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Neuro drug > Antiepileptics > Flashcards

Antiepileptics Flashcards

1
Q

Medication for epilepsy

A

Antiepileptics (I)
 Phenytoin
 carbamazepine
 Valproate

Antiepileptics (II) 
 Pregabalin
 Vigabatrin
 Lamotrigine
 Others eg, BZDs

BZD is additive therefore not a good choice coz epilepsy is lifelong

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2
Q

Seizure

A

A paroxysmal (“sudden attack”) event due to an abnormal discharge from a mass of CNS neurons.

• Diverse manifestations ranging from convulsion (observable) to an experience (subjective).

• Single seizure due to a correctable or avoidable circumstance (ie provoked) is not necessarily epilepsy:
–Alcohol 
–Blood glucose alterations 
–Pyrexia (fever) 
–Sleep deprivation
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3
Q

Epilepsy and causes

A

• A chronic disorders characterized by recurrent seizures.

• Can be primary (congenital, hereditary)
or
secondary:
- Infection, eg, meningitis or encephalitis
- Brain injury, scarring or tumor
- Blood glucose alterations
- Metabolic disorders,
eg, adrenal insufficiency —> hyponatremia

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4
Q

Clinical features of Epilepsy

A 
Recurrent seizures 
• Lower Risk (30-50%) 
    •Single seizure 
    •Normal EEG 
    •Normal brain scan
  • Higher Risk (80%)
  • Previous (undiagnosed) seizures
  • Epileptiform EEG
  • Abnormal brain scan
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5
Q

clinical approach to epilepsy

A

 Accurate diagnosis from clinical history and examination
 Appropriate investigations
• Blood tests
• EEG
• Brain Scan (CT/MRI)
 To determine risk of recurrent seizures

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6
Q

Classification of epilepsy

A
  1. Generalized seizures
    a) Tonic clonic (Grand mal):
    b) Absence (Petit mal):
    c) Myoclonic
    d) Atonic
  2. Partial seizures
    a) Simple (consciousness not impaired)
    b) Complex (consciousness impaired)
  3. Status epilepticus
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7
Q

pathophysiology of epilepsy

A
  • Neuronal depolarization (“firing”) depends on membrane potential.
  • A seizure occurs when there is excessive synchronous depolarization, usually starting from defined regions (“foci”) and spreading to other regions. • Due to unbalanced excitatory and inhibitory receptor / ion channel function which favour depolarization
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8
Q

Rational of AED

A
  • Decrease membrane excitability by altering Na+ and Ca2+ conductance during action potentials.
  • Enhance effects of inhibitory GABA neurotransmitters.
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9
Q

phenytoin

A
  • Blockade of voltage-depedent Na+ channels.
  • Suitable for all types of seizures except absence seizures.
  • A relative narrow therapeutic range (plasma concentration 40-100 μM), saturation kinetics and consequent non-linear relationship between dose and plasma concentration necessitates titration and monitoring.
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10
Q

ADR of Phenytoin

A

Dose dependent systemic effect

  • Endocrine gum
  • neurological ——–> convulsion/cerebellar/vestibular
  • skeletal
  • haemotological —— B12, folate

Overdose

  • convulsion/cerebellar/vestibular
  • B12 folate

Hypersensitivity idiosyncratic

  • Skin: morbilliform
  • lupus-like bone marrow
  • liver: necrosis

Teratogenic

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11
Q

Carbamazepine

A
  • Blockade of voltage-depedent Na+ channels (like phenytoin).
  • Suitable for all types of seizures except absence seizures.
  • Hepatic enzyme (CYP450) inducer, T½ shortens with repeated doses —–> accelerates elimination of other drugs.
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12
Q

Carbamazepine ADR

A

Dose dependent

  • GI Upset
  • Diplopia
  • nystamus
  • drowsiness
  • folate vit D def
  • antidiuretic effect

Overdose

  • Ataxia
  • Confusion
  • Behavioral-disturbance

hypersensitivity

  • Bone marrow
  • Rashes
  • SLE
  • SJS
  • Lymphadenopathy
  • Hepatitis

Teratogenic

  • In animals
  • In human??
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13
Q

Valproate

A
  • Blockade of voltage-dependent Na+ and Ca2+ channels.
  • Also inhibits GABA transaminase —-> increased GABA
  • Suitable for all types of seizures, including absence seizures.
  • Strongly bound to plasma proteins, displaces other antiepileptics.
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14
Q

Valproate ADR

A

Dose dependent

  • GI upset
  • Sedation
  • wt gain
  • hair loss

Hypersensitivity

  • hepatotoxicity
  • Thrombocytopenia

Teratogenic

  • Spina bifida
  • CVS
  • Orofacial
  • Digital
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15
Q

second gen AED

A

1) pregabalin
2) vigabatrin
3) Lamotrigine
4) BZDs
5) henobarbital

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16
Q

pregabalin

A

second gen AED
potentiate the release of GABA
–GABA analogue, increases synaptic GABA –> GABA receptor mediated Cl- currents resulting in hyperpolarization.

–Also acts on voltage-gated Ca2+channels.
–Besides GAD, also used as add-on therapy for partial seizures

–Adverse effects, mainly SEDATION, may be associated with emergence of worsening of SUICIDAL thoughts.

therefore not good for depression

17
Q

vigabatrin

A

second gen AED

–Inhibits GABA transaminase —> increased synaptic GABA (» valproate).
–Useful in all types of seizures, including those refractory to other AEDs.

–Side effects: Sedation, behavioural and mood changes (occasionally psychosis), visual field defects.

18
Q

Lamotrigine

A

second gen AED
- –Blockade of voltage-depedent Na+ channels.
–Also inhibits glutamate release.
–For all types of seizures.

–Side effects: Dizziness, sedation, rashes.

19
Q

BZDs

A

potentiate GABA actions by increasing the frequency of GABA-induced channel opening

20
Q

phenobarbital

A

increases frequency and duration of opening.

21
Q

Which antiepileptic drug should be chosen initially

A

Antiepileptic drug treatment strategy should be individualised according to the

  • seizure type,
  • epilepsy syndrome,
  • co-medication, comorbidity and the
  • individual’s lifestyle and preferences (and/or those of their family and/or carers as appropriate).

Patients should be commenced on monotherapy initially. Should the patient develop an adverse reaction to the initial drug or if the initial monotherapy is unsuccessful, monotherapy using another drug should be tried

22
Q

Monitoring: When are antiepileptic drug levels tested?

A

Physicians should be aware that the published “therapeutic range“ exists only as a guide. Patients may have good seizure control below this range, while others tolerate levels above the range.
“Treat the Patient, not the numbers”

Antiepileptic drug levels may help clinical management under the following clinical indications:

(1) assessment of compliance to drug treatment for patients with refractory epilepsy
(2) assessment of symptoms due to possible antiepileptic drug toxicity
(3) titration of phenytoin dose

Routine checking of antiepileptic drug levels without a clear clinical indication is not required, and is not cost effective.

23
Q

Increased risk for breakthrough seizures

A
  • Non-compliance to antiepileptic medication or drug
  • Interactions with antiepileptic medications lowering blood levels of antiepileptic drugs.
  • Alcohol abuse
  • Sleep deprivation
  • Concurrent illness

Neuro drug (21 decks)

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