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Meds Flashcards

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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
What is a unique adverse effect of lorazepam?
High-dose PG-related acidosis or renal failure
26
What is a unique adverse effect of propofol?
PRIS Infection risk Triglyceride elevation
27
What is a unique adverse effect of dexmedetomidine?
Bradycardia
28
What three sedation or pain drips can attenuate (be used for) seizures?
Midazolam Lorazepam Propofol
29
Which sedation or pain drip increases ICP and which decreases it?
Increase: morphine Decrease: propofol
30
Which sedation or pain drip has active metabolites?
Morphine Midazolam
31
What is beneficial about ketamine drip?
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
32
Which opiate is best for shivering but high doses cause respiratory depression, hypotension and tachycardia?
Meperidine
33
What meds can be used in therapeutic hypothermia and their issues?
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
34
What happens to the CYP450 enzyme system in therapeutic hypothermia?
Decreases Decreased metabolism of medications
35
Where does dexmedetomidine act?
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
36
Neuromuscular blocker preferred to prevent shivering in therapeutic hypothermia and why?
Cisatracurium Spontaneous (Hoffmann) dissociation, independent of liver or kidneys
37
Why can lorazepam cause AKI and metabolic acidosis?
Diluted in propylene glycol
38
Pathogenesis of PRIS?
Mitochondrial dysfunction Impaired fatty acid oxidation Metabolite accumulation
39
Where does flumezanil act?
GABA receptors (for benzos)
40
How can sedatives increase ICP?
Respiratory depression leads to increased CO2
41
Which sedative or pain drips can cause metabolic acidosis?
Propofol and lorazepam
42
How does buspirone help with fevers?
Synergistic with opioids to lower shivering threshold Serotonin 1A (5-HT1A) partial agonist and activates the hypothalamic heat-loss mechanism
43
How does magnesium help with fevers?
Causes cutaneous vasodilation Increases skin temperature Improves comfort Mild muscle relaxation
44
How does dexmedetomidine help with fevers?
Reduces shivering threshold Synergistic with meperidine and buspirone
45
How does meperidine help with fevers?
Lowers shivering threshold (K-receptor activity, also central alpha-2 agonist, mu-receptor activity)
46
Containdications to valproate?
Severe liver dysfunction THrombocytopenia Active bleeding
47
Valproate major drug interactions?
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
Main side effects of valproate?
Hepatotoxicity THrombocytopenia Pancreatitis Hyperammonenic encephalopathy (consider L-carnitine 33 mg/kg q8h) Hypotension
49
Keppra contraindicaitons?
None
50
Keppra major drug interactions?
Minimal Not hepatically metabolized
51
Keppra major side effects?
Psychosis Agitation
52
Major side effects of versed infusion?
Sedation Respiratory depression Hypotension
53
Major side effects of propofol?
Sedation Large lipid load Pancreatitis Hypotension Fatal multi-organ failure Propofol infusion syndrome
54
Contraindications to propofol?
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
Side effects of pentobarbital infusion?
Prolonged coma Hypotension Myocardial depression Immune Suppression Ileus Allergy: Stevens-Johnson syndrome
56
What drug can be added when weaning pentobarbital infusion?
Phenobarbital
57
Side effects of carbamazepine
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
Carbamazepine toxicity
Neuromuscular distrubances Hyperreflexia Cardiac dysfunction Respiratory depression Tachycardia, shock, urinary retention Seizures Tx: gastric lavage, charcoal
59
Carbamazepine metabolism
Hepatic to active metabolite
60
Carbamazepine contraindications
Bone marrow depression Hypersensitivity to drug or TCAs (amitryptiline) D/C MAOI's 14 days before starting Carbamazepine + nefazodone = decrease plasma nefazodone
61
Rare side effect of clonazepam?
Paradoxical disinhibition Suicide, psychosis, incontinence
62
Clonazepam drug-drug interactions
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
Contraindications to clonazepam
Narrow-angle glaucoma Significant liver disease Hypersensitivity
64
Clonazepam toxicity
CNS depression Cardiac arrest Tx: symptomatic tx, flumazanil
65
Side effects of phenytoin
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
Contraindications to phenytoin
Hypersensitivity to phenytoin or other hydantoins Pregnancy
67
Drug-drug interactions phenytoin
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
Felbamate adverse effects
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
Contraindications to felbamate
Hepatic dysfunction Blood dyscrasia Hypersensitivity
70
Felbamate toxicity
Aplastic anemia Hepatic failure
71
Cenobamate + Lamotrigine
Cenobamate reduces lamotrigine levels
72
Cenobamate and clobazam
Cenomatate increased exposure to clobazam
73
Severe reactions to cenobamate
Suicidal thoughts DRESS/multiorgan hypersentivity QT shortening
74
What does cenobamate do to the following drug levels: lamotrigine, carbamazepine, phenytoin, phenobarbital, clobazam, OCPs?
