Unit 4 Pharmacology: Intravenous Anesthetics Flashcards
Chemical name of propofol
2,6-diisopropylphenol
MOA of propofol
GABA-A agonist, chloride conductance and neuronal hyperpolarization
clearance of propofol
liver (CYP450) and extra hepatic metabolism. clearance exceeds liver blood flow. extra hepatic clearance occurs in the lungs (mostly)
CV effects of propofol
decreased BP (d/t decreased SNS tone, vasodilation, myocardial depression)
decreased SVR
decreased venous tone-> decreased preload
decreased myocardial contractility
respiratory effects of propofol
shifts CO2 response curve down and to the right (less sensitive to CO2). respiratory depression/apnea
inhibits hypoxic ventilatory drive
CNS effects of propofol
decreased CMRO2
decreased CBF, ICP, IOP
no analgesia
anticonvulsant properties
myoclonus may occur
risk factors of PRIS
propofol dose >4mg/kg/hr
infusion >48h
sepsis
continuous catecholamine infusion
high dose steroids
significant cerebral injury
clinical presentation of PRIS
acute refractory bradycardia and at least one of the following:
metabolic acidosis (base deficit >10mmol/L
rhabdomyolysis
enlarged or fatty liver
renal failure
HLD
lipemia
how to minimize or eliminate pain of propofol on injection
giving an opioid, giving lidocaine, injecting into a larger or more proximal vein
how is fospropofol metabolized
via the enzyme alkaline phosphatase to propofol.
chemical name of fospropofol
phosphono-O-methyl-2,6 diisopropylphenol
onset and DOA of fospropofol as compared to propofol
slower onset and longer DOA
initial dose and repeat bolus of fospropofol
initial dose 6.5mg/kg
repeat bolus 1.6mg/kg not more than 4 min
chemical name of ketamine
2-(o cholphenyl)-2(methylamino) cyclohexanone hydrochloride
MOA of ketamine
NMDA antagonist (antagonizes glutamate).
secondary receptor targets: opioid, MAO, serotonin, NE, muscarinic, Na+ channels.
dissociates the thalamus (sensory) from the limbic system (awareness)
DOA of ketamine
10-20 minutes (may require 60-90 minutes to return to full orientation
clearance of ketamine
liver (P450 enzymes).
active metabolite of ketamine
norketamine. 1/3-1/5 the potency of ketamine. renal excretion
CV effects of ketamine
increase in SNS tone, CO, HR, SVR, PVR (caution if severe RV failure). will act as a cardiac depressant in someone with catecholamine depletion (sepsis)
respiratory effects of ketamine
bronchodilator, intact airway reflexes, maintains respiratory drive, does not significantly shift CO2 response curve, increase in PO and pulmonary secretions
CNS effects of ketamine
increase in CMRO2, CBF, ICP, EEG activity. nystagmus, emergence delirium.
risk factors of ketamine induced emergence delirium
age >15 years, female gender, ketamine dose >2mg/kg, hx personality DO
describe analgesic effects of ketamine
relieves somatic pain better than visceral pain
blocks central sensitization and wind up in dorsal horn of spinal cord
prevents opioid induced hyperalgesia (ex after remi infusion)
analgesic properties make it good for burn patients or pre existing chronic pain patients
ketamine and etomidate should be avoided in patients with a hx of
acute intermittent porphyria
when compared to other induction agents, which drug undergoes the smallest amount of plasma protein binding?
ketamine (12%)
chemical name of etomidate
R-1-methyl-1-(a-methylbenzyl) imidazole-5-carboxylate
DOA of etomidate
5-15 minutes
clearance of etomidate
CYP450 and plasma esterases. rapid awakening due to redistribution (not metabolism)
MOA of etomidate
GABA-A agonist
CV effects of etomidate
hemodynamic stability (minimal change in HR, SV, CO)
SVR decreased, which accounts for small reduction in BP
does not block SNS response to laryngoscopy. opioid or esmolol would help
respiratory effects of etomidate
mild resp depression (less than propofol or barbiturates)
CNS effects of etomidate
decreased CMRO2, CBF, ICP.
