Anticonvulsants Pharm 125 PDF

ANTICONVULSANTS PHARM 125 (PHARMACOLOGY FOR PHARMACY 1) Ena Elizabeth L. Naoe, MD | HYNITH: BSP 2023 | YEAR 2 SEM 1 | AY 2024-2025 LEGEND OUTLINE Bold + highlight - DOH medici...

ANTICONVULSANTS PHARM 125 (PHARMACOLOGY FOR PHARMACY 1) Ena Elizabeth L. Naoe, MD | HYNITH: BSP 2023 | YEAR 2 SEM 1 | AY 2024-2025 LEGEND OUTLINE Bold + highlight - DOH medicine access I. INTRODUCTION program A. SEIZURE Bold - included in PNF-EML B. EPILEPSY Orange - Registered with the Philippine FDA, C. EPILEPSY TYPES but Non-PNF i. FOCAL Brown - Highlighted during the lecture ii. GENERALIZED iii. MYOCLONIC I. INTRODUCTION iv. ABSENCE A. SEIZURE D. SEIZURE GENERATION Transient S/Sx due to abnormal excessive or i. OVERVIEW OF synchronous neuronal activity NEUROTRANSMITTER FLOW ○ Due to various reasons such as infections, ii. ION-CHANNELS underlying episode of another condition like iii. SEIZURE GENERATION hypo/hypernatremia II. ANTI-SEIZURE MEDICATIONS A. DRUG LIST ○ Signs and symptoms - abnormal movements i. INHIBITION OF VOLTAGE-GATED (generalized jerking of the extremities) CHANNELS simple symptom - smell burn kahit wala nmn ii. ENHANCEMENT OF GABA burning = seizure neuronal activity SYNAPTIC TRANSMISSION ○ abnormal excessive or synchronous neuronal iii. MODULATION OF GLUTAMATE activities- continuous discharge of corticoneurons RELEASE = ↑ neuronal activity (↑↓ (-) mechanisms ) B. GENERAL MECHANISM OF ACTION ○ Not all seizures are epilepsy C. PHENYTOIN D. CARBAMAZEPINE B. EPILEPSY E. OXCARBAZEPINE At least two unprovoked seizures occurring >24 hrs F. LAMOTRIGINE apart G. LACOSAMIDE ○ Unprovoked - not caused by Sx (fever, metab, etc) H. GABAPENTIN, PREGABALIN One unprovoked seizure and a probability of further I. ETHOSUXIMIDE seizures similar to the general recurrence risk (at least J. PHENOBARBITAL 60%) after two unprovoked seizures, occurring over the K. BENZODIAZEPINES next 10 years i. BARBITURATES VS. ○ Ex. brain tumor - ↑↑ chance for seizure coz of BENZODIAZEPINES leasion = pwede epilepsy L. LEVETIRACETAM, BRIVARACETAM Diagnosis of an epilepsy syndrome M. PERAMPANEL ○ Seizure - clinical manifestation of epilepsy N. TOPIRAMATE ○ not all seizures need medications or Tx; it is O. ZONISAMIDE more on the epilepsy syndrome P. VALPROATE Q. OTHER MEDICATIONS i. VIGABATRIN ii. TIAGABINE iii. FELBAMATE R. POCKET GUIDE III. PHARMACOKINETICS IV. PHARMACODYNAMICS V. THERAPEUTIC DRUG MONITORING VI. QUESTIONS C. EPILEPSY TYPES PHARM 125 (PHARMACOLOGY FOR PHARMACY 1) Carles, Chua, De Guzman, Go, Magalued, Mendoza Page 1 of 10 ANTICONVULSANTS PHARM 125 (PHARMACOLOGY FOR PHARMACY 1) Ena Elizabeth L. Naoe, MD | HYNITH: BSP 2023 | YEAR 2 SEM 1 | AY 2024-2025 This is important to know because the medications Most abundant AA in the mammalian brain will depend on the epilepsy type For learning, memory, cognition Using Glu - get out of Glu Neuron i. FOCAL ○ calcium-dependent process - Glu released -> Glu Only one part of the body has seizure (ex. One part of act on other receptors brain) Regulate Excitatory - astrocyte (support cells in the ii. GENERALIZED brain) prevents the overexcitation ○ Reuptake -> astrocyte get Glu -> glutamine Both brain hemispheres