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Year 1: Patho/Pharm > Seizures PHARM > Flashcards

Seizures PHARM Flashcards

1
Q

Neurotransmitters CNS
vs. PNS

A

CSN: 21 neurotransmitters
PNS: 3 neurotransmitters (E, NE, Ach)

  1. Monoamines
    - NE, E, DA, 5HT3
  2. Amino acids
    - glycine, glutamate, GABA, aspartame
  3. purines
    - adenosine, AMP, ATP
  4. opioid peptides
    - endorphins, enkephalins, dynorphins, etc.
  5. non-opioid peptides
    - oxytocin, somatostatin, substance P, ADH (etc.)
  6. other:
    - histamine, acetylcholine
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2
Q

Excitatory/Inhibitory Post Synaptic Potential
Pathophysiology

A

Dendrites

  • Ligand (NT) gated ion channels
  • NT binds Na/C ion channels
  • Excitatory post synaptic potential: influx Na+, influx Ca+ (more positive)
  • Inhibitory post synaptic potential: efflux K+ (more negative)

*Depolarization towards threshold -55mV = fire action potential

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3
Q

Resting Membrane Potential
Pathophysiology

A

-70mV
Na/K ATPase
3 Na+ out
2 K+ in

High concentration Na+ outside cell
High concentration K+ inside cell

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4
Q

Action Potential
Pathophysiology

A

Excitatory Post synaptic potentials
- depolarization through influx Na+ and Ca+ ligand gated ion channels
- moves towards -55mV (depolarization towards threshold)

Action potential fires
- Voltage gated sodium channels OPEN
- influx of sodium
- depolarization to +40mV
- voltage gated sodium channels CLOSED INACTIVE STATE (absolute refractory)

Hyperpolarization
- Voltage gated potassium channels OPEN (slower)
- efflux of K+
- hyper polarization (beyond -70mV) voltage gated sodium channels CLOSED (relative refractory period)
- voltage gated potassium channels CLOSE

Na/K ATPase
- restores resting membrane potential -70mV
- 3 Na+ out
- 2 K+ in

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5
Q

Excitatory vs. Inhibitory NT

A

Excitatory NT
- Glycine
- Glutamate

Inhibitory NT
- GABA
- NE
- HT
- cannabinoids
- opioids

*Dependent on the pre-synaptic receptor

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6
Q

Drugs that affect sodium influx
CLOSED INACTIVE voltage gated sodium channels

A

Drugs that keep voltage gated sodium channels in inactive state (CLOSED)

  • Phenytoin
  • Carbamazepine (Eslicarbazepine, Oxcarbazepine)
  • Lamotrigine
  • Lacosamide
  • Rufinamide
  • Topiramate
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7
Q

Drugs that affect Calcium influx

A

Ethosuximide

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8
Q

Drugs that affect GABA

A
  • Benzodiazepines (ex. diazepam)
  • Barbiturates (phenobarbitol, primidone)
  • Gabapentin
  • Valproic Acid
  • Vigabatrin
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9
Q

Drugs that affect glutamate receptors

A
  • topiramate
  • perampanel
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10
Q

Drugs with unknown mechanism of action for AED

A
  • levetiracetam
  • bivaracetam
  • pregabalin
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11
Q

Drugs for Absence seizures

A

ethosuximide (block calcium influx)

valproic acid (agonist GABA)

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12
Q

AED used for all seizure types

A

VPA
Valproic acid

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13
Q

Goal of AED therapy

A

Decrease seizure frequency, severity, duration

*not seizure free

Minimize SE and impact on ADLs

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14
Q

Pregnancy and AEDs

A

monotherapy
lowest dosage
avoid valproic acid at all costs
folic acid supplementation
Vitamin K supplementation
90% will have normal pregnancy

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15
Q

Pregnancy and Epilepsy

A

Increase risk of abortion, still birth, preterm labour

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16
Q

Phenytoin/Fosphenytoin
MOA

A

Targets hyperexcitable neurons in the seizure focus

Keeps voltage gated sodium channels closed and INACTIVATED

Cannot fire new action potential

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17
Q

Phenytoin / Fosphenytoin
SE

A

EYES: Nystagmus, blurred vision, diplopia

MSK: Ataxia

CNS: confusion, sedation

CARDIO: cardiovascular collapse with fast infusion

HEME: Bleeding risk (suppression Vitamin K coagulation factors), infection risk (bone marrow suppression)

