CNS I Pharm - Anesthesia Flashcards
Local Anesthetics Overview
A drug that BLOCKS NERVE CONDUCTION when applied LOCALLY TO NERVE TISSUE
All locals share 3 structural features –> AROMATIC RING + TERTIARY NITROGEN and then either an ESTER OR AMIDE
Ester group = Procaine, Cocaine, Tetracaine
Amide = Lidocaine, Bupivacaine, Mepivacaine, Etidocaine
No tertiary nitrogen = BENZOcaine (hydrophobic, so only topical preps)
These preferentially act on PAIN FIBERS (A & C), can block motor neurons at higher doses
Mechanism of action for local anesthetics
Act by blocking SODIUM CHANNELS –> prevent membrane depolarization and AP propagation
Can act outside, middle or inside of receptor (locals work INSIDE except for BENZOCAINE, which works in the middle)
These are all weak bases (unprotonated, lipophilic base form) –> ADD HCL to preparations to ensure they stay in WATER-SOLUBLE SALT FORM (protonated, hydrophilic)
How do local anesthetics get into the cells?
Injected into the perineuronal space…pH = 7.4, pKa = 8.4 (assume) –> 7.4-8.4 = Log (base/salt) —> Salt:Base = 10:1
ONLY BASE FORM gets into the cell membrane and into the neuron
Inside, pH is again 7.4, so equilibrates to 10:1 Salt:base again
Salt form acts on the membrane receptor!
Areas of inflammation/abscesses –> require higher doses because inflammation LOWERS pH (more protons) so ratio of Salt:Base = 100:1 or higher –> even less gets into the neuron to begin with
Mechanism of Action of LA’s (detailed)
Sodium Channels have voltage-sensitive M gate and a time sensitive H gate
At rest, neuronal membrane is resting at about -90 mV (M gate is CLOSED, H gate is OPEN)
When there is a depolarization, the M gate opens (voltage sensitive) and the H gate stays open –> Na+ flies in
After a few milliseconds time-sensitive H gate closes, INACTIVATING the channel –> no APs can activate the sodium channel now as K+ channels repolarize the membrane
LOCAL ANESTHETICS ONLY BIND IN THE ACTIVE STATE (both M and H open)
Use Dependence
LA’s are USE DEPENDENT –> more nerves firing, more effective/more analgesic the drugs are
Decremental Firing
When a local is given, it reaches a limited number of sodium channels on a given neuron
Following injection and the first AP, some LA enters local channels, filling it up
As the second AP propagates, less Na can flow through the occluded/blockd channel – yields a diminished AP in the second channel
Eventually APs will die out! And this is good as it stops pain
BUT, while weaker APs die out, STRONGER APs may still push through the channel and regain strength after they pass the occluded channel!
Miscoding
4 consecutive APs at 2 Hz each are usually registered as “pain”
If those 4 APs a re reduced to 2 APs, the brain may “mis-code” the sensation
This accounts for facial droop seen with agents like lidocaine (think your face is droopy after lidocaine)
All local anesthetics are…
VASODILATORS except for COCAINE (CNS effects and blocks NE reuptake, resulting in vasoconstriction and HEART effects!!!)
These drugs increase blood flow, which shortens their duration of action –> can use EPINEPHRINE to vasoconstrict and slow down the flow, decreasing drug clearance
What is a common side effect of PROCAINE?
Broken down to para-aminobenzoic acid –> CONTACT DERMATITIS is possible
*overall, Locals are very safe drugs
Most common Locals Used?
LIDOCAINE and BUPIVACAINE
Five Types of Anesthesia
Local
Monitored Anesthesia Care –> requires an anesthesia team to monitor the patient’s functions (BP, HR, O2 sat, EKG)
IV delivery, patient sedated but
CONSCIOUS (breast biopsy)
Regional Anesthesia –> Monitored anesthesia care with the addition of a local anestethic at a specific body site to block an entire region of the body (Still conscious - epidural or brachial plexus block are examples)
General anesthesia –> same as regional but patient is UNCONSCIOUS –> mediated via inhalants, opioids, muscle relaxants
General and Regional –> Involves a REGIONAL BLOCK given followed by general anesthesia to render patient unconscious
Ideal Anesthetic Drug Criteria?
