week3 epilepsy

Question 1

what is the MOA of Valproate

Answer 1

blocks Na channel on presynamptic terminal
blocks Ca channel
clock GABA transaminase

Rainbow goggles: Broad-spectrum antiepileptic agents (e.g. valproate) treat generalized and focal seizures 4. Shaking Man FestiVAL: Valproate (aka sodium valproate, valproic acid) is a broad-spectrum antiepileptic; used in focal and generalized seizures, bipolar disorder (mood stabilizer) 5. Sold Out peanuts and Calci-Yum icecream: Valproate blocks Na+ channels (at a different site from carbamazepine or phenytoin) and T-type calcium channels → prevents repetitive neuronal discharge 6. CAB-A: Valproate ↑ GABA levels in the CNS due to enhanced GABA release via GABA(B) receptors, inhibition of GABA transaminase, activation of glutamic acid decarboxylase 7. Nauseated reveller: Valproate can cause GI distress (e.g. nausea, vomiting); valproate can be taken with food to reduce nausea cropped symbol image 7 8. Heavy box: Valproate can cause increased appetite and weight gain; monitor diet to avoid unwanted weight gain 9. Tremoring antenna: Valproate can cause tremor (at higher doses) 10. Liver fanny pack + ammonia cleaner: Valproate can cause hyperammonemia and rare, fatal hepatotoxicity; measure LFTs at baseline and monitor at frequent intervals thereafter, even though monitoring of liver aminotransferase (does not predict hepatic failure) 11. Squeezed pancreas sponge: Valproate can cause pancreatitis (rare); not related to dose or duration of therapy 12. Tubular tarantula: Valproate is teratogenic; associated with neural tube defects (e.g. spina bifida), orofacial clefts, and cardiac, urogenital and limb defects

Question 2

what are the clinical uses of Valproate

Answer 2

antileptic- broad spectrum (focal and generalized)
Biploar disorder

Rainbow goggles: Broad-spectrum antiepileptic agents (e.g. valproate) treat generalized and focal seizures 4. Shaking Man FestiVAL: Valproate (aka sodium valproate, valproic acid) is a broad-spectrum antiepileptic; used in focal and generalized seizures, bipolar disorder (mood stabilizer) 5. Sold Out peanuts and Calci-Yum icecream: Valproate blocks Na+ channels (at a different site from carbamazepine or phenytoin) and T-type calcium channels → prevents repetitive neuronal discharge 6. CAB-A: Valproate ↑ GABA levels in the CNS due to enhanced GABA release via GABA(B) receptors, inhibition of GABA transaminase, activation of glutamic acid decarboxylase 7. Nauseated reveller: Valproate can cause GI distress (e.g. nausea, vomiting); valproate can be taken with food to reduce nausea cropped symbol image 7 8. Heavy box: Valproate can cause increased appetite and weight gain; monitor diet to avoid unwanted weight gain 9. Tremoring antenna: Valproate can cause tremor (at higher doses) 10. Liver fanny pack + ammonia cleaner: Valproate can cause hyperammonemia and rare, fatal hepatotoxicity; measure LFTs at baseline and monitor at frequent intervals thereafter, even though monitoring of liver aminotransferase (does not predict hepatic failure) 11. Squeezed pancreas sponge: Valproate can cause pancreatitis (rare); not related to dose or duration of therapy 12. Tubular tarantula: Valproate is teratogenic; associated with neural tube defects (e.g. spina bifida), orofacial clefts, and cardiac, urogenital and limb defects

Question 3

Major adverse effects of Valproate

Answer 3

sedation, dizziness, weight gain, hair loss, easy bruising, drug interactions (CYP-450)hepatotoxicity, pancreatitis, teratogenicty- neuro tube deffects