ENDOCRINE: Hirsutism, gum hyperplasia and bleeding

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18
Q

Special considerations IV infusions
Phenytoin
Fosphenytoin

A
  1. Phenytoin (IV, PO)
    IV filter
    slow IV infusion to prevent cardiovascular collapse
  2. Fospheytoin (IV, IM)
    paraesthesia and pruritis of groin during IV infusion
    Pro-drug conversion, no filter needed
    decreased risk cardiovascular collapse
    can infuse faster
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19
Q

Phenytoin/Fosphenytoin
AE

A

HLA-1502
1. SJS, TENS, DRESS
Patient education: monitor for rash
*Asian Descent

  1. Teratogenic
    Patient education: condoms, oral contraceptives degraded
  2. Infection and bleeding risk
    Monitoring: CBC, INR
    Patient education: report bruising, signs of infection
  3. fractures
    - Phenytoin blocks vitamin D activation
    - results in hyperparathyroidism (secondary)
    - calcium is not absorbed from GI
    - bones are reabsorbed
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20
Q

Therapeutic Drug Monitoring
Phenytoin

A

Saturation Kinetics
- saturate hepatic enzyme quickly
- small change in dose, large change in drug level

Narrow therapeutic window
- small dose can cause 1. toxicity 2. therapeutic failure

Therapeutic drug monitoring
- plasma level
- trough level

*Drug interactions high

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21
Q

Administration considerations
Phenytoin/Fosphenytoin

A

Do not administer with food
1-2 hour hold

PRN
calcium
vitamin D

IV filter for phenytoin

Pharmacy to check drug interactions
saturation kinetics

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22
Q

Carbamazepine
MOA

A

Target: seizure focus (hyper excitable neurons) and surrounding neighbours

Keeps voltage gated sodium channels in INACTIVE and CLOSED state (prolongs absolute refractory period)

prevents firing of new action potential

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23
Q

Carbamazepine
SE

A

EYES: Nystagmus, blurred vision, diplopia
CNS: sedation
MSK: ataxia
- tolerance develops
- Patient education: start low, go slow, night admin

Bone marrow suppression: bleeding and infection risk

Teratogenic: NTD

SKIN: SJS, DRESS, TENS (HLA-1502)

OTHER:
Kidney failure
Increase ADH release: FVO, hyponatremia
Liver failure

24
Q

Carbamazepine
AE

A

Teratogenic: NTD
Patient education: folic acid, contraception condoms, oral

Kidney failure: FVO, hyponatremia, ADH hyper secretion
Patient education: weight gain, oliguria, S&S hyponatremia

Liver failure

Bone marrow suppression: Bleeding and infection (Fatal aplastic anemia D/C)