Rapid onset Short duration Predictable mechanism of elimination Minimal CV effects Easily identified levels of depth Ease of administration High degree of specificity of action Availability to all age groups No undesirable side effects
Four Criteria for a GENERAL ANESTHETIC
Must make the patient UNCONSCIOUS and AMNESIC with NO RECOLLECTION OF SURGERY
Must PROVIDE ANALGESIA and PAIN CONTROL during the surgery and after the patient wakes up
Drugs must cause IMMOBILITY
Must DECREASE SNS ACTIVITY (measuring SNS via HR, BP is a useful measure of DEPTH – too high HR and BP means not deep enough; too low HR and BP means too deep)
HALOTHANE, ENFLURANE, ISOFLURANE, SEVOFLURANE, DESFLURANE
Nitrous Oxide
Causes AMNESIA, UNCONSCIOUSNESS, ANALGESIA –> Cannot cause immobility or SNS depression
How do anesthetics work?
Liquid form —-vaporizer—> Gaseous anesthetic –> breathing system –> LUNG –> BLOOD –> BRAIN
B/G Solubility Coefficients
Relative affinity that the drug has for the BLOOD PHASE compared to the GAS PHASE when it is in equilibrium
Ex: Diethyl Ether = 12 (HIGH) –> with 13 molecules, 12 enter blood and 1 stays in gas phase
The 12 dissolved molecules DO NOT contribute to the partial pressure because they are bound up by proteins, so equilibrium requires a large amount of ether to be dissolved
Nitrous oxide has a B/G of 0.47 (LOW) –> When 9 molecules enter alveolus, 6 remain in GAS and 3 in BLOOD phase
Since it is low, LESS DRUG IS NEEDED to be dissolved in the blood to reach equilibrium
What do B/G coefficients mean?
LARGE B/G TAKE A LONG TIME TO WORK!
Large = Big blood reservoir to fill before equilibrium can be reached –> takes a longer time to work
Low BG = Small reservoir to fill, FASTER ONSET of ACTION
Specific B/G Values
Diethyl Ether = 12 HALOTHANE = 2.3 ENFURLANE = 1.8 ISOFLURANE = 1.4 SEVOFLURANE = 0.68 DESFLURANE = 0.42 NITROUS OXIDE = 0.47
Low B/G take about 3 minutes to reach equilibrium in vessel rich group (heart, liver, lungs, kidneys, brain) and High B/G take about 10 minutes
Emerging from anesthesia
Turn off the anesthesia 10-15 minutes before end of treatment
This reverses the pressure gradient of the drug so that the venous circulation has a higher anesthetic than the alveolar air, so the drug follows its gradient (out of the blood –> alveolus –> exhaled)
Leaves order it was received (VRG first, then muscle, then fat)
Muscle rich group may not have much anesthesia at all (depends on how long the case is, takes 1-4 hours to reach equilibrium)
Minimum Alveolar Concentration (MAC)
The concentration of anesthetic agent required to render 50% of patients immobile to a surgical stimulus
MAC DEFINES POTENCY
Increasing MAC decreases potency
DECREASING MAC INCREASES POTENCY
Lower MAC = Better Potency
1 MAC = Percent of anesthetic gas in O2 (meaning no other gas besides O2 is in the mixture)
At 1 MAC – 50% are IMMOBILE (all are unconscious at ~0.8 MAC) –> 2 MAC mixtures given to ENSURE immobility (95% are immobile)
0.8 - amnesia, unconscious; takes higher levels to suppress movement than it does to eliminate consciousness
1 MAC = 1 MAC = 1 MAC
MAC Values
HALOTHANE = 0.74 ISOFLURANE = 1.15 ENFLURANE = 1.68 SEVOFLURANE = 2.0 DESFLURANE = 6.0 NITROUS OXIDE = 103
Thus, Halothane is very potent but slow acting, and Des is very fast acting, but less potent
MAC examples
If 1 patient gets 1% Halothane, what does this mean?
