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Flashcards in Drugs for Test 1 Deck (80):
1

What are the first line DOC based on seizure type for partial seizures?

Carbamzepine
Phenytoin
Lamotrigine
Oxcarbazepine
Topiramate

2

What are the second line DOC based on seizure type for partial seizures?

Gabapentin
Levetiracetam
Phenobarbital
Pregabalin
Primidone
Tiagabine
Valproic acid

3

What are the first line DOC based on seizure type for absence seizures?

Ethosuximide
Lamotrigine
Valproic acid

4

What are the first line DOC based on seizure type for myoclonic and atonic seizures?

Valproic acid
Lamotrigine

5

What are the first line DOC based on seizure type for tonic-clonic seizures?

Valproic acid
Carbamazepine
Oxcarbazepine
Lamotrigine

6

Phenytoin (Dilantin) MOA and Indications

Blocks voltage gated Na+ channels reducin the propogation of abnormal impulses in the brain.
Indications- simple and complex partial sz, generalized tonic-clonic sz, and status epilepticus caused by recurrent tonic-clonic sz.

7

Phenytoin Pharmakokinetics and administration considerations

Metabolized by P450 system
Potent non-specific inducer of many drug metabolizing enzymes
Highly protein bound
Nonlinear kinetics
Requires dosing therapeutic monitoring
Enteral feeding reduces oral absorption, oral suspension shake vigoriously.
IV formulation can cause pain, phlebitis, and extravasation.
No IM injection

8

Phenytoin anti arrhythmia and drug interactions

Dont stop abruptly
Inducers- carbamazepine, OCP, doxyclycline, quinidine, cyclosporin, methadone, levodopa
Inhibitors- chloramphenicol, CIMETIDINE sulfonamide, and ISONIAZID

9

Phenytoin ADRs

Dose related- nystagmus, ataxia, drowsiness, cognitive impairment
Non-dose related- GINGIVAL HYPERPLASIA, hirsutism, acne, rash, hepatotoxicity
Teratogenic- Fetal hydantoin syndrome (cleft lip and palate, congenital heart disease, slowed growth and mental deficiency)

10

Carbamazepine (Tegretol) MOA and indications

Blocks Na+ channels
Indications- first line tx of simple partial, complex partial, and generalized tonic-clonic

11

Carbamazepine (Tegretol) Pharmakokinetics

Monitoring through autoinduction (first 20-30 days of tx, autoinduction is dose dependent, after complete, steady state concentrations are achieved after 3 days)
Potent non-specidic inducer of many drugs and transporters

12

Carbamazepine (Tegretol) ADRs

Dose related- vertigo, ataxia, diplopia, drowsiness, nausea
CNS side effects- HA, paraesthesis, confusion, psychosis
Non-specific- SIADH, leukopenia, thrombocytopenia, stevens johnson syndrome.

13

Phenobarbital (Luminal) MOA, indications, and side effects

MOA unknown
Indications- generalized tonic clonic, partial sz, neonatal sz, febrile sz,
Side effects- sedation, irritability, slowed thinking, ataxia, hyperactivity, and rash

14

Phenobarbital (Luminal) pharmacokinetics

Extremely long 1/2 life (96 hours)
Time to steady state is 20-30 days
Metabolized by P450 system

15

Primidone (mysoline) MOA and indication

Structurally related to phenobarbita l
Efficacy from metabolites (phenobarbital- tonic clonic sz and simple partial sz, and pehnyethylmalonamide- complex partial sz)
Well absorbed orally; poor protein binding, same ADRs as phenobarbital
Indications- alternative choice in partial sz and tonic-clonic sz

16

Valproic acid (Depakene) & Sodium Valproate (Depakote) MOA and indication

Completely absorbed
Saturable protein binding
Hepatic metabolism but DOESN'T induce P450
Inhibits metabolism of phenobarbital, carbamazepine, ethosuximide

17

What drugs does Valproic acid (Depakene) inhibit the metabolism?

Phenobarbital, carbamazepine, ethosuximide.

18

Valproic acid side effects

Dose related- N/V, Abd pain, diarrhea, sedation, tremor, unsteadiness
Non-dose related- acute hepatic failure, acute pancreatitis.

19

Ethosuximide (Zarontin) MOA and indication

MOA- inhibits calcium channels.
Indication- DOC for absence seizures.

