Term
Etomidate (Know this one)
Amidate (dont use this one) |
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Definition
0.2% solution 2mg/ml
ph 6.9
basic drug
carboxylated imidazole-midazolam is this too.
D isomer (packaged like this)
protein binding is 75%
Pka 4.2 |
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Term
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Definition
0.3 mg/kg
effect site equilibration 1 min
E 1/2 life 2-5 hours
so CV stable that you usally dont need to dec. the dose for the elderly pt.
Use this a lot in CV unstable pt.
They will wake in 6-8 minutes due to redistribution and not bc elimination |
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Definition
Good cardiac stability,
low circulating volume
good for vascular surgeries
emergent induction
some of the benefits you get from prop and pentathol. IF you give enough you can get all the way to burst suppression.
Its used in nuero surgery when you need burst suppresion bc you DONT get the bp drop.
allows pt seizure foci to fire so that you can see where the seizures are
interferes less with SSEP monitoring
(allowing seizures to fire is much different than causing them)
methohex:eliptogenic |
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Term
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Definition
Augments GABA (barash says its a direct Agonist..DEB says he is WRONG) for our class the only direct GABA agonist is BARBS.
Etomidate augments not direct agonist
Potent Cerebral vasoconstrictor
you can bring the oxygen requirements down to 60% but it continues to drop below that for autoreg. (UNCOUPLING) blood flow is dec below the metabolic requirements for O2. Not the best choice for nuero protection (barbs and propofol are better they are coupled)
has the potential to bring the blood flow down but it also doesnt drop mean arterial bp as much as propofol or pentathol, which is the lesser of 2 evils?
Constrict too much or too low of MAP
IF you need burst suppression you will most likely take etomidate bc constriction is better than dec in MAP
*could see changes in use of etomidate in the next few years
dec CMRO2, CBF, ICP
inc EEG activity in epileptic foci
can be used in higher doses as anticonvulsant
will see increased Beta waves in low doses of etomidate
(technically wont be monitoring this so wont see it) you can equate this to stage 2 because we are taking away inhibition before excitatory. |
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Definition
HUGE in Etomidat! dec and takes the foot off the break for extra pyramidal motion
you will see myoclonus with this drug! |
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Definition
Most CV stable
minimal HR and SV and CO
map could dec up to 15% (SVR)sometimes and could be from other drugs |
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Definition
less depressant than the other weve looked at
dec TV inc RR (at sedated levels) With barbs and propofol we actually see them stop breathing, Etomidate may not completely stop breathing.
may stimulate medullary CO2 centers, regulate breathing
makes it a little safer in pt who have COPD (pentathol depresses the medullary receptors much longer than the drug actually works etomidate will not do that ) |
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Term
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Definition
high extraction ration
mostly hydrolyzed
prolonged in liver disease
Hepatic enzymes and esterases metabolize it |
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Term
| Odds and Ends of Etomidate |
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Definition
dec IOP (all drugs do this so far)
intra atrial no prob (but why would you do it) (propofol does this prob if in the a line )
may cause thrombophlebitis
inhibits ALA symthetase (dont give to porphyria pt)
Sever N/V (evomidate)
cover for post op nv meds
Pain on Injections (just as much as propofol) |
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Term
| 3 drugs that hurt on injection so far.. |
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Definition
methohexitol
Propofol
Etomidate
burns only the vein not the hooha |
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Term
| Rare problems with etomidate |
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Definition
first invented as an iv sedation
causes long term adrenal cortical suppresion.
dose dependent inhibition of the enzyme that converts cholesterol to cortisol
suppress the enzyme that converts cholesterol to cortisol.
with a single iv induction dose that suppression only last 4-8 hours
no outcome differences in pt given etomidate for induction of anesthesia but no longer used for long term sedation in the ICU.
Enzyme inhibited is 11-B hydroxylase
Dont give to porphyria pt.
WE arent going to use this for TIVA
but don't be afraid of it for induction drugs |
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Term
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Definition
Adult induction dose = **1.5 mg/kg IV** use to put the pt asleep. (Onset is about 1 minute). Bolus dose will give dissociative anesthesia that lasts for 10 – 20 minutes. EPS symptoms will last up to an hour (i.e. critters).