Rainbow goggles: Broad-spectrum antiepileptic agents (e.g. valproate) treat generalized and focal seizures 4. Shaking Man FestiVAL: Valproate (aka sodium valproate, valproic acid) is a broad-spectrum antiepileptic; used in focal and generalized seizures, bipolar disorder (mood stabilizer) 5. Sold Out peanuts and Calci-Yum icecream: Valproate blocks Na+ channels (at a different site from carbamazepine or phenytoin) and T-type calcium channels → prevents repetitive neuronal discharge 6. CAB-A: Valproate ↑ GABA levels in the CNS due to enhanced GABA release via GABA(B) receptors, inhibition of GABA transaminase, activation of glutamic acid decarboxylase 7. Nauseated reveller: Valproate can cause GI distress (e.g. nausea, vomiting); valproate can be taken with food to reduce nausea cropped symbol image 7 8. Heavy box: Valproate can cause increased appetite and weight gain; monitor diet to avoid unwanted weight gain 9. Tremoring antenna: Valproate can cause tremor (at higher doses) 10. Liver fanny pack + ammonia cleaner: Valproate can cause hyperammonemia and rare, fatal hepatotoxicity; measure LFTs at baseline and monitor at frequent intervals thereafter, even though monitoring of liver aminotransferase (does not predict hepatic failure) 11. Squeezed pancreas sponge: Valproate can cause pancreatitis (rare); not related to dose or duration of therapy 12. Tubular tarantula: Valproate is teratogenic; associated with neural tube defects (e.g. spina bifida), orofacial clefts, and cardiac, urogenital and limb defects

Question 4

What is the MOA of Lamotrigine?
Clinical Use?
Adverse Effects/

Answer 4

Bolack NA channels on presynaptic terminal nerve

Antiepileptic and mood stabilizer in Bipolar

Sedation, dizziness, rash, Stephen Johnson Syndrome

20. Llama: Lamotrigine (broad spectrum antiepileptic drug; used for focal and generalized seizures, Lennox Gastaut syndrome, absence seizures (less effective than valproate and ethosuximide), bipolar disorder 21. Locked peanut box: Lamotrigine blocks voltage-gated sodium channels; may also inhibit glutamate and aspartate release 22. Cross-eyed: Lamotrigine can cause diplopia and blurred vision 23. Sloughed off red mask: Lamotrigine can cause Stevens-Johnson syndrome (incidence: 0.8% in children and 0.3% in adults); also can cause benign rash (10%) cropped symbol image 23

Question 5

What is the MOA of** Levetiracetam**
What is the clinical Use
What are the adverse effects?

Answer 5

Blocks synaptic vesicle protein 2A

broad spectrum antiepileptic

sedation, dizziness, fatigue,** Neuropsyciatric**

24. Elevator: Levetiracetam (broad spectrum antiepileptic drug); used for focal and generalized seizures, myoclonic seizures; bind to synaptic vesicle glycoprotein 2A (SV2A)26. Dizzy, nauseated rider: Levetiracetam and brivaracetam can cause dizziness, drowsiness and nausea 27. Falling brain hat: Levetiracetam (and brivaracetam, perhaps with better tolerability) can cause neuropsychiatric effects (e.g. depression, hostility, aggression and agitation); greater risk with history of psychiatric problems or learning difficulties

Question 6

MOA of topiramate
clinical USE
Adverse effects

Answer 6

blocks Na channel and increases GABAa receptor actibity

antiepileptic broad spectrum

sedation, dizziness, depression, weight loss, kidney stones, angle closure glaucoma

13. Toupee: Topiramate (broad-spectrum antiepileptic drug); used for focal and generalized seizures, Lennox-Gastaut syndrome, absence seizures, migraine prophylaxis 14. Locked peanut boxes: Topiramate blocks voltage-dependent sodium channels → stabilizes presynaptic neuronal membranes; also blocks NMDA-glutamate receptors 15. CAB-A pedicab passenger: Topiramate allosterically binds to the GABA-A receptor (a non-benzodiazepine binding site) 16. Sleeping driver: Topiramate can cause somnolence, fatigue, confusion and impaired concentration 17. Skinny driver: Topiramate can cause weight loss; combined with phentermine for weight management 18. Kidney-shaped wheels: Topiramate can cause urolithiasis (kidney stones); advise patients to stay hydrated, especially if prior history of kidney stones 19. Bulging eye balloon: Topiramate can cause acute angle-closure glaucoma; monitor for decreased visual acuity or ocular pain → cease immediately if this occurs cropped symbol image 19

Question 7

what is the MOA of Carbamazepine?