0.74% = 1 MAC, so 1% is HIGHER than a MAC –> Patient will be unconscious, amnestic and 50% chance of immobility
1% Isoflurane is LESS than 1 MAC (1.15)
Which WORKS FASTER? Iso because of the LOWER B/G
Which is more anesthetic? HALOTHANE because its MAC is lower and more potent (percentage of gas is the same so just need to look at MAC)
One guy receives 1 MAC HALOTHANE and another receives 1 MAC ISOFLURANE
Faster? Easy – Isoflurane b/c lower B/G
More potent/anesthetic? BOTH ARE THE SAME SINCE 1 MAC = 1 MAC! The mixtures are different (1 MAC Halo means .74% Halo, 99.26% O2, 1 MAC Iso means 98.85% O2)
NITROUS OXIDE
Weak Inhalation Agent – UNCONSCIOUSNESS, AMNESIA, ANALGESIA
NEVER causes immobility or lowers SNS
“Laughing gas” - colorless, odorless, tasteless
B/G = 0.47 (RAPID ONSET/OFFSET)
MAC = 105 = VERY LOW POTENCY!!!! Super High
Use of Nitrous
Sole anesthetic for MINOR SURGICAL PROCEDURES (tooth extractions)
Can be administered with an IV anesthetic or a PIA to create more desirable effect
Good analgesia – ER, Ambulances,e tc
Need about 70% in the mixture to get “light anesthesia” – unconsciousness
MINIMAL CARDIAC/RESPIRATORY DEPRESSION :-)
Side Effects of Nitrous
Diffusion Hypoxia –> such a low B/G; rapidly returns to the alveoli and lungs during emergence; occurs so quickly that Nitrous can actually dilute the normal exchange of O2 and CO2 resulting in diffusion hypoxia –> WEAN PATIENTS off while SIMULTANEOUSLY delivering 100% O2 for 5-10 min
Some toxicity (BM function, Cell mediated immunity, liver function, vitamin B12) but toxicity should NEVER be reached in typical clinical scenarios
What are the FOUR criteria for general anesthetics again?
AMNESIA
ANALGESIA
IMMOBILITY
LOWERED SNS ACTIVITY
Potent Inhalation Agents accomplish this
Ultimate goal of general anesthesia?
To provide anesthesia with as LITTLE CARDIAC AND RESPIRATORY DEPRESSION AS POSSIBLE (these drugs do have dose-related cardiac and resp depression)
Measuring DEPTH of anesthetics
Monitor brain concentration by monitoring the END-TIDAL CONCENTRATION of the agent –> if at equilibrium, there is anesthetic in brain
CV monitors –> HR and BP should be lowered for deep anesthesia (i.e. if HR and BP are too high, it isn’t deep enough and vice versa)
EEG monitor –> placed on forehead to constantly track electrical activity of the brain
Guedel’s Clinical Signs –> combination of ocular, respiratory and somatic muscle tone signs
What are the SIMILARITIES of the PIAs?
Depress the normal ventilatory response to hypercarbia and hypoxia –> these are normally compensatory responses (i.e. body rapidly corrects pH to normal with compensated ventilation) –> These drugs alter the function of peripheral chemoreceptors that detect changes in blood pH
BronchoDILATORS
Inhibit mucociliary function – all PIAs do this, which causes mucous pooling and potential atelectasis; no mucocilia to sweep away pathogens –> can predispose to respiratory infection
Depress CNS –> dose-related CNS depression and thus a decrease in cerebral metabolic O2 consumption that slows metabolism; increase cerebral blood flow thus decreasing cerebral metabolic demand; this is the end goal of all anesthetics!