are acting, causing the synthetase -> convert back to Gln -> transpo to generalized type of seizures glutamatergic neuron = cycle repeat ○ It involves all of your extremities On the other hand, your astrocyte can also give ○ Some focal seizures can be generalized glutamine to the GABAergic neuron Ex. start at one part then general ○ GABAergic Neuron - Gln -> glutaminase -> iii. MYOCLONIC Glutamate -> Glutamine decarboxylase -> GABA Sudden outbursts of movements or jerking of the -> GABA packaged into vesicle -> exocytosis -> extremities GABA receptor = inhibitory In the brain, all of these are balanced iv. ABSENCE ○ Excitatory + reuptake or inhib process via astocytes Sudden behavioral arrest ○ Once overexcited or decreased inhibitory ○ E.g. the patient is sleeping and suddenly wakes up occurs, seizure happens and blank stares then back to usual activity ii. ION-CHANNELS D. SEIZURE GENERATION Population of pathologically excitable neurons ○ Ex. brain tumor - may scar na coz of post-op = flow of electricity is weird for the excitable neurons + imbalance in the mechanisms of the brain Increase in excitatory, mainly glutamatergic activity through recurrent connections to spread the discharge ○ Imbalance between neuronal excitations and inhibitions ○ Excitatory = Glutamate Reduction in the activity of the normally inhibitory GABAergic projections Calcium (Ca2+) is important for the release of the ○ Decreased GABA = inhibitory neurotransmitter (NT) i. OVERVIEW OF NEUROTRANSMITTER FLOW ○ More Calcium = More NT released via exocytosis ○ presynaptically Postsynaptically, Na+ opening para may depolarizat ○ If sodium (Na+) is open -> certain magnitude -> Ca also open ○ Regulate overexcitation - Potassium (K+) to get out to attain repolarization ○ If you want movement = Na+ & Ca2+ ○ If you want depolarization = K+ outflux II. ANTI-SEIZURE MEDICATIONS Enhance GABA = more (-) Glutametergic Neuron - Gln -> glutaminase -> ○ seizures are excitatory events, so GABA to inhibit Glutamate + modulating excite w/ Glu ○ Glutamate = Main excitatory neurotransmitter PHARM 125 (PHARMACOLOGY FOR PHARMACY 1) Carles, Chua, De Guzman, Go, Magalued, Mendoza Page 2 of 10 ANTICONVULSANTS PHARM 125 (PHARMACOLOGY FOR PHARMACY 1) Ena Elizabeth L. Naoe, MD | HYNITH: BSP 2023 | YEAR 2 SEM 1 | AY 2024-2025 Inhibition of voltage-gated channels Pregabalin (PGB) ○ Not Na+ and Ca2+, but promote K+ (repolar) Enhancement of GABA synaptic transmission ii. ENHANCEMENT OF GABA SYNAPTIC TRANSMISSION ○ GABA Receptor allosteric modulators GABA-A Receptor Allosteric Modulators ○ GABA uptake inhibitors ○ ↑ membrane hyperpolarization and seizure ○ GABA metabolism inhibitors threshold Modulation of Glutamate Release ○ ↓ focal firing ○ Diminished synaptic excitation (AMPA, NMDA) ○ Drugs: diminish the synaptic excitation through our Benzodiazepines (BZDs) AMPA or NMDA receptors, may Glu that will Attenuate spike-wave discharges diminish excited neurons Phenobarbital (PB) ○ Modulation of synaptic release (SV2A) Aggravate spike-wave discharges Modulate the release of GABA through the Felbamate (FBM) Synaptic Vesicle Protein (SV2A). Primidone (PRM) ○ We choose between modulating the protein Topiramate (TPM) necessary for release, or modulating the end Carbamazepine (CBZ) point of the Glu for us to inhibit the action of Glu Aggravate spike-wave discharges Oxcarbazepine (OxCBZ) A. DRUG LIST Aggravate spike-wave discharges Stiripentol (STP) i. INHIBITION OF VOLTAGE-GATED CHANNELS Clobazam (CLB) Prolongation of inactive state of Na+ GABA uptake inhibitors/ GABAtransaminase ○ Block AP + Stabilize neuronal hormones metabolism inhibitors ○ ↓ Neurotransmitter release, focal firing, and ○ ↑ Extrasynaptic GABA levels and membrane seizure spread hyperpolarization ○ Fast inactivation Drugs ○ ↓ focal firing Phenytoin (PHT) ○ Aggravate spike-wave discharges Carbamazepine (CBZ) ○ Drugs: Lamotrigine (LTG) Tiagabine (TGB) Felbamate (FBM) Vigabatrin (VGB) Oxcarbazepine (OxCBZ) Topiramate (TPM) iii. MODULATION OF GLUTAMATE RELEASE Valproic Acid (VPA) AMPA/Kainate Receptor Antagonists Eslicarbazepine (ESL) ○ ↓ Fast excitatory neurotransmission and focal Rufinamide (RFM) firing Zonisamide (ZNS) ○ Drugs: Cenobamate (CNB) Phenobarbital (PB) ○ Slow inactivation Drugs Topiramate (TPM) Lacosamide (LCM) Perampanel (PER) Positive modulation of K+ NMDA Receptor Antagonists ○ Suppresses bursts of AP + Hyperpolarizes ○ ↓ Slow excitatory neurotransmission membrane potentials ○ ↓ Excitatory amino acid neurotoxicity Inhibition of Ca2+ ○ Drugs: ○ ↓ Neurotransmitter release (N– and P– types) Felbamate (FBM) ○ ↓ Slow-depolarization (T-type) and spike-wave SV2A Protein Ligand discharges ○ Unknown: may decrease neurotransmitter release Ethosuximide (ESM) ○ Drugs: Valproic Acid (VPA) Levetiracetam (LEV) Lamotrigine (LTG) Brivaracetam (BRV) Gabapentin (GBP) PHARM 125 (PHARMACOLOGY FOR PHARMACY 1) Carles, Chua, De Guzman, Go, Magalued, Mendoza Page 3 of 10 ANTICONVULSANTS PHARM 125 (PHARMACOLOGY FOR PHARMACY 1) Ena Elizabeth L. Naoe, MD | HYNITH: BSP 2023 | YEAR 2 SEM 1 | AY 2024-2025 Indications B. GENERAL MECHANISM OF ACTION ○ 2nd Line: Focal and Unknown Onset Seizures ○ 3rd Line: GTC +/- Myoclonic balance between your excitatory and inhibitory. ○ Status Epilepticus - non-stop seizures, emergency Half-Life ○ 12 – 36 hr (Long half-life) Dose ○ Children: 4-7 mg/kg ○ Adults: 300-400 mg/day ADR ○ Limited clinical use coz very toxic to use and limiting in terms of S/E. ○ Excessive IV Administration → Cardiac arrhythmia (Recommended rate: < 50mg/min) Adjust dose nlng ○ Ataxia, Diplopia, Supor, Hirsutism, Enlargement of genus ○ Teratogenic: Fetal Hydantoin Syndrome Do NOT give to pregnant women. Others Excitatory - Glu ○ CYP450 Inducer ○ ↓ release of Glu by modulating the ion channel Induces metabolism of CYP450 substrate drugs ○ Drug - inhibit Na+ Channels, Ca2+ Channels, and = lower levels of those drugs. Protein responsible for release of Glu (SV2A) ○ Nonlinear pharmacokinetics and narrow therapeutic index Zero order kinetics. Smol dose = disproportionate increase in your plasma concentration = smol TI ○ Formulation dependent ○ 90% mostly bound to albumin ○ Can exacerbate myoclonic seizures. Na+ Inhibitors = myoclonic seizures worse. D. CARBAMAZEPINE Drug Class ○ Fast Sodium Channel Inhibitor Indications ○ First-line for focal seizures and unknown onset ○ Third-line for generalized motor