Exam 3 Flashcards
Seizure begins at a single site in the cortex (only a few electrodes show synchronous activity)
Partial seizure
Seizure in both hemispheres of the brain (all electrodes go off simultaneously)
Generalized seizure
Type of seizure:
No loss in consciousness
Short duration (20-60 seconds)
Ex: one side of face may twitch
Simple seizure (partial)
Type of seizure:
Sudden loss of consciousness
Less than 30 seconds
Person may be staring and blinking (3 blinks per second)
More common in children than adults
Petit mal (absence seizure) (generalized)
Gradual loss of consciousness (30seconds to 2 minutes)
Starts with simple seizure and hallucinations then there are strong automatisms (lip smacking)
Complex seizure (partial)
Sudden loss of consciousness (1.5-2.5minutes)
20 seconds of muscle rigidity, then 1-2 minutes of rhythmic muscle contractions
Tonic-clinic (generalized)
Single shock like contraction in the whole body that lasts less than 1 second
More in children than in adults
Myoclonic (generalized)
Starts with a partial seizure and progresses to generalized seizure
Secondarily generalized seizure
Sodium and potassium bromide Use
Less seizures because of severe sedation
Sodium and potassium bromide ADRs
Severe sedation
Severe skin rash and/or lesions
First anti seizure drug (1912)
Phenobarbital (Luminal)
Barbiturate metabolized to phenobarbital and PEMA
Primidone
Animal model where repeated low intensity, electrical stimulation to the amygdala
Kindling model for partial and generalized seizures
Animal model where there were injections of excitatory neurotransmitters
Model for tonic clonic seizures
MOA: Potentiation of synaptic inhibition via GABAa receptor
Use: Monotherapy used for generalized tonic-clonic and partial seizures
Phenobarbital (Luminal)
MOA: Potentiation of synaptic inhibition via GABAa receptor
Use: Monotherapy for generalized tonic clonic, partial and adolescent Myoclonic seizures (*less effective than phenobarbital)
Primidone
MOA: prolong rate of recovery for voltage gated Na channels from inactivation (inactivated for longer)
Use: Monotherapy for generalized tonic clonic and partial seizures
Phenytoin (Dilantin)
Drug concentration for this drug increases disproportionately as the dosage is increased and is bound 90% to plasma protein
Phenytoin (Dilantin)
Side effects for phenobarbital
*Induction of CYP3A4 so increased drug metabolism of certain drugs like oral contraceptives
Sedation in adults
Hyperactivity/irritation in children
Side effects for Primidone
Induction of CYP3A4 so increased drug metabolism of certain drugs like oral contraceptives
Sedation in adults
Hyperactivity/irritation in children
PLUS dizziness Nausea Nystagmus Ataxia
Side effects for phenytoin
- Increases drug metabolism of drugs that are metabolized by the same enzyme (CYP2C9) because these enzymes are saturable (warfarin)
- Induces CYP3A4 so increased metabolism of drugs like contraceptives
- Gingival hyperplasia
- Steven johns syndrome
Adverse immune reaction
Blistering of skin and mucous membranes after flu like symptoms and a persistent fever
Steven johns syndrome
Treatment for Steven johns syndrome
*Discontinuation of drug
Possible immunosuppressants
- MOA: Inhibit T-type Ca channels
* Uses: Monotherapy for absence seizures
Ethosuximide
MOA: prolong the rate of recovery of Na channels from inactivation
Uses: Monotherapy for generalized Tonic clonic and partial seizures
Also for Manic depressive patients
Carbamazepine
MOA: prolong rate of recovery of Na channels from inactivation
Uses: Monotherapy in treatment of partial seizures 4-16 years old
Adjunctive treatment for partial seizures
Oxcarbazepine
Not bound to plasma protein so few drug-drug interactions
Ethosuxomide
Induces own metabolism so have to wait 3 weeks to get a good steady level to be reached
Carbamazepine
