KG - Pharm 3, Exam 1, Anticonvulsants Flashcards
1
Q
Where do seizures typically originate?
A
- cerebral cortex (abt 50% unknown origins)
2
Q
describe: partial seizure, simple
A
- focal, brief (20-90 sec)
- grimacing, focal clonic jerking of extremity
- NO LOSS CONSCIOUSNESS
3
Q
describe: partial seizure, complex
A
- longer (< 2 min)
- ALTERED/LOSS OF CONSCIOUSNESS
- HALLUCINATIONS
- temporal lobe
- automatic movements
4
Q
describe: partial seizure, partial w/ secondary general
A
- LOSS OF CONSCIOUSNESS
- muscle contractions alternating w/ relaxation
5
Q
describe: generalized seizure, tonic-clonic
A
- arise from reciprocal firing of thalamus & cortex
- aka GRAND MAL
- initial tonic rigidity
- subsequent tremor
- clonic jerking (60-120 sec)
- LOSS OF CONSCIOUSNESS
- pt usu stuporous & confused
6
Q
describe: generalized seizure, absence
A
- sudden onset (10-30 sec)
- loss of awareness, but not consciousness
- may be some mild clonic movements
7
Q
describe: generalized seizure, myoclonic
A
- brief spasm/rigidity
- often secondary to other seizure disorder
8
Q
describe: generalized seizure, atonic
A
- sudden loss of postural tone
- pt can fall down
9
Q
anticonvulsants: moa
A
- GABA NEUROTRANSMISSION
- protects against both partial & generalized seizures
- GOAL = ENHANCEMENT OF GABA INHIBITORY ACTIVITY
- -> INHIBIT GABA METABOLISM
- -> STIM GABA RECEPTORS - INHIBITION OF GLUTAMATE ACTIVITY
- inhibition Na+ & thalamic Ca2+ channels
10
Q
what causes seizures?
A
- BLOCKADE OF GABA RECEPTORS (flumazinel)
- ACTIVATION OF GLUTAMATE RECEPTORS (NMDA)
11
Q
Which anticonvulsants have a GABA moa?
A
- phenobarbital
- gabapentin
- valproic acid
- benzodiazepines
12
Q
How do anticonvulsant drugs work to inhibit glutamate activity?
A
- prolong inactivation state of Na+ channels (action potential can’t fire as quickly)
- T-type Ca2+ channels overactive in absence seizures???
13
Q
Phenytoin: uses
A
- PARTIAL SEIZURES, GENERALIZED TONIC-CLONIC SEIZURES
- NOT effective for absence seizures (doesn’t affect Ca2+ channels)
14
Q
Phenytoin: moa
A
- prolongs inactivation of Na+ channels
15
Q
Phenytoin: pharmacokinetics
A
- NOT WATER SOLUBLE –> NOT injected
- ELIMINATION = 1st ORDER at low doses (ZERO ORDER AT THERAPEUTIC AND HIGHER DOSES)
- -> small changes in dose = big change in plasma levels
16
Q
Which form of Phenytoin is injectable?
A
Fosphenytoin
17
Q
Phenytoin: drug interactions
A
- drugs that alter CYP450s (phenobarbital, carbamazepine)
- METABOLIZED & INDUCES CYP450s
18
Q
Phenytoin: side effects
A
- nystagmus, diplopia, ataxia, sedation
- GINGIVAL HYPERPLASIA
- skin rash - STOP USE!!! (RISK OF SJS)
- PREGNANCY CAT D
LONG TERM:
- coarse facial features
- peripheral neuropathy
- abn Vit D metabolism
19
Q
Carbamazepine: uses
A
- DOC for partial seizures
- gen tonic clonic seizures
- bipolar disorder
- TRIGEMINAL NEURALGIA
20
Q
Carbamazepine: moa
A
- blocks Na+ channels
- inhibits NE release & reuptake
21
Q
Carbamazepine: pharmacokinetics
A
- INDUCES CYP450s
- induces own metabolism (must monitor plasma levels)
22
Q
Carbamazepine: drug interactions
A
- increases metabolism of PHENYTOIN, ETHOSUXIMIDE, VALPROIC ACID, HALOPERIDOL, & OCPs
- metab increases by: PHENOBARBITAL, PHENYTOIN,VALPROIC ACID
- metab inhibited by cimetidine & fluoxetine
23
Q
Carbamazepine: side effects
A
- diplopia, ataxia, GI upset, drowsiness
- aplastic anemia, agranulocytosis