seizures Half-life Inhibitory - GABA. ○ 14-25h ○ ↓ reuptake of GABA through Tiagabine. Dose ○ ↓ the metabolism via the degradation enzyme of ○ Children - 20-30 mg/kg GABA (GABA-T) through Viagabrin. ○ Adults - 600-1200 mg/day ○ Increase activity of GABA receptors through ADR Barbiturates, Benzodiazepines. ○ High risk of SJS-TEN (HLA-B*1502 haplotype) Give at low dose -> check s/e. If rash = stop C. PHENYTOIN agad so Titrate slowly Drug Class ○ Water retention -> Hyponatremia (Diabetes ○ Fast Sodium Channel Inhibitor Insipidus) PHARM 125 (PHARMACOLOGY FOR PHARMACY 1) Carles, Chua, De Guzman, Go, Magalued, Mendoza Page 4 of 10 ANTICONVULSANTS PHARM 125 (PHARMACOLOGY FOR PHARMACY 1) Ena Elizabeth L. Naoe, MD | HYNITH: BSP 2023 | YEAR 2 SEM 1 | AY 2024-2025 ○ Leukopenia, Thrombocytopenia, Aplastic Anemia, ○ Cardiac arrhythmia Agranulocytosis ○ Rare case of reversible chorea if with phenytoin ○ Common - Dizziness Others Others ○ Synergistic effect with VPA ○ CYP450 Inducer ○ Favorable teratogenic profile - ok for preggers ○ Auto-induction - Drug levels decrease needing to ○ Does not provoke weight gain and ovarian increase the dose problems (vs VPA) ○ Can exacerbate myoclonic seizures ○ Mood stabilizing properties ○ Metabolite - 10, 11 epoxide ○ Titrate slowly frequent seizures = no slow to up-titrate E. OXCARBAZEPINE G. LACOSAMIDE Drug Class Drug Class ○ Fast Sodium Channel Inhibitor (Second Analogue ○ Slow Sodium Channel Inhibitor of Indications Indications ○ First-line for focal seizures and unknown onset ○ First-line for focal seizures and unknown onset seizures ○ Third-line for generalized motor seizures ○ Can be used for status epilepticus Half-life Half-life ○ 1 - 5 hr ○ 13 hr Dose Dose ○ Children - 10-40 mg/kg ○ Children - 6-8 mg/kg ○ Adults - 900 - 2,400 mg/day ○ Adult - 300-400 mg/day ADR ADR ○ Similar to Carbamazepine ○ Avoided in patients with cardiac condition ○ Some reported weight gain (prolong PR interval - AV block, bradycardia) Others ○ Headache, diplopia, dizziness, ataxia ○ Advantages of being titrated upward at a more Others rapid rate than Carbamazepine ○ Limited pharmacokinetic interaction ○ Less hepatic enzyme induction ○ Renally excretion ○ Metabolite - Eslicarbazepine ○ IV preparation is notable ○ Prodrug - Needs to be metabolized first to its active ○ Completely absorbed from the GI tract form H. GABAPENTIN, PREGABALIN F. LAMOTRIGINE Drug Class Drug Class ○ L-type Calcium Channel Blockers (ɑ2δ -1 protein) ○ Slow Sodium Channel Inhibitor Regulates the neuronal excitability. Indications Nothing abt GABA, it decreases calcium ○ First-line for focal seizures and unknown onset channels = less release excitatory NT start first with Lamotrigine but pricey ○ GABA receptor agonists but no mimic GABA Reco for monotherapy at first + adj as time Indications goes by ○ Third-line for focal seizures and unknown onset ○ Second-line for generalized +/- myoclonic Half-life Half-life ○ 5-7 hr ○ 15 - 60 hr (Doubles with VPA) Dose Dose ○ Gabapentin: Adults - 900-3,600 mg/day ○ Children - 0.5 mg/kg ○ Pregabalin - 150-600 mg/day ○ Adults - 300-500 mg/day ADR ADR ○ Somnolence, dizziness, ataxia, fatigue ○ Risk of SJS-TEN (HLA-B*1502 Haplotype) Others