20

Ethosuximide (Zarontin) pharmacokinetics and side effects

Absorbed orally; not protein bound; metabolized by but not inducer of P450
Side effects dose related- GI, lethargy, HA, dizziness, anxiety

21

What are the second generations anti-epileptic drugs?

Gabapentin (neurontin)
Oxcarbamazepine (Trileptal)
Tiagapine (Gabitril)
Felbamate (Felbatol)
Lamotrigine (Lamictal)
Zonisamide (Zonegran)
Levetiracetam (Keppra)
Pregabalin (Lyrica)

22

Oxcarbamazepine (trileptal) MOA and indication

Active metabolite blocks Na+ channels
Indication- partial sz with or w/out secondary generalization
Analogue of cabamazepine w/ fewer side effects than cabamazepine and phenytoin

23

Oxcarbamazepine (trileptal) Side effects

Dizziness, ataxia, fatigue, GI, hyponatremia, rash
30% reactivity for rash with CBZ
No PK monitoring; no autoinduction

24

Gabapentin (Neurotin) MOA and indication

Analog of GABA; MOA unknown
Indication- adjunct to partial and GTC sz, tx of peripheral neuropathy.

25

Gabapentin (Neurotin) favorable pharmacokinetic profile

Dose-dependent oral absorption
Not protein bound
Excreted unchanged via kidneys
No serum level monitoring

26

Gabapentin (Neurotin) Side effects

Somnolence, dizziness, ataxia, nystagmus

27

Tiagabine (Gabitril) MOA and Indication

Competitive inhibitor of GABA transporter in neurons and glia (inhibitors re-uptake)
Indication- adjunctive tx of partial sz
TAKE WITH FOOD

28

Tiagabine (Gabitril) pharmacokinetics and side effects

Quickly and completely absorbed
Increased clearance in peds, with enzyme inducers
Serum concentrations unnecessary
Side effects- Dose related: dizziness, fatigue, nervousness, difficulty concentrating

29

Lamotrigine (lamictal) MOA and indication

Blocks Na+ and Ca++ channels
Adjunctive in children and mono therapy in adults
Indications- GTC, partial seizures, absence

30

Lamotrigine (lamictal) adverse side effects

Rash (10%), confusion, depression, N/V, diplopia, severe idiosyncratic (skin, blood)
Slow taper essential, initial dose dependent on other meds

31

Topiramate (Topamax) MOA and indication

Blocks Na+ channels and binds GABA thus opening Cl- channels
Indication- tx for partial and generalized sz in pediatrics and adults.

32

Topiramate (Topamax) pharmacokinetics and adverse effects

70% renal elimination
1st order kinetics
Clearance increased w/ enzyme inhibitors
AE- dose related- drowsiness, parasthesias, psychomotor slowing, weight loss, renal calculi
NOTE- Maintain adequate fluid levels

33

Felbamate (felbtol) MOA and indication

Blocks Na+ channels, competes for NMDA receptor, prevents AMPA receptor stimulation, blocks Ca++ channels
Indication- partial sz and lennox-gastaut syndrome
Use restricted to refractory Lennox-Gastaut syndrome (active metabolism covalently binds liver, bone marrow proteins, and DNA resulting in aplastic anemia and liver failure.

34

Felbamate (felbtol) Side effects

Dose related- anorexia, N/V, insomnia, HA
Non-dose related- aplastic anemia, hepatic failure

35

Levetiracetam (Keppra) MOA and indication

MOA unknown
Indication- tx of generalized sz
Adjust dose in renal insufficiency

36

Levetiracetam (Keppra) favorable PK profile and Side effects

Almost completely absorbed
Metabolism NOT dependent on the P450 system
Minimal protein binding
MInimal drug interactions
Side effects- sedation, behavioral abnormalities

37

Zonisamide (Zonegran) MOA and Indication

Sulfonamide derivative: blocks Na+ and Ca++ channels and enhances GABA-receptor function
Indication- adjunctive therapy for partial sz

38

Zonisamide (Zonegran) pharmacokinetics and Side effects

Good oral absorption and renally and hepatically eliminated
Side effects: Dose related: sedation, dizziness, cognitive impairment, nausea
Non-dose related- rash, oligohydrosis, kidney stones

39

Pregabalin (lyrica) Indication and side effects

Indication- adjunctive tx for partial onset sz, peripheral neuropathy, postherpatic neuralgia, fibromyalgia syndome
Side effects- dizziness, somnolence, dry mouth, PERIPHERAL EDEMA, blurred vision, weight gain

40

Benzodiazepines

Act as positive allosteric modulators by enhancing channel gating in presence of GABA
Not indicated if sz already stopped or for maintenance therapy.

