ICU drugs Flashcards
This is the time dependency of a drug; relationship between the dose of a drug and its plasma/tissue concentration;
pharmacokinectics
What is pharmacokinectics?
relationship between dose of a drug and tissue concentration
This is what the body does to the drug; absorption, distribution, metabolism, and elimination;
pharmacokinectics
What is pharmacodynamics?
how plasma concentration of a drug exerts its effect on the body
This is what the drug does to the body;
pharmacodynamics
General anesthesia encompasses three parts:
unconsciousness (and amnesia)
analgesia
muscle relaxation
These drugs commonly used for unconsciousness and amnesia:
propofol
ketamine
etomidate
benzos/barbs
How does propofol work?
inhibits synaptic transmission thru its effects on GABA receptor
This drug is used for unconsciousness and is an alkylated phenol that inhibits synaptic transmission thru its effects on GABA receptor:
propofol
Why is propofol use attractive in smokers and asthmatics?
has bronchodilator properties
Why do we use propofol cautiously in pts with hypovolemia and CAD?
causes hypovolemia
Onset of action of propofol?
less than a minute
Propofol is metabolized by?
liver
cleared 60% by liver, 40% by kidneys
Half life of propofol?
biphasic
initially 40 minutes
terminal half life 4-7 hrs
Adverse reactions of propofol?
local pain at injection site hypotension myoclonus QT prolongation (rare) green urine (rare)
Propofol safe in pregnancy?
yes
crosses the placenta
Propofol effects on the brain?
decrease in cerebral blood flow
decrease in intracranial pressure
decrease in cerebral oxygen consumption
Propofol use for status epilepticus?
used off label for status epilepticus
suppresses seizure activity
Propofol also exerts anti-emetic effects post-op, how?
depresses chemoreceptor trigger zone and vagal nuclei
Cardiovascular effects of propofol?
causes vasodilation by inhibitis SNS vasoconstriction
can cause hypotension when given as a bolus
What is PRIS?
propofol infusion syndrome
rare side effect of prolonged prop infusion (>4 mg/kg/hr >24 hrs)
Clinical side effects of PRIS?
metabolic acidosis
hyperkalemia
hyperlipidemia
rhabdomyolysis
Onset of PRIS?
usually within 4 days of initial treatment
How do we manage PRIS?
discontinue prop
supportive care
Mortality of PRIS?
33%
Most commonly used IV benzos?
diazepam
lorazepam
midazolam
What do we use benzos for?
anxiety and amnesia
MOA of benzos?
inhibit synaptic transmission at GABA receptor
Can cause hyperlipidemia, pancreatitis, and local injection site pain;
prop
Does propofol have analgesic effects?
NO
Main disadvantages of prolonged propofol use?
high cost
dose-related hypotension
Mechanism of this syndrome thought to be decreased fatty acid metabolism coupled with damage to mitochondria resulting in cardiac and peripheral myocyte dysfunction:
PRIS
Do benzos have analgesic effects?
NO
they are sedative anxiolytic
3 main benzos?
diazepam
lorazepam
midazolam
Diazepam AKA?
valium
How do benzos work?
increase frequency of Cl channel opening at GABA-A receptors
neuron becomes hyper-polarized, reduced neuron excitability
This benzo has short onset of action and short half-life,;
diazepam (valium)
Dose of diazepam (valium) for anxiety?
PO: 2-10 mg 2-4x/day
IV: 2-10 mg Q 3-4 hrs
Lorazepam AKA?
ativan
ATIVAN AKA?
lorazepam
This benzo has slow onset, intermediate half life and most useful for medium to long-term sedation:
lorazepam (ativan)
Lorazepam and the elderly?
can accumulate in older pts with renal and hepatic dysfunction causing prolonged sedation
Midazolam AKA?
versed
Benzo of choice for acutely agitated pts?
midazolam (versed)
Rapid onset, short acting benzo?
midazolam (versed)
Benzos when used with opioids tend to cause what?
respiratory depression
This is an imidazole derivative used to IV induction?
etomidate
Etomidate is rapidly and completely hydrolized to inactive metabolites, thus;
results in rapid awakening
Where does etomidate work?
GABA receptor
Effect of etomidate on BP and HR?
very iittle compared to propofol
What does ketamine do?
produces amnesia + analgesia
MOA of ketamine?
blocks NMDA receptors
What can ketamine cause in pts with CAD?
can increase HR and BP and cause ischemia in pts with CAD
Why is ketamine useful in asthmatic pts?
direct bronchodilator effect
Half life of ketamine?
10-15 mins
Ketamine elimination depends on?
liver CYP450 metabolism
Most common side effects of ketamine?
nausea/vomiting
Do we use ketamine in head trauma?
NO
causes increased intracranial pressure
IV NSAID that produces analgesia by blocking COX:
ketorloac
Ketorolac blocks what?
COX-1 & COX-2
Side effects of ketorolac?
gastric bleeding
platelet dysfunction
liver/kidney damage
Analgesic and anti-pyretic that acts on CNS:
IV acetaminophen
Site of action of IV acetaminophen?
CNS
not peripherally
Addition of benzos to ketamine infusion has been shown to decrease what side effects?
delirium and hallucinations assc w/ketamine
What is dexmedetomidine?
sedative with analgesic properties
MOA of dexmedetomidine?
a2-adrenergic agonist
Side effects of dexmedetomidine?
hypotension
bradycardia
What are the 3 opioids used in ICU setting?
fentanyl
morphine
hydromorphone
Advantages of fentanyl over morphine?
more rapid onset of action (600x more lipid soluble)
less risk of hypotension (fentanyl does not cause histamine release)
fent does not have active metabolites
Opioids are primarily metabolized in the ?
liver
and metabolites excreted in urine
Maintenance dose of morphine should be adjusted to 50% in pts with renal failure, why?
