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Pediatric Pharmacology Exam 2 > Neurology > Flashcards

Neurology Flashcards

(42 cards)

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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)

Study These Flashcards
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)
Study These Flashcards
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)
Study These Flashcards
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)

Study These Flashcards
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)
Study These Flashcards
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)

Study These Flashcards
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

Study These Flashcards
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)
Study These Flashcards
A
  • Pancreatitis
  • Alopecia
  • Rash (including SJS)
  • GI abdominal pain, N/D/V
  • Thrombocytopenia
  • Hepatic toxicity (especially in neonates)
25
``` Valproic Acid, Divalproex Sodium (Depakote, Depakene) Dosage Forms (4) ```
Capsules and Tablets (IR and ER) Sprinkles in capsules IV Oral solution
26
Gabapentin (Neurontin) MOA (3) Dosing
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
Gabapentin (Neurontin) | Indications (2)
- Focal Seizures - Neuropathy – very beneficial for adjunctive therapy *DO NOT GIVE FOR ABSENCE AND MYOCLONIC SEZIURES
28
Gabapentin (Neurontin) ADE (4) Clinical Pearls
``` 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
Lamotrigine (Lamictal) MOA (2) Indications (3)
MOA - Blocks sodium and calcium channels - Inhibits excitatory neurotransmitter release i. e. glutamate Indications - Focal Seizures - Generalized Seizures - Potential Absence Seizures
30
Lamotrigine (Lamictal) ADE (3) Clinical pearls (4)
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
Levetiracetam (Keppra) MOA Indications
MOA - Blocks calcium channels - Potential reduction of GABA and glutamate Indications - Adjunct therapy - Neonatal seizures - Status epilepticus - Increasingly becoming first-line and monotherapy
32
Levetiracetam (Keppra) Side effects (3) ADE (3)
Side Effects o Somnolence o Asthenia o Nervousness Adverse Effects o Somnolence o Asthenia o Nervousness
33
Topiramate (Topamax) MOA (3) Indications (2)
MOA - Sodium and Calcium channel blockade - Carbonic anhydrase inhibition - GABA potentiation and glutamate receptor antagonism Indications o Focal Seizures o Generalized Seizures
34
Topiramate (Topamax) ADE (3) Clinical Pearls
Adverse Effects o Concentration difficulties o Anorexia o Hyperthermia Clinical Pearls o Caution in patients with existing baseline behavioral or learning disabilities
35
Zonisamide (Zonegran) MOA (3) Indications ADE (3)
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
Banzel (Rufinamide) | MOA
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
``` Banzel (Rufinamide) Side effects (5) Product availability (2) ```
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
``` Sabril (Vigabatrin) FDA Approved (2) ``` Major side effect
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
Sabril (Vigabatrin) MOA Available doasge forms (2)
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
Warnings and Discontinuation
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
Ketogenic Diet
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
Vitamin Responsive Seizures
Pyridoxyl-5-phosphate (B6) | Folic Acid

Pediatric Pharmacology Exam 2 (9 decks)

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