Depress NMJ –> depress neuromuscular activity, thus they can INCREASE THE DURATION OF MUSCLE RELAXANTS!
Malignant Hyperthermia RISK –> can be lethal!
HALOTHANE
Standard, prototype PIA
Rarely Used today (inexpensive though and used in the rest of the world!)
Addition of FLUORIDE MOIETY made it nonflammable and nonexplosive (direct contrast to ether!)
BUT…the alkane/fluoride structure is also responsible for the DYSRHYTHMIA potential –> sensitizes the heart to CATECHOLAMINES –> can be dangerous!
MAC = 0.74 = VERY POTENT B/G = 2.3 = DELAYED UPTAKE/RECOVERY
Non-pungent so it doesn’t irritate airways –> good for KIDS
Halothane effects on systems
CV –> dose-related cardiac depression (decreased MAP, contractility, CO and myocardial O2 consumption)
NO CHANGE SVR
NO CHANGE HR
Dysrhythmia potential
Pulmonary –> Dose related decrease in RESP FUNCTION –> decreased TV, leads to gradual rise in CO2 –> slight increase in RR
CNS –> Decreases electrical activity; INCREASES cerebral blood flow and blood volume through DILATION of cerebral vessels –> this INCREASES ICP!!!! Not good for neurosurge
Metabolism of HALOTHANE
Takes place in the LIVER! 15-20% recovered as metabolites –> HALOTHANE HEPATOTOXICITY
20% of patients receiving halothane get short-lived HEPATIC INJURY
Tiny percentage get FULMINANT TOXICITY = HALOTHANE HEPATITIS –> massive necrosis with 50-75% mortality rate!!!!!
This risk increases with previous halothane use/exposure
ENFLURANE
Primary PIA of 70s and 80s –> First ETHER anesthetic –> NO RISK FOR DYSRHYTHMIAS!
Moderately pungent, so not for kids!
B/G = 1.8 –> Lower than Halothane, so FASTER onset/offset
MAC = 1.68 –> HIGHER so LESS POTENT
Enflurane effects on systems
CV –> Dose related depression –> lowered MAP, CO, contractility and O2 consumption; ALSO DECREASES SVR and INCREASES HR (unlike halothane which doesnt affect either)
*Pulmonary –> Dose related depression (MORE SEVERE THAN HALO AND OTHERS!)
CNS –> Increases cerebral flow and volume (dilation of the vessels) – so increases ICP (less so than halo, but still concern)
Also has SEIZURE POTENTIAL!!!!! Contraindicated with seizure disorders
Metabolism of Enflurane
Only 2-3% recovered as metabolites
F- is the major one –> high levels cause RENAL IMPAIRMENT –> avoid in renal insufficient patients
ISOFLURANE
Less CV depression, NO CNS Excitatory effects (no seizures!), good muscle relaxation; ether, so no dysrhythmias
Moderately pungent (not for kiddos)
MAC = 1.15 –> Lower than others, HIGH potency
B/G = 1.4 –> Quick Onset/Offset
Isoflurane effects on systems
CV –> Dose related depression, but MAINTAINS CO (decreases SVR and increases HR!!!) –> best so far of Halo/Enflurane
Pulmonary –> Dose related depression, less severe than Enflurane (Halo is a little better)
CNS –> increases flow and volume, so ICP –> less so than Halo or Enflurane! Used with neuro patients but WITH CAUTION
Metabolism of Isoflurane
Good!! No evidence of renal OR hepatic failure!
DESFLURANE
Very popular modern PIA; natural vapor pressure is close to atmospheric – boils at room temp! Need special vaporizer. PUNGENT –> not for kids!
MAC = 6 = HIGH, LESS POTENT than other agents
B/G = 0.42 = FASTEST ONSET/OFFSET –> depth can be adjusted DURING a case!!
