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What is epilepsy
a nervous system disorder characterized by the repeated occurrence of seizures
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What are seizures
the abnormal, excessive discharges of the brain neurons and changes in the electrical activity in the brain
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What is the Prevalence of Epilepsy in the United States
0.9% or 1 in 200
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What are partial seizures and what are the types
starts in one part of the brain
- –Simple partial seizure (no loss of consciousness) Involuntary movement
- –Complex partial seizure (impairment of consciousness) Appearing spaced out
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what are generalized seizures and what are the types
instant loss of consciousness
- –Febrile seizures
- –Atonic seizures
- –Tonic-clonic seizures (formerly called grand mal)
- –Myoclonic seizures
- –Absence seizures (formerly called petit mal)
- –Clonic seizures
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What is a type of unclassified epileptic seizure
status epilepticus - an emergency situation characterized by continuous, prolonged seizures longer than 20 minutes.
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What are some risk factors for seizures
- Hypoxia (lack of oxygen)
- Birth injury to brain
- Fever
- Alcohol intoxication/withdrawal
- Brain tumors
- Head trauma
- Stroke
- Genetics
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What is the objective of the drug therapy of seizures
Suppress seizures by maintaining an effective concentration of the drug in the blood and brain cells at all times
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What is more effective monotherapy or polytherapy
Monotherapy
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The first antiepileptic drug
Phenobarbital (Luminal)
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What king of drug is Phenobarbital (______)
- Luminal
- It’s a sedative/hypnotic drug
- Use is declining in favor of newer drugs
- It’s a second-line drug in adults with partial and generalized seizures except absence seizures
- decreases excitation on the postsynaptic neuron
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What are some adverse side effects with Phenobarbital
- respiratory depression
- sedation
- abuse
- dizziness
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What first line has the same mechanism of action as phenobarbital
Primidone (Mysoline)
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What is the mechanisms of action of
Phenytoin (Dilantin) and what kind of seizures is it used for
- Blocks sodium channels, preventing sodium from entering brain cells and discharging from neurons
- First-line therapy for partial (both simple and complex) seizures and generalized tonic-clonic seizures
- May be teratogenic (drug-induced damage in fetus)
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What are the adverse effects of Phenytoin
- Narrow therapeutic index – small fluctuations can cause toxicity
- Gingival enlargement, nausea, vomiting, slurred speech
- Many drug interactions including Drug–drug interaction with doxycycline
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Carbamazepine (Tegretol):
- Controls partial and generalized tonic-clonic seizures
- Originally developed for the treatment of trigeminal neuralgia
- Metabolized by the P450 liver cytochromes
- Many drug interactions: Erythromycin, clarithromycin (↑ Carbamazepine)
- Doxycycline (↓ doxycycline)
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What are the adverse effects of Carbamazepine
- Agranulocytosis (decreased white blood cells), platelet decrease, aplastic anemia, bleeding gingiva
- Need medical consult for treatment
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What drug is similar to carbamazepine (Tegretol) but has fewer side effects and what is it used for
Oxcarbazepine (Trileptal):
Monotherapy for partial-mixed epilepsy and refractory partial seizures
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Valproic Acid (_______):
Valproate (________):
- Depakene, Depacon
- Controls all types of generalized seizures, and partial seizures
- Blocks sodium channels, increases GABA synthesis, inhibits GABA degradation in the brain
- Many adverse side effects
- Black box warnings
- Can cause xerostomia; monitor patients
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What kind of seizures is Ethosuximide (________) used for and what are the adverse effects
- Zarotin
- Drug of choice in controlling absence (petit mal) seizures
Adverse effects include nausea, vomiting, anorexia, dizziness, confusion, and leukopenia (low white blood cell count)
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What are the Benzodiazepines and what seizures are they used for
lorazepam (I.V.) – drug of choice in status epilepticus and in alcohol related seizures
clonazepam (Klonopin) – controls myoclonic seizures in children
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Describe the second generation anti-epileptic drugs and what are they