Increases plasma concentration of phenytoin, phenobarbital, clobazam Decreases plasma concentration of lamotrigine, carbamazepine, OCPs
75
Rare serous effects of Levatiracetam?
angioedema, anaphylaxis, Steven-Johnson syndrome, toxic epidermal necrolysis, hives, respiratory distress, and leukocytoclastic vasculitis, pancytopenia
76
Drug-drug interactions of levitiracetam?
Worsens CNS depressants effects Enzyme inducing drugs (phenytoin and carbamazepine) increase clearance Enzyme inhibitor drugs (valproate) decrease clearance and increase levels
77
Side effects of phenobarbital
CNS Respiratory CVS GI Dermatologic: exfoliative dermatitis, TEN, SJS Angioedema, liver damage, megaloblastic anemia
78
Contraindications to phenobarbital
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
ICH Score
80
Headaches and seizures diagnosis
Thrombosis of vein of Labbe Tx: anticoagulation (like all other cerebral venous thrombosis)
81
Rare side effect of rtPA and treatment?
Angioedema Steroids + histamine antagonists (ranitidine, diphenhydramine)
82
Thrombophlebitis of IJ with bacteremia after recent oropharyngeal infection/abscess diagnosis and treatment
Lemierre syndrome Tx: antibiotics, anticoagulation, surgical drainage, IV fluids
83
Ischemic stroke + livedo reticularis or livedo racemosa: diagnosis and associations
Sneddon syndrome Idiopathic or autoimmune: SLE, anti-phospholipid antibody
84
Reversal riveroxaban
Andexanet alfa
85
Hemorrhagic and ischemic strokes with b-amyloid deposits
Cerebral amyloid angiopathy
86
Hunt and Hess score and mortality
87
World Federation of Neurologic Surgeons Scale
88
Modified Fisher Scale
89
Data on phenytoin use as prophylaxis in SAH
Poor neurologic outcomes No change in rate of seizures Increased complications
90
Nimodipine on incidence of vasospasm?
Does not decrease incidence Reduces symptoms Improved neurologic function after aneurysmal SAH
91
What part of triple H therapy actually helps?
Euvolemic hypertension
92
Elevation in mean velocity and Lindegaard ratio versus global elevation in velocity but normal Lindegaard?
Elevation in mean velocity and Lindegaard ratio: vasospasm Global elevation velocity with normal Lindegaard: cerebral hypoperfusion
93
Valproic acid contraindications
Hepatic impairment Mitochondrial disorders Pregnancy
94
Side effects of valproic acid
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
Drug-drug interactions valproic acid
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
Topiramate clearance and increased clearance in which meds?
Renal Increased: phenytoin, barbiturates, carbapazepine (enzyme-inducing drugs)
97
Topiramate side effects
Glaucoma Oligohidrosis and hyperthermia Metabolic acidosis, SI Neuropsych Fetal toxicities Hyperammonemia and encephalopathy Kidney stones Paresthesia Adjust in renal failure
98
Topiramate drug-drug interactions
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
Warnings on topiramate
Acute myopaia and secondary angle-closure glaucoma negative effect on growth
100
Primodone adjustment
Decrease dose in renal impairment Class D in pregnancy
101
Primidone (barbiturate) side effects
Connective tissue disorder Decreased bone density Folate deficiency -> megaloblastic anemia Hyperhomocystienmia Newborns develop coagulation defect (like vit K deficiency)
102
Drug drug interactions primidone
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
Contraindications to primidone
History of prophyria Severe respiratory depression or pulmonary insufficiency, hepatic impairment, alcoholism, renal impairment, sleep apnea, suicial potential or uncontrolled pain
104
Rufinamide SE
Shorten QT DRESS Leukopenia SJS
105
Lamotrigine black box
SJS TEN multi-organ sensitivity, hemophagocytic lymphohistiocytosis, blood dyscrasias, suicidal behavior/ideations, aseptic meningitis, status epilepticus, and sudden unexplained death in epilepsy
106
Side effects lamotrigine
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
Contraindications to Lamotrigine
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
Oxcarbazepine
CNS SJS/TEN Exacerbate myoclonus Liver injury
109
Ethosuximide side effects
GI SJS/TEN Agranulocytoisis, aplastic anemia, SLE Drug induced ITP
110
Ethosuximide drug-drug interactions
Enzyme inducers like valproic acid Can increase phenytoin levels INH reduces it's metabolism Rifampin increases it's clearance Reduces keppra
111
Clobazam SE
Benzo SJS/TEN Hypersensitivity (life threatening)
112
Lacosamide
Dizziness, ataxia, nausea PR prolongation
113
Zonisamide SI
Renal calculi Sulfa like allergy Neutropenia Oligohidrosis Metabolic aciosis
114
Zonisamide drug-drug interactions
Metabolized by CYP3A4 Ketoconazole, dihydroergotamine, cyclosporine A and triazolam inhibit metabolism 85-95%
115
Vigabatrin SE
Visual problems

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