ANTIEPILEPTICS Flashcards
(155 cards)
1
Q
Seizures
A
TRANSIENT alteration of behavior due to disordered, synchronous and rhythmic firing
2
Q
Epilepsy
A
Sudden recurrent attacks of motor, sensory, autonomic, psychic
3
Q
Motor component is the
A
Seizure
4
Q
Epilepsy classification
A
Partial (focal) : begin one hemisphere of the brain
Generalized seizures
5
Q
Simple partial
A
no LOC
6
Q
Complex partial seizures
A
Loss of concsciousness
7
Q
Partial with secondary generalized seizures
A
evolves to both sides of the brain, convulsive seizure.
8
Q
Generalized seizures begin where?
A
both hemispheres of the brain and usually result in LOC
9
Q
Absence seizures also known as
A
petit mal
10
Q
Types of generalized
A
absence myoclonic tonic-clonic tonic clonic atonic (akinetic) Status epilepticus
11
Q
Status Epilepticus
A
any seizure that last more than 20 minutes OR
seizures of sufficient frequency that the patient does not regain consciousness between episodes.
12
Q
Status Epilepticus
A
more than 30-60 minutes –> CNS damage
13
Q
Give first in SE
A
fast acting medications f/B
Longer acting
14
Q
Neuromuscular blocking drugs are
A
CONTRAINDICATED or not the first drug of choice for SE
15
Q
DO not stop seizure
A
NMB
16
Q
Drug of choice for Absence seizure
A
Ethosuximide
17
Q
Stratus Epilepticus first line for treatment
A
LORAZEPAM - CHOICE drug
18
Q
Anti-epileptic and drug interactions
no effect on these meds.
A
Chronic anticonvulsant therapy are resistant Nondepolarzing NMJ such as ROCURONIUM (INCREASE rate)
No effect on ATRACURIUM, MIVACURIUM, CISATRACURIUM
19
Q
Patients being treated with AEDs have increased dose requirement
A
THIOPENtAL
PROPOFOL
MIDAZOLAM
OPIODS
20
Q
AED numbers interaction gbecause
A
Highly metabolized in the liver
They are inducers/ inhibitors or both
21
Q
Highly protein bound to this protein
A
ALBUMIN
22
Q
For those AED agents that are highly protein bound,
A
displacement from binding site by other highly poroten bound drugs can occur and lead to increase plasma concentration of the AED medications
HYPOALBUMINIA can results in INCREASE PLASMA CONCENTRATION of unbound AED, resulting in toxicity
23
Q
Acute administration of phenytoin
A
Prolong Non-Depolarizing neuromuscular blockers
24
Q
Decrease glutamate (excitatory neurotransmitter) synaptic activity
A
NMDA (N-methyl-D-aspartate) receptor antagonists
• AMPA/kainate receptor antagonist
4. Inhibition of brain carbonic anhydrase enzyme
25
Enhance GABA-mediated neuronal inhibition synaptic activity
* GABA (γ-aminobutyric acid) modulators/enhancers
* GABA (γ-aminobutyric acid) re-uptake inhibitors
* GABA (γ-aminobutyric acid) transaminase inhibitors
26
• Antiepileptic drugs (AEDs) exert their anticonvulsant activity by
the following proposed general mechanisms:
.
1. Inactivate either voltage-gated Na+ or voltage-gated Ca++ currents
via blockade. Some AEDs can inactive both currents
2.Enhance GABA-mediated neuronal inhibition synaptic activity
3. Decrease glutamate (excitatory neurotransmitter) synaptic activity
4. Inhibition of brain carbonic anhydrase enzyme
27
AEDs and Pregnancy
* AEDs can cause teratogenic effects
* NEURAL TUBE defects such as spina bifida can occur, cleft lip & palate
* Phenobarbital, phenytoin, carbamazepine, valproic acid increase the incidence of congenital malformations
28
AVOIDED AT ALL COST in pregnancy
Phenobarbital, phenytoin, carbamazepine, valproic acid increase
29
the highest incidence of teratogenic malformations of all AEDs.
