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Neurology > Pharm 31 > Flashcards

Pharm 31 Flashcards

1
Q

seizure definition

A
  • Abnormal, excessive brain electrical discharges
  • A single seizure does not indicate a diagnosis of epilepsy
  • There may be a non-epileptic identifiable cause
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2
Q

epilepsy definition

A
  • Involves idiopathic, recurrent, transient disturbances of brain function
  • May manifest as:
  • Episodic impairment or loss of consciousness
  • Abnormal motor phenomena
  • Psychic or sensory disturbances
  • Perturbation of ANS
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3
Q

types of seizures

A

focal and generalized

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4
Q

Simple focal seizures

A

consciousness is not impaired

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5
Q

complex focal seizures

A

alteration in consciousness

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6
Q

generalized seizures

A
  • involve entire brain
  • always involve a LOC
  • described by clinical manifestations
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7
Q

drugs with established therapeutic ranges (4)

A
  1. phenytoin
  2. valproic acid
  3. carbamazepine
  4. phenobarbital
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8
Q

Main pharmacokinetic features that can be problematic for phenytoin

A

Saturable (non-linear) metabolism

broad spectrum hepatic enzyme inducer (loss of hormonal contraceptive efficacy)

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9
Q

Main pharmacokinetic features that can be problematic for valproic acid

A

Hepatic enzyme inhibitor, especially “UGT”

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10
Q

Main pharmacokinetic features that can be problematic for carbamazepine

A

Broad spectrum hepatic enzyme inducer (loss of hormonal contraceptive efficacy)
induces its own metabolism

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11
Q

Main pharmacokinetic features that can be problematic for phenobarbital

A

Broad spectrum hepatic enzyme inducer (loss of hormonal contraceptive efficacy)

very long half-life

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12
Q

Drugs that can induce congenital abnormalities if taken during pregnancy and cause osteoporosis (4)

A
  1. phenytoin
  2. valproic acid
  3. carbamazepine
  4. phenobarbital
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13
Q

Drugs that require renal monitoring due to >50% renal excretion

A
  1. acetazolamide
  2. gabapentin
  3. pregablin
  4. topiramate
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14
Q

autoinducer drugs (2)

A

carbamazepine

lamotrigine

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15
Q

common MOA of antiseizure drugs: modulate ion channels. How does this occur?

A
  1. prolonging inactivated state of Na+ channel or enhancing inactivation of the Na+ channel.
  2. Modulate/block voltage gated Ca2+ channels
  3. Activation or opening of Cl- channels (hyperpolarizes)
  4. alteration of neuronal bicarb flux
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16
Q

common MOA of antiseizure drugs: some work via neutrotransmitters and/or neurotransmitter receptors. How does this occur?

A
  1. pharmacologic enhancement of GABA neurotransmission

2. inhibited glutamate neurotransmission

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17
Q

MOA ion channel blockade of phenytoin and fosphenytoin

A

block Na+ channel

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18
Q

MOA ion channel blockade of gabapentin and pregabalin

A

block Ca2+ channels

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19
Q

MOA ion channel blockade of carbamazepine

A

block Na+ channels

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20
Q

MOA ion channel blockade of lamotrigine

A

block Na+ channels

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21
Q

MOA ion channel blockade of ethosuximide

A

block Ca2+ channels

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22
Q

MOA of barbiturates and phenobarbital

A

Positive allosteric effector of GABA-A

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23
Q

MOA of benzodiasepines and clonazepam

A

Positive allosteric effector of GABA-A

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24
Q

Benzodiasepines effect on GABA-A receptors

A

bind GABA receptors and increase the likelihood of GABA-linked-chloride channel opening

do not directly activate GABA receptors

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25
Q

Barbiturates effect on GABA-A receptors

A

at low to moderate doses prolong the time of opening of the Cl- channel

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26
Q

Z drugs (zolpidem, zaleplon, eszopiclone) effect on GABA-A receptors

A

agonists of GABA receptors and sepcific to GABA-A receptors with alpha-1 subunit

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27
Q

ethosuximide MOA

A

blocks T-type Ca2+ channels

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28
Q

ethosuximide use

A 
highly effective (first line) for absence seizures ('petit mal')
ONLY for absence seizures
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29
Q

ethosuximide ADE

A

GI
CNS
idiosyncratic reactions of HA, hiccups, blood dyscrasias, lupus-like, behavioral disturbances, and parkinsonism

hypersensitivity reactions

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30
Q

phenytoin MOA

A

blockade of sodium channels and inhibits rapidly repetitive action potentials

binds preferentially to inactivated state of Na+ channel and prolongs the duration of the closed state

