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Stage 3 - Case 2 (Central Nervous System) > Lecture 10 & 11: Epilepsy: Pathophysiology And Pharmacology & Pharmaceutical Care > Flashcards

Lecture 10 & 11: Epilepsy: Pathophysiology And Pharmacology & Pharmaceutical Care Flashcards

1
Q

What is Epilepsy?

A
  • Tendency to have recurrent seizures caused by sudden burst of intense electrical activity of the brain
  • Umbrella term w/ lots of types
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2
Q

What are seizures?

A
  • Episodes of altered consiousness
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3
Q

What is ictogenesis?

A
  • The development of a seizure
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4
Q

What is epileptogenesis?

A
  • Development of epilepsy
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5
Q

How do you diagnose Epilepsy?

A
  • Clinical history & presentation
  • EEG: looking for interictal activity: transient abnormal focal neural discharges
  • Family Hx
  • Blood tests: FBC, U&Es, CBG (circulating blood glucose)
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5
Q

What is ictal and interictal?

A
  • Ictal: The seizure
  • Interictal: Between seizures
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6
Q

What are causes of epilepsy?

A
  • Genetic
  • Brain Injury: Trauma/stroke
  • Brain Infection: HPV/measles
  • Brain disease
  • Drugs/alcohol
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7
Q

What are some co-morbidities with epilepsy?

A
  • Excess mortality
  • Memory deficits
  • Schizo
  • Depression, stress, anxiety
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8
Q

What are the main types of seizures?

A
  • Focal: Focal aware or focal impaired awareness
  • Generalised: Atonic, Tonic, Tonic-clonic, myoclonic and absence
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9
Q

What are focal seizures?

A
  • More common than generalised
  • Burst of electrical activity on a specific part of brain
  • Can be fully aware: focal aware seizure (conscious & unable to move) or focal impaired awareness (unconscious)
  • Common site: temporal lob (affects hearing, speech
  • Can spread from focal to entire brain
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10
Q

What is an Atonic seizure?

A
  • Sudden loss of muscle tone
  • Immediately drop to the ground
  • No spasmodic/jerking movements
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11
Q

What is a Tonic seizure?

A
  • Happens when asleep can cause falls
  • Sudden stiffening or contracting of muscles
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12
Q

What is a Tonic Clonic seizure?

A
  • Unconscious then all of a sudden get shakes/jerk (clonic) where muscles contract and relax rhythmically
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13
Q

What is myoclonic seizure?

A
  • Sudden brief jerks or twitches peripheries and extremities
  • Ages 3 and 12yrs
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14
Q

What is absence seizure?

A
  • Look blank, eyelids flutter
  • Mostly in children
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15
Q

What are other conditions that present similar way to a seizure?

A
  • Vasovagal syncope: Fainting
  • Pseudoseizures: non-epileptic attacks
  • Cardiac syncope: arrhythmias
  • Hypo
  • TIA
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16
Q

What are some causes of seizures?

A
  • Drugs/alcohol
  • Electrical stimulation
  • Sensory triggers: flashing lights
  • Metabolic imbalance
  • Fatigue/stress
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17
Q

What are some impacts of epilepsy on living?

A
  • DVLA: Need to be seizure free for a significant period to drive
  • No baths or swimming
  • Employment and education
  • Epilepsy/anti-epileptic meds on cognitive function
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18
Q

What are some core principles of anti-epileptic meds?

A
  • Individualised to patient’s co-morbidity, lifestyle, seizure type and preferemce
  • OD/BD dosing
  • No single pathway: need highest dose to manage w/o side effects
  • If monotherapy w/ 1 drug doesnt work, try another med
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19
Q

What is first and 2nd line med for focal seizure w/ or w/o evolution to tonic-clonic?

A
  • First line: Lamotrigine or Levetiracetam
  • 2nd line: Carbamazepine, oxcarbazepine, zonisamide
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20
Q

What is the First and 2nd line meds for Generalised seizures Tonic-Clonic?

A
  • First line: Sodium Valporate
  • 2nd line: Lamotrigine or Levetiracetam
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21
Q

What is the First and 2nd line meds for Generalised seizures Tonic/Atonic?

A
  • First line: Sodium Valproate
  • 2nd line: Lamotrigine
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22
Q

What is the First and 2nd line meds for Generalised seizures Absence?

A
  • First line: Ethosuximide
  • 2nd line or add-on therapy: Sodium valproate
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23
Q

What is the First and 2nd line meds for Generalised seizures Myoclonic?