VALPROIC ACID
30
AED
```
First generation (Traditional, old)
Second generation (newer)
```
31
Second generation AED
```
Pregabalin
Lacosamide
Rufinamide
Vigabatrin,
EGOzabine
perampanel
eslicarbazepine, and brivaracetam
```
32
Benzo
display anxiolytic, sedative, muscle relents
33
Benzo MOA
Potentiate GABA-mediated neuronal inhibition by binding to the benzodiazepine receptor site on GABAA receptors, which increases
the frequency of GABA-mediated ion channel opening and increases chloride permeability and thereby leads to cellular hyperpolarization and inhibition of neuronal firing
34
• Diazepam
| •
Useful for treatment of status epilepticus
| • Has a rapid onset and short duration of action
35
Diazepam VS LORAZEPAM
• Has a faster onset but has a shorter duration of action than
lorazepam since diazepam is more lipophilic (gets in and out of the
CNS faster than lorazepam)
36
Diazepam important
SEVERAL ACTIVE METABOLITES
37
First benzo for SE
LORAZEPAM
38
Lorazepam
onset, not as fast as diazepam still fast
| Less liphophillic than diazepam
39
pHenytoin class________ class anti-epileptic agent
• Available in both
•
Hydantoin ;ORAL and IV formulations
40
Phenytoin MOA
Fast Na+ Channel Blocker
• Regulates neuronal excitability and prevents the spread of seizure
activity from a seizure focus by regulating Na+ across neuronal
membranes. The effect is mediated by a slowing of the rate of
recovery of the Na+ channel
• Associated with use-dependent blockade of Na+ channels
41
Pharmacological effects of Phenytoin
```
Exerts anti-seizure activity without causing general depression of
the CNS (usually not associated with excessive sedation)
• In toxic cases, it may produce excitatory CNS signs & symptoms
```
42
Phenytoin is a (acid/base)
WEAK ACID
43
Phenytoin pharmacokinetics
Protein binding ____________
Half life
Half life increases if concentration is
Protein Binding: >90% protein bound
• Primarily bound to albumin
• Plasma t 1/2: 6-24 hours but the t1/2 increases when phenytoin’s
plasma concentration becomes > 10 mcg/mL
44
• Metabolism of Phenytoin
Liver via several CYP 450 enzyme systems
• Exhibits saturable metabolism OR Michaelis-Menten pharmacokinetics (a type of non-linear pharmacokinetics)
• Metabolized to inactive metabolites
• Excretion
45
with plasma concentrations < 10 mcg/mL, phenytoin follows
linear
| pharmacokinetics
46
with plasma concentrations > 10 mcg/mL, the enzymes necessary for metabolism of phenytoin
pharmacokinetics (zero-order kinetics).
become saturated and the half-life
| becomes dose-dependent and elimination follows non-linear
47
Target total concentration
10-20 mcg/ml (1-2mcg/ml)
48
CLASSIC ENZYME INDUCER
PHENYTOINC
49
METABOLIZED BY
multiple CYP 450 Enzymes
50
Phenytoin highly protein bound to
Albumin
51
Since phenytoin is metabolized by CYP 450 enzymes, administering phenytoin with CYP 50 inducers or inhibitors will alter phenytoin’s plasma
CYP 450 inducers will decrease phenytoin’s plasma concentrations
• CYP 450 inhibitors will increase phenytoin’s plasma concentrations
Administering other drugs that are bound to albumin will increase phenytoin’s free, unbound concentration and potentially increase the risk of toxicity
52
IM never an option for
Phenytoin
53
• IV infusion rate should NEVER exceed________
| why?
exceed 50 mg/min
The propylene glycol diluent in the phenytoin injection dosage formulation is a known cardiac depressant and can cause severe hypotension, bradycardia and other cardiac arrhythmias if infused too fast!
