Meds Flashcards

1
Q

Lorazepam side effects

A

Sedation
Respiratory depression
Hypotension

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2
Q

Lorazepam: loading dose, onset of action, duration of effect and elimination half life

A

Loading dose: 4-8 mg IV (or 0.1 mg/kg)
Onset of action: 3-10 min
Duration of effect: 12-24 hours
Elimination half life: 14 hrs

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3
Q

Phenytoin loading dose, maintenance dose, onset of action and contraindications

A

Loading dose: 20 mg/kg, max rate: 50 mg/min (25 mg/min in elderly or those with preexisting cardiovascular conditions)
Maintenance: 5-7 mg/g in 2-3 divided doses
Onset of action: 20-25 min
Contraindication: heart block, can’t use if hepatic and renal impairment

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4
Q

Phenytoin main drug interactions

A

Can displace protein bound drugs and increase their free level
Induces hepatic metabolism of many meds (including other AED)
Precipitates if given with potassium, insulin, heparin, norepinephrine, cephalosporin, dobutamine

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5
Q

Phenytoin main side effects

A

Cardiac arrhythmias
Hypotension
Hepatotoxicity
Pancytopenia
Phlebitis
Soft tissue injury from extravasation
Purple glove syndrome
Allergy including Steven-Johnsons syndrome

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6
Q

Phenytoin target serum levels

A

Total 15-25 microgram/mL
Free level: 2 - 3 microgram / mL
Monitor free level when on valproate, benzodiazepines and other highly protein-bound medications, low albumin or critically ill
Adjustment if free level not available: total level / (Albumin x 0.1) + 0.1 [ in patients with renal failure: total level / (Alb x 0.2) + 0.1]

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7
Q

Fosphenytoin loading dose, maintenance dose, onset of action

A

Loading dose: 20 mg/kg (max infusion rate: 150 mg/min), if still seizing after 20 mg/kg - an additional 5 - 10 mg/kg can be given
Maintenance: 5 - 7 mg/kg in 2-3 divided doses
Onset of action: 20 - 25 mins (can give faster than phenytoin but needs to be converted to phenytoin and takes 15 mins to do so)

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8
Q

Main side effect of fosphenytoin

A

Cardiac arrhythmias
Hypotension
Hepatotoxicity
Pancytopenia
Phlebitis
Soft tissue injury from extravasation
Allergy including Steven-Johnsons syndrome
PLUS: transient pruritus from solvent

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9
Q

Target serum level fosphenytoin

A

Same as phenytoin
Serum phenytoin levels should be measured >2 hours after IV or 4 hours after IM administration to allow for complete conversion to phenytoin

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10
Q

Drugs that can precipitate seizures

A

Antibiotics: imipenem, penicillin, cephalosporin, isoniazid, metronidazole
Antihistamines (including OTC diphenhydramine)
Antipsychotics (especially clonazepam and low potency phenothiazines)
Antidepressants: maprotiline, bupropion, tricyclics
Baclofen
Antiarrhythmic: lidocaine, flecainide
Bronchodilators: theophylline
Fentanyl
Flumazanil
Ketamine
Lithium
Meperidine
Propoxyphene

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11
Q

What does pentobarbital infusion do to cerebral oxygen demand, ICP and lipid peroxidation

A

Lowers O2 demand, ICP and lipid perodixation

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12
Q

What is lacosamide?

A

Enteral and parenteral forms
Indication: partial-onset seizure in adults with epilepsy
Acts of slow sodium channel activation
Relatively lacks side effects and drug interactions so popular for treating SE

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13
Q

Enteric topiramate use in RSE, mechanism of action,

A

Prevent breatkthrough and withdrawal seizures while tapering cIV medications
Multiple mechanisms of action: synergistic effect on Na channel block, GABA potentiation at sites other than benzos (benzo targets GABA-A), calcium channel inhibition, AMPA/kainate receptor inhibition
Allows for multiple receptor targeting, particularly those that are affected by prolonged SE (GABA and NMDA/AMPA)

