Pharm 1 - Anticonvulsants

isabellepjk's version from 2017-05-06 19:44


Question Answer
What are seizures?Clinical manifestation of abnormal electrical activity in the brain
What is epilepsy?Multiple seizures occurring over a prolonged period of time (two or more over a month or more), unpredictable & often violent
*What is a convulsion? What is important to know about them w/ seizures?Not all seizures have convulsions! A convulsion is an abnormal violent & involuntary contraction or series of contractions of the mm
What are convulsions associated with?W/ episodic ↑ freq. discharge of impulses by a group of neurons (focus). May spread to other parts of the brain, & the location determines clinical signs.
How can you diagnose a seizure?Electroencephalography (EEG)
What is a provoked/reactive seizure?Reaction of normal brain to intoxication, metabolic insult, or short term illness
What are cluster seizures?2 or more discrete seizures w/in 24hrs
What are the 2 kinds of epilepsy? (In terms of causes)(1) Idiopathic/primary
(2) Symptomatic
What are the 3 types of seizures?(1) Provoked/reactive
(2) Cluster seizures
(3) Epilepsy
What are the 2 types of seizures, if you are categorizing according to location?Partial (localized) vs generalized (whole brain)
What is the difference between a simple & complex seizure?Simple = no loss of consciousness. Complex = loss of consciousness (yeah, I’d say losing consciousness is making thing complicated alright)
What is status epilepticus?Continuous seizure activity lasting more than 5 minutes or when the animal does not recover fully between recurrent seizures (can get excitotoxicity)
What are the 2 kinds of 2⁰ epilepsy? (Either idiopathic or 2⁰)(1) Structural (brain tumor, encephalitis)
(2) Metabolic (hepatic encephalopathy)
Realize that there are "seizures" or "epilepsy" which BOTH could be w/ or w/o convulsions, & then BOTH conv. or no conv. can be idiopathic OR 2⁰, & all 2⁰s can be structural or metabolic. Either way, at the end, it all ends up resulting in - (what types of activities)↑ excitatory or ↓ inhibitory activity
*Explain the ↑ excitatory neurotransmission in seizures/epilepsyfacilitates/induces the glutamate & aspartate NTs (sugar-induced seizure)
*In seizures/epilepsy what NT is affected in what way?Inhibits/reduces the GABA (inhibitory) NT (mouth opens & closes like theyre gabbing)
What is excitotoxicity?Repeated seizure activity can lead to neuronal degeneration
*What are seizure-associated problems? (5)(1) Brain edema
(2) Hyperthermia
(3) Aspiration pneumonia
(4) Disseminated intravascular coagulation
(5) Permanent brain injury
*For emergency Tx of seizures/epilepsy, what 3 things do you try to do to the CNS?(1) Stim GABA
(2) GABA agonist
(3) Inhibition of Na+ channels
*What are the drugs used in emergencies to STOP seizures and what is their MoA?Barbituates, Benzodiazepines, Valproate (GABA stimulation)
Propofol, Etomidate (GABA Agonists)
Fos-phenytoin (Na Channel Inhibition)
*What drugs are associated w/ the stimulation of GABA Tx in emergencies? (3)Barbiturates, Benzodiazepines, Valproate
*What drugs are associated w/ GABA agonist Tx in emergencies? (Not stim of GABA) (2)Propofol, Etomidate (watch our talking agonist pee)
*What drugs are associated w/ inhibition of Na+ channels Tx in emergencies?Fos-Phenytoin,