Answer 7

Blocks Na channels on pres synaptic terminal

“Seize the Night”: narrow-spectrum antiepileptic agents (e.g. carbamazepine, oxcarbazepine, phenytoin, phenobarbital) 2. Focal arm shaking: narrow-spectrum antiepileptic agents (e.g. carbamazepine, oxcarbazepine, phenytoin) treat focal seizures and generalized tonic-clonic 3. Classic car: carbamazepine (narrow-spectrum antiepileptic drug) 4. Inactivated salty sodium chip bags: carbamazepine ↑ voltage- and use-dependent Na + channel inactivation 5. Three gems: carbamazepine is a first line therapy for trigeminal neuralgia; oxcarbazepine is sometimes preferred due to ↓ adverse effects and drug-drug interactions 6. Unbalanced stack: carbamazepine can cause ataxia; may be more pronounced when beginning therapy or increasing dose; consider controlled-release tablets to reduce peak concentration-related effects like dizziness/unsteadiness 7. Misaligned headlights: carbamazepine can cause diplopia 8. Inappropriate wet head: carbamazepine can cause syndrome of inappropriate ADH (SIADH) 9. Sand timer: carbamazepine can cause agranulocytosis; conduct complete blood count prior to initiation and then periodically; cease carbamazepine if significant bone marrow suppression occurs; contraindicated with Hx of bone marrow depression 10. Activated chrome bumper: carbamazepine induces CYP450 (CYP2B6, CYP2C9, CYP3A4/5); results in ↓ substrate serum levels 11. Eosinophilic dress: carbamazepine can cause drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome; cease carbamazepine, treat with corticosteroids, do not restart carbamazepine 12. Tarantula: Carbamazepine is teratogenic; avoid use 13. Neural exhaust tube: Carbamazepine therapy during pregnancy can cause neural tube defects (e.g. spina bifida) 14. Contraceptive pack wheel: Carbamazepine ↓ serum levels of estrogenic and progestogenic components of hormonal contraceptives due to CYP3A4 induction; consider using non-hormonal contraception (e.g. copper I

Question 8

What is the clinical use and class of carbamazipine?

Answer 8

focal seizures
Narrow spectrum antiepileptics

“Seize the Night”: narrow-spectrum antiepileptic agents (e.g. carbamazepine, oxcarbazepine, phenytoin, phenobarbital) 2. Focal arm shaking: narrow-spectrum antiepileptic agents (e.g. carbamazepine, oxcarbazepine, phenytoin) treat focal seizures and generalized tonic-clonic 3. Classic car: carbamazepine (narrow-spectrum antiepileptic drug) 4. Inactivated salty sodium chip bags: carbamazepine ↑ voltage- and use-dependent Na + channel inactivation 5. Three gems: carbamazepine is a first line therapy for trigeminal neuralgia; oxcarbazepine is sometimes preferred due to ↓ adverse effects and drug-drug interactions 6. Unbalanced stack: carbamazepine can cause ataxia; may be more pronounced when beginning therapy or increasing dose; consider controlled-release tablets to reduce peak concentration-related effects like dizziness/unsteadiness 7. Misaligned headlights: carbamazepine can cause diplopia 8. Inappropriate wet head: carbamazepine can cause syndrome of inappropriate ADH (SIADH) 9. Sand timer: carbamazepine can cause agranulocytosis; conduct complete blood count prior to initiation and then periodically; cease carbamazepine if significant bone marrow suppression occurs; contraindicated with Hx of bone marrow depression 10. Activated chrome bumper: carbamazepine induces CYP450 (CYP2B6, CYP2C9, CYP3A4/5); results in ↓ substrate serum levels 11. Eosinophilic dress: carbamazepine can cause drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome; cease carbamazepine, treat with corticosteroids, do not restart carbamazepine 12. Tarantula: Carbamazepine is teratogenic; avoid use 13. Neural exhaust tube: Carbamazepine therapy during pregnancy can cause neural tube defects (e.g. spina bifida) 14. Contraceptive pack wheel: Carbamazepine ↓ serum levels of estrogenic and progestogenic components of hormonal contraceptives due to CYP3A4 induction; consider using non-hormonal contraception (e.g. copper I

Question 9

What are the side effects of Carbamazipine?