Intense analgesia = **0.2 to 0.5 mg/kg**.
Catch the kid = **4 – 8 mg/kg IM** - given to calm a child. (ketamine dart) (Five minutes until onset of effects; but it lasts a little longer).
*no pain on injection
Coming back for its use in analgesia! |
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Term
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Definition
Chemistry: BASE
Phencyclidine Derivative (PCP parent drug)
pH = 4.5, pKa = 7.5, Racemic mixture (L isomer better), Protein Binding = 12%
Mechanism of Action: Causes dissociative anesthesia. Not a hypnotic. Depresses the neuronal function of the cortex and the thalamus, however, it stimulates the limbic system. Activates opioid receptors and subcortical neurons in the spinal tract. These factors contribute to its analgesic effects. Provides intense analgesia and is profoundly amnistic. Patient will lie there with their eyes open and breath, but not remember a thing.
Use: Dissociative Anesthesisa
Preparation: Comes in 1%, 5%, and 10% solutions – 5% (50 mg/ml) is most common. Does not burn on injection
Good for multi modal pain control methods |
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Term
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Definition
↑CBF, ↑CMRO2, ↑ICP, ↑IOP. This is more focal issues. The area with more activity gets more blood flow. Global is still kept in check with auto regulation unless already compromised from head injury.
Delirium: with small sub anesthetic dose it is rare. With induction dose, the delirium will come after the dissociation has worn off – post op / pacu issues.
Augments NMB – has to do with it’s role in the NT suppression in the spine. Never enough for surgery by itself.
will prob see critters, onset is slower, longer acting delerium and critter seeing can last up to 60 min. |
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Term
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Definition
↑SVR – PVR, ↑HR, ↑CO, ↑MVO2, ↑SNS outflow, ↑Epi,Norepi – inhibit reuptake.
*A note she goes over is that all these increases are catecholamine driven. The response will only occur if we have the catecholamines present. If they are catecholamine depressed (shock/drug users/no volume), or if you suppress catacholamines then Ketamine is a myocardial depressant.
Does not release histamines.
Does not trigger MH – malignant hyperthermia (although some have been fooled by the ↑SNS response) |
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Definition
Little depression –but because of dissociation their air way is not protected.
Bronchodilaor – intense. Can treat status asthmaticus.
↑salivary secretions - a Salagog (patient salivates like all hell). Pre-treat with Robinol (anti-salagog).
Airway tone intact: Pharyngeal and Laryngeal reflexes are intact; but this is not a protected airway, again dissociation.
lower doses does not blunt their airway control
careful you could have a semi concious patient with a lot of spit
Atropine could block some bronchodilation properties so look out. |
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Term
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Definition
• Halucinations: administer with benzodiazepines at the end of procedure. Vitamin V. Barbiturates/Propofol can also work. (just remember we may be using Ketamine because pt couldn’t tolerate Barbs or Propofol
Other notes:
It can be used in emergency obstetrics – like placenta abrupt – where they are going to be cardiovascularly at risk. This may help keep BP with blood loss.
Not the drug of choice with some form of mass lesion-inc intra ocular pressure. |
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Term
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Definition
IT is NOT a hypnotic
It is a dissociative anesthetic
NMDA antagonist-sensitive to glutamate/so we are blocking an excitatory glutamate receptor/ greatly effects pain transmission up the cord, NMDA antagonist greatly effects pain transmission up the cord think about this later with actions of opiods
catecholamine reuptake inhibitor (what causes it is a side effect)inc the amounts of ne and epi
opiod agonist-at the MU receptor
monoaminergic agonist
anticholinergic symptoms-muscarinic ach receptor agonist.
will have inc salivation and inc salivary secretions
this may be a problem in kids, so may need to pre treat with atropine to prevent the drool. |
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Term
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Definition
disconnects important parts of brain interrupts thalamic to cortical connection while stimulating the limbic system.
NMDA antagonist –Cortical depression – but at the same time the Limbic system is stimulated. The pt may not even close their eyes - dissociative.