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14
Q

Ketamine caution

A

Elevated ICP
TBI
Ocular injuries
Hypertension
Chronic congestive heart failure
MI
Tachyarrythmias
History of alcohol abuse

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15
Q

Lidocaine bolus dose, maintenance dose, use in RSE and issues

A

Bolus: 1.5 - 2 mg/kg
Maintenance: 3 - 4 mg/kg/hr
Terminates RSE after initial bolus in 75%
Narrow pharmacological range and neurotoxicity side effects (> 5 micro gm/mL) = limits use

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16
Q

Pyridoxine Hydroloride in SE

A

Data extrapolated from pediatric patients with pyridoxine metabolism deficiencies HOWEVER, it is a cofactor for synthesis of inhibitors neurotransmitter GABA and may play a role in initial phases of SE

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17
Q

Does fentanyl have an active metabolite and is it’s metabolism altered in renal failure? How is fentanyl altered in uremia? What about liver dysfunction?

A

No
No
Uremia potentiates its pharmacodynamic effect, sensitivity to sedation and increased respiratory depression
High hepatic extraction ratio - metabolism slowed in liver disease or liver dysfunction

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18
Q

What ultrashort-acting opioid with half life 8-9 minutes is a “forgiving opioid” with clearance that is independent of liver or renal function? Why isn’t it used in the US?

A

Remifentanil
Expensive

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19
Q

How are morphine and meperidine active metabolites cleared?

A

Renally

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20
Q

Does hydromorphone accumulate in renal failure?

A

No

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21
Q

What is a unique adverse effect of fentanyl?

A

Accumulation of parent compound

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22
Q

What is a unique adverse effect of remifentanil?

A

Hyperalgesia

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23
Q

What is a unique adverse effect of morphine?

A

Histamine release
Accumulation of metabolite in renal failure

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24
Q

What is a unique adverse effect of midazolam?

A

Accumulation of parent compound
Accumulation of metabolite in renal failure

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25
Q

What is a unique adverse effect of lorazepam?

A

High-dose PG-related acidosis or renal failure

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26
Q

What is a unique adverse effect of propofol?

A

PRIS
Infection risk
Triglyceride elevation

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27
Q

What is a unique adverse effect of dexmedetomidine?

A

Bradycardia

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28
Q

What three sedation or pain drips can attenuate (be used for) seizures?

A

Midazolam
Lorazepam
Propofol

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29
Q

Which sedation or pain drip increases ICP and which decreases it?

A

Increase: morphine
Decrease: propofol

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30
Q

Which sedation or pain drip has active metabolites?

A

Morphine
Midazolam

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31
Q

What is beneficial about ketamine drip?

A

Sedation
Prevents opioid-induced hyperalgesia
Decreases inflammation
Reduces bronchoconstriction
Binds (blocks) NMDA (in neuronal injury NMDA receptor stimulation leads to release of Ca and glutamate from ischemic neurons causing cell necrosis and apoptosis) and sigma opioid receptors (analgesia), crosses blood brain barrier
Blocking the NMDA receptor also decreases windup pain and central hyperexcitability and opioid-induced hyperalgesia

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32
Q

Which opiate is best for shivering but high doses cause respiratory depression, hypotension and tachycardia?

A

Meperidine

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33
Q

What meds can be used in therapeutic hypothermia and their issues?

A

Meperidine - most effective, respiratory depression, hypotension and tachycardia, avoid in MAOI (can cause serotonin syndrome if given with linezolid), seizure disorder and renal insufficiency
Dexmedetomidine - alpha-2 agonist, decreases catecholamine levels (bradycardia and hypotension)
Clonidine - long acting
Buspirone - mild anxiolytic, central antiserotonin effects, synergistic with meperidine and dexmedetomidine, avoid in myasthenia gravis, glaucoma and MSOF
Magnesium - not super effective
Propofol - higher doses -> vasodilatation and hypotension
Neuromuscular blockade - last resort

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34
Q

What happens to the CYP450 enzyme system in therapeutic hypothermia?