Organ effects are IDENTICAL to isoflurane –> Good CV effects (no change in CO), moderate respiratory depression, safe for neuro patients if MONITORED (slight ICP increase)
NO TOXIC METABOLITES
NO DYSRHYTHMIA RISK! Ether
Desflurane and CO poisoning?
When it mixes with the CO2 absorber (extracts CO2 in exhaled gas and recycles the remaining PIA), CO is produced
This occurs when the absorber is exceptionally DRY (left on overnight) so make sure to turn it off!!
SEVOFLURANE
Another very popular drug nowadays
ETHER –> No dysrhythmias
LITTLE PUNGENCY –> Good for KIDS!
MAC = 2 = More potent than Des
B/G = 0.69 = Also very quick, can be very precise with the depth
Identical effects on CV, CNS, Resp as Iso and Des
Sevoflurane toxicity
Metabolized by the liver, 5-8% recovered as Metabolites –> can mix with CO2 to form “Compound A” which could be RENALLY TOXIC
Cardiac Depression and PIAs
H > E > I = S = D
Respiratory Depression of PIAs
E > I, S, D > H
Cerebral Blood Flow INCREASE (ICP increase)
H > E > I, S, D (these 3 can be used for neuro surgery)
NMJ Depression
E (seizure potential!) > I, S, D > H
MAC Comparison
H (0.74 most potent) < I < E < S < D (6.0 - least potent)
Nitrous = 100+ = LOWWWW potency
B/G Comparison
D (0.42 - fastest) < S < I < E < H (highest, slowest - 2.3)
Nitrous = 0.47 FAST
Good for kids?
HALOTHANE (not in US) and SEVOFLURANE!
Can cause dysrhythmias?
HALOTHANE
IV Anesthetics Overview
Cause AMNESIA –> NO ANALGESIA or MUSCLE RELAXATION
At higher doses, may affect SNS
Generally used for INDUCTION during surgery (transition between consciousness and unconsciousness)
Small doses for sedation
Once they are “under” we can give them gas without worrying about pungency
SODIUM THIOPENTAL
Ultra-short acting barbiturate
Used for smooth induction (no coughing, breath holding, laryngospasm) or as a component of MAINTENANCE
Light anesthetic (only unconsciousness) – not used as the sole anesthetic unless for minor dental procedures
After administration patient probably has apnea, so BAG THEM until they breathe properly
VERY LIPOPHILIC –> rapid onset! Quick loss of consciousness that lasts 5-10 MINUTES
Mechanism of Sodium Thiopental
Quick travel to CNS
75-85% BINDS TO ALBUMIN, remaining 15-25% is ACTIVE
Changes in protein binding affect efficacy –> NSAIDS and SULFA DRUGS compete for binding proteins –> this increases the amount of active drug!!!
Renal/Hepatic insufficiency = Less protein, so we need less drug to have the same effect (careful!)
Modulates GABA transmission via the barbiturate receptor on the post-synaptic GABA channels
Metabolism of Sodium Thiopental
Half life of 10-12 hours, relatively low clearance, large volume of distribution
Short acting in terms of loss of consciousness, but the LONG HALF LIFE causes RESIDUAL CNS EFFECTS (CNS depression) post-op
will be woozy with poor coordination, etc
Thiopental effects on systems
CV –> dose dependent depression; BP, MAP, SC and CO all decrease with a Reflexive INCREASE in HR
CNS – Acts as a depressant and anticonvulsant; can be used to “rest the brain” and induce a coma in CNS trauma patients; CEREBRAL PROTECTANT – decreases blood flow (constricts vessels!!), thus ICP decreased!!!!!! SAFE In NEURO PATIENTS!!!
Resp – dose related depression; stop breathing after 2-3 large breaths when administered - BAG THEM
Renal – decrease in CO can lead to decrease in RBF and thus a decrease in function; not really significant
Side effects of Thiopental
High pH!!! Greater than 10 –> Very alkaline, so when injected it could HURT; SC injection will cause necrosis of tissue; artery? could cause GANGRENE to the tissue it supplies; administer a test dose to make sure it’s in the right place
Long half life, long drowsiness (longer hospital stay)
not really used today…womp
What is the drug of choice for IV anesthesia?
