Epilepsy Pharmacotherapy Flashcards

Question

Stevens-Johnson syndrome

Answer 1

Prodrome of malaise and fever followed by rapid onset of erythematous/purpuric macules (oral, ocular, genital) Skin lesions progress to epidermal necrosis and sloughing

Answer 2

Mech Use-dependent blockade of Na channels; ↑ refractory period; inhibition of glutamate release from excitatory presynaptic neuron Clinical Use Tonic clonic seizures Also a class IB antiarrhythmic ``` Toxicity Nystagmus Ataxia Diplopia Sedation SLE-like syndrome Induction of cytochrome P450 Chronic use produces gingival hyperplasia in children, peripheral neuropathy, hirsutism, megaloblastic anemia (↓ folate absorption). Teratogenic (fetal hydantoin syndrome) ```

Answer 3

Phenobarbital, pentobarbital, thiopental, secobarbital Mech Facilitate GABA A action by ↑ duration of CL- channel opening, thus ↓ neuron firing Clinical Use Sedative for anxiety, seizures, insomnia, induction of anesthesia (thiopental) Toxicity Dependence, additive CNS depression effects with alcohol, respiratory or CV depression (can lead to death) DDI owing to induction of liver P450 enzymes Treat overdose with sx management (assist respiration, ↑ BP) Contraindicated in porphyria

Answer 4

Diazepam, Lorazepam, Triazolam, Temazepam, oxazepam, midazolam, chlordiazepoxide, alprazolam Mech Facilitate GABA A action by ↑ frequency of Cl channel opening ↓ REM sleep most have long half-lives and active metabolites ``` Clinical Use Anxiety Spasticity Status epilepticus (lorazepam and diazepam) Detox (esp alcohol – DT’s) Night terrors Sleepwalking General anesthetic (amnesia, muscle relaxant) Hypnotic (insomnia) ``` Toxicity Dependence, additive CNS depression effects with alcohol. Less risk of respiratory depression and coma than with barbiturates Tx overdose with flumazenil (competitive antagonist at GABA benzo rec)

Answer 5

Short acting = TOM Triazolam Oxazepam Midazolam Also the highest addictive potential

Answer 6

Benzos Barbs EtOH

Answer 7

Enhance GABA

Answer 8

Modulate Na channels

Answer 9

Modulate Ca Channels

Answer 10

Enhance GABA

Answer 11

Modulate Ca Channels

Answer 12

Modulate Na Channels

Answer 13

Modulate Na channels

Answer 14

Enhance GABA

Answer 15

modulate Na Channels

Answer 16

modulate Ca channels

Answer 17

Enhance GABA

Answer 18

Module Na channels Enhance GABA Inhibit excitatory NTs

Answer 19

Modulate Na channels Modulate Ca channels Enhance GABA

Answer 20

Modulate Na channels | Modulate Ca channels

Answer 21

 Focal but can become generalized  Effective drugs limit sustained repetitive discharges

Answer 22

 May have brief impairment or loss of consciousness  Effective drugs reduce T-type Ca++ conductance

Answer 23

Tonic spasm followed by synchronous clonic jerking Effective drugs limit sustained repetitive discharges

Answer 24

``` 1st line: CBZ Oxcarbazepine Valproate Lamotrigine Phenytoin ``` ``` 2nd line: Topiramate Phenobarbital Levetiracetam (A) Zonisamide (A) Pregabalin (A) Gabapentin (A) Tiagabine (A) ``` Other drugs to consider: Felbamate (R) acetazolamide Drugs to avoid: None

Answer 25

``` 1st line: CBZ Oxcarbazepine Valproic Acid Lamotrigine Phenytoin ``` 2nd line: Topiramate Levetiracetam (A) Zonisamide (A) Other drugs to consider: Phenobarbital acetazolamide Drugs to avoid: Tiagabine