A prodrug that is converted to active metabolite in the Iiver
*does not autoinduce like carbamazepine
Oxcarbazepine
Phenobarbital, phenytoin, and valproic acid increase the metabolism for this drug
Carbamazepine
Side effects for carbamazepine
Chronic side effects
*induces drug metabolism of OCs from CYP3A4
Drowsiness, vertigo, ataxia, blurred vision
Acute side effects:
Stupor, coma, hyper irritability convulsions
Side effects for oxcarbazepine
*Increases drug metabolism of CYP3A4 enzyme like OCs. Not as much as carbamazepine though
Dizziness, nausea, ataxia
Side effects for ethosuximide
Nausea, vomiting, anorexia
CNS drowsiness, lethargy, euphoria
SJS, aplastic anemia
MOA: *inhibits T-type Ca channels
prolongs inactivation of Na and increases GABA synthesis
Use: *used as monotherapy for absence, myoclonic, partial, and tonic-clonic seizures. “broad spectrum” anti epileptic
Valproic acid (Depakote)
ADRs for Valproic Acid (Depakote)
increase in hepatic blood enzymes, increases hepatic toxicity
inhibits CYP2C9 so increased concentration of phenytoin & phenobarbital
MOA: starts synaptic inhibition via GABAa receptors
Use: adjuncitve treatment for absence seizures and juvenile myoclonic seizures
benzodiazepines (clonazepam and clorazepate)
ADRs for benzodiazepines
Drowsiness, lethargy
In children, aggression, hyperactivity, irritability
MOA: unknown…even though binds to Ca channels, nothing happens and nothing happens with GABA either
Use: adjunctive treatment for partial with and without secondary generalized seizures
Gabapentin (Neurontin)
this drug is not metabolized but excreted unchanged in the urine so renal function must be determined before dosing
gabapentin (Neurontin)
Gabapentin side effects
fatigue and ataxia
GABA molecule bound to lipophilic hexane ring but doesnt interact with GABA receptors at all
gabapentin (Neurontin)
GABA molecule bound to isobutane
pregabalin (Lyrica)
MOA: unknown
Use: adjunctive therapy for partial onset seizures and fibromyalgia
pregabalin (Lyrica)
MOA: inhibits Ca, Na, NMDA, and AMPA-kainate receptors
Use: monotherapy and adjunctive therapy for LGS, partial and generalized seizures in adults
felbamate (Felbatol)
Felbatol side effects
GI upset, anorexia, and insomnia
may have aplastic anemia and hepatotoxicity
childhood onset of epilepsy that can causes severe cognitive dysfunction
multiple seizure types including atonic or “drop” seizures and is resistant to drug therapy
LGS (Lennox-Gustaut syndrome)
this drug was taken off the market for causing hepatotoxicity and aplastic anemia but was later brought back as a last resort drug for resistant seizures
flebamate (Felbatol)
MOA: prolongs the rate of recovery of Na channels from inactivation. To a small extent, inhibits Ca
Use: *a monotherapy and adjunctive treatment for partial and generalized tonic/clonic seizures like LGS.
considered a broad spectrum anti epileptic
Lamotrigine (Lamictal)
when used with other anti epileptics, can get rash and SJS
Lamotrigine (Lamictal)
Lamotrigine side effects
dizziness, ataxia, blurred vision, nausea
rash and SJS when combined with other anti epileptics
MOA: inhibit Na channels and AMPA-kainate receptors enhance GABA receptors
Use: *monotherapy and adjunctive treatment for partial and tonic clonic seizures (LGS). considered a broad spectrum anti epileptic
Topiramate (Topamax)
side effects for Topiramate:
ataxia, fatigue, somnolence, weight loss
Reduces plasma levels of OCs and estradiol
Topiramate (Topamax)
MOA: inhibit GABA reuptake at synapse and prolong GABA action
Use: treats partial with and without secondarily generalized tonic clonic seizures
Tiagabine (Gabitril)
side effects for tiagabine (Gabitril)
dizziness, somnolence, tremor (mild after initial treatment)
MOA: unknown
Uses: *adjunctive treatment for partial and tonic clonic seizures in adults
- myoclonic seizures in children.