PROPOFOL!
PROPOFOL
Drug of choice for IV anesthesia
Milky white emulsion
ANTIEMETIC too!
Used for INDUCTION and also for MAINTENANCE (like Thiopental)
Sedative at low doses
LOC –> Highly lipid soluble –> 30-60 second onset!!! 4-8 minutes duration of action; PATIENT WAKES UP CLEAR HEADED!
Similar GABA mech to Thiopental
Short half life (1-1.5 hours), high clearance, no metabolites – less post-op sedation/impairment
Propofol effects on organ systems
CV –> LOWERS MAP, CO and SV; DROPS BP;
NOT GOOD FOR PATIENTS WITH CARDIAC DISEASE!!!!!!!!
CNS –> similar to thiopental, reduces ICP, cerebral blood flow, and metabolic oxygen consumption –> SAFE FOR NEURO!
Respiratory –> Dose-dependent depression; need to bag until they breathe normally
Side effects of Propofol
Causes PAIN on INJECTION (burning) – can give lidocaine before or fentanyl
Lipid mixture –> good for bacterial growth –> risk of infection if sitting out for a while
KETAMINE
Can be sedative, hypnotic, amnestic, analgesic –> INTENSELY analgesic
Can be given IM, good for patients w/ bad veins!
Helpful in trauma
Asthmatic patients can benefit (dilator)
Works RAPIDLY and LOC lasts 10-15 minutes
Ketamine Mechanism
“Dissociated anesthetic” meaning it functionally and electrophysiologically dissociates the limbic and thalamo-neocortical system by blocking ACh
Pain signals can’t get from SC to the brain
Also blocks NMDA (glutamate) receptors in the brain (blocks excitatory instead of helping inhibitory GABA)
Ketamine effects on organ systems
CV – direct cardiac depressant; but if the patient has a functioning SNS, it can act as a CV stimulant (increases MAP, SV, HR and CO) – contraindicated in heart failure or when SNS is “fatigued”
CNS – can cause “catalepsy” where the patient loses muscle tone and is still conscious; NYSTAGMUS and INTACT CORNEAL LIGHT REFLEXES (hard to tell depth);
should be AVOIDED in neuro patients because of INCREASED ICP
Resp –> only a mild depressant of resp fxn; maintain breathing, don’t need to bag; Bronchodilator (good for asthmatics)
Side effects
This is an ANALOG of PCP –> hallucinations, really bad dreams (wake patients up slowly in a dark room) - benzos or propofol can help diminish these hallucinations
Salivation – tough to keep clear airways (use anti-cholinergic - dry mouth!)
Can be abused! Special K!
ETOMIDATE
Great drug because of CV stability*
Can be administered if patients have CV DYSFUNCTIONS; good for NEURO PATIENTS
Quick LOC, lasts 5-10 min
Works at GABA receptors
Half-life 2-5 hours
Etomidate effects on organ systems
CV –> VERY GOOD (BP, HR, CO, MAP all remain STABLE)
CNS – Basically the same as THIOPENTAL and PROPOFOL (good! no ICP increase)
Respiratory –> Depresses like Propofol; BAG initially
Side Effects of Etomidate
Myoclonus – stiffens up patient when administered
Pain/Burning on injection
N/V (give antiemetic)
Transient adrenal suppression - not great b/c we need stress response in surgery! Only happens after repetitive dosing
MIDAZOLAM
Benzo!
Anxiolytic, sedative, hypnotic, amnestic
Versatile –> Premedication, induction, maintenance, intraoperative sedation
IM possible (bad veins!) and can be mixed with apple juice
LOC is quick; short onset/duration
Midazolam effect on organ systems
CV – good (not as good as etomidate) but better than thiopental or propofol
CNS – good for neuro, lowers ICP
Respiratory – DOSE RELATED RESPIRATORY DEPRESSION (severe!) –> Reversed by FLUMENAZIL
This is the ONLY IV drug with a reversal agent!