Catecholamine reuptake inhibitor (like methamphetamines or cocaine) SNS stimulant.
Opiod agonist – usually blocking afferents transmissions at the first order or second order neurons. Blocks NMDA receptors and Increases Norepinephrine receptors.
Monoaminergic agonist – works like epi/norepi in pain suppression in the spinal cord.
Cholinergic symptoms – a lot of spit can increase airway/laryngeal agitation and increase risk of spasm.
brain isnt talking to its other parts |
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Term
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Definition
has active metabolite: Nor ketamine 20-30 % as potent as parent compound which explains the tail.
if you give iv induction thats going to onset in 1-2 minutes it is going to peak a little later and last 10-20 minutes. good dissociative anesthesia/pain control and it will be gone in 60-90 minutes
long pain control prob due to active metabolite
high clearance
induces cyp 450-ramp up enzymes that metabolize it
tolerance-people build tolerance easily and rapidly require more ketamine, commonly used for burn changes and dressing. Could look similar to tachyphylaxis instead of tolerance |
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Term
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Definition
no histamine
rare allergies
no pain on injection
wont trigger MH
dont give with MAOI-they inhibit metabolism of catecholamines, so you have an inc catecholamine and you feel better (anti depressant)dont give with cocain either.
alterations in blood flow to liver could decrease clearance of ketamine.
If the pt just has some cocaine this drug is bad because you will have profound htn and tachycardic response
chronic on their cocain but hadnt had any today-may see cv depression because they dont have enough circulation catecholamines for the ketamine to increase and work on. |
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Term
| one case where low dose ketamine pain control dose is good |
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Definition
wont see many critters
pregnant ladies
still going to have intact reflexes
no resp issues
profound analgesia
old lady is good-spinal placement
plastic surgery centers |
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Term
| Dexmedetomidine (not really an induction drug) |
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Definition
very alpha 2 selective
basic drug
very highly protein bound
Pka 7.1
Chemistry: Base pKa = 7.1 Protein Binding = 94%. Enantiomer of medetomidine. α1:α2 selectivity 1:1620. Is more α2 selective than Clonidine.
Mechanism of Action: Stimulation of α2 receptors causes pre-synaptic inhibition. (Turns down the SNS). It affects different classes of the α2 receptors:
α2A: Sedation, Hypnosis, Sympatholysis
α2B: Vasoconstriction, Anti-shivering, Analgesia, Ca linked– may be excitatory
α2C: Learning, Startle response
*Most people miss the α2B: Vasoconstriction in periphery and coronary artery constriction that this drug can trigger.
Sedative (Comes from inactivation of the Locus Ceruleus, which is normally responsible for wake/sleep patterns in humans).
sedation not a hypnotic
all the other drugs you give on induction you can use less of if you give dexmedetomidine with those drugs |
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Term
| drugs that top the >90% protein bound |
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Definition
dexmedetomidine
propofol
will be effected in low protein states |
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Term
| additional uses for ketamine |
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Definition
propofol and ketamine allows lower dosage use of drugs(good for plastics)
Multi modal pain therapy spinal surgery to block nMDA receptor and block up reg of pain.
Prone people in OR control their post op pain, increase effect of other drugs and inc bp.
being used in pain managment in cancer patietns and developed tolerance to opiods
Ketamine and precedex can help reverse tolerance to opoids and get better pain management.
really bad airway-->mix ketamine and precedex |
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Term
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Definition
Dexmedetomidine inactivates the LC
1. LC is continually tonically firing to keep the VLPO suppressed. When we stop this action, the VLPO can take over and cause sleep. Dexmedetomidine inactivates the LC by activating the α2 receptor. α2 inhibits cAMP, K+ efflux, inhibits Ca voltage channels = hyperpolarized cells. It decreases the tonic stimulation of the VLPO. This is a much more natural sleep producing agent then anything else we have, beneficial for treatment in ICU. Rarely used as an induction.
2. LC also sends it’s inhibitory signals to the spinal cord and inhibits pain transmission of the first/second order neurons. It does this much more better than Ketamine. (this part unclear to me as I thought we were inhibiting the LC???).