MS has several active metabolites that accumulate in the kidney
Does fentanyl need to be adjusted for pts with renal failure?
no, it does not have metabolites
How does MS cause hypotension?
promotes release of histamine
causes systemic vasodilation
Onset of morphine?
5-10 minutes
Onset of fentanyl?
1-2 minutes
Why is fentanyl better than morphine?
more lipid soluble
more rapid onset of action
no active metabolites
no need for renal adjustment
no histamine release–> no hypotension
Advantages of hydromorphone over morphine?
hydromorphone does not cause histamine release
does not need to be adjusted in renal failure
Meperidine (demerol) is an opioid analgesic no longer used in ICU, why?
potential for neurotoxicity
normeperidine is a metabolite that causes CNS excitation, myoclonus, delirium
Cardiovascular effects of opioids?
decrease HR and BP due to decrease in SNS activity
BP responds to fluid boluses or pressor boluses
Opioid effects in GI motility?
depressed GI motility via opioid receptors in GI tract
How do opioids cause vomiting?
stimulate chemoreceptor trigger zone
Why are IV doses of ketorlac preferred over IM?
IM doses can cause hematomas
Recommended dosage of ketorolac?
30 mg IV Q 6 hrs
reduce it to 15 mg IV Q 6 hrs for elderly or pts with body weight <50kg
Adverse rxns with ketorolac?
gastric mucosal injury
upper GI bleed
renal function impairment
Maximum daily dose of ibuprofen?
3.2 grams
Maximum allowed dose of IV acetaminophen?
4 grams daily
***to prevent acetaminophen hepatoxicity
How do we measure agitation in the ICU?
sedation agitation scale SAS
richmond agitation severity score RASS
Preferred benzo for rapid sedation?
midazolem (versed)
Onset of action of midazolem (versed)?
1-2 minutes due to its high lipid solubility
Effects of midazolam (versed) last how long?
1-2 hrs (cleared rapidly from blood stream and taken avidly into tissue)
Why do we limit midazolam (versed) infusion to less than 48 hrs?
prevents excessive sedation from drug accumulation in tissues
Lorazepam (ativan) is a longer acting drug that midazolam, with effects up to?
6 hrs after a single dose
The IV preparation of lorazepam contains what?
propylene glycol (a solvent which increased drug solubility)
its toxic when it accumulates
Midazolam vs loparezepam, which has a metabolite?
midazolam has a metabolite –> cleared by the kidneys
Why can changes in renal function affect midazolam?
has a metabolite that’s cleared by the kidneys
Benzos are metabolized where?
liver
Onset of action of midazolam vs lorazepam:
midazolam; 2-5 mins
lorazepam; 15-20 mins
Toxicity assc with midazolam vs lorazepam:
midazolam; metabolite toxicity in renal impaired pts
lorazepam; propylene glycol toxicity
What is propylene glycol toxicity seen with lorazepam?
IV preparations of lorazepam contain propylene glycol to enhance solubility
converted to lactic acid in the liver
causes; lactic acidosis, delirium, hypotension, multi-organ failure
AN unexplained metabolic acidosis after > 24 hrs of lorazepam should prompt evaluation for?
serum lactate levels
raise suspicion for propylene glycol toxicity
Onset of action of prop?
1-2 minutes
Arousal after prop wears off?
10-15 mins
Adverse effects of prop?
Hypotension
Hyperlipidemia
PRIS
respiratory depression
Why can we use propofol in pts with intracranial injuries?
reduces intracranial pressures
allows for frequent arousal to check mental status
How is propofol dose?
dose for IBW
not adjusted for renal failure or moderate liver failure
Prop is suspended in what?
10% lipid emulsion to enhance plasma solubility
Green urine with prop?
rare
due to phenolic metabolites
Prop well known for producing what?
resp depression
hypotension
(should be ideally started in pt’s that are vented)
How to avoid risk of PRIS?
avoid prop infusion rates > 5mg/kg/hr for more than 48 hrs
This is an a2-receptor agonist that produces sedative, amnestic and mild analgesic effect;
dexmedtomidine
Onset of action of dex?
5-10 mins
time to arousal; 6-10 mins
Does dex cause respiratory depression like prop?
NO
What’s so nice about dex?
patients can be aroused even though they’re sedated., don’t need to stop the infusion
when awake pt’s can communicate and follow commands
Why is dex good for vented pts?
sedation can be continued from transition period from mechanical ventilation to spontaneous breathing
Adverse effects of dex?
dose dependent decrease in HR, BP
How does haldol work?
produces its sedative and antipsychotic effects by blocking dopamine receptors in brain
Onset of haldol?
10-20 mins
lasts 3-4 hrs
Does haldol cause respiratory depression?
NO
hypotension rare
Extrapyramidal effects of haldol?
rare with IV administration (seen with PO)
rigidity, spasmodic rxns
Neuroleptic malignant syndrome seen with what drug?
IV haldol
rare
(fever, muscle rigidity, rhabdo)
Why do we avoid haldol in pts with prolonged qtC?
haldol prolongs Qtc
causes polymorphic vtach like torsades
