CNS I Pharm - Anesthesia

Question 1

Local Anesthetics Overview

Answer 1

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

Question 2

Mechanism of action for local anesthetics

Answer 2

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)

Question 3

How do local anesthetics get into the cells?

Answer 3

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

Question 4

Mechanism of Action of LA’s (detailed)

Answer 4

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)

Question 5

Use Dependence

Answer 5

LA’s are USE DEPENDENT –> more nerves firing, more effective/more analgesic the drugs are

Question 6

Decremental Firing

Answer 6

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!

Question 7

Miscoding

Answer 7

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)

Question 8

All local anesthetics are…

Answer 8

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

Question 9

What is a common side effect of PROCAINE?

Answer 9

Broken down to para-aminobenzoic acid –> CONTACT DERMATITIS is possible

*overall, Locals are very safe drugs

Question 10

Most common Locals Used?

Answer 10

LIDOCAINE and BUPIVACAINE

Question 11

Five Types of Anesthesia

Answer 11

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

Question 12

Ideal Anesthetic Drug Criteria?

Answer 12

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

Question 13

Four Criteria for a GENERAL ANESTHETIC

Answer 13

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

Question 14

Nitrous Oxide

Answer 14

Causes AMNESIA, UNCONSCIOUSNESS, ANALGESIA –> Cannot cause immobility or SNS depression

Question 15

How do anesthetics work?

Answer 15

Liquid form —-vaporizer—> Gaseous anesthetic –> breathing system –> LUNG –> BLOOD –> BRAIN

Question 16

B/G Solubility Coefficients

Answer 16

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

Question 17

What do B/G coefficients mean?

Answer 17

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

Question 18

Specific B/G Values

Answer 18

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

Question 19

Emerging from anesthesia

Answer 19

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)

Question 20

Minimum Alveolar Concentration (MAC)

Answer 20

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

Question 21

MAC Values

Answer 21

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

Question 22

MAC examples

Answer 22

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)

Question 23

NITROUS OXIDE

Answer 23

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

Question 24

Use of Nitrous

Answer 24

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 :-)

Question 25

Side Effects of Nitrous

Answer 25

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

Question 26

What are the FOUR criteria for general anesthetics again?

Answer 26

AMNESIA ANALGESIA IMMOBILITY LOWERED SNS ACTIVITY Potent Inhalation Agents accomplish this

Question 27

Ultimate goal of general anesthesia?

Answer 27

To provide anesthesia with as LITTLE CARDIAC AND RESPIRATORY DEPRESSION AS POSSIBLE (these drugs do have dose-related cardiac and resp depression)

Question 28

Measuring DEPTH of anesthetics

Answer 28

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

Question 29

What are the SIMILARITIES of the PIAs?

Answer 29

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!

Question 30

HALOTHANE

Answer 30

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

Question 31

Halothane effects on systems

Answer 31

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

Question 32

Metabolism of HALOTHANE

Answer 32

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

Question 33

ENFLURANE

Answer 33

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

Question 34

Enflurane effects on systems

Answer 34

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

Question 35

Metabolism of Enflurane

Answer 35

Only 2-3% recovered as metabolites F- is the major one --> high levels cause RENAL IMPAIRMENT --> avoid in renal insufficient patients

Question 36

ISOFLURANE

Answer 36

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

Question 37

Isoflurane effects on systems

Answer 37

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

Question 38

Metabolism of Isoflurane

Answer 38

Good!! No evidence of renal OR hepatic failure!

Question 39

DESFLURANE

Answer 39

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

Question 40

Desflurane and CO poisoning?

Answer 40

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!!

Question 41

SEVOFLURANE

Answer 41

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

Question 42

Sevoflurane toxicity

Answer 42

Metabolized by the liver, 5-8% recovered as Metabolites --> can mix with CO2 to form "Compound A" which could be RENALLY TOXIC

Question 43

Cardiac Depression and PIAs

Answer 43

H > E > I = S = D

Question 44

Respiratory Depression of PIAs

Answer 44

E > I, S, D > H

Question 45

Cerebral Blood Flow INCREASE (ICP increase)

Answer 45

H > E > I, S, D (these 3 can be used for neuro surgery)

Question 46

NMJ Depression

Answer 46

E (seizure potential!) > I, S, D > H

Question 47

MAC Comparison

Answer 47

H (0.74 most potent) < I < E < S < D (6.0 - least potent) Nitrous = 100+ = LOWWWW potency

Question 48

B/G Comparison

Answer 48

D (0.42 - fastest) < S < I < E < H (highest, slowest - 2.3) Nitrous = 0.47 FAST

Question 49

Good for kids?