- SJS
- PREGNANCY CAT D
24
Q
Phenobarbital: moa
A
- PROLONGS OPENING OF Cl- channel at GABA RECEPTOR
- alters Na+ and Ca2+ conductance at high concentrations
25
Phenobarbital: uses
- PARTIAL SEIZURES
| - GENERALIZED TONIC CLONIC SEIZURES
26
Phenobarbital: drug interactions
- induction of CYP450s increases metabolism of PHENYTOIN & CARBAMAZEPINE
27
Phenobarbital: pharmacokinetics
- binds to GABA receptors, stimulates Cl- influx
| - produces INHIBITION of GABA
28
Lamotrigine: moa
- VOLTAGE & USE DEPENDENT INACTIVATION OF Na+ CHANNELS
29
Lamotrigine: uses
- PARTIAL SEIZURES
| - bipolar disorder
30
Lamotrigine: pharmacokinetics
- inducers of CYP450s (phenytoin, carbamazepine, phenobarbital) will affect metabolism
- half life doubled by valproic acid
31
Lamotrigine: side effects
- CNS = dizziness, HA, diplopia, ataxia, somnolence
- GI - N/V
- skin task & SJS
32
Gabapentin: uses
- ADJUNCT for PARTIAL OR GENERALIZED TONIC-CLONIC SEIZURES
- NEUROPATHIC PAIN
- bipolar dz
33
Gabapentin: moa
- GABA analog
34
Gabapentin: pharmacokinetics
- 1st order elimination
- EXCRETED BY KIDNEY
- short half life, take 3x daily
35
Gabapentin: side effects
- sleepiness
- dizziness
- ataxia
- fatigue
36
Gabapentin: drug interactions
- NEGLIGIBLE!!! (good if already on lots of drugs)
| - PREGNANCY CAT C
37
Topiramate: uses
- PARTIAL & GENERALIZED TONIC-CLONIC SEIZURES
| - MIGRAINE PREVENTION
38
Topiramate: moa
- BLOCKS Na+ CHANNELS
- potentiates GABA receptors
- inhibits glutamate receptor
39
Topiramate: side effects
- dizziness, sedation, nervousness, confusion
| - ACUTE MYOPIA, GLAUCOMA
40
ethosuximide: use
- DOC: ABSENCE SEIZURES
41
ethosuximide: moa
- INHIBITS LOW-THRESHOLD (t-type) Ca2+ channels
| - inhibits "pacemaker" for rhythmic cortical discharge
42
ethosuximide: pharmacokinetics
- metabolized by liver
| - variable half-life 18-72 hrs
43
ethosuximide: side effects
- GI irritation, lethargy, fatigue, HA, dizziness
- HICCUPS
- SJS = RARE
44
ethosuximide: drug interactions
- INHIBITED by VAPRORATE
45
Valproic acid: use
- SECOND CHOICE for ABSENCE SEIZURES
- MYOCLONIC SEIZURES
- BIPOLAR DISORDER
- prophylaxis migraine
46
Valproic acid: moa
- blocks Ca2+ channels and Na+ channels
47
Valproic acid: pharmacokinetics
- ABSORPTION PROLONGED BY FOOD
| - taken after meals
48
Valproic acid: drug interactions
- INHIBITS OWN METABOLISM at low doses
| - INHIBITS METABOLISM OF PHENYTOIN, PHENOBARBITAL, CARBAMAZEPINE
49
Valproic acid: side effects
- nausea, abd pain, heartburn, weight gain, sedation, tremor, alopecia
- HEPATOTOXICITY
- PREGNANCY CAT D
50
Diazepam, Lorazepam: class
- Benzos
51
Diazepam, Lorazepam: moa
- STIMULATE GABA CHANNEL
52
Diazepam, Lorazepam: use
- DIAZEPAM = DOC: STATUS EPILEPTICUS
53
Diazepam, Lorazepam: pregnancy?
- PREGNANCY CAT D
54
how do anticonvulsants affect pregnancy?
- failure of contraceptives higher
- higher birth defect rate
- more congenital heart defects, neural tube defects
55
What are options for women who want to be pregnant, but need to take meds?
- gradual withdrawal therapy
- monotherapy
- lower doses
- folate supplementation
- vitamin K supplementation during last month
56
describe: SJS
- TOXIC EPIDERMAL NECROSIS
- SEROUS AUTOIMMUNE REACTION
- HYPERSENSITIVE REACTION
- WIDESPREAD RASH
- ARTHRITIS, NEPHRITIS
- CNS abnormalities
57
SJS: life threatening interactions
- PHENYTOIN, LAMOTRIGINE, CARBAMAZEPINE, VALPROATE