A

Decreases
Decreased metabolism of medications

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35
Q

Where does dexmedetomidine act?

A

Presynaptic neurons in sympathetic nervous system -> decreased norepinephrine release
Central postsynaptic receptors hyperpolarizes neurons
Both cause decreased sympathetic activity
Spinal receptors - analgesia, opioid sparing
Suppresses shivering
May impair autoregulation of cerebral vasculature in septic patients who are hypercapnic
Alpha 2A receptors in locus ceruleus - decrease transmission of noradrenergic output -> anxiolysis and sedation

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36
Q

Neuromuscular blocker preferred to prevent shivering in therapeutic hypothermia and why?

A

Cisatracurium
Spontaneous (Hoffmann) dissociation, independent of liver or kidneys

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37
Q

Why can lorazepam cause AKI and metabolic acidosis?

A

Diluted in propylene glycol

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38
Q

Pathogenesis of PRIS?

A

Mitochondrial dysfunction
Impaired fatty acid oxidation
Metabolite accumulation

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39
Q

Where does flumezanil act?

A

GABA receptors (for benzos)

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40
Q

How can sedatives increase ICP?

A

Respiratory depression leads to increased CO2

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41
Q

Which sedative or pain drips can cause metabolic acidosis?

A

Propofol and lorazepam

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42
Q

How does buspirone help with fevers?

A

Synergistic with opioids to lower shivering threshold
Serotonin 1A (5-HT1A) partial agonist and activates the hypothalamic heat-loss mechanism

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43
Q

How does magnesium help with fevers?

A

Causes cutaneous vasodilation
Increases skin temperature
Improves comfort
Mild muscle relaxation

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44
Q

How does dexmedetomidine help with fevers?

A

Reduces shivering threshold
Synergistic with meperidine and buspirone

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45
Q

How does meperidine help with fevers?

A

Lowers shivering threshold (K-receptor activity, also central alpha-2 agonist, mu-receptor activity)

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46
Q

Containdications to valproate?

A

Severe liver dysfunction
THrombocytopenia
Active bleeding

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47
Q

Valproate major drug interactions?

A

Phenytoin and valproic acid: monitor unbound levels, watch for phenytoin tocixity
Phenobarbital + valproate: severe impaired mental status
Valproate + merrem: merem decreases valproate concentrations drastically

48
Q

Main side effects of valproate?

A

Hepatotoxicity
THrombocytopenia
Pancreatitis
Hyperammonenic encephalopathy (consider L-carnitine 33 mg/kg q8h)
Hypotension

49
Q

Keppra contraindicaitons?

A

None

50
Q

Keppra major drug interactions?

A

Minimal
Not hepatically metabolized

51
Q

Keppra major side effects?

A

Psychosis
Agitation

52
Q

Major side effects of versed infusion?

A

Sedation
Respiratory depression
Hypotension

53
Q

Major side effects of propofol?

A

Sedation
Large lipid load
Pancreatitis
Hypotension
Fatal multi-organ failure
Propofol infusion syndrome

54
Q

Contraindications to propofol?

A

Allergy to soybean oil, egg lecithin or glycerol
Caution in combination with carbonic anhydrase inhibitors (zonisamide and topiramate) due to risk of refractory acidosis

55
Q

Side effects of pentobarbital infusion?

A

Prolonged coma
Hypotension
Myocardial depression
Immune Suppression
Ileus
Allergy: Stevens-Johnson syndrome

56
Q

What drug can be added when weaning pentobarbital infusion?