FENTANYL/SUFENTANYL
Strong opioids; used as premedicants and sedatives; has to be administered at a higher dose for induction; component of MAINTENANCE and for POST-OP PAIN; can be administered as a regional anesthetic epidurally
In low doses –> short acting (like a bolus dose)
In high doses –> Long acting (continuous dose)
VERY POTENT DRUGS!!! Amnesia, analgesia, decrease SNS activity; can carry patient through induction, maintenance and emergence;
CV STABLE! Can use just fentanyl and a muscle relaxant for CV surgery!
Sufentanyl = 1000x more potent than morphine (10x more potent than fentanyl)
Four goals of general anesthesia?
AMNESIA/UNCONSCIOUSNESS
ANALGESIA
IMMOBILITY
DECREASED SNS ACTIVITY
It is tough to get these with the other agents, so adding an NMJ blocker helps a lot
Specific needs for muscle relaxants?
Intubation –> relax laryngeal muscles to avoid vocal cord damage
Orthopedic surgery –> to avoid tearing of large skeletal muscle groups, can make cleaner incisions
COMPETITIVE BLOCKING MUSCLE RELAXANTS (NON-DEPOLARIZERS)
Compete with ACh at the NMJ –> bind to nACHR, blocking ACh from binding –> weakens the end plate potential –> PREVENTS CONTRACTIONS
Need to block 70-80% of the nACHR to block contractions
EPPs may still be seen, but far beneath threshold to generate contractions
For all these drugs, NEED RESPIRATORY SUPPORT because they block the diaphragm and intercostals!!!
D-TUBOCURARINE
Stops the fastests moving muscles first –> blocks extra-ocular muscles then facial muscles –> then limbs, thoracic and intercostals
For all these drugs, NEED RESPIRATORY SUPPORT because they block the diaphragm and intercostals!!!
Slowwwww onset, LONG duration 1-2 hours
Side effects
Histamine release Ganglionic blockade (not selective for nicotinic sub muscle receptors) --> Hypotension
VECURONIUM
Primarily excreted by the liver, 2nd by kidney
Rapid Onset (60 seconds), good duration (30-40 min)
Few side effects
ROCURONIUM
Primarily liver, secondarily kidney (excretion)
Immediate onset (less than 60 seconds!) Intermediate duration 20-35 minutes
Can cause TACHYCARDIA due to muscarinic ACHR effects (good drug overall)
ATRACURIUM
Plasma cholinesterase –> “spontaneous elimination)
90 second onset, less than 30 minute duration
Histamine mediated hypotension
CISTRACURIUM
Exact same as atracurium with fewer side effects
Duration of action problems?
Could be a problem for SHORT procedures because the patient will wake up and not have use of muscles!
Problem for LONG procedures because they reach steady state before end of procedure
Reversal Agents
Acetylcholinesterase inhibitors –> prevent breakdown of ACh –> EDROPHONIUM, NEOSTIGMINE
Anti-muscarinic Agents –> In order to SAFELY give an AChE inhibitor (neostigmine or edrophonium) –> need these drugs to PREVENT BRADYCARDIA (there will be lots of ACh if it isn’t broken down! ACh is parasympathetic, hence bradycardia)
ATROPINE, GLYCOPYRROLATE
SUCCINYLCHOLINE
SUCCINYLCHOLINE – 2 ACh bound together
Strong ACh receptor agonist – produces sustained depolarization and prevents contractions! Succinylcholine is destroyed by PLASMA cholinesterase (not acetylcholinesterase which is readily at the cleft) –> means that it lasts longer at the NMJ –>
Na+ channels are essentially in the “inactive” state for about 10 minutes (adjacent channels can’t go back to resting unless cell returns to -90 mV, which it doesn’t when this long depol is occurring)
patient is essentially paralyzed for the duration of succinycholine binding
Side effects of Succinylcholine
Allelic mutations in plasma cholinesterase can occur and wouldn’t be able to break it down – would have to wait for kidney to eliminate it –> LONG paralysis!