Answer 9

hyponatremia, rare aplastic anemia, luekopenia, hepatitis, stevenjohnson syndome, ataxia, diplopia

“Seize the Night”: narrow-spectrum antiepileptic agents (e.g. carbamazepine, oxcarbazepine, phenytoin, phenobarbital) 2. Focal arm shaking: narrow-spectrum antiepileptic agents (e.g. carbamazepine, oxcarbazepine, phenytoin) treat focal seizures and generalized tonic-clonic 3. Classic car: carbamazepine (narrow-spectrum antiepileptic drug) 4. Inactivated salty sodium chip bags: carbamazepine ↑ voltage- and use-dependent Na + channel inactivation 5. Three gems: carbamazepine is a first line therapy for trigeminal neuralgia; oxcarbazepine is sometimes preferred due to ↓ adverse effects and drug-drug interactions 6. Unbalanced stack: carbamazepine can cause ataxia; may be more pronounced when beginning therapy or increasing dose; consider controlled-release tablets to reduce peak concentration-related effects like dizziness/unsteadiness 7. Misaligned headlights: carbamazepine can cause diplopia 8. Inappropriate wet head: carbamazepine can cause syndrome of inappropriate ADH (SIADH) 9. Sand timer: carbamazepine can cause agranulocytosis; conduct complete blood count prior to initiation and then periodically; cease carbamazepine if significant bone marrow suppression occurs; contraindicated with Hx of bone marrow depression 10. Activated chrome bumper: carbamazepine induces CYP450 (CYP2B6, CYP2C9, CYP3A4/5); results in ↓ substrate serum levels 11. Eosinophilic dress: carbamazepine can cause drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome; cease carbamazepine, treat with corticosteroids, do not restart carbamazepine 12. Tarantula: Carbamazepine is teratogenic; avoid use 13. Neural exhaust tube: Carbamazepine therapy during pregnancy can cause neural tube defects (e.g. spina bifida) 14. Contraceptive pack wheel: Carbamazepine ↓ serum levels of estrogenic and progestogenic components of hormonal contraceptives due to CYP3A4 induction; consider using non-hormonal contraception (e.g. copper I

Question 10

MOA of oxacarbazepine
clinical use/class
adverse effects

Answer 10

Na channel blocker on presynaptic cleff
focal seizures/ narrow antiepileptic
ataxia, diplopia, may exasperate tonic clonic, myclonic and absence seizures

16. Ox car: oxcarbazepine (narrow-spectrum antiepileptic drug); focal seizures (adjunctive or monotherapy) in children and adults 17. Inactivated salty sodium chip bags: oxcarbazepine ↑ voltage-dependent Na + channel inactivation 18. Helmet + tinted windows: oxcarbazepine has ↓ CNS side effects and interactions than carbamazepine; may be a suitable alternative for people unable to take carbamazepine; comes with risk of SJS, DRESS, blood dyscrasias 19. Tarantula jacket: Oxcarbazepine is teratogenic (likely, few clinical studies)

Question 11

****Phenytoin- **
MOA
clinical USE
SIDE EFFECTS

Answer 11

blocks Na channel and inhibits potentiation of AP

narrow spectrum focal and complex seziures or status epilepticus for resistant cases when benzos dont work.

