Meds Flashcards
Lorazepam side effects
Sedation
Respiratory depression
Hypotension
Lorazepam: loading dose, onset of action, duration of effect and elimination half life
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
Phenytoin loading dose, maintenance dose, onset of action and contraindications
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
Phenytoin main drug interactions
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
Phenytoin main side effects
Cardiac arrhythmias
Hypotension
Hepatotoxicity
Pancytopenia
Phlebitis
Soft tissue injury from extravasation
Purple glove syndrome
Allergy including Steven-Johnsons syndrome
Phenytoin target serum levels
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]
Fosphenytoin loading dose, maintenance dose, onset of action
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)
Main side effect of fosphenytoin
Cardiac arrhythmias
Hypotension
Hepatotoxicity
Pancytopenia
Phlebitis
Soft tissue injury from extravasation
Allergy including Steven-Johnsons syndrome
PLUS: transient pruritus from solvent
Target serum level fosphenytoin
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
Drugs that can precipitate seizures
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
What does pentobarbital infusion do to cerebral oxygen demand, ICP and lipid peroxidation
Lowers O2 demand, ICP and lipid perodixation
What is lacosamide?
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
Enteric topiramate use in RSE, mechanism of action,
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)
Ketamine caution
Elevated ICP
TBI
Ocular injuries
Hypertension
Chronic congestive heart failure
MI
Tachyarrythmias
History of alcohol abuse
Lidocaine bolus dose, maintenance dose, use in RSE and issues
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
Pyridoxine Hydroloride in SE
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
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?
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
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?
Remifentanil
Expensive
How are morphine and meperidine active metabolites cleared?
Renally
Does hydromorphone accumulate in renal failure?
No
What is a unique adverse effect of fentanyl?
Accumulation of parent compound
What is a unique adverse effect of remifentanil?
Hyperalgesia
What is a unique adverse effect of morphine?
Histamine release
Accumulation of metabolite in renal failure
What is a unique adverse effect of midazolam?
Accumulation of parent compound
Accumulation of metabolite in renal failure
What is a unique adverse effect of lorazepam?
High-dose PG-related acidosis or renal failure
What is a unique adverse effect of propofol?
PRIS
Infection risk
Triglyceride elevation
What is a unique adverse effect of dexmedetomidine?
Bradycardia
What three sedation or pain drips can attenuate (be used for) seizures?
Midazolam
Lorazepam
Propofol
Which sedation or pain drip increases ICP and which decreases it?
Increase: morphine
Decrease: propofol
Which sedation or pain drip has active metabolites?
Morphine
Midazolam
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
Which opiate is best for shivering but high doses cause respiratory depression, hypotension and tachycardia?
Meperidine
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
What happens to the CYP450 enzyme system in therapeutic hypothermia?
Decreases
Decreased metabolism of medications
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
Neuromuscular blocker preferred to prevent shivering in therapeutic hypothermia and why?
Cisatracurium
Spontaneous (Hoffmann) dissociation, independent of liver or kidneys
Why can lorazepam cause AKI and metabolic acidosis?
Diluted in propylene glycol
Pathogenesis of PRIS?
Mitochondrial dysfunction
Impaired fatty acid oxidation
Metabolite accumulation
Where does flumezanil act?
GABA receptors (for benzos)
How can sedatives increase ICP?
Respiratory depression leads to increased CO2
Which sedative or pain drips can cause metabolic acidosis?
Propofol and lorazepam
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
How does magnesium help with fevers?
Causes cutaneous vasodilation
Increases skin temperature
Improves comfort
Mild muscle relaxation
How does dexmedetomidine help with fevers?
Reduces shivering threshold
Synergistic with meperidine and buspirone
How does meperidine help with fevers?
Lowers shivering threshold (K-receptor activity, also central alpha-2 agonist, mu-receptor activity)
Containdications to valproate?
Severe liver dysfunction
THrombocytopenia
Active bleeding