Internal Medicine Seizures Flashcards
(67 cards)
0
Q
Phenytoin kinetics
A
- Saturable
- follow Michaelis-Menten kinetics
1
Q
General definition of seizure (layman’s terms)
A
-overactive electric activity of the brain
2
Q
Dosing of phenytoin
A
-once a day (half-life anywhere from 30 minutes to 24 hours)
3
Q
Protein binding of phenytoin
A
-highly protein bound (90%)
4
Q
Free range vs total range of phenytoin levels in plasma
A
- free range is about 10% of total range
- total phenytoin 1-20 mcg/ml; free 1-2 mcg/ml
5
Q
Drug interactions with phenytoin
A
- enzyme inducer
- any other drug that is metabolized in liver, probably going to see decreased concentrations of including cyclosporin, warfarin, protease inhibitors
- going to lower levels of other antiseizure drugs including lamotrigine, carbamazepine, valproic acid, phenobarbital, need to be careful when dosing
- metabolism can be inhibited by cimetidine, fluconazole, valproic acid
- levels may be decreased by antacids, carbamazepine, phenobarbital, continuous enteral tube feedings
- may interact with other highly protein bound drugs such as valproic acid, warfarin, salicylates
6
Q
Counseling point with phenytoin and enteral tube feeds
A
-hold tube feeds for an hour before and after giving phenytoin dose
7
Q
Concentration dependent Side effects of phenytoin
A
- ataxia
- nystagmus
- behavior changes
- sedation
- lethargy
- sedation
- dizziness
- neurotoxicity–can lead to neuropathies
8
Q
Idiosyncratic side effects of phenytoin
A
- hirsutism
- gingival hyperplasia
- blood dyscrasias
- rash
- hepatotoxicity
- folate deficiency
9
Q
Why does phenytoin have to have a slow rate of infusion for IV (<50mg/min)?
A
-faster rates could result in hypotension/bradycardia due to propylene glycol component of IV formulation
10
Q
Purpose of fosphenytoin?
A
- activated in vivo
- IV only
- allows phenytoin (as a prodrug) to be infused at a faster rate
- useful in status eptilepticus or other emergency situations
- makes it more soluble
11
Q
Pharmacokinetics of valproic acid/divalproex sodium
A
- half-life of 5-20 hours
- highly protein bound
12
Q
Best monitoring parameter for seizures?
A
-how many seizures a patient has had
13
Q
therapeutic range of valproic acid
A
50-100 mcg/ml
14
Q
Valproic acid drugs interactions
A
- potent CYP inhibitor.
- increases concentrations of: lamotrigine, phenytoin, carbamazepine, phenobarbital, warfarin
- enzyme inducers can lower valproic acid concentrations such as phenytoin, phenobarbital, carbamazepine, carbapenems
- may interact with other highly protein bound drugs: phenytoin, warfarin, salicylates
15
Q
Valproic acid and warfarin drug interaction
A
-inhibition of metabolism and both are highly protein bound drugs, so INR is going to go up.
16
Q
Concentration dependent adverse effects of valproic acid
A
- GI upset
- sedation
- unsteadiness
- tremor
- thrombocytopenia
17
Q
Idiosyncratic adverse effects of valproic acid
A
- acute hepatic failure
- acute pancreatitis
- alopecia
- weight gain
- blood dyscrasias
- hyperammonemia/encephalopathy
**denotes BBB
Pregnancy category X
18
Q
What other indications other than seizures may valproic acid be used for?
A
- bipolar disorder
- migraines
19
Q
carbamazepine PK
A
- highly lipophilic
- 98-99% metabolized in liver (CYP3A4)
- autoinducer–usually complete after 20-30 days
- major active metabolite
- half-life initially 30-60 hours, then 5-25 hours after chronic dosing
20
Q
Therapeutic range of carbamazepine
A
4-12 mcg/ml
21
Q
Drug interactions with carbamazepine
A
- inducer
- may decrease concentrations of: cyclosporine/tacrolimus, warfarin, oral contraceptives, other antiepileptic drugs
- metabolism can be inhibited by: erythromycin/clarithromycin, isoniazid, itraconazole/ketoconazole, cimetidine
22
Q
Concentration adverse effects of carbamazepine
A
- blurred double vision
- ataxia
- slurred speech
- somnolence
- dizziness
23
Q
idiosyncratic adverse effects of carbamazepine
A
- neutropenia
- skin rash
- hepatotoxicity
- hyponatremia (SIADH)
- blood dyscrasias
24
oxcarbazepine PK
- no auto-induction
- T1/2: 8-12 hours
- time to steady state: 2-3 days
- metabolized in liver
25
oxcarbazepine drug interactions
- metabolism can be induced by: phenytoin, phenobarbital, carbamazepine
- may induce metabolism of lamotrigine and oral contraceptives
26
concentration dependent adverse effects of oxcarbazepine
- sedation
- ataxia
- nausea
- dizziness
27
idiosyncratic adverse effects of oxcarbazepine
- skin rash
| - hyponatremia
28
Levetiracetam (Keppra) PK
- 65% of dose is excreted unchanged in urine: dosage adjustment is necessary with renal insufficiency
- half-life 5-10 hours
- not metabolised by liver (limited drug interactions)
29
levetiracetam interactions
-no known interactions
30
levetiracetam concentration dependent ADRs
- sedation
- behavioral disturbances
- irritability
31
Idiosyncratic ADRs with levetiracetam
-none reported to date
32
Primidone is similar to??