Spinal Analgesia: release ACH and Enkephalins. Inhibits post synaptic neuron. Pre-synaptic inhibition of substance P release.
***Think Sedation in the Brain and Analgesia in the Cord. |
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Term
| Dexmedetomidine use/prep and dose |
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Definition
Use: ICU Sedation, Cardiovascular surgery
Preparation: Supplied in 2 cc vials (100mcg/cc); mix with 48 cc NS = 4 mcg/cc.
Dose:
Loading dose = **1 mcg/kg over 10 minutes**. (Usually done in pre-op holding). If given to fast will cause hypertension initially.This is transient and is attenuated by giving is slowly.
Infusion = **0.2 – 0.7 mcg/kg/hr**.
Kinetics: Onset 5 min, Peak 15 min (D ½ 6 min)
Contraindications contains |
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Term
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Definition
Cerebral vasoconstrictor without reducing the CMRO2. (use with caution if inc ICP)
CO2 autoregulation still intact.
Sedation. More natural sleep
Neuroprotectant (by dec in apoptosis) programmed cell death from alpha 2
this is big..no amnesia |
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Term
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Definition
↓SNS out flow = Hypotension,(number one reason MD dont like it )Bradycardia
↓HR, ↓SVR, ↓PVR, CO
Initial vasoconstriction - α2 peripheral affect that is overridden by the central affect.
Bolus dose will give a flash hypertension**
usually improved myocardial oxygen supply/demand (nitrous oxide released. ↓preload/↓afterload).
NO Reboud hypertension – wing of slowly
Can be a coronary artery constrictor can happen but its combated with nitric oxide release |
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Term
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Definition
Minimal respiratory depressant effects (respiratory sparing) the least of all the induction drugs. Sleep like deeprssion. relaxed upper airway adn obstructive sleep apnea
Anti-salagog (Dries them up).
Watch for obstruction (sleep apnea) still not protected airway – especially in obese.
ABG normal, no big change in TV, RR |
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Term
Dexmedetomidine Extra Extra
Doesnt work on GABA |
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Definition
1.Widens thermoregulation / Antishivering
good to give for post op shivers/they are still cold but stops shivering
can use it for anti itch too from opiods
2.Decrease muscle rigidity seen with high opiods
3.Drug addicts and alcoholic with drawl is well offset with this drug (alcoholic withdrawl under anesthesia is almost 50% fatal)
4.Chronic pain patients become extremely tolerant. This can help increase drugs effects without all the side affects.
gaining pop in pedi ICU
only approved for sedation for 24 hours
less resp depression
Ligand gated receptor/not an ion channel
inhibits ca and hyper polarizes membranes.
SEdation in the brain
Analgesia in the cord
Why not see it all over??$$ and hypotension
does have antagonist:atipamezole
alpha2 antagonist not really used, usually just shut off the gtt.
nasal dose is 2mcg/kg in kids
Never use it pregnant ladies-makes mom and baby hypoxic |
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Term
| Benzos pharmacology effects |
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Definition
Sedation.
Anxiolysis.-how they become addictive
Hypnotic.
Anticonvulsant.
Spinal cord – mediated skeletal muscle relaxation.
1. Do not interfere with the actions of depolarizers and/or non-depolarizers.
2. Valium is used in the treatment of chronic back pain.
Anterograde amnesia.
Can be used for induction – but it is not pretty and we have better drugs
No Burst Suppression
amnestic no retrograde amnesia |
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Term
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Definition
No allergic reactions.
Abuse or physical dependence potential.
1. Valium was the most abused prescription drug in America at one time.
2. Have wide therapeutic range when taken PO and by themselves.
Selective antagonist is available. |
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Term
| structural activity relationships |
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Definition
BZD are structurally similar and share many active metabolites.
BENZODIAZEPINE refers to a benzene ring fused with a diazepine ring
lots of aromatic rings and incredibly lipid soluble and work as they cross the blood brain barrier. this is important |
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Term
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Definition
Binds to specific site on GABA A receptors – post synaptic. Increases Cl and hyperpolarizes the cell. It will be synergistic to all the other things Facilitates the actions of GABA. ↑ Frequency and duration, but cannot work without GABA. Both have to be present.