Answer 26

1st line: Ethosuximide Lamotrigine Valproate 2nd line: Topiramate Clonazepam Other drugs to consider: Levitiracetam ``` Drugs to avoid (could worsen seizure): CBZ Oxcarbazepine Gabapentin Tiagabine phenytoin ```

Answer 27

1st line: Valproate Topiramate ``` 2nd line: Clonazepam Lamotrigine Levetiracetam Zonisamide (A) ``` Other drugs to consider: Felbamate ``` Drugs to avoid: CBZ Oxcarbazepine Gabapentin Tiagabine pregabalin ```

Answer 28

1st line: Valproate Lamotrigine 2nd line: Clonzazepam Topiramate Zonisamide Other drugs to consider: Levetiracetam Felbamate Phenobarbital Drugs to avoid: CBZ Oxcarbazepine phenytoin

Answer 29

1st line: Lamotrigine Valproate 2nd line: Clonazepam Topiramate ``` Other drugs to consider: Levetiracetam Zonisamide Phenobarbital Phenytoin Acetazolamide Felbamate (R) ``` Drugs to avoid: CBZ oxcarbazine

Answer 30

1st line: Valproate 2nd line: Topiramate Lamotrigine Zonisamide (A) Other drugs to consider: Felbamate Drugs to avoid: None

Answer 31

1st line: ACTH Corticosteroids 2nd line: Clonazepam Valproate Other drugs to consider: None Drugs to avoid: None

Answer 32

1st line: Phenobarbital Valproate 2nd line: None Other drugs to consider: none Drugs to avoid: Phenytoin CBZ

Answer 33

1st line: Phenobarbital 2nd line: Phenytoin Other drugs to consider: None Drugs to avoid: None

Answer 34

 Used primarily as a guide to direct therapy  Useful in optimizing AED therapy, teasing out drug interactions, detecting noncompliance, and during pregnancy  Important to consider that individual patients determine their “therapeutic” and “toxic” concentrations  AED serum concentrations are not monitored with newer agents

Answer 35

 Phenytoin undergoes capacity-limited metabolism (elimination NOT proportional to serum concentration) and the capacity is reached at therapeutic concentrations  Phenytoin is highly protein bound to albumin (90%). The “free” phenytoin concentration (unbound) is a more accurate description of the therapeutic effects of this drug. Thus, changes in protein binding in certain disease states (renal or hepatic disease, burns, etc.) can effect the free concentration and the effect of the drug.

Answer 36

Carbamazepine undergoes “autoinduction” whereby it induces its own metabolism such that concentrations may be initially “therapeutic” only to be reduced once autoinduction occurs. This process begins within the 1st week after starting therapy and plateus at 2-3 weeks.

Answer 37

Onset of action Half life Duration of anti-seizure effect 0.5-2 min 24-57 hr 10-20min Highly lipophilic; may be given rectally

Answer 38

Onset of action Half life Duration of anti-seizure effect 2-3 min 8-25 hr ~6hr DOC in SE – longer duration vs diazepam

Answer 39

Onset of action Half life Duration of anti-seizure effect <5 min 1.5-4hr 5-10min

Answer 40

Onset of action Half life Duration of anti-seizure effect 15min IV: 10-15hr Similar to ½ life

Answer 41

Onset of action Half life Duration of anti-seizure effect 10-30min IV: 10-15hr Similar to ½ life

Answer 42

Induction = increased synthesis of drug metabolizing isoenzymes in the liver resulting in an increase in the rate of metabolism of drugs that are substrates of those enzymes and thus the plasma concentration of those drug is decreased. If the affected drug has an active metabolite, induction can result in increased metabolite concentration and possibly an increase in drug toxicity. The time course of induction is dependent on the rate of enzyme synthesis and degradation and the time to reach steady state concentrations of the inducing drug. Thus the time course is generally gradual and dose-dependent. AED MAJOR INDUCERS: CARBAMAZEPINE, PHENYTOIN, PHENOBARBITAL, FELBAMATE