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31
Q

phenytoin metabolism

A

metabolized b 2C9 and 2C19

cyp enzyme broad inducer

32
Q

phenytoin administration: oral

A

prevents seizures

33
Q

phenytoin administration: IV

A

for status epilepticus and must be administered slowly: 1 gram at least 20 minutes to infuse

34
Q

fosphenytoin administration: IV

A

1 gram phenytonin equivalent dose may be administered over only seven minutes

PRODRUG: thus takes just as long to start working

35
Q

fast phenytoin IV administration ADE

A
  • purple glove syndrome
  • ataxia, confusion, dizziness
  • dysrhytmia, hypotension, bradycardia
36
Q

4 BZDs most useful as antiseizure drugs

A
  1. Clonazepam
  2. Lorazepam
  3. Diazepam
  4. Clobazam
37
Q

daily benzo for seizure prevention

A

clonazepam

38
Q

carbamazepine MOA

A

Na+ Channel Blocker – similar to phenytoin
Some effects similar to tricyclic antidepressants…
NE and serotonin re-uptake inhibition

39
Q

carbamazepine metabolism

A

Self inducer (CYP3A4)

Full enzyme induction takes 3-6 weeks on a fixed dose regimen

1/2 life reduces by more than half after autoinduction period of a few weeks (about 40 days)

40
Q

carbamazepine black box warning

A

aplastic anemia, agranulocytosis, hyponatremia

41
Q

carbamazepine ADE

A

thrombocytopenia, leukopenia, hyponatremia

42
Q

antiseizure drug requiring genetic testing

A

oxcarbazepine and carbamazepine requires HLA-B*1502 to be checked –> esp. asian populations due to life threatening rash risk

43
Q

lamotrigine MOA

A

produces a voltage- and use-dependent inactivation of sodium channels

44
Q

lamotrigine use

A

Focal (partial) seizures (monotherapy or adjunct)

Generalized seizures (adjunct)

Including the difficult-to-treat Lennox-Gastaut syndrome

45
Q

lamotrigine ADE

A
  • lamictal rash (serious, can be fatal, rash) –> to reduce this risk, slow and low dosing titrated up over four weeks
  • CNS effects of dizziness, HA, diplopia, somnolence
46
Q

valproate use

A

effective against many seizure types: generalized seizures: absence, myoclonic, and generalized tonic-clonic seizures

Valproate is also used for partial (focal) seizures, bipolar disorder, and migraine prophylaxis. “Broad spectrum”

47
Q

valproate MOA

A

blocks high-frequency repetitive firing of neurons via Na+ channel blockade

Blockade of the NMDA receptor as well as increased [GABA] in the brain may also contribute to its mechanism of action.

48
Q

gabapentin MOA

A

Prevents presynaptic calcium entry, which then…

Reduces presynaptic NT release; = reduced glutamate release from glutaminergic neurons.

49
Q

gabapentin use

A

adjunct treatment of partial seizures and post-herpetic neuralgia

50
Q

pregabalin use

A
  1. Partial epilepsy
  2. Diabetic peripheral neuropathy
  3. Post-herpetic neuralgia
  4. Fibromyalgia
51
Q

pregabalin ADE

A

Common: dizziness, blurred vision
Can cause some euphoria
Schedule-V controlled substance

52
Q

levetiracetam use

A

adjunctive therapy of partial seizures, with some potential advantages:

Not extensively metabolized and does not interact with other drugs via cytochrome P450 pathways

Relatively well tolerated compared to other agents

The starting dose can be an effective dose

53
Q

acetazolamide use

A

altitude sickness, as a diuretic, or to reduce intraocular pressure, but also has anti-seizure effects.