- IV prep for status epilepticus
Levitracatem (Keppra)
highest safety of margin in animal studies
rapid dose titration makes this drug useful in adjunctive therapy
Levitracatem (Keppra)
MOA: prolong rate of recovery for Na channels.
inhibit T-type Ca channels
Uses: adjunctive treatment for partial seizures in adults
Zonisamide
Side effects for Zonisamide
somnolence, dizziness, anorexia, fatigue
1% get renal calculi
What are the following drugs used to treat?
Lacosamide (Vimpat)
Rufinamide (Benzel)
Vigabatrin (Sabril)
Egozabine (Potiga)
epilepsy
drug of choice for a partial seizure secondarily generalized
carbamazepine and phenytoin
alternative drugs for partial secondarily generalized seizures
lamotrigine and valproic acid
drugs of choice for generalized absence seizures
ethosuximide and valproic acid
alternative drug of choice for generalized absence seizures
clonazepam
drug of choice for generalized tonic clonic seizures
carbamazepine, phenytoin, valproic acid
alternative drug of choice for generalized tonic clonic seizures
lamotrigine and topiramate
a disease in which there are a series of seizures and where a full recovery doesnt occur before there is an onset of second seizure
status epilepticus
how to treat status epilepticus
give either diazepam or lorazepam IV (lorazepam is preferred). avoid hypoventilation and hypotension. then give IV fosphenytoin (water soluble prodrug for phenytoin) or Levitracatem, phenobarbital or valproic acid
what do long term use of AEDs cause?
osteoporosis
true/false
women on OCs have a higher failure rate. if yes, by what 3?
true. they have a 3X higher failure rate.
AEDs are safe to take while pregnant
true or false
false. there is a 2-3X higher increase in birth defects
how to reduce the likelihood of neuronal rube defecfts from AEDs?
0.4mg/day of folate throughout pregnancy
give vitamin K during the last month
which drug to completely avoid during pregnancy
valproic acid…teratogenic
are generic drugs ok to give for seizures?
No because switching even from brand to generic can cause major seizures
what are the 4 phases of migraines?
premonitory, aura, headache, and resolution
what is the premonitory phase of a migraine?
can have neurologic symptom (photophobia and phonophobia), psychological symptoms (anxiety and depression), constitutional symptoms (stiff neck, yawning, thirst, food cravings)
when is the premonitory phase?
hours to days before the actual migraine
what is the aura phase of a migraine?
an aura refers to focal, neurological symptoms (vision or other sensations) occurs in ~31% of people with migraine
how do migraines work (the headache part)
start from a dull ache in frontotemporal region and extends to the back of the skull and goes on to intense pulsations (usually unilateral) and these worsen over time. ~90% of patients have GI symptoms as well like nausea, vomiting and also photphobia and phonophobia
how long does a migraine normally last?
4-72 hours
what is a tension headaches
a muscle contraction headache.
a dull persisting, non pulsating and non debilitating bilateral pain. no nausea/vomiting and no aura or photophobia/phonophobia
what is a cluster headache
brief episodes of extremely excruciating unilateral pain that come in clusters with periods of remission (months to years)
what to migraines result from?
inappropriate dilation of intracranial extracerebral blood vessels
what is the serotonergic abnormality theory for migraines?
drugs that deplete serotonin from tissue stores can induce migraines and so an intravenous injection of 5-HT can abort spontaneous migraines
name a couple drugs that are known to deplete serotonin levels from the tissue stores thus causing migraines
reserpine and fenfluramine
what is a rebound headache and why does it occur?
a rebound headache is a medication overuse headache and occur if you use the drug too much which induces a higher headache frequency
what does the abortive therapy include?
combination analgesics, opiates, ergotamine tartrates, and triptans
how do you avoid rebound headaches?
use abortive therapy no more than 2 times a week
possible triggers for migraines (food)
alcohol
chocolate (phenylethylamine)
beer, red wine, cheese (tyramine)
frozen dinners, canned food, chinese food (MSG)
processed meats and fish (sodium nitrate)
possible triggers for migraines (general)
irregular sleep pattern
stress
environmental changes
hormonal changes
what is the first line therapy for mild to moderate migraines?
analgesiscs (NSAIDS, Midrin, Opiates)
MOA: blocks prsotaglandin synthesis which prevent inflammation in the trigeminovascular system and lessens pain sensitization
NSAIDS
a combination therapy that is as effectice as oral ergotamine in some patients with lower side effects
Midrin
what are the 3 ingredients used in midrin?