Answer 43

Inhibition = drug or its metabolite blocks the activity of one or more drug metabolizing enzymes, resulting in a decrease in the rate of metabolism of the affected drug and thus higher plasma concentrations. Inhibition is competitive & dose-dependent and begins as soon as sufficient concentrations of the inhibitor are achieved. (can be seen within 24 hour of inhibitor administration) AED MAJOR INHIBITORS: VALPROIC ACID

Answer 44

Baseline (i.e. prior to starting therapy) lab tests should include liver function tests (SGOT, SGPT, alkaline phosphatase), serum albumin, complete blood cell count with differential, urinalysis, serum creatinine (for renally eliminated drugs) and serum electrolytes. Additionally for carbamazepine should obtain baseline urinalysis and serum sodium; and for valproic acid obtain baseline serum ammonia. In otherwise healthy and asymptomatic patients, routine laboratory monitoring after starting therapy is unnecessary with clinical laboratory tests only being repeated if indicated by the patient's clinical condition. For patients with abnormal baseline laboratory tests, further workup is required to evaluate their cause and follow-up monitoring performed as indicated.

Answer 45

``` Conc-related: Ataxia Diplopia Nystagmus Sedation Drowsiness ``` ``` Idiosyncratic: Acne Gum Hypertrophy Hirsutism Megaloblastic anemia Rash Lupus-like syndrome Behavior changes Metabolic bone disease Intellectual blunting ``` ``` Pregnancy category: D -Fetal hydantoin syndrome -cleft lip and palate -mental retardation -low set ears -skeletal spinal abnormalities -heart malformation ```

Answer 46

Conc-related: Sedation Drowsiness Ataxia ``` Idiosyncratic: Rash cognitive impairment Hyperactivity ADD Passive-aggressive Behavior (mood change) Intellectual blunting ``` Pregnancy category: D

Answer 47

Conc-related: Diplopia Nausea Drowsiness ``` Idiosyncratic: Hyponatremia Leukopenia Aplastic anemia Rash ``` ``` Pregnancy category: D -neural tube defects -minor craniofacial defects nail hypoplasia ```

Answer 48

``` Conc-related: GI upset Sedation Unsteadiness Thrombocytopenia Tremor ``` ``` Idiosyncratic: Acute hepatic failure Acute pancreatitis Alopecia Weight gain Hyperammonemia ``` ``` Pregnancy category: D -neural tube defects -fetal valproate syndrome (developmental delays, limb and digit abnormalities) -black box warning in pregnancy ```

Answer 49

Conc-related: GI upset Drowsiness Dizziness Idiosyncratic: Hiccups Blood dyscrasias Headache Pregnancy category: C

Answer 50

Conc-related: GI upset Insomnia Anorexia Idiosyncratic: Aplastic anemia Hepatotoxicity Weight loss Pregnancy category: C

Answer 51

Conc-related: Sedation Drowsiness Ataxia Idiosyncratic: Weight gain Aggressive behavior Pedal edema Pregnancy category: C

Answer 52

Conc-related: Insomnia Ataxia Diplopia Idiosyncratic: Rash Headache Pregnancy category: C

Answer 53

``` Conc-related: Slowed thinking Psychomotor slowing Speech/language problems Drowsiness Ataxia Dizziness ``` ``` Idiosyncratic: Renal calculi Weight loss Glaucoma Paresthesia Metabolic acidosis ``` Pregnancy category: C

Answer 54

Conc-related:Somnolence Dizziness Diplopia Nausea Idiosyncratic: Hyponatremia Rash Pregnancy category: C

Answer 55

``` Conc-related: Dizziness Somnolence Blurred vision Depression Weakness Irritability Slowed thinking ``` Idiosyncratic: Non-convulsive status Mood instability Pregnancy category: C

