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Pediatric Pharmacology Exam 2 > Neurology > Flashcards

Neurology Flashcards

1
Q

Define Seizures

A

Transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain

~ 10% of the population will experience a seizure

Benign febrile seizure occurs in 2 – 5% of children < 5 years of age

  • Centralized Seizures
  • Focal Seizures
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2
Q

Epilepsy

A
  • Disorder of the brain characterized by an enduring predisposition to seizures
  • Epilepsy requires the occurrence of at least one epileptic seizures
  • ~ 1% of the general population will develop epilepsy
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3
Q

Focal seizures include…

A

specific aura, motor autonomic features

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4
Q

Pharmacotherapy of Seizure Control (3)

A
  1. Anti-Epileptic drugs (AEDs)
  2. Ketogenic
  3. Vitamin Supplementation
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5
Q

Carbamazepine (Tegretol)
MOA
Indications (2)

A

MOA
- Blocks sodium channels to decrease frequency and voltage of rapidly firing nerve cells

Indications

  1. Tonic-Clonic Seizures
  2. Focal Seizures
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6
Q 
Carbamazepine (Tegretol)
Adverse Effects (4)
A
  1. Ataxia
  2. Diplopia
  3. Hyponatremia
  4. Stevens-Johnson Syndrome
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7
Q

Carbamazepine (Tegretol)

Drug-drug interactions (3)

A
  1. CYP3A4 substrate and inducer (makes half-life variable depending on duration of treatment). At induction is complete within 3 – 5 weeks
  2. Strong inhibitor for CYP2C19, 2C9, 1A2
  3. Moderate inhibitor of 2B6
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8
Q

Benzodiazepines
MOA
PK (2)
ADE (4)

A

MOA
- Binds to GABAA receptor increasing the activity of GABA

PK:

  1. Similar efficacy
  2. Onset of action and half-life differ

Adverse Effects

  1. Respiratory Depression
  2. Hypotension
  3. Bradycardia
  4. Delirium
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9
Q

Benzodiazepines
Indications (4)
Available Agents (4)

A

Indications

  1. Delirium Tremens
  2. Absence Seizures
  3. Myoclonic Seizures
  4. Status Epilepticus

Available Agents

  1. Diazepam (Diastat®/Valium®)
  2. Lorazepam (Ativan®)
  3. Midazolam (Versed®)
  4. Clonazepam (Klonipin®)
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10
Q

Benzodiazepines
Clinical Pearls

Other uses (3)

Administration and dosage forms (4)

A

Other Uses

  1. Nausea and Vomiting
  2. Pre-procedure sedation
  3. Anxiety

Administration andƒ dosage forms

  1. Diazepam: IV/PO/PR (Diastat®)
    - Lorazepam: IV/PO
    - Midazolam: IV/PO
    - Both lorazepam and midazolam can be administered intranasally
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11
Q

Ethosuximide, Zarontin
MOA
Indications

A

MOA

  • Succinamide
  • Blocks sodium and calcium channels

Indications
- Absence Seizures **ONLY INDICATION

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12
Q

Ethosuximide, Zarontin
ADE
Clinical Pearls

A

Adverse Effects
- Blood dyscrasias

Clinical Pearls

  • Many drug interactions (CYP3A4)
  • Can measure serum concentrations
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13
Q

Phenytoin (Dilantin)

Mechanism Of Action

A

Blocks sodium channels to decrease frequency and voltage of rapidly firing nerve cells

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14
Q

Phenytoin (Dilantin)

Absorption and therapeutic drug concentrations

A

Absorption: Variable depending on dosage form (increase with food)

Therapeutic drug concentration

  • Total = 10 – 20 mcg/ml
  • Unbound = 1 – 2 mcg/ml
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15
Q

Phenytoin (Dilantin)

Distribution

A

Highly protein bound

Adjusted C = C/0.2 x serum albumin + 0.1

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16
Q

Phenytoin (Dilantin)

Metabolism
Half-life

A

Metabolism
- CTP 2C9 and 2C19

Half-Life
- Depends on formulation

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17
Q

Phenytoin (Dilantin)
Indications (3)
Effects (4)