PHARM 125 (PHARMACOLOGY FOR PHARMACY 1) Carles, Chua, De Guzman, Go, Magalued, Mendoza Page 5 of 10 ANTICONVULSANTS PHARM 125 (PHARMACOLOGY FOR PHARMACY 1) Ena Elizabeth L. Naoe, MD | HYNITH: BSP 2023 | YEAR 2 SEM 1 | AY 2024-2025 ○ Renal Excretion Others ○ Absorbed after oral administration and are not ○ CYP450 Inducer metabolized ○ Hepatic excretion ○ Not bound to plasma proteins ○ 40-60% bound to plasma proteins ○ Tolerance may also develop I. ETHOSUXIMIDE ○ Pregnancy (hypothrombinemia with hemorrhage) Drug Class > Vitamin K ○ T-type Calcium Channel Blockers Managed using Vitamin K lik calcium channel in your thalamus (sight of DO NOT GIVE to pregnant women seizure generation) ○ Megaloblastic anemia (folate) and osteomalacia Indications (vit D) on chronic use ○ First-line for absence seizures (sudden behavioral arrest) K. BENZODIAZEPINES Not available in the Philippines Examples: Half-life ○ Clonazepam - Intermediate-acting (6-24h) ○ 20-60 hr ○ Clobazam - Long-acting (>24h) Dose ○ Diazepam - Long-acting (>24h) ○ Children - 20-40 mg/kg ○ Lorazepam ○ Adults - 750-1,500 mg/day ○ Midazolam - Short-acting (6h) ADR Drug Class ○ GI complaints (N/V, anorexia) ○ GABA-A receptor agonist (increased frequency of ○ Lethargy, drowsiness, headache Cl- channel opening) ○ Parkinson-like symptoms, photophobia With Benzodiazepines, you increase the ○ Restlessness, agitation, anxiety frequency when GABA channel is open. Others Indications ○ Absorption appears to be complete with peak ○ CLN: First line for myoclonic (Clonazepam); third concentration reaching within 3 hours line for GTC +myoclonic +/-absence ○ Not significantly bound to plasma proteins ○ Status epilepticus Midazolam (IV) J. PHENOBARBITAL Half-life Drug Class ○ CLZ 18-50h ○ GABA-A receptor agonist (increased duration of ○ CLB 5-40h Cl- channel opening) “barbiDURATION” ○ DZP 60-72h GABA is a Cl receptor = more (-) coz Metabolite: nordiazepam hyperpolarization = want promote the Dose opening of the GABA so increase duration of ○ Adults: opening CLZ 2-10mg/day Indications CLB 5-40mg/day ○ Third-line for focal, generalized (+/- myoclonic), DZP 2-40mg/day unknown onset seizures ADR Not that used compared to benzodiazepines ○ Drowsiness and lethargy Half-life Titrate to lessen ADR ○ 40-120 hr (Long half-life) ○ Hypotonia, dysarthria, behavioral disturbances, Dose anorexia, hyperphagia ○ Children: 3-5 (8 for infants) mg/kg ○ Cardiovascular and respiratory depression (IV use) ○ Adults - 90-200 mg/day Not as much compared to barbiturates ADR Others ○ Sedation ○ Well-absorbed, maximal within 1-4h, redistribute ○ Irritability, hyperactivity, confusion like a highly lipid soluble agents ○ Nystagmus and ataxia at excessive dosage ○ May have tolerance within 1-6 months PHARM 125 (PHARMACOLOGY FOR PHARMACY 1) Carles, Chua, De Guzman, Go, Magalued, Mendoza Page 6 of 10 ANTICONVULSANTS PHARM 125 (PHARMACOLOGY FOR PHARMACY 1) Ena Elizabeth L. Naoe, MD | HYNITH: BSP 2023 | YEAR 2 SEM 1 | AY 2024-2025 ○ Diazepam metabolite: nordiazepam ○ Favorable teratogenic potential - ok preggers i. BARBITURATES VS. BENZODIAZEPINES Note: Pregnant Women are given the “L medicines” Lamotrigine ○ Ok for agitations Levetiracetam ○ No