54
IV infusion PHENYTOIN not to infused fast because of the
Diluent that's in there
55
Watch drug-drug compatibility interaction so precipitation does not occur
• AVOID ______
• Phenytoin precipitates in solutions with ph of
dextrose solutions
| pH < 7.8
56
CYP 450 inducers will (increase/decrease)
decrease phenytoin’s plasma concentrations
57
• CYP 450 inhibitors will (Increase/decrease)
increase phenytoin’s plasma concentrations
58
Non dose related phenytoin
```
Steven johnson Syndrome
FETAL abnormalities (Fetal Hydantoin syndrome)
```
59
Fosphenytoin
prodrug of phenytoin
water soluble
INJECTABLE Only
60
Fosphenytoin routes
IV or IM
61
Once converted fosphenytoin is
highly protein bound
| effect comes from phenytoin
62
Metabolism of phenytoin
by PHOSPHOTASE ENZYMES in the liver and RBCs
63
No drugs are known to
interferer with the metabolic conversion of fosphenytoin to phenytoin
64
Fosphenytoin compatible with either _____or _____
NS or D5W
65
Do not need IV filter for
Fosphenytoin
66
Fosphenytoin allow the administration of IV form
Faster
67
Loading dose of fosphenytoin
15-20 PE/Kg for SE
| PE is PHENYTOIN Equivalents
68
Fosphenytoin and phenytoin is not a
1:1
69
Because of the risk of hypotension, administer fosphenytoin no faster than _______
150mg PE/min (3x as fast)
70
Carbamazepine (TegretoL)
TCA chemically
| Oral agent
71
Tegretol vs phenytoin: 2 differences
1.Produces therapeutic responses in manic depressive patients
2 Has an anti-diuretic effect that is sometimes associated with increase concentration of ADH in the plasma
72
Mechanism of action tegretol
Fast Na+ channel blocker
| THERE IS AN active metabolite
73
One of the Clinical uses of Tegretol for NON-SEIZURE
TRIGEMINAL NEURALGIA
74
Tegretol has a unique metabolic pathway
AUTO-INDUCER (induces its own metabolism)
75
Tegretol is metabolized by the liver to
an active metabolite, which is then burster metabolized into inactive metabolites & Excreted via urine
76
Tegretol requires
Adequate renal and liver function
77
Tegretol and CYP 450
Is a strong enzyme inducer of CYP450 and NON CYP 450 liver enzymes
78
Adverse effects of Tegretol
CAN CAUSE SIADH (water retention and hyponatremia)
79
Nondepolarizing NMB such as Vecu and rocuronium
May have resistance occur in patients CHRONICALLY receiving anticonvulsant agents such as tegretol or phenytoin
IF TEGRETOL is being used pre-operatively, patient will be resistant and is a KNOWN-GUARANTEED INTERACTION (standard dose of vec or ROC won't work)
80
Will a standard dose of Nondepoleraizing NMB have safe effect of chronically treated patient
no
81
Phenobarbital is a
long acting barbiturates, oral
82
Phenobarbital MOA
binds to GABAa receptores via the barbiturate binding site and increases GABA mediated chloride influx.
Prolongs the opening of the chloride channels, which increases chloride influx , which intern increases membrane polarization (causes HYPERPOLARIZATION)
83
Phenobarbital has ______metabolites
NO ACTIVE METABOLITES
84
Phenobarbital half life is _______and about
80-100 hours
85
Phenobarbital metabolism
| Interact with what system
CYP 450 Enzyme inducer and UGT enzymes system
86
Most common side effect of PHENOBARBital
Sedation, Sedation
87
What is primidone
Oral only anti-epileptic, prodrugs
| 2 active metabolites (phenobarbital and PEMA)
88
ETHOSUXIMIDE (succinimide)
oral only
100% bioavaillabitliy
0% protein binding
NO drugs to drug interaction
89
Ethosuximide type (maintenance)
T type Ca2+ channel blocker reduces the flow of Ca2+ through that fast channel.