A

Phenobarbital

57
Q

Side effects of carbamazepine

A

Severe dermatologic reactions (black box warning): SJS, TENs
Agranulocytosis and aplastic anemia (black box warning)
Suicidal thoughts
Increased intraocular pressure
Precipitates porphyria (if hx)
Bone marrow suppression
Exacerbate heart failure
Mild low Na
Homocystenemia
Teratogenic - Category D in pregnancy

58
Q

Carbamazepine toxicity

A

Neuromuscular distrubances
Hyperreflexia
Cardiac dysfunction
Respiratory depression
Tachycardia, shock, urinary retention
Seizures
Tx: gastric lavage, charcoal

59
Q

Carbamazepine metabolism

A

Hepatic to active metabolite

60
Q

Carbamazepine contraindications

A

Bone marrow depression
Hypersensitivity to drug or TCAs (amitryptiline)
D/C MAOI’s 14 days before starting
Carbamazepine + nefazodone = decrease plasma nefazodone

61
Q

Rare side effect of clonazepam?

A

Paradoxical disinhibition
Suicide, psychosis, incontinence

62
Q

Clonazepam drug-drug interactions

A

Clonazepam + kratom = increased CNS depression and death
Clonazepam + CYP3A4 inducers (carbapazepine, phenobarbital, phenytoin, primidone) - reduced clonazepam concentrations
Clonazepam + CYP3A4 inhbitors (clarithromycin, itraconazole, ketoconazole, nirmatrelvir/ritonivir, telithromycin, voriconazole) - increased serum clonazepam levels

63
Q

Contraindications to clonazepam

A

Narrow-angle glaucoma
Significant liver disease
Hypersensitivity

64
Q

Clonazepam toxicity

A

CNS depression
Cardiac arrest
Tx: symptomatic tx, flumazanil

65
Q

Side effects of phenytoin

A

Rash
Sedation
Peripheral neuropathy[6]
Phenytoin encephalopathy[7]
Psychosis
Locomotor dysfunction
Hyperkinesia
Megaloblastic anemia
Decreased bone mineral content
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Immunoglobulin A deficiency
Gingival hyperplasia
Dress syndrome (drug reaction accompanied by eosinophilia and systemic symptoms)
Cardiovascular collapse
Hypotension
Arrhythmias
Hydantoin syndrome in newborns
Purple glove syndrome[8]
Hypertrichosis[9]

66
Q

Contraindications to phenytoin

A

Hypersensitivity to phenytoin or other hydantoins
Pregnancy

67
Q

Drug-drug interactions phenytoin

A

Bound to plasma proteins, metabolized by CYP2C9 and CYP2C19 to inactive metabolites
Inducer of CYP3A4
Inhibitors of enzyme (increase concentration): amiodarone, cimetidine, cotrimoxazole, disulfuram, fluconazole, flagyl, chloramphenicol, sodium valproate, 5-FU, sulphonamides
Inducers of CYP2C9 and CYP2C19 (reduce concentration): alcohol, barbiturates, carbamazepine, theophylline, rifampin, carbamazepine, rifampin, St. John’s wort, precedex, phenytoin and phenobarbital

68
Q

Felbamate adverse effects

A

Relatively little systemic toxicity and less CNS depression when compared to the older generation AEDs. Common side effects include drowsiness, insomnia, anorexia, nausea, dizziness, and headache.[8] Anorexia and other side effects are more likely to occur with higher serum levels.[9]

69
Q

Contraindications to felbamate

A

Hepatic dysfunction
Blood dyscrasia
Hypersensitivity

70
Q

Felbamate toxicity

A

Aplastic anemia
Hepatic failure

71
Q

Cenobamate + Lamotrigine

A

Cenobamate reduces lamotrigine levels

72
Q

Cenobamate and clobazam

A

Cenomatate increased exposure to clobazam

73
Q

Severe reactions to cenobamate

A

Suicidal thoughts
DRESS/multiorgan hypersentivity
QT shortening

74
Q

What does cenobamate do to the following drug levels: lamotrigine, carbamazepine, phenytoin, phenobarbital, clobazam, OCPs?

A

Increases plasma concentration of phenytoin, phenobarbital, clobazam
Decreases plasma concentration of lamotrigine, carbamazepine, OCPs

75
Q

Rare serous effects of Levatiracetam?

A

angioedema, anaphylaxis, Steven-Johnson syndrome, toxic epidermal necrolysis, hives, respiratory distress, and leukocytoclastic vasculitis, pancytopenia

76
Q

Drug-drug interactions of levitiracetam?