1. Benzodiazepine, alcohol, barbiturate have different binding site on the same receptor and are synergistic.
A patient who is tolerant to alcohol will also be tolerant to benzodiazepines and/or barbiturates.
If the patient is acutely intoxicated, this will potentiate the effect of benzodiazepines and/or barbiturates.
2. Two receptor subunits:α1α2 (Benz. activate both)
α1 – Sedation, Amnesia, Anticonvulsant
α2 – Muscle relaxation, anxiolytic |
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Term
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Definition
Cerebral cortex (memory centers) in high concentrations. (Especially in the memory centers).
Hypothalamus.
Hippocampus.
Medulla.
Substantia Nigra.
Spinal cord (these receptors mediate muscle relaxation).
After versed cant consent to anything |
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Term
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Definition
20% occupied = anxiolysis.
30% - 50% occupied = sedation.
Over 60% occupied = hypnosis
Receptor sites can be saturated:Ceiling Effect. (no burst suppression). |
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Term
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Definition
Lorazepam > Midazolam > Diazepam.
Lorazepam ~ 5 times more potent than Midazolam.
Midazolam ~ 5 times more potent that Diazepam.
What Affects Potency?
Receptor affinity.
Efficacy at the receptor. (how well the drug works)
Duration of time it is attached to the receptor. |
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Term
| increased potency speed up the action ? |
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Definition
No, a more potent drug has a slower onset.
Increased potency means ↓amount of the drug = ↓ concentration gradient of the drug = slower movement to receptor site, and also slower movement away from the receptor site.
5 mg of a drug to get a good effect versus 50 mg of another drug to get a good effect. Which has the stronger concentration gradient? The larger mass of drug (50mg) has the stronger concentration gradient. Remember, everything moves down a concentration gradient. The more potent drug (5mg) has a weaker concentration gradient. |
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Term
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Definition
work of the brain is dec
nerve to nerve communication is less
CMRO2, CBF in coupled fashion
Anticonvulsant: more specific than Barbiturates which are more global.
Co2 responses maintained / Auto regulation intact. constric or dilate?
Elderly more sensitive They will stop breathing. START SLOW AND GO SLOW..calculate dose then dec by 30% then go even lower than that
No ischemic protection
No change in ICP with “head patients’
1. Unless you ↓ breathing and ↑ Co2 (vasodilator – auto regulation still intact)
2. Could ↑ ICP with a SNS reflex secondary to laryngeal stimulation (does not blunt SNS)
Cannot use benzodiazepines for burst suppression (ceiling effect).
never have flat line EEG |
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Term
| Most specific anticonvulsant |
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Definition
Benzo
more specific than pentathol or propofol. it is still not the first thing we reach for in anesthesia, icu yes its the first thing we reach for. |
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Term
| protein A1 on the GaBA receptor |
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Definition
sedation
amnesia
anticonvulsant |
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Term
| protein receptor A2 on the GABA receptor |
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Definition
muscle relaxation (spinal cord and there are GABA receptors in the spinal cord)
anxiolytic |
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Term
| what can you get burst suppression with? |
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Definition
Barbs
Etomidate
propofol
Def not ketamine (might even decrease some neuro protection from gasses
Not from dexmed and not with benzo's |
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Term
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Definition
Minimal effects with sedative dose.
1. May get a small drop in blood pressure with sedation, but it is minimal.
Lorazepam has the least CV effects. Best one to use if pt has no BP
? Induction doses: (we don’t normally use for induction) If midazolam is used, will see ↓ BP/SVR like Pentathol but baroreceptor reflex is still intact so we will see ↑ HR.
? Use with narcotics: Administer Midazolam with narcotics and a more profound decrease in blood pressure will be seen, than with the Midazolam alone.
by itself cardiac stable but does potentiate other mechanisms
some barorecptors depression
not enough to blunt sns response to intubation |
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Term
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Definition
Dose dependent respiratory depression.