90
Only clinical use of Ethosuximide
ABSENT SEIZURE
91
Valproic acid is
non-selective anti-seizure medication
| CAN BE USED FOR MAJORITY OF SEIZURE BECAUSE MULTIPLE MECHANISM OF ACTION
92
Valproic acid MOA (4)
- fast Na+ Channel blocker
- T type Ca2+ blocker
- increases GABA production by stimulating GABA synthesis
- inhibiting GABA metabolism
93
Non seizure indication for valproic acid
Headache prevention
94
GI irritant drugs
Valproic acid , GI, GI
95
Valproic acid metabolism
Extensive metabolism in the liver,
NON dependent on CYP 450
Dependent on UGT enzymes
Has active metabolites.
96
What bad about valproic acid
- Lots of side effects
| - drug to drug interactions
97
Valproic acid given with Phenytoin and diazepam
can displace and increase the free plasma concentration of those medication (phenytoin and diazepam)
98
Valproic acid and CYP 450
Strong enzyme inhibitor of CYP 450 and UGT enzymes
99
Valproic acid is an another drug that display
NON LINEAR PHARMACOKINETICS
100
This drug displays NON-LINEAR PHARMACOKINETICS
Valproic acid
101
Trileptal (oxcarbazepine)
prodrugs (not related to carbamezipine)
| CONVERT TO ACTIVE METABOLITES that carries out reaction (10-monohydroxy metabolite)
102
Trileptal (oxcarbazepine) metabolism
| ALWAYS eliminated
```
UGT enzymes (no auto induction)
Phase II Glucuronide CONJUGATION and renal elimination
```
103
Trileptal (oxcarbazepine) metabolism
Fast Na+ Channel blocker
104
Trileptal (oxcarbazepine) both an enzyme
strong enzyme inducer/ inhibitor dependent on the pathway.
105
Trileptal can also causes
SIADH
106
Lamotrigine (Lamictal)
Broader spectrum of seizures
107
Exact mechanism of action of lamictal is
unknown
| but decrease excitatory amino acids (glutamate and aspartate)
108
Protein binding of lamictal
| half life is
55%
| 25 hours
109
Drug- Drug interaction : lamictal
- Not an inhibitor or inducer of CYP450
| - Valproic acid decrease lamotrigine metabolism and increases its serum concentration and half life.
110
Hallmark of Lamictal
| 2 rashes and _____related
RASH (dose related) is the most serious potential adverse effect
2Stevens-Johnson Syndrome
Toxic Epidermal necrolysis (TEN)
111
Levetiracetam is a
Pure S-isomer ( not racemic)
| FATAL and life threatening by which levetiracetam
112
Precise of MOA keppra
suggested binds to synaptic vesicle glycoprotein SV2A in the brain and alter its function and this may mediate the anticonvulsant activity
113
Absorption of Keppra is
100%
114
CLINICAL USES of Keppra
PREVENTION In surgical patients of seizure in some NEURO patients
115
Pharmacokinetics of Keepra (good drug because)
| Excretion via ___________exclusive?
low protein bound
Not extensively metabolized.
ISSUE: EXCLUSIVE EXCRETION via kidneys
116
Brivaracetam (briviact)
expensive
Partial onset seizures in patients
SCHEDULED V meds (abuse potential)
117
Brivaracetma is same as keppra pharmacokinetics
100% oral bioavailability
| Half life is 9 hours
118
Brivaracetam Metabolized through the
CYP450 Pathway
119
GABAPENTIN is a
Related to the neurotransmitter GABA but DOES NOT modify GABAa or GABAb ligand binding.
120
GABAPENTIN both a
Analgesic and antiepileptic drug
121
****MOA of GABAPENTIN
Bind to alpha 2 delta subunit of voltage dependent Ca2+ Channels, and inactivates them.