important interactions ○ May cause agitation Lacosamide Are not as teratogenic compared to other medications M. PERAMPANEL Barbiturate Overdose: Coma, Medullary depression (may cause respiratory arrest) Drug Class ○ Benzodiazepine even at high doses do not reach ○ AMPA antagonist medullary depression and coma AMPA - glutamate receptor Benzodiazepines is more used than Barbiturates Indications ○ s/e of benzos not first line for seizures ○ Second-line for focal and unknown onset ○ Third-line for generalized +/ - myoclonic L. LEVETIRACETAM, BRIVARACETAM ○ Adjunct for status epilepticus Half-life Drug Class ○ 105h (long half life) ○ SV2A (synaptic vesicle protein) inhibitor Dose SV2A - protein responsible for the exocytosis; ○ Adults: 2-12 mg/day (-) it prevents the release of levetiracetam ADR Indications ○ Somnolence, anxiety, confusion, dizziness, GI ○ First-line for focal seizures, myoclonic, unknown distress onset ○ Adverse behavioral reactions, aggression, suicidal ○ Second-line for generalized tonic-clonic seizures thoughts Half-life Others ○ 6-8h ○ Hepatic excretion Dose ○ Good oral bioavailability ○ Children: 20-60 mg/kg ○ Expensive ○ Adults 500-3,000 mg/day ADR N. TOPIRAMATE ○ Sleepiness and dizziness ○ Irritability, depression Drug Class Others ○ Multiple MOAs: Sodium channel inhibitor, AMPA ○ Renally excreted inhibitor, GABA modulator ○ Well tolerated if initiated slowly Useful for various kinds of seizures; BUT many ○ No important interactions with other side effects antiepileptic drugs Indications Easy drug to prescribe ○ Second-line for focal seizures and unknown BUT high behavioral and mood side effects ○ Third-line for generalized +/- myoclonic, absence (ex. aggressive, agitated, etc.) Half-life ○ First line if with numerous medical conditions and ○ 20-30h numerous medicines Dose Not rly given if w/ psychiatric conditions ○ Adults: 400 mg/day PHARM 125 (PHARMACOLOGY FOR PHARMACY 1) Carles, Chua, De Guzman, Go, Magalued, Mendoza Page 7 of 10 ANTICONVULSANTS PHARM 125 (PHARMACOLOGY FOR PHARMACY 1) Ena Elizabeth L. Naoe, MD | HYNITH: BSP 2023 | YEAR 2 SEM 1 | AY 2024-2025 ADR ○ Adults: 1000-3000 mg/day ○ Somnolence, fatigue, weight loss, nervousness ADR ○ May precipitate renal calculi (kidney stokes) > can ○ Hepatotoxic also inhibit carbonic anhydrase Check first for liver problems ○ Cognitive impairment ○ Weight gain during the first months, menstrual Brain fog, slowing - not recommended for irregularities and PCOS working patients, progressive ages ○ Sedation, ataxia, tremor (simulate parkinsonism) Others ○ Rare: pancreatitis ○ Rapidly absorbed after oral administration Others ○ Little binding to plasma proteins ○ CYP450 Inhibitor ○ Undergoes hepatic metabolism O. ZONISAMIDE ○ Highest teratogenic risk (neural fold defects) Drug Class Q. OTHER MEDICATIONS ○ Multiple MOAs: Na+ and Ca+ onhibitor Indications Vigabatrin ○ Second-line for focal and unknown onset ○ Inhibits GABA transaminases (prevents ○ Third-line for generalized +/- myoclonic, absence degradation) Half-life Tiagabine ○ 63h ○ Inhibits GABA transporter GAT-1 (prevents Dose reuptake) ○ Children: 100-600 mg/day Felbamate ○ Adults: Max 600 mg/day ○ NMDA antagonist ADR ○ Not indicated