A

Indications

  • Neonatal seizures
  • SE
  • Prevention of seizures following trauma or surgery

Effects

  • Lethary
  • Bradycardia
  • Hirsutism
  • Gingival hyperplasia
18
Q

Phenytoin (Dilantin)

Clinical Pearls (2)
Drug-drug interactions (2)
A

Clinical Pearls

  • Pay attention to dosage forms
  • Due to half-life it will take about 1 week to reach steady state with dose changes

Drug-drug interactions

  • Inducer of CYP3A4
  • CYP2C9 and CYP 2C19 substrate
19
Q

Fosphenytoin (Cerebyx)

Place in Therapy
Clinical Pearls (2)
A

Place in therapy
- Short-term parenteral administration for same indications as phenytoin

Clinical Pearls

  • Should always be dosed in milligrams of Phenytoin Equivalents (PE)
  • Optimal IV choice in pediatrics due to the risk of extravasation with phenytoin
20
Q

Oxacarbazepime (Trileptal)

MOA
PK (2)

A

Mechanism of Action
- Acts on voltage-gated Na+ channels inhibiting neuronal synaptic impulses

PK:

  • Bioavailability is not consistent with immediate release and extended release (caution when switching)
  • Does not auto-induce metabolism
21
Q 
Oxacarbazepime (Trileptal)
Side effects (5)
A
  • Hyponatremia
  • Pancytopenia
  • Hypothyroidism has been reported (as well as altering TFTs)
  • Hypersensitivity skin reaction (SJS)
  • DRESS
22
Q

Valproic Acid, Divalproex Sodium (Depakote, Depakene)

MOA
PK (3)

A

Mechanism of Action:
- Exact mechanism is undefined but likely acts as a GABA aminotransferase inhibitor; increases GABA concentrations

PK:
Absorption – Variable depending on dosage form

Distribution – Highly protein bound (80 – 90%)

Metabolism – Extensive hepatic metabolism via glucuronidation

23
Q

Valproic Acid, Divalproex Sodium (Depakote, Depakene)

Therapeutic monitoring

A

Therapeutic: 50 – 100 mcg/ml

Toxicity: > 100 mcg/ml can see toxic effects (but sometimes have to get close to 100 to see effectiveness)

24
Q 
Valproic Acid, Divalproex Sodium (Depakote, Depakene)
Side Effects (6)
A
  • Pancreatitis
  • Alopecia
  • Rash (including SJS)
  • GI abdominal pain, N/D/V
  • Thrombocytopenia
  • Hepatic toxicity (especially in neonates)
25
Q 
Valproic Acid, Divalproex Sodium (Depakote, Depakene)
Dosage Forms (4)
A

Capsules and Tablets (IR and ER)
Sprinkles in capsules
IV
Oral solution

26
Q

Gabapentin (Neurontin)
MOA (3)
Dosing

A

MOA

  • Complete MOA unknown.
  • Structurally related to GABA but does not bind to GABA sites on the receptor.
  • Potentially do to calcium channel blockade

Dosing
- Start low and titrate up due to risk of side-effects

27
Q

Gabapentin (Neurontin)

Indications (2)

A
  • Focal Seizures
  • Neuropathy – very beneficial for adjunctive therapy

*DO NOT GIVE FOR ABSENCE AND MYOCLONIC SEZIURES

28
Q

Gabapentin (Neurontin)
ADE (4)
Clinical Pearls

A 
Adverse Effects
o Somnolence
o Weight gain
o Neutropenia
o Nystagmus

Clinical Pearls
o May exacerbate absence and myoclonic seizures

*DO NOT GIVE FOR ABSENCE AND MYOCLONIC SEZIURES

29
Q

Lamotrigine (Lamictal)

MOA (2)

Indications (3)

A

MOA

  • Blocks sodium and calcium channels
  • Inhibits excitatory neurotransmitter release
    i. e. glutamate

Indications

  • Focal Seizures
  • Generalized Seizures
  • Potential Absence Seizures
30
Q

Lamotrigine (Lamictal)
ADE (3)
Clinical pearls (4)