-prodrug for phenobarbital
33
phenobarbital PK
- T1/2 is 2-5 days
- half-life is prolonged with hepatic impairment, neonates, inhibitors
- linear kinetics
34
Therapeutic range of phenobarbital
15-40 mcg/ml
35
therapeutic range for primidone
5-12 mcg/ml
36
phenobarbital drug interactions
- potent hepatic enzyme inducer--may increase metabolism of any drug metabolized by CYPs including warfarin, oral contraceptives, carbamazepine, lamotrigine, oxcarbazepine, phenytoin, valproic acid
- metabolism may be inhibited by valproic acid
37
Most common use for primidone
-essential tremor
38
Concentration dependent adverse effects of phenobarbital
- sedation
- ataxia
- nausea
- dizziness
- unsteadiness
- hyperactivity
- headache
39
DOC for neonatal seizures?
-phenobarbital (due to the 'hyperactivity' side effect)
40
What other use other than seizures is secobarbital, a drug similar to pentobarbital used for?
-drug induced coma
41
idiosyncratic ADRs with phenobarbital
- skin rash
| - blood dyscrasias
42
Major use for gabapentin
-neuropathic pain
43
PK of gabapentin
- 100% renally cleared as unchanged drug
| - antacids may decrease absorption
44
major use for pregabalin
-neuropathic pain
45
PK of pregabalin
-90% renally cleared
46
lamotrigine PK
- extensively hepatically metabolized
- minimal protein binding
- half-life dependent on concurrent medications
47
drug interactions with lamotrigine
- metabolism is induced by:
- -phenytoin
- -phenobarbital
- -carbamazepine
- Metabolism is inhibited by: valproic acid (also do not use together because of SJS)
48
concentration dependent ADRs with lamotrigine
- double vision
- unsteadiness
- headache
- dizziness
49
idiosyncratic effects with lamotrigine
- *skin rash*
| - hepatotoxicity
50
tiagabine indications
-seizures
51
topiramate PK
-70% excreted unchanged in urine
| half-life 12-25 hours
52
Drug interactions with topiramate
- enzyme inducers can decrease topiramate concentrations: carbamazepine, phenytoin, phenobarbital
- may decrease concentrations of oral contraceptives
53
Concentration ADRs of topiramate
- difficulties concentrating
- psychomotor slowing
- speech or language problems
- somnolence
- fatigue
- dizziness
54
idiosyncratic side effects of topiramate
- kidney stones
- oligohidrosis
- decreases sodium bicarbonate
55
other indications for topiramate
- bipolar
- weight loss
- migraine prophylaxis
56
lacosamide drug interactions
- enzyme inducers can decrease lacosamide concentrations;
- carbamazepine
- phenytoin
- phenobarbital
57
ADRs of lacosamide
- dizziness
- headache
- nausea
- double vision
- may increase PR interval (check EKG)
58
lacosamide kinetics
-excreted by kidneys
59
zonisamide PK
half-life: 60 hours as monotherarpy; 30 hours with enzyme inducers
60
zonisamide is contraindicated in ____
sulfa allergy
61
Drug interactions with zonisamide
-enzyme inducers
62
concentration ADRs with zonisamide
- sedation
- dizziness
- cognitive impairment
- nausea
63
idiosyncratic ADRs with zonisamide
- skin rash
- kidney stones
- oligohidrosis
64
Indication for ezogabine
-anti-seizure drug
65
indication for perampanel
-anti-seizure drug
66
ethosuximide
-used for *absence* seizures--first line