A

Worsens CNS depressants effects
Enzyme inducing drugs (phenytoin and carbamazepine) increase clearance
Enzyme inhibitor drugs (valproate) decrease clearance and increase levels

77
Q

Side effects of phenobarbital

A

CNS
Respiratory
CVS
GI
Dermatologic: exfoliative dermatitis, TEN, SJS
Angioedema, liver damage, megaloblastic anemia

78
Q

Contraindications to phenobarbital

A

Barbiturate sensitivity
Latent porphyria
Liver impairment
Large doses in nephritic syndrome
P450 inducer - speeds up metabolism of estrogens and progesterones (OCPs less effective)
Obstructive lung disease
Decreases steroid and theophylline levels

79
Q

ICH Score

A
80
Q

Headaches and seizures diagnosis

A

Thrombosis of vein of Labbe
Tx: anticoagulation (like all other cerebral venous thrombosis)

81
Q

Rare side effect of rtPA and treatment?

A

Angioedema
Steroids + histamine antagonists (ranitidine, diphenhydramine)

82
Q

Thrombophlebitis of IJ with bacteremia after recent oropharyngeal infection/abscess diagnosis and treatment

A

Lemierre syndrome
Tx: antibiotics, anticoagulation, surgical drainage, IV fluids

83
Q

Ischemic stroke + livedo reticularis or livedo racemosa: diagnosis and associations

A

Sneddon syndrome
Idiopathic or autoimmune: SLE, anti-phospholipid antibody

84
Q

Reversal riveroxaban

A

Andexanet alfa

85
Q

Hemorrhagic and ischemic strokes with b-amyloid deposits

A

Cerebral amyloid angiopathy

86
Q

Hunt and Hess score and mortality

A
87
Q

World Federation of Neurologic Surgeons Scale

A
88
Q

Modified Fisher Scale

A
89
Q

Data on phenytoin use as prophylaxis in SAH

A

Poor neurologic outcomes
No change in rate of seizures
Increased complications

90
Q

Nimodipine on incidence of vasospasm?

A

Does not decrease incidence
Reduces symptoms
Improved neurologic function after aneurysmal SAH

91
Q

What part of triple H therapy actually helps?

A

Euvolemic hypertension

92
Q

Elevation in mean velocity and Lindegaard ratio versus global elevation in velocity but normal Lindegaard?

A

Elevation in mean velocity and Lindegaard ratio: vasospasm
Global elevation velocity with normal Lindegaard: cerebral hypoperfusion

93
Q

Valproic acid contraindications

A

Hepatic impairment
Mitochondrial disorders
Pregnancy

94
Q

Side effects of valproic acid

A

GI, neuro, hematological
VPA can lead to several severe adverse reactions, including hepatotoxicity, hallucinations, suicidality, psychosis, toxic epidermal necrolysis, Stevens-Johnson syndrome, anaphylaxis, hyponatremia, SIADH, pancreatitis, thrombocytopenia, pancytopenia, hyperammonemia, myelosuppression, hypothermia, aplastic anemia, bleeding, erythema multiforme, polycystic ovarian syndrome, cerebral pseudoatrophy, encephalopathy, and coma.
Black box: hepatic failure, mitochondrial disease, pancreatitis, congenital malformations

95
Q

Drug-drug interactions valproic acid

A

Wean inhibitor of CYP2C9 and CYP2C19
Combined with inducers -> increased metabolism (decreased levels)
Metabolized by UGT enzymes: drugs that inhibit UGT: asa, felbamate, NSAIDs -> increase plasma concentraitons
Protein bound - increased free fraction salicylates and sulfonamides

96
Q

Topiramate clearance and increased clearance in which meds?