A

Adverse Effects

  • Skin Rash
  • Stevens-Johnson Syndrome
  • Toxic Epidermal Necrolysis

Clinical Pearls

  • Significant drug interactions (valproate)
  • Valproate increases serum concentration of lamotrigine
  • Rashes are usually delayed
  • Because of the skin rash an uptitration schedule is required
31
Q

Levetiracetam (Keppra)
MOA

Indications

A

MOA

  • Blocks calcium channels
  • Potential reduction of GABA and glutamate

Indications

  • Adjunct therapy
  • Neonatal seizures
  • Status epilepticus
  • Increasingly becoming first-line and monotherapy
32
Q

Levetiracetam (Keppra)
Side effects (3)
ADE (3)

A

Side Effects
o Somnolence
o Asthenia
o Nervousness

Adverse Effects
o Somnolence
o Asthenia
o Nervousness

33
Q

Topiramate (Topamax)
MOA (3)
Indications (2)

A

MOA

  • Sodium and Calcium channel blockade
  • Carbonic anhydrase inhibition
  • GABA potentiation and glutamate receptor antagonism

Indications
o Focal Seizures
o Generalized Seizures

34
Q

Topiramate (Topamax)
ADE (3)
Clinical Pearls

A

Adverse Effects
o Concentration difficulties
o Anorexia
o Hyperthermia

Clinical Pearls
o Caution in patients with existing baseline behavioral or learning disabilities

35
Q

Zonisamide (Zonegran)

MOA (3)
Indications
ADE (3)

A

MOA

  • Sodium and calcium channel blockade
  • Carbonic anhydrase inhibition
  • GABA potentiation and glutamate receptor antagonism

Indications
- Adjunct therapy for focal seizures

Adverse Effects

  • Cognitive impairment
  • Oligohydrosis (deficient sweat production)
  • Fatigue
36
Q

Banzel (Rufinamide)

MOA

A

FDA approved for lennox-gaustaut syndrome (LGS) in patients > 1 year of age

Mechanism of Action
- Proposed: prolongs the inactive state of Na channels decreasing the Nadependent action potentials

37
Q 
Banzel (Rufinamide)
Side effects (5)
Product availability (2)
A

Side Effects

  1. Dizziness
  2. Headache
  3. Fatigue
  4. Nausea
  5. Severe: Steven Johnson syndrome and DRESS

Product availability

  1. Only as brand
  2. Tablets and Suspension

CX in patients with familial shortened QT

38
Q 
Sabril (Vigabatrin)
FDA Approved (2)

Major side effect

A

FDA approved indications

  • Refractory complex partial seizures (CPS) in children > 10 years
  • Infantile spasms

Major side effect: vision loss

  • Requires REMS enrollment
  • Requires regular eye exams
39
Q

Sabril (Vigabatrin)
MOA
Available doasge forms (2)

A

Mechanism of Action
- Irreversibly inhibits GABA transaminase (GABA-T) increasing GABA within the synapse and neuron

Available dosage forms

  • 500 mg tablet or powder for administration
  • Powder for suspension administration: Dissolve in 10 ml water (final concentration = 50 mg/ml); then draw up the required dose and discard the remainder (1 packet = 1 dose even if you do not use the whole packet)
40
Q

Warnings and Discontinuation

A

Many of these agents have warnings on suicidal thoughts or increase in psychosis, etc.

Discontinuing anti-epileptic medications
o Avoid cold turkey
o Tapering off is recommended
Changing dosage forms

41
Q

Ketogenic Diet

A

Dietary medical therapy used to treat intractable epilepsy
Fat provides majority of calories
o Protein: minimum RDA
o Carbohydrates: severely restricted

Today in conjunction with AEDs
o Watch CHO content
o Avoid liquids
o Content of carbohydrates can vary from generic to generic to brand

42
Q

Vitamin Responsive Seizures

A

Pyridoxyl-5-phosphate (B6)

Folic Acid

Pediatric Pharmacology Exam 2 (9 decks)

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