A
  • First line: Sodium Valproate
  • 2nd line: Levetiracetam
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24
What are 3 antiepileptic meds that suppress excitation?
- Phenytoin - Sodium Valproate - Carbamazepine
25
What are 3 meds that enhance inhibition?
- Benzos (diazepam) - Barbiturates - Tiagabine
26
What are the main rules of PPP for Sodium Valproate?
- Dispense full original packs only - Annual reviews - Patient guide: at start and each new box - 1highly effective contraception or 2 types
27
What is the mechanism of action of Sodium Valproate?
- Blocks voltage gated sodium channels, stops repeated frequency of neurons firing - GABA is an inhibitory neurotransmitter, it increases its levels - Inhibits T-type Ca2+ channels : lowers threshold for bursts (absence)
28
What are the 5 anti-epileptic meds to learn in more detail?
- Sodium Valproate - Lamotrigine - Carbamazepine - Phenytoin - Levetiracetam
29
What are the red flag signs of Sodium Valproate and some counselling points?
- Hepatotoxicity: persistent vomiting, abdominal pain, malaise, drowsiness. Monitor LFTs - Blood dyscrasias/thrombocytopenia (low platelets): unexplained bleeding or bruising - Pancreatitis: Same as hepatotoxicity. Test: amylase
30
What are some other side effects of Sodium Valproate?
- Weight gain - CNS: aggression, confusion, drowsiness - Transient hair loss
31
What are groups of meds that interact with Sodium Valproate?
- Medications that lower seizure threshold: easier for seizure to occur - Medicines that cause hepatotoxicity - Medicines that antagonise AED effect
32
What are the meds that lower seizure threshold in Sodium Val, Carbamazepine and Phenytoin
- Antibiotics (B-lactam) - Opioids - Antipsychotics
33
What are the meds that may cause hepatotoxicity in Sodium Val, Carbamazepine and Phenytoin?
- Paracetamol - Rifampicin - Methotrexate
34
What are some meds that can antagonise effects of AED?
- Quinolones - SSRIs - TCAs - Antipsychotics
35
What are the common CYP450 inhibitors (SICKFACES.COM)?
- Sodium Valproate - Isoniazid - Cimetidine - Ketoconazole - Fluconazole - Alcohol and Grapefruit Juice - Chloramphenicol - Erythromycin - Sulfonamides - Ciprofloxacin - Omeprazole - Metronidazole
36
Does Lamotrigine have long or short half life and why?
- Long half life: OD dosing
37
What is a red flag symptom of Lamotrigine?
- Rash: possible Steven Johnson syndrome - Body rejecting its skin - This is dose related
38
What are some other side effects of Lamotrigine?
- N&V - Dizziness - Slight daytime drowsiness
39
What does Lamotrigine interact with?
- CYP450 enzyme inhibitors - CYP450 enzyme inducers - Contraceptives
40
What are the CYP450 enzyme inducers (CRAP GPs)?
- Carbamazepine - Rifampicin - Alcohol - Phenytoin - Griseofulvin - Phenobarbitone - Sulphonylureas
41
What is the mechanism of action of Lamotrigine
- Binds to voltage-dependent sodium channels and blocks them. - It stabilizes the channels and prevents repetitive neuronal firing. - This reduces the release of excitatory neurotransmitters, especially: Glutamate, Aspartate
42
What dosage form is Levetiracetam in, what are common side effects and does it have many interactions?
- PO/IV - Well tolerated, most common SE are psychological (irritability, drowsiness, anxiety) - Few drug-drug interactions
43
What are 2 anti-epileptics with narrow therapeutic window?
- Carbamazepine: over 12mg (trough sample) - Phenytoin: 1-20mg/L (trough sample)
44
What are the signs of Carbamazepine toxicity?
- Cerebellar signs: Ataxia (lack of voluntary control of muscle), nystagmus (uncontrolled eye movement), drowsiness - Cardio: arrhythmias (Prolongation of QT), tachycardia, hyper/hypo tension - Electrolyte imbalance: Na+ and K+ low, CBGs are high
45
What are red flag symptoms of Carbamazepine?
- Blood dyscrasias, leucopenia, thrombocytopenia - Hepatotoxicity - Rash - Hyponatraemia - Similar to lamotrigine: dose related (Can change to M.R)
46
What are groups of meds that interact with Carbamazepine?
Meds that - Lower seizure threshold - Cause hepatotoxicity - That antagonise AED effect - Enzyme inhibitors and inducers - Lowers Na+ lvls
47
What is the mechanism of action of Carbamzepine?
- Blocks voltage-gated sodium channels
48
What are the different categories 1,2,3 and what do they mean in terms of brand and generic?
- Category 1: Advised to remain on same brand - Category 2: Only change based on clinical judgement and patient input - Category 3: unnecessary to be kept on same manufacturers brand
49
What meds are in category 1 for brands and generic?
- Carbamazepine - Phenytoin - Phenobarbital - Primidone
50
What meds are in category 2 for brands and generic?
- Sodium valproate - Lamotrigine
51
What meds are in category 3 for brands and generic?
- Levetiracetam
52
What are the MHRA rules on Withdrawal of these meds?
- Decision to withdraw is usually after 2 years of being seizure free - If receiving lots of AEDs: 1 withdrawn at a time - Avoid abrupt withdrawal esp w/ benzo and barbiturates: rebound seizures - Should be gradual over 3 months, benzo/barb should be longer
53
What is status epilepticus?
- A major medical emergency - A seizure that lasts longer than 5 mins or more than 1 seizure in 5 mins w/o returning to normal lvl of consciousness
54
How is status epilepticus treated?
- IV lorazepam preferred : lower risk of thrombophlebitis (inflammation/damage to BV) - IV diazepam but higher risk of thrombo - Can give Diazepam rectal solution or Midazolam oromucosal solution if in community pharmacy: repeat dose after 10mins if no improvement
55
What is the mechanism of action of phenytoin and what are some complicated issues w/ it?
- Stabilises inactive state of Na channels - No linear relationship between dose and plasma drug conc
56
What are signs of Phenytoin toxicity?
- At 20mg/L and presents as Nystagmus at 30mg/L ataxia - Slurred speech, Confusion, hyperglycaemia, Blurred vision - Send to get level in hospital
57
What are some other side effects of phenytoin?
- Antifolate drug like methotrexate: potential for blood dyscrasias - Rashes - Low Vit D - Hepatotoxicity
58
What are some groups of meds that interact w/ phenytoin?
- Medicines that antagonise AED effect - Enzyme inhibitors and inducers - Other antifolate drugs - Efficacy of meds phenytoin may impact
59
What is the mechanism of action of Ethosuximide?
- Target voltage dependent Ca2+ channels (VDCCs) for treatment of absent seizures
60
When is Phenytoin used?
- Phenytoin is often used after benzodiazepines if seizures continue (especially in status epilepticus rescue protocols).

Stage 3 - Case 2 (Central Nervous System) (10 decks)

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