Pharm 1 - Anticonvulsants

martinezdvm's version from 2015-11-01 20:22


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 3 kinds of epilepsy? (In terms of causes)(1) Idiopathic/primary- genetic/hereditary
(2) Symptomatic- structural brain defects
(3) Cryptogenic- (probably symptomatic) epilepsy (metabolic or structural brain disorders that are yet undetectable)
What are the 4 types of seizures?(1) Provoked/reactive
(2) Cluster seizures
(3) Generalized
(4) Focal
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 focal & generalized seizure?Focal = no loss of consciousness. Generalized = loss of consciousness
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 drugs are associated w/ the stimulation of GABA Tx? (3)Barbiturates, Benzodiazepines, Valproate
What drugs are associated w/ GABA agonist Tx? (Not stim of GABA) (2)Propofol, Etomidate (watch our talking agonist pee)
What drugs are associated w/ inhibition of Na+ channels Tx? (2) (5 on chart)Fos-Phenytoin, Phenytoin (remember: oral absorption, PP bound, hard to predict conc) ((eating salty food is PHEN!) -CHART SAYS: Phenytoin, Carbamazepine, Valproate, Felbamate, Zonisamide (salt on my PC FVZ!)
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 Tx? (5)Gabapentin
Zonisamide (PG movie? V. EZ to make in Ca) (Clonazepam too)
What drugs are associated w/ the misc. Tx for maintenance therapy for epilepsy? (3)Potassium Bromide
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) (I -am Ben)
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) - short duration of action (←I think that refers to all of them?)
Which is longer a/o stronger...Diazepam or Midazolam?Midazolam is stronger but shorter.
What does Clonazepam deal w/?Inhibition of T-type Ca++ channels
What is the strongest benzodiazepine used in Tx of seizures?Lorazepam (might also be longest, he was vague on this)
What kinda duration of action do benzos have in general for Tx of seizures?Shorter duration of action (barb the woman is more tenacious than ben)
What ion does the GABA gate deal w/?Cl-
If you use Benzodiazepines often or for a long time, what 2 things (related) can happen?Tolerance & CROSS-tolerance (so if tolerance to Diazepam, then tolerant to the rest)
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, & Clonazepam also inhibits T-type Ca++ channels
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 (barb loves phenotypic dogs.)
What are the side-effects of Barbiturates? (3)(1) Autoinduction (CYP450 enzymes in, tolerance bc ↑ metabolism)
(2) Sedation/polyphagia/PU/PD
(3) hepatotoxicity (minimal in cats) (Barb is a toxic lady)
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 & so requires TDM= therapeutic drug monitoring= so doesn't OD) (Think about it - kidney prolly thinks its potassium, so it wants to save it)
How do you start to give potassium bromide?Needs a LOADING dose, reaches steady state (SS) after 80-120 days (why it's a weirdo & you cant give it as emergency etc)
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)
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 of neuronal Na+ & Ca++ channels
(4) Protects neurons from hypoxic/ischemic damage (so down NMDA, up GABA, down Na+/Ca++) (fel down trippin, saw ALL the effects. so NMDA, Na channel, Ca channel, GABA)
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 does Felbamate affect different age groups?Puppies more sensitive bc their gut is more "open" & their BBB isn't as strong
How safe is/what is the toxicity of Felbamate?WIDE safety margin, toxicity is rare, but will cause bone marrow suppression
Gabapentin & Pregabalin are structural analogues of what?GABA....duh.
What is the mode of action of Gabapentin/Pregabalin? (2)(1) MIGHT enhance release of GABA
(2) MOST effect = binds (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, & 30-40% metabolized (she gab & gabed, so fast I ran out the urethra before I was done being metabolized)
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
What is Levetiracetam an analogue of? What is similar to?Analogue of Piracetam, similar to Brivaracetam (more potent)
Mode of action of Levetiracetam?Binds to synaptic vesicle protein 2A (SV2A: vesicle docking & fusion) (levitate over the vesicle, only have to get off to pee)
How is Levetiracetam excreted?Renal excretion (I'll be level w/ you -I pee a lot)
What kind of compound is Zonisamide?Sulfonamide
Mode of action of Zonisamide?Inhibition of Na+ & T-type Ca++ channels (Zon, you're NAT seizing anymore! let's tell Cal)
Side effects of Zonisamide?Free of major unwanted side effects (zon is zen. :) )
(Pharmacokinetics) half-life, metabolism, & excretion of Zonisamide?LONG plasma half-life, it is partly excreted unchanged, partly glucuronidated (Zen is long - a lifestyle long. It is ying & yang- partly unchanged when excreted, party changed)
Which drug is not related to any other anticonvulsant?Valproate (Val is the odd girl out)
Mode of action of Valproate? (3)Multiple modes of action
(1) Weak inhibition of GABA transaminase
(2+3) Some effect on Na+ & T-Type Ca++ channels
Why is Valproate not often used? When IS it used?Limited use in vetmed bc of short half-life. Used in multi-therapy (add to other stuff) (Val is a very short chick)
How can you reduce the vomiting caused by Valproate?Concurrent food intake
Mode of action of (fos-) PhenytoinUse-dependent block of Na+ channels (eating salty foods is phen!)
Best absorption of (fos-) Phenytoin is when it is taken _________?Orally (eating is phen)
What does (fos-) Phenytoin bind to?Highly plasma protein bound (competition) (pheny protein)
What is fos-Phenytoin converted into? By what?Conversion to Phenytoin (phosphatases)
Why it is difficult to predict what concentration (fos-) Phenytoin will be at? (NOT PP BINDING DAMNIT)metabolized by mixed-function oxidases, shows characteristics of saturation
Is Fenytoin a recommended anti-convulsant medication?No
What is the mode of action of Vigabatrin? (2)(1) Inhibits the GABA metabolizing enzyme GABA-transaminase
(2) Forms an irreversible covalent bond - ↑ GABA content & release (lasts longer)
Side effects of Vigabatrin?Peripheral visual field defect- depression (weird sounding word, weird side-effect)
What is Carbamazepine (category it's in)Tricyclic antidepressant drug (car rides make me happy)
What does Carbamazepine resemble?Phenytoin (car rides are phen?)
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!
Does tachyphylaxis occur w/ Carbamazepine?Yes - strong inducer of hepatic enzymes, so speed up metabolism, so ↓ effectiveness