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KG - pharmacology 3 > KG - Pharm 3, Exam 1, Anticonvulsants > Flashcards

KG - Pharm 3, Exam 1, Anticonvulsants Flashcards

1
Q

Where do seizures typically originate?

A
  • cerebral cortex (abt 50% unknown origins)
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2
Q

describe: partial seizure, simple

A
  • focal, brief (20-90 sec)
  • grimacing, focal clonic jerking of extremity
  • NO LOSS CONSCIOUSNESS
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3
Q

describe: partial seizure, complex

A
  • longer (< 2 min)
  • ALTERED/LOSS OF CONSCIOUSNESS
  • HALLUCINATIONS
  • temporal lobe
  • automatic movements
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4
Q

describe: partial seizure, partial w/ secondary general

A
  • LOSS OF CONSCIOUSNESS

- muscle contractions alternating w/ relaxation

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5
Q

describe: generalized seizure, tonic-clonic

A
  • arise from reciprocal firing of thalamus & cortex
  • aka GRAND MAL
  • initial tonic rigidity
  • subsequent tremor
  • clonic jerking (60-120 sec)
  • LOSS OF CONSCIOUSNESS
  • pt usu stuporous & confused
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6
Q

describe: generalized seizure, absence

A
  • sudden onset (10-30 sec)
  • loss of awareness, but not consciousness
  • may be some mild clonic movements
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7
Q

describe: generalized seizure, myoclonic

A
  • brief spasm/rigidity

- often secondary to other seizure disorder

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8
Q

describe: generalized seizure, atonic

A
  • sudden loss of postural tone

- pt can fall down

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9
Q

anticonvulsants: moa

A
  1. GABA NEUROTRANSMISSION
    - protects against both partial & generalized seizures
    - GOAL = ENHANCEMENT OF GABA INHIBITORY ACTIVITY
    - -> INHIBIT GABA METABOLISM
    - -> STIM GABA RECEPTORS
  2. INHIBITION OF GLUTAMATE ACTIVITY
    - inhibition Na+ & thalamic Ca2+ channels
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10
Q

what causes seizures?

A
  • BLOCKADE OF GABA RECEPTORS (flumazinel)

- ACTIVATION OF GLUTAMATE RECEPTORS (NMDA)

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11
Q

Which anticonvulsants have a GABA moa?

A
  • phenobarbital
  • gabapentin
  • valproic acid
  • benzodiazepines
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12
Q

How do anticonvulsant drugs work to inhibit glutamate activity?

A
  • prolong inactivation state of Na+ channels (action potential can’t fire as quickly)
  • T-type Ca2+ channels overactive in absence seizures???
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13
Q

Phenytoin: uses

A
  • PARTIAL SEIZURES, GENERALIZED TONIC-CLONIC SEIZURES

- NOT effective for absence seizures (doesn’t affect Ca2+ channels)

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14
Q

Phenytoin: moa

A
  • prolongs inactivation of Na+ channels
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15
Q

Phenytoin: pharmacokinetics

A
  • NOT WATER SOLUBLE –> NOT injected
  • ELIMINATION = 1st ORDER at low doses (ZERO ORDER AT THERAPEUTIC AND HIGHER DOSES)
  • -> small changes in dose = big change in plasma levels
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16
Q

Which form of Phenytoin is injectable?

A

Fosphenytoin

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17
Q

Phenytoin: drug interactions

A
  • drugs that alter CYP450s (phenobarbital, carbamazepine)

- METABOLIZED & INDUCES CYP450s

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18
Q

Phenytoin: side effects

A
  • nystagmus, diplopia, ataxia, sedation
  • GINGIVAL HYPERPLASIA
  • skin rash - STOP USE!!! (RISK OF SJS)
  • PREGNANCY CAT D

LONG TERM:

  • coarse facial features
  • peripheral neuropathy
  • abn Vit D metabolism
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19
Q

Carbamazepine: uses

A
  • DOC for partial seizures
  • gen tonic clonic seizures
  • bipolar disorder
  • TRIGEMINAL NEURALGIA
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20
Q

Carbamazepine: moa

A
  • blocks Na+ channels

- inhibits NE release & reuptake

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21
Q

Carbamazepine: pharmacokinetics

A
  • INDUCES CYP450s

- induces own metabolism (must monitor plasma levels)

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22
Q

Carbamazepine: drug interactions

A
  • increases metabolism of PHENYTOIN, ETHOSUXIMIDE, VALPROIC ACID, HALOPERIDOL, & OCPs
  • metab increases by: PHENOBARBITAL, PHENYTOIN,VALPROIC ACID
  • metab inhibited by cimetidine & fluoxetine
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23
Q

Carbamazepine: side effects

A
  • diplopia, ataxia, GI upset, drowsiness
  • aplastic anemia, agranulocytosis
  • SJS
  • PREGNANCY CAT D
24
Q