Answer 49

HALOTHANE (not in US) and SEVOFLURANE!

Question 50

Can cause dysrhythmias?

Answer 50

HALOTHANE

Question 51

IV Anesthetics Overview

Answer 51

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

Question 52

SODIUM THIOPENTAL

Answer 52

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

Question 53

Mechanism of Sodium Thiopental

Answer 53

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

Question 54

Metabolism of Sodium Thiopental

Answer 54

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

Question 55

Thiopental effects on systems

Answer 55

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

Question 56

Side effects of Thiopental

Answer 56

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

Question 57

What is the drug of choice for IV anesthesia?

Answer 57

PROPOFOL!

Question 58

PROPOFOL

Answer 58

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

Question 59

Propofol effects on organ systems

Answer 59

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

Question 60

Side effects of Propofol

Answer 60

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

Question 61

KETAMINE

Answer 61

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

Question 62

Ketamine Mechanism

Answer 62

"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)

Question 63

Ketamine effects on organ systems

Answer 63

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)

Question 64

Side effects

Answer 64

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!

Question 65

ETOMIDATE

Answer 65

***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

Question 66

Etomidate effects on organ systems

Answer 66

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

Question 67

Side Effects of Etomidate

Answer 67

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

Question 68

MIDAZOLAM

Answer 68

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

Question 69

Midazolam effect on organ systems

Answer 69

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!

Question 70

FENTANYL/SUFENTANYL

Answer 70

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)

Question 71

Four goals of general anesthesia?

Answer 71

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

Question 72

Specific needs for muscle relaxants?

Answer 72

Intubation --> relax laryngeal muscles to avoid vocal cord damage Orthopedic surgery --> to avoid tearing of large skeletal muscle groups, can make cleaner incisions

Question 73

COMPETITIVE BLOCKING MUSCLE RELAXANTS (NON-DEPOLARIZERS)

Answer 73

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!!!

Question 74

D-TUBOCURARINE

Answer 74

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

Question 75

Side effects

Answer 75

``` Histamine release Ganglionic blockade (not selective for nicotinic sub muscle receptors) --> Hypotension ```

Question 76

VECURONIUM

Answer 76

Primarily excreted by the liver, 2nd by kidney Rapid Onset (60 seconds), good duration (30-40 min) Few side effects

Question 77

ROCURONIUM

Answer 77

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)

Question 78

ATRACURIUM

Answer 78

Plasma cholinesterase --> "spontaneous elimination) 90 second onset, less than 30 minute duration Histamine mediated hypotension

Question 79

CISTRACURIUM

Answer 79

Exact same as atracurium with fewer side effects

Question 80

Duration of action problems?

Answer 80

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

Question 81

Reversal Agents

Answer 81

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

Question 82

SUCCINYLCHOLINE

Answer 82

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

Question 83

Side effects of Succinylcholine

Answer 83

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!)

Question 84

Uses of Succinylcholine

Answer 84

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

Question 85

Step by Step: PRE-OP

Answer 85

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

Question 86

Step by Step: MONITORS

Answer 86

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)

Question 87

Step by Step: INDUCTION

Answer 87

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

Question 88

Step by Step: MAINTENANCE

Answer 88

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

Question 89

Step by Step: EMERGENCE

Answer 89

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%!

Question 90

What is best for patient who wants to leave on same day?

Answer 90

PROPOFOL -- antiemetic effect too!!!

Question 91

Least pungent PIA?

Answer 91

SEVOFLURANE - GOOD FOR KIDS!

Question 92

Anxiety?

Answer 92

MIDAZOLAM

Question 93

History of nausea with anesthesia?

Answer 93

ANDANSETRAN

Question 94

Long acting local anesthetic?

Answer 94

BUPIVACAINE

Question 95

CV problems?! Best IV anesthetic?

Answer 95

ETOMIDATE!

Question 96

Arterial line for monitoring?

Answer 96

Allows us to look at Hb, Hct, electrolytes, arterial O2, CO2, pH, Ca2+, lactate and blood glucose