41

Benzodiazepines ADRs

Infusion rate related to arrhythmias and hypotension
Respiratory depression
Impairment of consciousness

42

Lorazepam (Ativan)

DOC for patient w/ IV access
Onset of action 3-5 min
Can cause vein irritation (Dilution of dose)

43

Lorazepam (ativan) vs diazepam (valium)

Lorazepam is preferred over diazepam secondary to duration of action
Diazepam highly lipophilic and quickly redistributes out of brain to other fat stores.
Diazepam DOA- 15 min to 2 hrs
Lorazepam DOA- 12-24 hrs

44

Diazepam (valium)

Rapid onset, short duration
option if IV route not available (rectally)

45

Midazolam (versed)

Reserved for refractory sz
Buccal, intranasal, IM routes
Give by continuos infusion for refractory SE

46

Hydantoins place in therapy

Second line (loading dose) if sz continue after 2-3 doses of benzos
Consider loading dose and maintenance dose if sz recur or if recurrence anticipated
Initiate maintenance doses 12-14 hrs after loading dose
Less CNS and respiratory depression than benzo and barbituates

47

Hydantoins Side effects

Arrhythmias, nystagmus, dizziness, ataxia

48

Phenytoin Onset of action and administration

Onset of Action- longer time to stop sz than benzos, less lipid soluable and requres slower administration
Admin- erractic absorption and pain w/ IM injections
Dilute with NS
Contains propylene glycol (result in arrhythmias, hypotension, metabolic acidosis with repeated doses)

49

Fosphenytoin (Cerebyx)

H20 soluble prodrug of phenytoin converted by plasma esterases
Available IM and IV
Doesn't contain propylene glycol
Compatible with most IV solutions w/ less phlebitis
Paresthesias and pruritis are more frequent

50

Phenobarbital

3rd line agent, if sz persists despite 2-3 doses of benzos and loading dose of hydantoin
2nd line agent if sz persists after 2-3 doses of benzos and hydantoins contraindicated
Used in pediatric patients
Onset of action w/in minutes of loading dose administration

51

Phenobarbital ADR

More CNS and respiratory depression than hydantoins
Contains propylene glycol

52

NSAIDs

Non-specific meds for migraines
FIrst line for mild to moderate migraines.
Inhibit prostaglandin synthesis (inhibits inflammation in trigeminovascular system)
Includes- ASA (aspirin), naproxen, ibuprophen, APAP + ASA + Caffeine (Excedrin Migraine)

53

What are the first line NSAIDs?

ASA (aspirin), naproxen, ibuprophen, APAP (acetaminophen) + ASA + Caffeine (Excedrin Migraine)

54

Butorphanol (Stadol nasal spray)

Synthetic narcotic antagonist-agonist
Abuse potential

55

Barbiturate Combinations (hypnotics)

Non-specific migraine treatment
Combined w/ analgesics or codein
Potential for overuse, mod-severe migraine
EX- butalbital, aspirin & caffeine (fiorinal)

56

What are the drug interactions of barbiturate combinations (hypnotics)?

Effects reduced by barbiturates- phenotiazine, quinidine, cyclosporine, theophylline, & BETA BLOCKERS
Effects increased by barbiturates- chloramphenicol, benzodiazepines, CNS depressents

57

Ergot Alkaloids-MOA

5-HT1 agonist, activity of alpha, beta-adrenergic receptors and DA receptors
-Constricts intracranial blood vessels
-Inhibits development of neurogenic inflammation in the trigeminovascular system

58

Ergotamine tartrate pharmacokinetics

Oral tablet and retal tablet

59

Dihydroergotamine

Nasal spray

60

Ergotamine acute side effects

N/V (pretreatment with antiemetic)
Diarrhea
Abdominal pain
Weakness
Leg cramps
Tremor
Dizziness
Syncope
Chest pain
Intermittent Claudication
Syndrome of ergotism

61

Ergotamine chronic side effects

Cerebral/peripheral ischemic disorders
Hypertension
TACHY/BRADY
Medication overuse HA
Renal D/O
Withdrawal signs: severe HA, N/V, malaise