Acetazolamide is generally used as adjunct therapy for seizure disorders.

Acetazolamide may produce its antiseizure effects by causing a mild brain acidosis or by altered bicarbonate flux.

54
Q

acetazolamide MOA

A

a carbonic anhydrase inhibitor

Bicarbonate moving out of neurons via GABA-receptor ion channels is a depolarizing effect, which is reduced by carbonic anhydrase inhibitors

55
Q

acetazolamide ADE

A

Metabolic acidosis.

Headache, hearing dysfunction, tinnitus, paresthesias.

GI disturbances: nausea and vomiting, appetite loss, taste alteration, polyuria.

Drowsiness or confusion

56
Q

zonisamide MOA

A

Na+ channel blockade

Also a mild carbonic anhydrase inhibitor, but CA inhibition is milder than seen with acetazolamide

57
Q

zonisamide use

A

Increasing use across the lifespan children (liquids), pregnancy and older adults

58
Q

zonisamide ADE

A

may cause metabolic acidosis (CA)

The FDA recommends monitoring serum bicarbonate before starting treatment, and during treatment with zonisamide, even in the absence of symptoms

59
Q

topiramate MOA

A

Na+ channels blockade

60
Q

topiramate use

A

Partial or primarily generalized tonic-clonic seizures

Monotherapy for ages 10+

Adjunctive therapy for patients aged 2+; including seizures associated with Lennox-Gastaut syndrome
Migraine prophylaxis.

To promote weight loss (in combo with phentermine)
Several additional intriguing uses are off-label

61
Q

topiramate metabolism

A

Selective inducer of CYP3A4

Primarily cleared by the kidneys, so not a “self-inducer”

Increases the rate of metabolism of drugs metabolized by CYP3A4 (there are many!) – including hormonal contraceptives

62
Q

topiramate ADE with D/C

A

difficulty with memory

paresthesias

psychomotor slowing

63
Q

FDA approval for post-herpetic neuralgia:

A

gapapentin and pregabalin

64
Q

FDA approval for diabetic peripheral neuropathy:

A

pregabalin

65
Q

FDA approval for fibromyalgia pain:

A

pregabalin

66
Q

FDA approval for trigeminal neuralgia:

A

carbamazepine (Tegretol®)

67
Q

Identify three antiseizure drugs FDA approved for bipolar disorder

A

Valproic acid, carbamazepine, and lamotrigine are mood stabilizers that can be used in bipolar disorder

68
Q

Drugs initiated during acute mania

A

Lithium, +/- valproic acid +/- atypical antipsychotic drug

69
Q

Drugs used long term for PREVENTING mania and cycling

A

Lithium, +/- valproic acid +/- atypical antipsychotic drug, lamotrigine

70
Q

Migraine Prevention: FDA approved uses for topiramate

A
  • epilepsy
  • migraine prophylaxis
  • weight loss
71
Q

topiramate migraine use ADE

A
  • paresthesia
  • memory difficulty
  • language problems

increasing dose pass recommended daily dose of 100mg/day can result in even more and severe ADE

72
Q

valproate for migraine prevention indications

A

Mania associated with bipolar disorder

Migraine prophylaxis

73
Q

valproate of migraine use MC ADE

A 
weight gain
nausea
somnolence
tremor
dizziness
hair loss
74
Q

valproate of migraine use pregnancy use

A

contraindicated in pregnancy:

  • Highest risk of AEDs for major congenital malformations.
  • Lower IQ is also seen in children of women who used valproate during pregnancy.
75
Q

try to avoid these drugs in pregnancy (4) due to major malformations of the fetus (esp. male fetuses)

A

valproate
phenobarbital
topiramate
phenytoin

76
Q

drugs that are considered safer during pregnancy

A

lamotrigine
levetiracetam
gabapentin
zonisamide

Neurology (12 decks)

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