Phenytoin (remember: oral absorption, PP bound, hard to predict conc)
*For maintenance therapy for epilepsy, what 4 things can you do to the CNS?(1) Stim of GABA
(2) inhibition of Na+ channels
(3) Inhibition of Ca++ channels
(4) Misc
*What drugs are associated w/ inhibition of Ca++ channels seizure control tx? (5)Ethosuximide
*What drugs are associated w/ the misc. Tx for maintenance therapy for epilepsy? (3)Potassium Bromide
*Which drugs will work as GABA stimulants in seizure control maintenance? (3)Barbituates
*Which drugs will work as Na Channel Inhibitors in seizure control maintenance? (5)Carbamazepine
*What is the receptor & what is the effect on the receptor for Benzodiazepines?Enhancement of GABA (A) activation, ↑ FREQ of opening of gate (BenZo FrequenZy)
*In which situation are Benzodiazepines mostly used, in regards to seizure treatment?Emergencies; but can be used for maintenance as well. (benzoDIazepine in DIre situations)
*What are the 4 Benzodiazepines used for seizures? Quick info on things unique about them?Diazepam & Midazolam (Mida. is more potent, shorter half-life compared to Diaz.)
Clonazepam (inhibition of T-type Ca++ channels)
Lorazepam (most potent, longer half-life)
What are good routes of administration for most of the benzodiazepines, and what are the exceptions?IV, IM, IN, IR
IntraRectal NOT for lorazepam or midazolam
*Which drug class is the best choice for maintenance therapy?Barbituates
How do barbituates function in maintenance therapy?Enhancement of GABAa activation --> Prolongs opening of the Cl channel, antiglutaminergic, decreased Na and Ca influx (leading to NO release of NT, NO AP, NO depolarization)
*Which drug causes idiopathic hepatic necrosis in cats?Diazepam
What ion does the GABAa gate deal w/?Cl-
What are the side effects of using Benzodiazepines?Sedation & withdrawal (← can EXACERBATE seizures)
Are benzos used for emergency Tx, maintenance Tx, or both? What do they affect?Both! All affect/stim ↑ (inhibitory receptor) GABA (A) opening frequency
Is GABA an inhibitory or excitatory NT/Receptor?Inhibitory → ↑ freq (benzos) or ↑ opening time (barbs) = make sleepier
Are barbs used for emergency Tx, maintenance Tx, or both? What do they affect?Both! Enhance of GABA (A) activation, PROLONGS opening of Cl- channel
*Which barbiturate drug is used for seizures? How effective & what species?Phenobarbital, effective in 60-80% of DOGS
What are the side-effects of Barbiturates? (3)(1) Autoinduction (CYP450 enzymes in, tolerance bc ↑ metabolism)
(2) Sedation/polyphagia/PU/PD/panting
(3) hepatotoxicity (minimal in cats)
blood dyscrasia
How/for what is potassium bromide used in seizures?As emergency & add-on (boosts effects of benzos & barbs)
What is the mode of action of potassium bromide?Competes w/ Cl-, which HYPERpolarizes neuronal membranes (harder to reach threshold)
What happens to potassium bromide in the kidney?Glom. Filtration (competes w/ Cl-), & goes through tubular reabsorption (which leads to a long half-life)
needs a loading dose (Think about it - kidney prolly thinks its potassium, so it wants to save it)
*What are the side-effects of potassium bromide? (5)(1) Bromism (dz from too much bromide)
(2) Sedation
(3) Ataxia
(4) Pancreatitis
(5) Pneumonitis in cats (inflammation of lung tissue)
*What is the MoA of Zonisamide? How is it metabolized?Inhibition of Na and T-Type Ca channels (NO depolarization and NO NT release)
partly excreted unchanged, partly glucuronidated
*What are adverse effects of Zonisamide?Teratogenic in dogs (don't use in pregs!)
may need higher doses when on phenobarbital, cyclosporin, or antifungals
causes mild sedation and anorexia
*How is levetiracetam used for seizures?Potentially as tx for status epilepticus (levitate to stop)
What is the MoA of Levetiracetam and how is it excreted?Binds to the synaptic vesicle protein and regulates vesicle exocytosis
renal excretion
*Felbamate (misc. drug) has demonstrated efficacy for _________ & _________ seizures.Both local (partial) & generalized seizures (fel in love w/ eating all 1 type of food, & all the different foods)
What is the mode of action for Felbamate? (4!)(1) Block NMDA-mediated neuronal excitation
(2) Potentiation of GABA-mediated neuronal inhibition
(3) Inhibition/blocking of neuronal Na+ & Ca++ channels
What are the routes of admin for benzos?IV, IM, intranasal, intrarectal (← NOT lorazepam or Midazolam) (not even a ml of anything in my butt please)
(Pharmacokinetics) best absorption of Felbamate after what admin?Oral (fel in love w/ food)
How safe is/what is the toxicity of Felbamate?WIDE safety margin, toxicity is rare, but will cause bone marrow suppression
What is the mode of action of Gabapentin/Pregabalin? binding to the Ad subunit (blocks) to L-type calcium channel (reduces trafficking to the plasma membrane of these channels, & reduce Ca++ entry into nerve terminals & release of NTs & modulators)
What is absorption of Gabapentin/Pregabalin dependent on?Depends on L-amino acid carrier- SATURABLE process (gabbing of preteens burns my soul like acid)
How safe is Pregabalin/Gabapentin? What are the side effects? Which is more potent?Relatively safe & free of side-effects. Pregabalin is more potent. (PREteens gab more)
How is Gabapentin/Pregabalin excreted?Excreted unchanged in urine
How long is Gabapentin/Pregabalin's half-life? How often does it need to be administered?Short half-life, so would need to be administered 3-4 times daily (every 6-8 hrs) which is kinda impractical for owners
In which drug class is CarbamazepineTricyclic antidepressant drug (car rides make me happy)
What is the MoA of Carbmazepine?inhibition of voltage gated Na channels
Aside from seizures, what else is Carbamazepine used to treat?Neuropathic pain & manic-depressive illness (road trips calm my nerves down & make me happy)
How is the absorption, what is half-life of Carbamazepine?Slow absorption, long half-life (when it takes you that long to start, you know it'll be a longggg car ride)
Metabolism of Carbamazepine?Hepatic metabolism - active metabolites!
Which drugs are NOT recommended as Anticonvulsant medications?Lamotrignine
Valproic acid/valproate