HLA1502: TENS, DRESS, SJS

25
Patient Monitoring Carbamazepine
CBC and diff HLA-1502 status LFTs BUN, creatinine serum sodium serum ferritin Weight HCG S&S liver failure: jaundice, anorexia, n/v S&S kidney failure: weight gain, oliguria S&S bleeding: bruising, pale, fatigue S&S infection: fever, sore throat S&S hyponatremia: fatigue, anorexia, loss muscular tone, depressed reflexes, orthostatic hypotension, etc.
26
Carbamazepine Indications
All seizures *Exception - absence seizures
27
Carbamazepine Hepatic Metabolism
Induces its own metabolism Induces metabolism of other AEDs - phenytoin - phenobarbital - oral contraceptives
28
Carbamazepine Contraindications
Liver disease Kidney disease pregnancy HLA1502 Blood disorders Caution secondary Hyperparathyroidism Heart failure Hypertension
29
Ethosuximide MOA
Blocks calcium channels in pre-synaptic (Blocks EPSP) and post synaptic membrane (Blocks NT release) Prevents transmission of excitatory impulse
30
Ethosuximide Indication
Absence seizures
31
Ethosuximide SE
EYES: Nystagmus, blurred vision, diplopia CNS: sedation Patient education: take at night, tolerance develops GI: nausea, vomiting, weight loss Patient education: take with food SKIN: Rash HEME: Bone marrow suppression, SLE
32
Patient monitoring Ethosuximide
Clinical response - no drug monitoring - absence seizures occur at high frequency CBC and diff Patient monitoring S&S bleeding, infection, rash, weight loss
33
Phenobarbital/Primidone MOA
GABA agonist increase activity of GABA CNS depressant *Phenobarbital is a metabolite of primidone
34
Phenobarbital/Primidone SE
CNS: sedation, dizziness, fatigue, learning impairment Patient education: take at night, tolerance develops PSYCH: depression/suicide adults, paradoxical agitation children/older people HEME: porphyrin accumulation RESP: respiratory depression
35
Phenobarbital/Primidone AE
Respiratory depression and death Contraindicated: respiratory disorders, CNS depressants, liver/kidney disease (drug accumulation) Addiction, depression, suicide Contraindicated: psych history Withdrawal
36
Phenobarbital/Primidone Contraindications
Respiratory disorders liver and kidney disorders (drug accumulation) history addiction, suicide, depression
37
Patient Monitoring Phenobarbital/Primidone
CBC and diff LFT BUN and Creatninine Respiratory disorders Medication: CNS depressants Hx. addiction, mental health
38
Primidone MOA
Phenobarbital is a metabolite of primidone GABA agonist increase CNS depression
39
Indication Phenobarbital vs. Primidone
Phenobarbital - All seizures exception absence Primidone - all seizures exception absence and status
40
Valproic Acid Indication
ALL SEIZURES * absence included Rx combination seizures
41
Valproic Acid MOA
Unknown Thought to be a GABA agonist Increase CNS depression
42
Valproic Acid SE/AE
CNS: *Minimal sedation MSK: tremor GI: N/V/anorexia/abdominal pain, weight gain Patient education: administer with food HEME: bone marrow suppression Kidney: Ammonia accumulation Hepatitis and liver failure pancreatitis Teratogenic
43
Valproic Acid AE
Teratogenic: 4x higher than other AEDs Kidney: Ammonium accumulation and encephalopathy (N/V/anorexia, HA, ataxia, seizures, coma) Liver: hepatitis and liver failure (anorexia, N/V, jaundice, dark urine, pale stools) Pancreatitis: debilitating RUQ pain, radiation back, hypotensive shock, ARDs, DIC, GI hemorrhage, multiple organ failure
44
Contraindications Valproic acid
1. Pregnancy - teratogenic 4x 2. < 2 years of age and multiple AEDs - hepatitis and pancreatitis - death 3. Liver disease, pancreatic disease 4. blood dyscarias
45
Patient monitoring VPA
CBC and diff LFTs BUN and creatininine serum lipase HCG
46
Patient education VPA
S&S: bleeding, bruising, pallor, fatigue, infection (bone marrow suppression) S&S: anorexia, nausea, vomiting, jaundice (liver failure) S&S: RUQ pain, hypotensive shock, DIC, fever (pancreatitis) pregnancy: oral contraceptive and condom S&S encephalopathy ammonium: ataxia, N/V/HA, coma, seizures
47
levetiracetam MOA and indication
unknown MOA All seizures exception absence
48
Levetiracetam safety profile
safest AED doesn't require hepatic metabolism doesn't interact with other AEDs
49
Levetiracetam SE
CNS: Sedation Psych: aggression, agitation, anxiety, depression, psychosis MSK: asthenia (lack of strength) Kidney: query renal failure
50
Seizure Threshold and Pregnancy
Pregnancy hormones (estrogen) lowers the seizure threshold Increased plasma volume lowers the AED level *predisposes people to seizures
51
Seizure effect on fetus and mother
Increase risked of fetal and maternal death Fetus - decrease heart rate, perfusion - increase risk of pre-term labour, stillborns, miscarriage Mother - increased risk of death
52
AED Strategy during pregnancy
AEDs teratogenic - phenytoin - carbamazepine: NTD (folic acid supplementation) - Valproic acid: absolute contraindication 4x risk Monotherapy lowest dose Vitamin K and folic acid supplements
53
AEDs that lower oral contraceptive levels (hepatic metabolism)
- Phenytoin - carbamazepine - valproic acid - phenobarbital/ primidone - toperiamate - lamotrigine
54
Ketogenic Diet Therapeutic effect
Indication: Medication resistant epilepsy Decrease seizure frequency, severity Diet high in fat, protein, low in carbohydrate Induce a state of ketosis Ketone bodies produced Increase the seizure threshold
55
Ketogenic Diet SE
Metabolic acidosis - ketone bodies (keto acids) Hypoglycemia - SNS effects: diaphoresis, sweating, tachycardia - CNS effects: lethargy, sedation, coma Systemic: - CAD, atheroscelerosis, dyslipidemia - pancreatitis - kidney stones (high protein)
56
Weaning AED
six weeks to wean wean 1 drug at a time
57
Driving and Epilepsy
- 6 to 12 months seizure free before can drive - 16 years of age mandatory reporting in Ontario (even if do not have licence)

Year 1: Patho/Pharm (45 decks)

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