Answer 56

``` Conc-related: Sedation Dizziness Cognitive impairment GI upset ``` ``` Idiosyncratic: Rash Weight loss Kidney stones Hypohidrosis ``` Pregnancy category: C

Answer 57

Conc-related: Somnolence Dizziness Idiosyncratic: Depression Aggression Infection Pregnancy category: C

Answer 58

Conc-related: Somnolence Dizziness Blurred vision ``` Idiosyncratic: Weight gain Peripheral edema Increased CK Decreased platelet count ``` Pregnancy category: C

Answer 59

Bone Disorders: Bone disorders particularly osteoporosis have been associated with AEDs. Bone mineral density decreases leading to osteoporosis and fractures have been associated with some AEDS (phenobarbital, phenytoin, carbamazepine and valproate) in both women and men. The newer AEDs have not been systematically evaluated for these relationships. Potential mechanisms of osteoporosis development include increased catabolism of vitamin D, impairment of calcium absorption, impaired bone resorption and formation, hyperparathyroidism, vitamin K deficiency, and calcitonin deficiency. Osteoporosis is of particular concern in patients with epilepsy because of the increased risk of fractures during seizures. Experts recommend bone density testing every 5 years during AED treatment in men and premenopausal women and before AED initiation in postmenopausal women. Treatment with vitamin D at doses of 400-4000IU/day, calcium supplementation, bisphosphonates, or calcitonin may be necessary.

Answer 60

Recent studies have demonstrated that significant interference with higher cognitive functions; including attention span, concentrating ability, memory, information processing, motor speed and IQ; occurs during AED therapy

Answer 61

Based on published data from prospective, chronic dosing studies, phenobarbital and topiramate have the highest potential for causing cognitive dysfunction. AEDs with traditional gamma-aminobutyric acid (GABA)ergic mechanisms have the most detrimental effects on cognitive function, possibly because they impair attention. A number of consistent risk factors have been established. Polypharmacy and high blood levels of an antiepileptic drug (AED) increase the risk of cognitive side effects.

Answer 62

Impaired memory is among the most common complaints of patients with epilepsy. Multiple factors contribute to memory impairment in patients with epilepsy.

Answer 63

Sex hormone fluctuations during maturation may exacerbate seizures at particular points during the life of women, eg. during menarche, menses, pregnancy, or later in the perimeno- pausal years. American Academy of Neurology recommends monotherapy during reproductive years. There is a teratogenic potential of anti epileptic drugs. Ideally, in well-controlled seizures, taper and discontinue anti epileptic drugs before conception. Risk of continuing must be weighed against the benefits. Post partum adjustment of the anti epileptic drugs dose will be necessary if the dose was increased during pregnancy, and usually can be reduced by eight weeks after delivery. All women of child bearing years should receive folate supplementation (at leaset 1 mg/day) before and during the pregnancy.

Answer 64

In utero exposure to antiepileptic drugs (AEDs) can cause intrauterine growth retardation, congenital malformations, and cognitive dysfunction. The most common major malformations are cleft lip/palate, heart defects, neural tube defects, and urogenital defects. Current treatment guidelines advise use of AED monotherapy and folate supplementation beginning before and continuing throughout pregnancy. Prenatal screening for major malformations should be offered.

Answer 65

Safety while breast-feeding is a common concern. Authorities recommend that it is safe with no risk of hematological or hepatotoxicity, although some sedation may occur with phenytoin, carbamazepine and phenobarbital. The efficacy of birth control pills is decreased by the use of enzyme-inducing anticonvulsants. Some prescribe estrogen/progesterone pill with higher hormonal doses or an alternative and preferred approach, is to use a second method of contraception.

Answer 66

``` CBZ Felbamate Oxcarbazepine Phenobarbital Phenytoin Primidone Topiramate (doses >200mg/day) ```

Answer 67

``` Benzodiazepines Gabapentin Lamotrigine Levetiracetam Tiagabine Valproate Zonisamide ```

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Epilepsy Pharmacotherapy Flashcards

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