyperplasia, hirsutism. Route: bradycardia, hypoten; P450: induce phen metabolism: Carbamezapine. Inhibit: Cimetidine.
Fosphenytoin: General/Use Prodrug of phenytoin; fewer admin effects, given faster and IM w/ less hypotension
Carbamazepine: Use, MOA, Interactions, Adverse First line for tonic-clonic & partial. MOA: sodium channel blocker. INDUCES OWN METABOLISM. ^ metabolism of oral contraceptives. Diplopia/blurred vision, fatigue, vertigo, lowers bone marrow
Oxcarbazepine: Use prodrug of carba. Improves mood/reduces anxiety. Na channel blocker, less drug interactions/P450 issues is why you'd use it over carbamezapine.
Eslicarbazepine Acetate: Use/MOA Adverse Novel antiseizure medication that shares with carbamazepine and oxcarbazepine the dibenzazepine nucleus. Better efficacy with less toxicity than carbamazepine. Impedes repeated neural firing, works best on hyperactive neurons. Heart block gets a bit worse
Valproic Acid (Valproate): Use/MOA, Adverse first line option for all types. MOA: Blocks T-type calcium currents (drops glutamate release!), blocks sodium channels, increases GABA production. Rapid onset. Alopecia, Wt gain, hepatotoxicity. Minimal long term effects.
Valproic Acid Monitoring CBC, Wt, Lipids (TG ^, LDL and HDL decrease), monitor liver enzymes. Don't know exact therapeutic levels best within range.
Phenobarbital: Use/MOA, Adverse, Interactions WHO drug of choice for seizures in developing world, DOC for neonates worldwide. Enhances GABAa activity, glucose/O2 use decreased in brain. Sedative and has P450/oral contraceptives interactions. Tolerance built until resp depr. Strong cog. depression.
Ethosuximide: Use/MOA, Adverse, Interactions. First line for Absence. Poorly understood but thought to block T-type calcium currents. Metabolism induced by carbamazepine. Hyperactivity and variable somnolence. Compliance an issue.
Felbamate: Use/MOA, Adverse, Interactions Only for refractory epilepsy. Poorly understood but thought to bind GABA receptors and stabilize neurons. Major P450 interacdtions and interactions w/ carbamazepine, phenytoin, phenobarb. Major adverse: hepatic failure, aplastic anemia.
Gabapentin: General/MOA, Adverse GABA analog; binds to voltage dependent Ca channels and stabilizes neurons. Approved for partial seizures and neuropathic pain. Adverse effects: dose dependent: dizziness, somnolence, edema, cog depression.
Pregabalin: Use/MOA, Adverse Adjunctive therapy for partial seizures, neuropathic pain, fibromyalgia; binds to voltage dependent Ca channels stabilizing neuron. Adverse: dependency (makes you feel euphoric), blurred vision.
Lamotrigine: Use/MOA, Contraceptive use Inhibition of Na channels to stabilize neuron. Dose depends on other meds (several interactions). Must adjust dose when you come off oral contraceptives because the effects of Lamotrigine can dramatically increase to toxic levels if you don't.
Lamotrigine: Adverse HA, dizziness, myoclonic epilepsy. 10% develop benign rash -> Stevens-Johnson or TEN possible. Muscle aches and fatigue.
Levetiracetam: Use/MOA, Interactions, Adverse Keppra; thought to bind to a synaptic protein and interfere/slow conduction. NO significant drug reactions. Adjust dose in renal dysfunction. Adverse effects: Stronger effect on psych and emotions than other drugs; paresthesias.
Tiagabine: Use/MOA, Interactions, Adverse partial seizures; blocks GABA re-uptake permitting higher concentration and enhancing inhibitory activity. No P450 isoenzyme induction. Take w/ food. Speech impairment, GI issues, cognition retardation.
Topiramate: Use/MOA, Interactions, Adverse Partial, generalized seizures and migraine. Enhances GABA dependent Cl channels. P450 interactions: ^ plasma levels of phenytoin, hepatotoxicity w/valproate. Decreases effect of oral contraceptives. Dull continuous HA, N/V/D, renal stones.
Zonisamide: Use/MOA, Adverse partial seizures; thought to block Na channels/inhibit Ca flow. Beneficial in Parkinsonian tremor. Adverse: Carboonic anhydrase inhibitor: metabolic acidosis & nephrolithiasis. Sulfa drug, can cause Stevens-Johnson Syndrome, TEN, others.
Rufinamide: Use/MOA, Adverse seizures in Lennaux-Gastauat Syndrome; thought to block Na channels prolonging inactivity. Renal excretion after hepatic conjugation. Adverse: hypersensitivity rxns, QT shortening (potential risk for VTach -> VFib), depression/suicidal ideation.