Depresses airway reflexes and ability to swallow – usually seen at higher doses.
Hypoxic Drive to Breath is depressed. Normally breathing is driven of CO2, however with some patients they now use Oxygen/hypoxia to trigger breathing. 1. Chronic COPD, 2. Sleep Apnea, 3. Morbid Obesity. This drug will depress their drive to breath.
ANY DOSE, ANY PATIENT, CAN CAUSE APNEA WITH MIDAZOLAM.
1. Do not administer Midazolam and then walk away.
2. Patient must be monitored following administration of BZDs, especially respiratory function.
SYNERGISTIC WITH OPIODS.
Does not blunt the SNS Response to Intubation
PO Diazepam and lorazepam has almost no respiratory depression when used alone. need 30-60 mins to work but really safe!
obese and elderly=resp depression bad! |
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Term
| Muscle Relaxation in Benzo |
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Definition
• Spinal Innernuncial Neurons: Especially good for Lumbar disc disease
• NOT adequate for Surgical muscle relaxation (dec muscle spasms)
• Does not work at NMJ: Des not potentiate neuromuscular blockers, so we do not have to change our dose with benzodiazepines. dont change dose of nmb |
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Term
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Definition
. Hydroxylation and Conjugation : Phase 1 and Phase 2
1. The liver changes a lipid soluble compound into a water soluble compound that can be eliminated in the urine.
2. Cytochrome P450: (compete with other drugs that use cyp 450)
1. Inducible – enzyme induction will lead to faster metabolism of BZDs.
2. Saturable – BZDs could be competing with another drug for CYP450 and thus will metabolize more slowly. *Example is Fentanyl and Versed.
3. Diazepam and Midazolam – active metabolites: (Debra said we don’t have to memorize metabolite names)
1. Diazepam: Desmethyldiazepam (1/2 life is twice as long as Valium). Oxozepam. (Is marketed as a separate BZD).
2. Midazolam : 1-hydroxymidazolam, 4-hydroxymidazolam (not clinically significant except in extreme renal failure). active metabolites are metabolized faster than valium.
*in a pt with renal failure the drug will hang out longer, not really change its onset.
3. Metabolites can accumulate in renal failure.
4. Lorazepam:
1. No Phase I. Phase II conjugated with glucuronic acid (it is not CYP 450 dependent)
2. No active metabolites
3. Less change in the elderly. *however Debra points out that this is not our priority because Lorazepam is a 15 hour drug – so it really wipes them out for the whole day regardless.
Midazolam
(Versed) Lorazempam (Ativan) Diazepam
(Valium) Flumazenil (Romazicon)
E 1/2 2 hours 15 hours 30 hours 1 hour
Age No change No change Prolonged
↑age = ↑½ life No change
Liver Failure No change Prolonged Prolonged No change
Metabolism CYP450 **Phase II Reaction CYP450 CYP450
Drugs that interfere with the CYP 450: Decrease the drug dose if used together with these.
Ca++ Channel Blockers, Erythromycin, Cinetidine.**Fentanyl** competes with the pathway |
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Term
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Definition
• ↑ Sensitivity
• ↑ Vd – peripheral = ↓muscle and ↑ fat so it last longer
• ↑ ½ life
• ↓ hepatic blood flow
Odds and Ends:
• Very lipid soluable (encourages placental crossing – rare to use on pregnant until cord is clamped)
• Large volume of distribution
• Hight Protein Bound
• No N/V
• No Analgesia – it can even ↓ the effects of some opiods.
will augment the sedation and resp depression from your opiods but will not augment the pain control |
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Term
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Definition
only one that is water soluble
in the vial water soluble
in the person ring closes and becomes lipid soluble
2times affinity for benzo receptor more potent more
Basic drug
any ph less than 4 ring opens and its water soluble.
ph over 4 ring closes and its lipid soluble.
onset .9-5.6 minutes consider more sedation after 5-6 min.
duration 15-80 minutes
94% protein bound
doesnt burn
supplied in 1 mg/cc or 5mg/cc
like more concentrated formula and use less liquid. |
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Definition
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