as first line far any type of seizures ○ Weight-loss ○ High risk for aplastic anemia and liver failure Prominent side effect Not used as much ○ Somnolence, dizziness, cognitive impairment, GABA inhibitors ataxia, anorexia, ○ Tiagabin - Transporters ○ Rare: skin rashes ○ Vigabatrin - Degradation ○ High chance for metabolic acidosis and renal calculi > carbonic anhydrase inhibitor R. POCKET GUIDE Wary w/ renal disease and respiratory acidosis Others ○ Renally excreted ○ Well-tolerated ○ Very Expensive P. VALPROATE Aka Valproic Acid Drug Class ○ Multiple MOAs: sodium channel blocker, calcium channel blocker, potentiates GABA (acts through glutamic acid decarboxylase) Indications ○ First-line for generalized +/- myoclonic, absence ○ Second-line for focal and unknown Half-life ○ 6-15h Dose ○ Children: 30-60 mg/kg PHARM 125 (PHARMACOLOGY FOR PHARMACY 1) Carles, Chua, De Guzman, Go, Magalued, Mendoza Page 8 of 10 ANTICONVULSANTS PHARM 125 (PHARMACOLOGY FOR PHARMACY 1) Ena Elizabeth L. Naoe, MD | HYNITH: BSP 2023 | YEAR 2 SEM 1 | AY 2024-2025 III. PHARMACOKINETICS absorption is extensive with high bioavailability ○ Gabapentin displays a dose-related absorption. Most ASMs are lipid soluble, allowing them to cross BBB and are generally widely distributed PHARM 125 (PHARMACOLOGY FOR PHARMACY 1) Carles, Chua, De Guzman, Go, Magalued, Mendoza Page 9 of 10 ANTICONVULSANTS PHARM 125 (PHARMACOLOGY FOR PHARMACY 1) Ena Elizabeth L. Naoe, MD | HYNITH: BSP 2023 | YEAR 2 SEM 1 | AY 2024-2025 ○ Valproate, Gabapentin, Pregabalin are ionized in Choice and dose of medication is dependent on many serum and their distribution is very dependent on factors including sex, age, medications, comorbidities the uptake transport (medical and psychiatric) Degree of Protein Binding varies between drugs General rule is to start in lower dose range and ○ >90% protein bound: PHT, VPA, CLB, CLZ, PMP, TGB uptitrate slowly ○ mediate the amount of side effects, low protein Do not give two medications that use the same MOA binding = allows more free drug distribution Undergo Extensive Metabolism, mainly through V. THERAPEUTIC DRUG MONITORING oxidaton by CYP450 (phase 1) or glucuronidation by UGTs (phase 2) ○ EXCEPT LEV, PGB, GBP (excreted through kidney, without metabolism) For inducers just memo, Carbamazepine, Phenobarbital, Phenytoin For inhibitors just memo Valproic acid VI. QUESTIONS Is it possible for patients with epilepsy to experience different kinds of seizures? If yes, is it recommended to use an ASM that has multiple MOAs? ○ Yes there are some but a very limited amount of patients experience different types of seizures. ○ First anu common type tas use ASM, ASMs with multiple MOAs are generally used last coz ↑ S/E What is the trend when it comes to the similar drugs (Barbiturates) when used as a sedative and ASM? ○ Sedatives - higher dose, ASMs - light sedate/control to help not experience seizures IV. PHARMACODYNAMICS Goal of Tx : Seizure free state (if possible) with the fewest S/E ○ Increase seizure threshold without motor excitability ○ Balance effect + s/e esp Na+ everywhere PHARM 125 (PHARMACOLOGY FOR PHARMACY 1) Carles, Chua, De Guzman, Go, Magalued, Mendoza Page 10 of 10