Gingival hyperplasi, hirsitis, coarsening of facial features, DRESS syndrome

20. Classic tow truck: phenytoin (narrow-spectrum antiepileptic drug); simple and complex focal seizures, generalised tonic-clonic seizures 21. Inactivated salty sodium chip bags: phenytoin ↑ voltage- and use-dependent Na + channel inactivation 22. Unbalanced stack: phenytoin can cause ataxia 23. Misaligned headlights: phenytoin can cause diplopia 24. Expanding gum: phenytoin can cause gingival hyperplasia 25. Big bushy beard: phenytoin can cause hirsutism 26. Lupus wolf: phenytoin, carbamazepine and oxcarbazepine can drug-induced lupus 27. Eosinophilic dress: phenytoin can cause drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome 28. Sloughed off red mask: phenytoin can cause Stevens-Johnson syndrome (SJS/TEN) 29. Tarantula: Phenytoin is teratogenic; phenytoin therapy during pregnancy can cause cleft palate 30. Activated chrome bumper: Phenytoin induces CYP450 (CYP1A2, CYP2B6, CYP2C9, CYP3A4/5); results in ↓ substrate serum levels 31. Contraceptive pack hubcap: Phenytoin ↓ serum levels of estrogenic and progestogenic components of hormonal contraceptives due to CYP3A4 induction; consider using non-hormonal contraception (e.g. copper IUD), or levonorgestrel IUD or medroxyprogesterone depot (unaffected by CYP3A4 induction) 32. Fractured osteoporotic axle: phenytoin can ↓ bone density; monitor BMD, supplement with vitamin D and calcium if therapy is long-term

Question 12

Vigabatran-
MOA
clinical use
adverse effects

Answer 12

irreversibly binds GABAt, increasing GABA conc.

epileptic spasms in tuberous sclerosis, refractory focal onset seizures- narrow spectrum

visual field defects, may increase myotonic seizures and absence seizures

36. Raised CAB-A: vigabatrin and tiagabine (narrow-spectrum antiepileptic drugs) ↑ GABA 37. V cab transmission: vigabatrin irreversibly inhibits GABA transaminase (↓ GABA degradation) 38. Tied up cab driver: tiagabine inhibits GABA reuptake

Question 13

Ethosuximide-
MOA
Clinical Use
Side effects

Answer 13

Ttype Calcium channel blocker on pre synamptic terminal

Absenece Seizures

nausea vomiting sedation

1. "Seize the day": antiepileptic therapy for absence seizures (e.g. ethosuximide) 2. "Absences": absence seizure (a type of generalized seizure) 3. Inattentive student: absence seizures are characterized by sudden momentary lapse in awareness accompanied by staring, blinking, or clonic jerks 4. "3 spikes": absence seizure manifest as 3 Hz spike wave complexes on EEG 5. "Ethos": ethosuximide (a narrow spectrum anti-epileptic drug used to treat absence seizures) 6. Closed Calci-Yum chocolate: ethosuximide blocks Ca2+ channels 7. Closed T-thermos: ethosuximide blocks T-type Ca2+ channels in the thalamus 8. Punched in stomach: ethosuximide can cause GI distress (e.g. pain, nausea, vomiting) 9. Sleeping student: ethosuximide can cause lethargy or fatigue 10. FestiVAL banner: valproate is effective against absence seizures 11. Llama: lamotrigine is effective against absence seizures

Question 14

Gabapentin/ Pregabalin-
MOA
Clinical Use
Side effects

Answer 14

blocks Ca channels at pre synaptic terminal

narrow spectrum antiepileptic (focal seizures), Neuropathy

Dizziness, Ataxia, Sedation

“Grab a pint”: gabapentin and pregabalin (narrow-spectrum antiepileptic drug); focal seizures, with or without secondary generalization, that are refractory or poorly controlled by other antiepileptic drugs cropped symbol image 1 2. Closed Calci-Yum ice cream cooler: gabapentin and pregabalin block voltage gated Ca 2+ channels → ↓ Ca 2+ influx and neurotransmitter release cropped symbol image 2 3. Chronically frayed wire: gabapentin and pregabalin treat chronic pain (e.g. neuropathic pain) 4. Diasweetes: gabapentin and pregabalin treat painful diabetic neuropathy 5. Fiber bars: gabapentin and pregabalin treat fibromyalgia 6. Zeus: gabapentin and pregabalin treat postherpetic neuralgia (reactivated varicella-zoster virus - VZV) 7. Unbalanced scoops: gabapentin and pregabalin can cause CNS side effects (e.g. ataxia, dizziness, sedation)

Question 15

Midazolam, Alprazolam, Lorazepam, Clonazepam-
MOA
Clinical Use
Side Effects

Answer 15

moa- facilitate GABA frequency via increasing frequency of Cl- channel opening. Long half life

USE- anxiety, status epilepticus, night terrors, spasticity, alcohol withdrawal.