Newer anti-epileptic drugs, have more specific sites of action, fewer adverse effects
- Gabapentin (Neurontin)
- Levetiracetam (Keppra)
- Zonisamide (Zonegran)
- Topiramate (Topamax)
- Pregabalin (Lyrica)
- Tiagabine (Gabitril)
- Felbamate (Felbatol)
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What are the Other Indications for Antiepileptic Drugs
- Bipolar disorder
- Anxiety disorders
- Migraine
- Neuropathic pain
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What is Parkinson’s Disease and what effect does it have on the body
- age-related Chronic, progressive, degenerative disorder of the CNS (65)
- Reduction in the neurotransmitter dopamine in the brain
- There is also high level of acetylcholine (ACh), which also controls muscle movement
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Normal control of normal muscle movement is through the
extrapyramidal system
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In Parkinson’s disease there is an increase in extrapyramidal side effects due to a _________which is responsible for ________ the extrapyramidal system
- decreased synthesis and release in dopamine (DA),
- “turning off
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In Parkinson’s Disease there is an imbalance between
dopamine and ACh
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What are some Classic symptoms of Parkinsonism
- Postural instability
- Resting tremor
- Muscle rigidity
- -Poker face
- Bradykinesia (muscular movement becomes slow and rigid)
- -Masked facial expression
- -“Short step” walk
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The Objective of the Pharmacologic Treatment of Parkinson’s Disease:
Increasing the activity of DA or decreasing the activity of ACh
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Dopamine cannot get through the _________ and get into the brain, so _______ is given, which then converts to dopamine in the brain. Then _______ is added to the formulation to lessen the adverse side effects of levodopa
- blood-brain barrier
- levodopa
- Carbidopa
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What effect does carbidopa-levodopa (_______) have
- (Sinemet)
- “Wearing off effect” – Levodopa is most effective during the first year of the disease with a marked decrease in effectiveness by three years and by five years, when the signs and symptoms are back to the predrug level
- “On-off effect” - "On" and "off" periods occur without warning as a result of fluctuating dopamine levels in the brain
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What are the two mechanism of action of anti-parkinson drugs
- levodopa therapy increases dopamine production
- cholinergic blocker decreases acetylcholine reaching the receptor
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Name a dopamine agonist prototype drug for Parkinsons and what it is used for and what is an adverse side effect
- bromocriptine (Parlodel)
- act directly to stimulate dopamine receptors
They are used with levodopa in treating the “on-off effect” of levodopa
Can cause orthostatic hypotension
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When are anticholinergic agents used, what is it primarily effective for, what is the prototype drug and what is the adverse side effect
Used in early or mild stages of the disease or later on in combination with carbidopa-levodopa
- Primarily effective for tremors
- Prototype drug: Benztropine (Cogentin)
Adverse side effects: Xerostomia
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What is the mechanism of action of
Monoamine Oxidase B (MAO-B) Inhibitors, what are the prototype drugs used and what drug may interact with it
Blocks the enzyme MAO-B, which metabolizes dopamine
- Selegiline (Eldepryl)
- Rasagiline (Azilect)
- Do not use Cipro when taking rasagiline
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What Parkinsons treatment is the newest class of drugs and used in conjunction with carbidopa-levodopa to help with motor complications due to levodopa
COMT (Catechol-O-Methyltransferase) Inhibitor
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Alzheimer’s is a _________ where there is destruction of ________. It has an _________ etiology. Accounts for ____% of cases of dementia in people over 65 in US and _______ deaths per year
- neurodegenerative disease
- cholinergic and other neurons in CNS
- unknown
- 60%
- 100,000
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There are _____ Rx drugs approved by the FDA for Alzheimer’s. Three of them are _________ that prevent breakdown of ________ and they are
- four
- Cholinesterase inhibitors
- acetylcholine
- Galantamine (Razadyne)
- Donepezil (Aricept)
- Rivastigmine (Exelon)
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The fourth Alzheimer’s drug is a _________ used for _________ and the prototype drug used is _________
- N-methyl-D-aspartate (NMDA) antagonist
- for moderate to severe disease
- Memantine (Namenda)
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Primary headache disorders are characterized by a _______ and include ______. Some precipitating factors include ______