Isomethoheptene,
dichlorophenazone
acetaminophen
this drug should be used with extreme caution in patients with peptic ulcer disease, renal disease or hypersensitivity to aspirin
NSAIDS
what is isomethoheptene do?
Mild vasocontrictor activity
what does dichlorophenazone do?
sedative action
this drug is used for severe, infrequent headaches where conventional therapies either do not work or are contraindicated so a rescue medication is needed
opiates (Butorphanol…a nasal spray)
what are the ADRs for butorphanol?
dizziness, nauseam vomiting, drowsiness, and bad taste
what are ergotamine tartrates used for?
they are used in the acute treatment of moderate to severe migraines
where are ergot-like compounds found in nature?
found in rye contaminated with the fungus claviceps purperea
what is ergotism?
gangrenous mummified limbs and spontaneous abortions
what are the 3 dosage forms ergotamine are available in?
oral, sublingual and suppository
what is the maximum dose of oral/sublingual ergotamine?
not to exceed 6mg/attack or 10mg/week
___ is added to some ergotamine containing products for vasoconstriction and to help it absorb in the intestines
caffeine
why is ergotamine called a dirty drug?
it interacts with serotonin, dopamine, and adrenergic receptors
how do ergotamines work?
activation of 5-HT1b receptors and by causing vasoconstriction. in addition, it may reduce neurologic inflammation by decreasing vasodilators
___ is a powerful vasoconstricor and a contraindication in patients with peripheral vascular disease
___ may potentiate the vasoconstriction that is caused by ergotamines
ergotamine
B blocker
one of the side effects of ergotamines include GI upset. How does this happen and what needs to be added to counteract it?
there is an activation of central dopamine receptors in the chemoreceptor trigger zone. we need to add metoclopramide to the regimen as an antiemetic
___ (antibiotic) can interferew with the liver metabolism of ergotamine and cause ergot toxicity
erythromycin
Aside from peripheral vascular disease, what is one contraindication of ergotamine?
cardiovascular disease
MOA: direct vasoconstriction of dilated intracranial arteries, reduced neurologic inflammation by decreasing the release of vasodilators and proinflammatory neuropeptide transmitter (works like ergotamine)
Dihydroergotamine (DHE45)
true/false
DHE45 needs to be administered parenterally
true it is not absorbed in the GI tract at all
1st line treatment for the acute treatment of moderate to severe migraines
Dihydroergotamine (DHE45)
what is the only thing that is different between ergotamine and DHE45 (dihydroergotamine) regarding ADRs
DHE45 is less likely to have vasospasms because of less arterial vasoconstrictor activity. with DHE45 there is more alpha blocking activity
what are triptans used for?
they are used for the acute treatmetn of moderate to severe migraines
sumatriptan is a derivative of _____ and can be administered by _____, _____, and _____ (routes).
it is metabolized by _____
can be administered up to ____ hours after onset of attack and be effective
serotonin (5-HT)
SQ injection, oral tablets, or nasal spray
MAO-A
4 hours
how does sumatriptan work?
causes constriction of inflamed/dilated intracranial arteries and inhibits the release of vasodilator/proinflammatory mediators
what side effects of migraines does sumatriptan relieve?
nausea, vomiting, photophobia, and phonophobia
what is the one huge contraindication in using sumatriptan and why?
contraindicated in pateints with cardiovascular disease. many fatalities are reported in patients who have cardiovascular disease and use SQ sumatriptan. High chance of getting MIs so do not give IV
True/false
it is ok to give sumatriptan and another ergot-type compound together
false!!!! do not give them within 24 hours of each other!!
common triptan symptoms
chest and throat tightness, difficulty breathing, panic/anxiety
this drug is contraindicated with the use of an MAO inhibitor
sumatriptan
these have a greater bioavailability than triptans
they act at the peripheral components of the trigeminovascular system
act centrally to inhibit pain transmission in he trigeminal nucleus (greater lipid solubility)
second generation triptans