A

Renal
Increased: phenytoin, barbiturates, carbapazepine (enzyme-inducing drugs)

97
Q

Topiramate side effects

A

Glaucoma
Oligohidrosis and hyperthermia
Metabolic acidosis,
SI
Neuropsych
Fetal toxicities
Hyperammonemia and encephalopathy
Kidney stones
Paresthesia
Adjust in renal failure

98
Q

Topiramate drug-drug interactions

A

Topiramate + metformin = increased risk metabolic acidosis
Increases OCP clearance
Decreased clearance with amitryptiline, carbamazepine
Topiramate + carbonic anhydrase inhibitors (acetazolamide, dorzolamide, brinzolamide) = increased risk metabolic acidosis and nephroloithiasis
Increased systemic exposure to lithium at high doses

99
Q

Warnings on topiramate

A

Acute myopaia and secondary angle-closure glaucoma
negative effect on growth

100
Q

Primodone adjustment

A

Decrease dose in renal impairment
Class D in pregnancy

101
Q

Primidone (barbiturate) side effects

A

Connective tissue disorder
Decreased bone density
Folate deficiency -> megaloblastic anemia
Hyperhomocystienmia
Newborns develop coagulation defect (like vit K deficiency)

102
Q

Drug drug interactions primidone

A

Using primidone with any of the following drugs is not recommended:

Atazanavir
Boceprevir
Cobicistat
Darunavir
Delamanid
Elvitegravir
Maraviroc
Mavacamten
Nirmatrelvir
Paritaprevir
Ranolazine
Rilpivirine
Ritonavir
Rivaroxaban
Telaprevir
Tenofovir
Voriconazole

103
Q

Contraindications to primidone

A

History of prophyria
Severe respiratory depression or pulmonary insufficiency, hepatic impairment, alcoholism, renal impairment, sleep apnea, suicial potential or uncontrolled pain

104
Q

Rufinamide SE

A

Shorten QT
DRESS
Leukopenia
SJS

105
Q

Lamotrigine black box

A

SJS
TEN
multi-organ sensitivity, hemophagocytic lymphohistiocytosis, blood dyscrasias, suicidal behavior/ideations, aseptic meningitis, status epilepticus, and sudden unexplained death in epilepsy

106
Q

Side effects lamotrigine

A

Nausea, vomiting
Chest pain, back pain
Xerostomia
Edema
Dysmenorrhea
Weight changes
Constipation
Abdominal pain
Pain, weakness
Insomnia, drowsiness
Dizziness, ataxia, diplopia.
Headache
Anxiety, irritability
Visual disturbances

107
Q

Contraindications to Lamotrigine

A

Consideration for other drugs’ effects on glucuronidation merit consideration, as glucuronic acid conjugation primarily metabolizes lamotrigine.
Drugs that induce lamotrigine glucuronidation include carbamazepine, phenytoin, phenobarbital, rifampin, lopinavir/ritonavir, atazanavir/ritonavir, and primidone.
Valproic acid inhibits lamotrigine glucouronidation.
Concurrent use with central nervous system (CNS) depressants may increase the potency of CNS depression.
Lamotrigine reportedly interferes with urine drug screening and can cause false-positive readings of phencyclidine.

108
Q

Oxcarbazepine

A

CNS
SJS/TEN
Exacerbate myoclonus
Liver injury

109
Q

Ethosuximide side effects

A

GI
SJS/TEN
Agranulocytoisis, aplastic anemia, SLE
Drug induced ITP

110
Q

Ethosuximide drug-drug interactions

A

Enzyme inducers like valproic acid
Can increase phenytoin levels
INH reduces it’s metabolism
Rifampin increases it’s clearance
Reduces keppra

111
Q

Clobazam SE

A

Benzo
SJS/TEN
Hypersensitivity (life threatening)

112
Q

Lacosamide

A

Dizziness, ataxia, nausea
PR prolongation

113
Q

Zonisamide SI

A

Renal calculi
Sulfa like allergy
Neutropenia
Oligohidrosis
Metabolic aciosis

114
Q

Zonisamide drug-drug interactions

A

Metabolized by CYP3A4
Ketoconazole, dihydroergotamine, cyclosporine A and triazolam inhibit metabolism 85-95%

115
Q

Vigabatrin SE

A

Visual problems