Dependence, CNS depression alcohol or and barbituates

Ben's diner: benzodiazepines 2. PAM-cakes: "-pam" suffix of benzodiazepines (e.g. diazepam, lorazepam, oxazepam) 3. Fast ox: oxazepam (a short-acting benzodiazepine) 4. "All A.M.": "-olam" suffix of short-acting benzodiazepines (triazolam, alprazolam, midazolam) 5. "Addictive flavor": benzodiazepines have the potential to cause addiction (more common with short-acting agents) 6. Liver spot: benzodiazepines are metabolized by the liver (long acting agents form active metabolites) 7. Cab-A: benzodiazepines bind to an allosteric site on the GABA-A receptor 8. CNS light: benzodiazepines potentiate GABA-A transmission in the CNS 9. "Chlo-Rider": the GABA-A receptor is a chloride channel 10. "Take it easy": GABA (with glycine) is a major inhibitory neurotransmitter in the CNS 11. "Open more frequently": benzodiazepines increase the frequency of ion channel opening 12. Alcoholic on Cab-A: alcohol binds the GABA-A receptor at a separate allosteric site 13. Hangover special: benzodiazepines treat alcohol withdrawal 14. Anxious tremulous customer: alcohol withdrawal symptoms (8-12 hours) - insomnia, tremulousness, anxiety, autonomic instability 15. Falling customer: alcohol withdrawal symptoms (12-48 hours) - seizures

Question 16

**Phenobarbital, pentobarbital- **
MOA
Clinical Use
Adverse Effects

Answer 16

moa- Increases duration of Cl- channel opening thus decreasing neuron firing. (barbidurates- duratoin)

USE- sedative for anxiety, seizures, insomnia

Adverse Effects- respiratory and CV depression, dependance, drug interactions, contraindicated in porphoria, alcohol use.

1. Activated chrome bumper: barbiturates (e.g. phenobarbital) are potent inducers of the cytochrome P450 system 2. Cab-A: barbiturates bind to an allosteric site on the GABA-A receptor 3. Ben's diner next to Cab-A: benzodiazepines bind the GABA-A receptor at a separate allosteric site 4. Alcoholic on Cab-A: alcohol binds the GABA-A receptor at a separate allosteric site 5. "Chlo-Rider": the GABA-A receptor is a chloride channel 6. CNS light: barbiturates potentiate GABA-A transmission in the CNS 7. "Take it easy": GABA (with glycine) is a major inhibitory neurotransmitter in the CNS 8. "Open longer": barbiturates increase the duration of opening of the GABAA receptor 9. Long tapering flag: barbiturates have long durations of action ("hangover" effects more common) 10. Intubated customer: IV thiopental can be used for induction of anesthesia 11. Ivy: IV administration of barbiturates is useful for induction of anesthesia (thiopental) and management of seizures (phenobarbital) 20. Collapsed heart and lungs: barbiturates can cause profound cardiac and respiratory depression 21. Fainting: barbiturates can cause hypotension 22. Brain hair dryer: barbiturates can cause severe CNS depression (e.g. coma) and should be avoided in the elderly 23. "All are welcome": chronic barbiturate use leads to tolerance 24. "Addicted": chronic barbiturate use leads to physical dependence

Question 17

Zolpidem, Zaleplon, Eszopidone-
MOA
Clinical Use
Adverse Effects

Answer 17

partial benzo agonist- binds to bzd receptor on alpha 1 subunit fo GABA receport, decreases latency to persistant sleep…?

insomnia