lack of an identifiable and treatable underlying cause
- Migraine
- Tension-type
- Cluster headaches
caffeine (and caffeine withdrawal), menstruation, stress, smoking, lack of sleep, certain foods, and strenuous exercise
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Secondary headache disorders have ________ such as _________
an identifiable cause
headache or facial pain attributed to disorder of neck, eyes, ear, nose, sinuses, teeth, mouth, or other facial or cranial structures; head or neck trauma; drug substance or its withdrawal; infection; cranial neuralgias; brain tumors; meningitis; temporal arteritis; intracranial lesions; and primary angle closure glaucoma
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Migraine headaches are a ______, ______, ______ headache disorder with attacks lasting _______ and associated with
- recurring, episodic, and often severe
- 4 to 72 hours
Phonophobia (fear of sounds, including your own voice), nausea, vomiting, and cutaneous allodynia
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About 20% of patients with migraines are preceded by ______ which gradually develops over 5-20 min and 25% experience a ______ involving ________
- aura
- postdrome
- changes in mood and behavior after the attack
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In migraine pain ________ may result in ________ ,initiating pain Then, pain is due to ________ caused by _________ releasing ________
- low levels of serotonin
- vasodilation of cerebral blood vessels
- vasodilation of cerebral blood vessels
- neurons in the trigeminal nerve
- substance P
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What are the three mechanism of action in Drug Therapy for Migraine
- aborting a migraine at the time it occurs
- symptomatic pain relief
- preventing a migraine from occurring
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Symptomatic therapy for migraines either prescription or OTC, should not be used more than
twice a week
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What is the newest abortive drug for migraines, what is the mechanism of action and what is a prototype drug
- Triptans
- stimulate serotonin receptors
- sumatriptan (Imitrex)
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What is the adverse reaction with Triptans
- blood pressure elevation
- Caution should be used when using local anesthetics containing epinephrine
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What is the mechanism of action of the Ergot Derivative Abortive Migraine drugs and what are the prototype drugs
Alpha-adrenergic blockers and vasoconstrictors of cranial smooth muscle
Ergotamine (Ergomar) and dihydroergotamine nasal spray (Migranel)
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Elevated blood levels of Ergot derivatives occur when taken with
erythromycin and clarithromycin
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For mild migraine attacks, _______ alone or in combination with _______ have been used
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To avoid the aggravation of the migraine use NSAIDS alone or in combination with
triptan
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Fiorinal with codeine is a ________ used for ________ and contains a combination of ________
- Narcotic analgesics
- Abortive Migraine Drugs
- combination of aspirin, butalbital, and caffeine and codeine
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What kind of drugs are prescribed for Prophylaxis Migraine drugs
- Anticonvulsants
- Beta Blockers
- Botulinum Toxin Type A (Botox)
- Calcium Channel Blockers
- Tricyclic Antidepressants
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Butalbital is a
barbiturate that relaxes muscle contractions involved in the headache
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What type of migraine Drugs are used for Prophylaxis and what are the drugs
Anticonvulsants:
- Topiramate (Topamax)
- Valproic acid (Valproate) – side effects are:
- Weight gain
- Xerostomia
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What are the beta blockers used for Prophylaxis migraine treatment
Migraine Drugs for Prophylaxis
Timolol and propranolol (“olol”)Nonselective beta-blockers
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What is the mechanism of action of calcium channel blockers and what are the drugs
Work to stabilize blood vessel membranes by preventing them from over dilating. It can take up to two months to see effects
- diltiazem (Cardizem)
- nifedipine (Procardia):
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How long does it take for Tricyclic antidepressants to take effect tin Prophylaxis migraine treatment and what is the caution
up to three to four weeks before the drug is effective
Limit EPI use to 0.04 mg (2 cartridges of 1:100,000).
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What are the uses of Botulinum Toxin Type A (Botox)
- Used cosmetically
- Used for TMJ disorders
- Migraine prevention for up to six months
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