Lennaux-Gastaut Syndrome onset before age 6, frequent seizures and different seizure types; frequently associated with mental retardation along with psychological and behavioral issues
Vigabatrin: Use/MOA, Interactions, Adverse refractory partial complex seizures. irreversible inhibitor of gamma-aminobutryic acid transaminase increasing CNS GABA level, renally eliminated. Visual loss/changes: LEADS TO BLINDNESS. Must be an expert and have pt sign consent.
Lacosamide: Use/MOA, Adverse partial seizures; slow activaiton in voltage-gated Na channels. PR prolongation, induce AFib, hypersensitivity rxns
Perampanel: Use/MOA, Adverse partial seizures; AMPA-type gultamate receptor antagonist (lowering glutamate release in brain). Adverse: none serious
When to withdrawal anti-seizure 2-5 years seizure free after neurology consult. Uncomplicated, single type of seizure w/ normal neurologic exam, EEG normal w/ Tx. Always risk of relapse (10-70%)
For NC Gov 6-12 months seizure free w/ some exceptions. Must provide medical updates annually. Exceptions being: 1) change in meds 2) nocturnal seizures 3) no LOC/motor function/appropriate sensation/processing 4) if proceeded w/ aura lasting 2-3 min
Brief Hx of Tx Egyptians: Herbs -> Incas: trepanation -> Arabs: hot iron incision -> Dr. Willis: enemas, blood letting, leeches -> cold bandage on head/quiet room/sleep -> present options
Initial Tx of mild/moderate HA Flurbiprofen/naproxen > aspirin/acetaminophen but acetaminophen/aspirin/caffeine > ibuprofen. Fiorcet GREAT for tension HA
Ergot potent neurotoxin/constrictor to control postpartum bleeding (precursor to LSD) and was preferred for migraine in 1940s. N/V, angina exacerbations. Less effective than triptans, enhanced w/ nicotine/BB
Lack of 5-HT1 receptor stimulation implicated in: vasodilation and vascular HA. (Seratonin controls vasodilation)
Triptans: Use/MOA, CONTRAs Serotonin 1B/1D agonists stimulate to cause CeV constriction. CONTRA: Ischemic HD/angina, HTN, ergot, preg, MAO inhibitor (-> serotonin syndrome). Recurrence 20-40% in 24 hours
Sumatriptan: Use, dosing constricts, first approved for migraines, H/L: 2.5 hours. LARGE first pass metabolism. (200 mg orally/day, 6 mg IV/day)
Zolmitriptan: Use oral tablet w/ improved bioavailability (50%), but second dose has not shown to have appreciable effect
Naratriptan: Use, CONTRA Not as effective as sumatriptan. Bioavailability improved to 60%. Dose can be repeated after 4 hours. CONTRA if creatinine is less than 15mg/ml
Rizatriptan: Use fastest onset, blood levels increased by propranolol
Triptan Adverse sleepiness, chest pain/SOB, rarely severe abdominal pain
Dihydroergotamine (DHE-45): Use less marked arterial constrictive properties, give w/ metroclopramide to prevent nausea
Need for HA prophylaxis? Which are the best? Disabling attacks, frequent attacks, poor tolerance to abortive Tx. BB best (propranolol). CCB can be used as well (Verapamil), antidepressant (don't work as well as BB/CCB), anticonvulsants (suicidal ideations possible). Botox for chronic migraines.
Beta blocking adverse fatigue/exercise intolerance, airway resistance, angina, orthostatic hypotension
Valproic Acid: Use, Adverse Blocks T-type calcium currents, blocks sodium channels, increases GABA production (GABA is a inhibitory/calming neurotransmitter). Adverse: wt gain, alopecia, hepatic failure.
Topiramate: Use, Adverse Carbonic anhydrase inhibitor (also drop CSF produced) that blocks sodium channels and enhances GABA activity. Adverse: paresthesias, cognitive impairment (biggest compliance issue), nephrolithiasis.
Tricyclic anti-depressants: Adverse anticholinergic, antihistamine, NA channel blockade (QRS prolongation, arrhythmias), Alpha blockade; Cardiotoxicity
Tx of Cluster HA 100% O2 for 15 min aborts, ergotamine (can be preventative at bedtime), triptans, intranasal lidocaine, Prophylaxis: Verapamil, prednisone, ERGOTAMINE is the standard as is Valproic acid
Overuse problems -> chronic dull headache
HA warning signs "Worst HA I've ever had", sudden/thunderclap onset, 50 yo+, systemic effects, existing systemic disease, change in chronic HA pattern, neurologic or abnormal physical findings.
Created by: crward88