62

Ergotamine Contraindications

Sepsis
Renal/hepatic failure
Pregnancy/lactation
Gluacoma
Peptic ulcer disease
Uncontrolled HTN
CHD/Stroke/PVD
Potential interactions w/ protease inhibitors
USE OF TRIPTANS W/IN 24 HOURS

63

Ergotamine Drug Interactions

CYP 3A4 substrate
Interactions w/ strong 3A4 inhibitors (azole antifungals, macrolides, protease inhibitors)
Triptans (additive vasoconstrictive effect)
Fluoxetine, fluvoxamine (competes for metabolism by 3A4)

64

Triptans

Selective 5-HT1b/d agonists- intracranial vasoconstriction, inhibition of neuropeptide release from trigeminovascular nerves, interrupts pain signal w/in brain stem trigeminal nuclei
1ST LINE FOR MODERATE TO SEVERE MIGRAINE

65

Triptan- sumatriptan (imitrex)- ROA

SQ injection, oral tabs, nasal spray

66

Triptans- Rizatriptan (Maxalt)-ROA

Oral tabs, oral disintegrating tabs

67

Zolmitriptan (Zomig)

Oral tabs, oral disintegrating tabs, nasal spray

68

Triptan Side effects

Dizziness
Fatigue
Flushing
Nausea
Chest tightness, pressure, heaviness, pain
Injection rxn
Taste perversion from nasal spray

69

Triptan Contraindications

Ergot alkaloid in last 24 hrs
MAOI in last two weeks
Ischemic heart disease/cerebrovascular
Uncontrolled HTN
Hemiplegic and basilar migraines

70

Triptan- drug interactions

MAOI: inhibits clearance of triptans
Risk of serotonin syndrome
SSRIs
Risk of serotonin syndrome
Ergotamine containing products
Increased vasoconstrictive effects

71

Beta-blockers MOA and contraindications

1st line agents for prophylactic treatment- agents include propranalol (inderal), metoprolol (lopressor), atenolol(tenormin), & nadolol
MOA- unknown theory is that it may regulate serotonin transmission in cortical pathways
Contraindications- pts w/ peripheral vascular disease, depression, asthma

72

Beta-blocker ADRs

Fatigue, vivid dreams, depression, impotence, BRADYCARDIA, HYPOTENSION

73

Tricyclic antidepressants (TCAs) MOA

Also used as 1st line agents for migraines- include imipramine (tofranil), nortriptyline (pamelor), & AMITRIPTYLINE (elavil)
MOA- antagonist of 5-HT2 receptors inhibiting the reuptake of serontonin and causing increased concentration of serotonin in the synaptic cleft

74

Tricyclic antidepressants (TCAs) ADRs and Drug interactions

ADRs-Sedation, constipation, blurred vision, HPOTN
Drug interactions- MAOIs

75

Valproic acid (depakene) and divalproex sodium (depakote) MOA and contraindications

Anticonvulsant
MOA- increased activity of GABA inhibitory transmitter
Contraindications- liver-disease, monitor liver enzymes

76

Valproic acid (depakene) and divalproex sodium (depakote) ADRs and drug interactions

Anticonvulsant
ADRs- tremor, weight gain, hair loss, nausea
Drug interactions- other anticonvulsants, CNS depressants, absence sz in combo w/ clonazepam

77

What other anticonvulsants besides Valproic acid (depakene) and divalproex sodium (depakote) can be used in the prophylaxis of migraines?

Carbamazepine (tegretol), topiramate (topamax), gabapentin (neurontin)

78

Calcium channel blockers

Verapamil, nimodipine, diltiazem
Vasodilators that cause decrease in smooth muscle tone and vascular resistance

79

Methysergide (Sansert)

Should not be used unless nothing else worse and a patient has severe migraines due to black box warning of fatal pulmonary fibrosis
MOA- peripheral 5-HT inhibitor but central 5-HT agonist
Use only for 6 mo. followed by 3-4 week drug free period.
Effective but has serious side effects

80

Botulinum Toxin Type A (Botox)

Prophylaxis of migraines
Inhibits acetylcholne release at the presynaptic cholinergic junction (inhibition of overactive peripheral neurons, possibly modulates substance P, and does not cross BBB)
Not FDA approved indication
Prophylactic effect seen 60-90 days after injection
Inconsistent clinical trials