Bradycardia –> can act on nicotinic AND muscarinic –> give Atropine
Malignant hyperthermia (like INHALED anesthetics!)
Uses of Succinylcholine
Rapid onset and quick duration –> use for INTUBATION at beginning of surgery –> then give ROCURONIUM for the maintenance of paralysis
NO REVERSAL AGENT! Giving edrophonium or neostigmine would decrease breakdown of SCh (inhibit cholinesterase) and INCREASE ACh at the synapse – yikes
Step by Step: PRE-OP
All patients must be NPO for at least 8 hours so that there is no risk of vomiting (they won’t be conscious, have a gag reflex, or be able to protect their airway)
Can give drugs to reduce stomach acidity in those with acidity problems
Address anxiety! MIDAZOLAM is a good one
Address N/V if history with anesthesia – ANDANSETRAN
Step by Step: MONITORS
BP cuff, ECG, pulse-ox, temperature probe, CO2 monitor, NMJ monitor – FOR EVERYBODY
Invasive monitors –> arterial line, central venous catheter, pulmonary artery catheter, Echo, EEG, SSEP (monitors SC)
Step by Step: INDUCTION
MASK or ENDOTRACHEAL TUBE?
Endotracheal tube if procedure goes through a body cavity
USE ET if PRONE (no mask if prone), Almost all other cases below neck and anterior side = MASK
Intra-abdominal? ET
Achilles Tendon? ET (prone!)
Mastectomy? MASK
IV anesthetics –> PROPOFOL (most popular); Thiopental, Etamidate (CV PROBS!!), Ketamine, Midazolam (benzo), Opioids
Choose drug, then it depends on MASK or ET
Mask –> give bolus of IV anesthetic; patient sleeps, mask placed on
ET –> Muscle relaxant after patient sleeps then maintenance
Step by Step: MAINTENANCE
Nitrous Oxide, Halothane, Enflurane, Isoflurane, Sevoflurane, Desflurane
3 techniques – BALANCED (amnesia –> 70% N2O or PROPOFOL or BOTH; analgesia = OPIOIDS Fentanyl; Muscle Relaxants = NDMR (non-depolarizers – Vecuronium, Rocuronium both good for CV; decrease SNS –> up the dose of OPIOIDS, watch for resp depression)
INHALATION –> PIAs can do all 4 things! Watch for CV and Resp depression; ADD NITROUS OXIDE and then PIAs can be given in a LOWER DOSE!!!
INHALATION MAINTENANCE is the ONLY WAY FOR PATIENTS WITH A MASK!
COMBINED –> Most popular; balanced technique with some PIAs; more drugs so more side effects
Step by Step: EMERGENCE
Turn of relaxant; then REVERSAL of relaxant (edrophonium or neostigmine)
Bradycardia (lots of ACh) so then give…
ATROPINE or GLYCOPYRROLATE (anticholinergics) – block muscarinic receptors from excess ACh
Then turn off the rest of the agents (PIAs, propofol, Nitrous in this order)
Turn O2 to 100%
If inhalation maintenance, just turn of the PIAs and crank O2 to 100%!
What is best for patient who wants to leave on same day?
PROPOFOL – antiemetic effect too!!!
Least pungent PIA?
SEVOFLURANE - GOOD FOR KIDS!
Anxiety?
MIDAZOLAM
History of nausea with anesthesia?
ANDANSETRAN
Long acting local anesthetic?
BUPIVACAINE
CV problems?! Best IV anesthetic?
ETOMIDATE!
Arterial line for monitoring?
Allows us to look at Hb, Hct, electrolytes, arterial O2, CO2, pH, Ca2+, lactate and blood glucose