122
GABAPENTIN protein binding
low
| NOT CYP450 dependent
123
Do not abruptly discontinue those 2 medications
GABAPENTIN, or lyrica
| May have withdrawal syndrome
124
2 Clinical uses of gabapentin
POST HERPETIC NEURALGIA
| Diabetic neuropathy
125
Pregabalin (LYRICA) is a derivative of
GABA and Chemically similar to gabapentin
Does NOT DIRECTLY BIND TO GABAa, GABAb,
DOES NOT AUGMENT Gabaa responses or have effects on GABA uptake or degradation
126
Lyrica
Schedules V
analgesic and antiepileptic effect
Same MOA as gabapentin (voltage gated Ca2+)
127
Low protein bound lyricA?
yes
128
CLINICAL use of lyrica
nerve pain syndrome
| pain syndrome
129
ANESTHESIA IMPLICATIONS of GABAPENTIN
Decrease 3 things
when given ?
Side effects ; 3 possible
- Decrease opioid requirements/ consumption post op
- Decrease early post op pain
- Decrease post of N/V
Given typically 2 hours prior to surgey
can increase risk of dizziness, sedation, and confusion post op
Exact mechanism is known for the above effects.
130
```
Topiramate:
Route
Potentiates what?
Enhances ?
NO effects on ______
```
oral only
Fast voltage gated Na channel blocker
Enhances post synaptic GABAa, receptor currents.
low protein bound
Potentiates?
No effects on concentration of other medications
131
Decrease serum concentration of topiramate
phenytoin
Carbamezipine
Valproic acid
132
Most common adverse effects TOPAMAX
PSYCHOMOTOR SLOWRING
Difficulty with memory.
HYPERCHLOREMIC METABOLIC ACIDOSIS
133
Zonisamide
Sulfa derivative
134
Zonisamide metabolism ***
| Half life is
• Extensively binds to erythrocytes, resulting in an eight-fold higher concentration in red blood cells (RBC) than in plasma
Plasma t1/2 = ~63 hours
135
Seizure meDICATION HALF LIFE ______
long
136
PHENYTOINC , CARBAMEZAPINE < PHENOBARBITLA
Are all enzyme inducers
137
LACOSAMIDE (VIMPAT)
Extremely expensive
| Selectivlty enhances slow inactivation of voltage gated Na+ channels
138
Lacosamide Metabolism
metabolized CYP 450 enzymes
139
Lacosamide can cause
Can cause HB
dose dependent
Afib or aflutter
140
Rufinamide
Triazole derivative
| Modulation of the activity of Na channel
141
CLINICAL USE of RUFINAMIDE (hard to treat)
Lennox-GASTAUT SYNDROME
142
Adverse effects of RUFINAMIDE on conduction
SHORT QT syndrome
143
VIGABATRIN is a
Irreversible inhibitor of GABA-T the enzyme responsible for the metabolism of the inhibitory neurotransmitter GABA
144
Vigabatrin side effects (3)
PERMANANT BLINDNESS
Peripheral neuropathy
Birth defects
145
Ezogabine (POTIGA)
Potassium channel opener enhance transmembrane potassium current mediated by the KCNQ family of ion channels
146
Pharmacokinetics of EZOGABINE
Metabolized by
Active metabolites?
effect on conduction?
several nonCYP
Has active meablites
PROLONG QT INTERVAL
147
PERAMPANEL (FYCOMPA)
First and only AMPA Glutamate Receptor antagonist
148
First and only AMPA Glutamate Receptor antagonist
Perampanel (Fycompa)
149
Non-competitive at receptor site_____
stay longer
150
Eslicarbazepine acetate : Protein binding is _____and excreted via _______
has a low protein binding
| Via renal excretion
151
Felbamate: when use
SEVERE TROUBLE, LAST effort medicaiton
152
****Felbamate SERIOUS ADVERSE EFFECTS (2)
- Aplastic anemia
| - HEPATOTOXICITY
153
Additional, only approved for partial seizures
PERAMPANEL
154
Phenytoin Dose
16-20mg/Kg of TBW
155
Fosphenytoin loading dose
15-20mg PE/kg for status epilepticus