Phenobarbital: moa

A
  • PROLONGS OPENING OF Cl- channel at GABA RECEPTOR

- alters Na+ and Ca2+ conductance at high concentrations

25
Q

Phenobarbital: uses

A
  • PARTIAL SEIZURES

- GENERALIZED TONIC CLONIC SEIZURES

26
Q

Phenobarbital: drug interactions

A
  • induction of CYP450s increases metabolism of PHENYTOIN & CARBAMAZEPINE
27
Q

Phenobarbital: pharmacokinetics

A
  • binds to GABA receptors, stimulates Cl- influx

- produces INHIBITION of GABA

28
Q

Lamotrigine: moa

A
  • VOLTAGE & USE DEPENDENT INACTIVATION OF Na+ CHANNELS
29
Q

Lamotrigine: uses

A
  • PARTIAL SEIZURES

- bipolar disorder

30
Q

Lamotrigine: pharmacokinetics

A
  • inducers of CYP450s (phenytoin, carbamazepine, phenobarbital) will affect metabolism
  • half life doubled by valproic acid
31
Q

Lamotrigine: side effects

A
  • CNS = dizziness, HA, diplopia, ataxia, somnolence
  • GI - N/V
  • skin task & SJS
32
Q

Gabapentin: uses

A
  • ADJUNCT for PARTIAL OR GENERALIZED TONIC-CLONIC SEIZURES
  • NEUROPATHIC PAIN
  • bipolar dz
33
Q

Gabapentin: moa

A
  • GABA analog
34
Q

Gabapentin: pharmacokinetics

A
  • 1st order elimination
  • EXCRETED BY KIDNEY
  • short half life, take 3x daily
35
Q

Gabapentin: side effects

A
  • sleepiness
  • dizziness
  • ataxia
  • fatigue
36
Q

Gabapentin: drug interactions

A
  • NEGLIGIBLE!!! (good if already on lots of drugs)

- PREGNANCY CAT C

37
Q

Topiramate: uses

A
  • PARTIAL & GENERALIZED TONIC-CLONIC SEIZURES

- MIGRAINE PREVENTION

38
Q

Topiramate: moa

A
  • BLOCKS Na+ CHANNELS
  • potentiates GABA receptors
  • inhibits glutamate receptor
39
Q

Topiramate: side effects

A
  • dizziness, sedation, nervousness, confusion

- ACUTE MYOPIA, GLAUCOMA

40
Q

ethosuximide: use

A
  • DOC: ABSENCE SEIZURES
41
Q

ethosuximide: moa

A
  • INHIBITS LOW-THRESHOLD (t-type) Ca2+ channels

- inhibits “pacemaker” for rhythmic cortical discharge

42
Q

ethosuximide: pharmacokinetics

A
  • metabolized by liver

- variable half-life 18-72 hrs

43
Q

ethosuximide: side effects

A
  • GI irritation, lethargy, fatigue, HA, dizziness
  • HICCUPS
  • SJS = RARE
44
Q

ethosuximide: drug interactions

A
  • INHIBITED by VAPRORATE
45
Q

Valproic acid: use

A
  • SECOND CHOICE for ABSENCE SEIZURES
  • MYOCLONIC SEIZURES
  • BIPOLAR DISORDER
  • prophylaxis migraine
46
Q

Valproic acid: moa

A
  • blocks Ca2+ channels and Na+ channels
47
Q

Valproic acid: pharmacokinetics

A
  • ABSORPTION PROLONGED BY FOOD

- taken after meals

48
Q

Valproic acid: drug interactions

A
  • INHIBITS OWN METABOLISM at low doses

- INHIBITS METABOLISM OF PHENYTOIN, PHENOBARBITAL, CARBAMAZEPINE

49
Q

Valproic acid: side effects

A
  • nausea, abd pain, heartburn, weight gain, sedation, tremor, alopecia
  • HEPATOTOXICITY
  • PREGNANCY CAT D
50
Q

Diazepam, Lorazepam: class

A
  • Benzos
51
Q

Diazepam, Lorazepam: moa

A
  • STIMULATE GABA CHANNEL
52
Q

Diazepam, Lorazepam: use

A
  • DIAZEPAM = DOC: STATUS EPILEPTICUS
53
Q

Diazepam, Lorazepam: pregnancy?

A
  • PREGNANCY CAT D
54
Q

how do anticonvulsants affect pregnancy?

A
  • failure of contraceptives higher
  • higher birth defect rate
  • more congenital heart defects, neural tube defects
55
Q

What are options for women who want to be pregnant, but need to take meds?

A
  • gradual withdrawal therapy
  • monotherapy
  • lower doses
  • folate supplementation
  • vitamin K supplementation during last month
56
Q

describe: SJS

A
  • TOXIC EPIDERMAL NECROSIS
  • SEROUS AUTOIMMUNE REACTION
  • HYPERSENSITIVE REACTION
  • WIDESPREAD RASH
  • ARTHRITIS, NEPHRITIS
  • CNS abnormalities
57
Q

SJS: life threatening interactions

A
  • PHENYTOIN, LAMOTRIGINE, CARBAMAZEPINE, VALPROATE

KG - pharmacology 3 (11 decks)

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