Flashcards in PHARM - anti-epileptic drugs Deck (63):
1
4 types of AEDs
- Na blockers
- Ca blockers
- GABA agonists
- glutamate antagonists
2
Na blockers
- phenytoin
- carbamazapine
- valproate
- topiramate
- lamotrigine
3
Ca blockers
ethosuximide
4
GABA agonists
- topiramate
- barbs
- benzos
- gabapentin?
5
glutamate antagonists
- topiramate
- lamotrigine
6
absorption is essentially complete for all AEDs except...
gabapentin, which has a saturable transporter at high doses
7
speed of AED absorption
- takes hours
- slowed by food
8
TIs in AEDs
generally good but hard to compare
9
typical cytochrome P-450 enzymes
2C9, 2C19, 3A4
10
some UGTs and what they metabolize
1A9 - valproate
2B7 - valproate, lorazepam
1A4 - lamotrigine
11
what do cytochrome P-450 inducers do?
- increase clearance and decrease steady state concentrations of other drugs
- phenobarbitol, ethosuximide, phenytoin, carbamazepine, tobacco
12
what do cytochrome P-450 inhibitors do?
- decrease clearance and increase steady state concentrations of other drugs
- erythromycin, valproate, fluconasol, trimethoprim, Ca blockers
13
what pharmacokinetic factors change in the elderly?
distribution - more fat, less albumin
metabolism slowed - less hepatic enzyme, less blood flow
excretion - less renal clearance
14
pharmacokinetic factors in pediatrics
neonates - need lower doses, low protein binding and metabolic rate
children - need higher per kg doses, faster metabolism
15
pharmacokinetic factors in pregnancy
- increased volume of distribution
- low serum albumin, but may not affect free drug level
- faster hepatic metabolism
- may need higher AED doses, but not as high as predicted
16
drug of choice for pregnancy
lamotrigine, few side effects
17
AEDs that cause weight gain
gabapentin, valproate, carbamazepine
18
AEDs that cause weight loss
topiramate
19
AEDs associated with PCOS
- carbamazepine
- valproate
20
AEDs associated with osteoporosis
- phenobarbitol
- carbamazepine
- phenytoin
21
phenobarbitol effective for:
all seizure types but absence
22
phenobarbitol mechanism
GABA agonist, opens Cl channels for hyper polarization
23
phenobarbitol metabolism
- PO or IV
- inducer
- hepatic metabolism
- needs to be loaded
- half life 100hrs
24
phenobarbitol toxicity
- hyperactivity in children
- sedation in adults
- joint problems
25
phenytoin used for
- all seizure types except absence
- better for localized and secondary generalized than for primary generalized
26
phenytoin mechanism
blocks voltage gated Na channels
27
phenytoin metabolism
- IV or PO, PO bad in children
- inducer
- zero order kinetics at high doses due to enzyme saturation
- half life 6-24hrs
- hepatic metabolism
28
phenytoin toxicity
- gingival hyperplasia
- ataxia
- osteomalacia
29
benzo used for
- everything
- especially status epilepticus, alcohol seizure and withdrawal
- sedative and anxiolytic
30
benzo mechanism
GABA agonist
31
benzo metabolism
- PO or IV
- hepatic
- non-inducer
32
benzo toxicity
sedation, depression, withdrawal seizures
33
carbamazepine use
- good for focal and secondary
- mood stabilizer
- NOT a benzo
34
carbamazepine mech
Na blocker
35
carbamazepine metabolism
- oral only
- half life 12 hours
- hepatic
- inducer
- levels increased by Ca blockers and microlide antibiotics
36
carbamazepine toxicity
Blurred vision, sedation, neutropenia, hyponatremia, weight gain.
37
ethosuximide use
only for absence
38
ethosuximide mech
blocks T-type Ca channels
39
ethosuximide metabolism
- oral only
- good GI absorption
- half life 24-48hrs
- hepatic
- mild inducer
40
ethosuximide toxicity
- GI distress
- sedation
- behavioral
41
valproate use
- all seizures
- migraine
- bipolar disorder
42
valproate mech
not well understood, Na? Ca? K? GABA?
43
valproate metabolism
- PO or IV
- half life 15 hours
- hepatic
- non-inducer
44
valproate toxicity
- GI upset,
- weight gain
- menstrual problems
- hair loss
- low platelet count
- hepatic encephalopathy sometimes but not always associated with elevated ammonia levels and carnitine deficiency
45
gabapentin use
- focal and secondarily generalized seizures
- anxiolytic
- sedative
- anti-spasmodic
46
gabapentin mech
- increases GABA levels in brain
- may block Ca channels
47
gabapentin metabolism
- oral only
- half life 6 hours
- not in urine
- not inducer
- well absorbed
48
gabapentin toxicity
- sedation, especially in elderly
- pedal edema
- GI distress
49
lamotrigine use
- all seizures
- bipolar
- neuropathic pain
50
lamotrigine mech
- blocks glutamate release presynaptically
- blocks Na channels post synaptically
51
lamotrigine metabolism
- oral
- non-inducer
- hepatic metabolism and renal excretion
- half life 24 hours
52
lamotrigine toxicity
allergic rash
53
topiramate use
- broad, not good for absence
- migraine
- neuropathic pain
54
topiramate mech
- Na blockade
- GABA agonist
- glutamate antagonist
55
topiramate metabolism
- oral
- non-inducer
- half life 24 hours
- some hepatic metabolism, mostly renal clearance unchanged
56
topiramate toxicity
- sedation
- aphasia
- parasthesias
- kidney stones
57
levetiracetam use
- broad spectrum
- favorite in hospitals
58
levetiracetam mech
- Ca channels
- affects SV2 protein that allows vesicles to release NT
59
levetiracetam metabolism
- 2/3 renal unchanged
- not inducer
- not protein bound
- some hepatic metabolism to inactive metabolites
60
levetiracetam toxicity
cognitive and behavioral problems
61
what is the most effective AED for generalized epilepsy?
valproate
62
2 best drugs for child bearing women?
lamotrigine, levetiracetam
63