CPP remains stable
does etomidate provide analgesia
no
etomidate decreases cortisol and aldosterone synthesis via inhibition of
11 beta hydroxylase (located in the adrenal medulla)
relationship between etomidate and seizures
if the patient has a hx of seizures then it decreases the seizure threshold. if they do not have a hx of seizures then it has no effect.
chemical make up of thiobarbiturates
sulfur molecule in the second position ex) thiopental, thiamylal
chemical make up of oxybarbiturates
theres an oxygen molecule in the second position ex)methohexital, pentobarbital
chemical name of thiopental
5-ethyl-5-(1-methylbutyl)-2-thiobarbituric acid
is there pain on IV administration of thiopental
no
MOA of thiopental
GABA-A agonist. depresses reticular activating system in the brainstem. low/normal dose increases affinity of gaba for its binding site while high dose directly stimulates the GABA-A receptor
thiopental dose for adult and children
adult 2.5-5mg/kg
children 5-6mg/kg
OOA thiopental
30-60 seconds
DOA of thiopental
5-10 minutes
clearance of thiopental
CYP450
active metabolite after high dose of thiopental
pentobarbital
CV effects of thiopental
HoTN is primarily the result of ventilation and decreased preload. myocardial depression is secondary cause.
causes non immunogenic histamine response.
baroreceptor reflex is preserved
respiratory effects of thiopental
respiratory depression (shifts CO2 response curve to the right)
histamine release can cause bronchoconstriction (caution with asthma)
CNS effects of thiopental
decrease in CMRO2, CBF, ICP, EEG activity.
does thiopental have neuroprotection for focal or global ischemia
yes for focal ischemia (ex carotid endarterectomy), no for global ischemia
what is acute intermittent porphyria caused by
defect in heme synthesis that promotes accumulation of heme precursors
s/sx of acute intermittent porphyria
severe abdominal pain, n/v
anxiety, confusion, seizures, psychosis, coma, skeletal muscle weakness
anesthetic management of acute intermittent porphyria
liberal hydration, glucose supplementation, heme arginate, prevention of Hothermia.
gold standard for electroconvulsive therapy and dose
methohexital (induction dose 1-1.5mg/kg)
dexmedetomidine class
imidazole
dexmedetomidine MOA
alpha 2 agonist, decreases cAMP and inhibits the locus coeruleus in the pons (sedation)
dose of dexmedetomidine (loading, maintenance)
1mcg/kg over 10 min
maintenance infusion .4-.7mcg/kg/h
onset and DOA of dexmedetomidine
with loading dose: 10-20 min
after infusion is stopped: 10-30 min
clearance of dexmedetomidine
liver (p450)
describe the dexmedetomidine modulated alpha 2 negative feedback loop
acts on pre synaptic alpha 2 receptors which produces a negative feedback loop by decreasing NE release from pre synaptic nerve terminal. reduces SNS tone and produces sedation
CNS effects of dexmedetomiding (CBF, CMRO2, ICP)
decreases CBF but no change in CMRO2 and ICP
describe the MOA of dexmedetomidine as it relates to analgesia
alpha 2 stimulation in the dorsal horn of the spinal cord (decreases substance p and glutamate release)
how can you administer precedex to a kid without an IV
nasal or buccal (3-4mcg/kg 1 hour before surgery)
formulation of midazolam (and what happens in bottle versus body)
imidazole ring. in the vial (low pH), ring is open and hydrophilic. when it enters the body, ring closes and it becomes more lipophilic so it can cross the BBB more easily
MOA of midazolam
gaba a agonist. increases frequency of channel opening- neuronal hyper polarization.
dose of midazolam for sedation, induction, PO in kids
iv sedation: .01-.1mg/kg
iv induction .1-.4mg/kg
PO sedation .5-1mg/kg
OOA and DOA of midazolam
IV 30-60 seconds
IV DOA 20-60 min
active metabolite of midazolam
1 hydroxymidazolam (.5x potency of midazolam)
CV effects of midazolam
decreases BP and SVR
respiratory effects of midazolam
induction dose cases respiratory depression
CNS effects of midazolam
induction dose (not sedation dose) decreases CMRO2 and CBF.
anterograde amnesia
anticonvulsant
anxiolysis
spinally mediated skeletal muscle relaxation (antispasmodic)
no analgesia
why does diazepam take forever to metabolize
undergoes enterohepatic recirculation
half life of diazepam
43 hours
onset of lorazepam
slow
greatest to least potency of diazepam, midazolam, lorazepam
lorazepam>midazolam>diazepam
describe a time when remimazolam would be a good option
indicated for induction and maintenance for adults undergoing procedural sedation lasting 30 minutes or less
flumazenil initial dose
.2 (titrated in increments until desired response is achieved)
flumazenil DOA
30-60 min (for this reason, repeat dosing is necessary)
