Pharm Unit 4 Flashcards
List the intermediate acting NMBDs in order of fastest to longest time to maximum block
Roc (1.7 min) < Vec (2.4 min) < Atracurium (3.2 min) < Cisatracurium (5.2 min)
Which paralytics do not have an intubating dose of 0.1 mg/kg?
D-tubocurarine/Rocuronium (both are 0.6 mg/kg), atracurium (0.5 mg/kg) and mivacurium (0.15 mg/kg)
What are 3 synonymous terms for NMBD reversal agents?
AChE inhibitors, cholinergic agents and competitive antagonists
How do our NMBD reversal drugs work?
By inhibiting AChE there is more ACh around to bind to alpha subunits
What is the max ceiling range for Neostigmine and edrophonium?
Neo = 40 - 70 mcg/kg
Edro = 1 mg/kg
What 5 factors affect NM blockade reversal?
Depth of the NM Block
AChE Inhibitor choice
Dose administered
Rate of plasma clearance of NMBD
Anesthesia agent choice and depth (affects residual blockade)
Per the table from lecture one, what is the only paralytic that does not achieve 100% block?
d-tubocurarine
What is the dose of neostigmine, onset and duration?
0.04 - 0.07 mg/kg (or 40 - 70 mcg/kg)
Onset = 5 - 10 minutes
Duration = 60 min
What is neostigmine paired with and at what dose?
Glycopyrrolate at 0.2 mg per mg of Neostigmine
What is the dose, onset and duration of sugammadex?
2-16 mg/kg
Onset = 1 - 4 min
Duration = 1.5 - 3 hours
What is the dose, onset and duration of edrophonium?
0.5 - 1 mg/kg
Onset = 1 - 2 minutes
Duration = 5 - 15 minutes
What is another name for TOF testing?
Acceleromyography
What is the duration of clinical response of short, intermediate and long acting paralytics?
Short = ~15 minutes
Intermediate = 35 - 45 minutes
Long = ~80 - 85 minutes
What is the max dose of neostigmine?
5 mg
Describe the clearance of Neostigmine
50% renal, 30-50% is cleared by the liver if there is no renal function, making the kidneys the primary organ that gets rid of neostigmine
What are the s/e of Neostigmine?
Increased Nicotinic/Muscarinic activity
CV: Bradycardia, dysrhythmias, asystole, ↓SVR
Pulmonary: Bronchoconstriction, increased airway resistance, increased salivation
GI: Hyperperistalsis, enhanced gastric fluid secretion, PONV
Eyes: Miosis
What are our anti-cholinergic agents we pair with reversal agents?
Atropine and glycopyrrolate
What is the dose of atropine and glycopyrrolate?
Atropine = 7 - 10 mcg/kg (watch for tachycardia)
Glycopyrrolate = 7 - 15 mcg/kg (1 mg max)
What anti-cholinergic would you give alongside edrophonium?
Atropine (both drugs have a short duration)
What anti-cholinergic would you give alongside neostigmine or pyridostigmine?
Glycopyrrolate (both drugs have a longer duration)
What anti-cholinergic would you give in a patient with heart disease?
Glycopyrrolate slowly over 2 - 5 minutes
What is the rule of thumb when giving glycopyrrolate and neostigmine together?
You need the ml’s of both to match, or have neostigmine be higher
What reversal drugs work on Mivacurium, Gantacurium and Rocuronium?
Miva = Purified human plasma cholinesterase
Gan = Cystiene
Roc = Sugammadex
What is the trade name of sugammadex?
Bridion
What are the generic names of glycopyrrolate and neostigmine?
Glyco = Robinul
Neo = Prostigmin
What are some chemical characteristics of sugammadex?
Y-cyclodextrin, made up of dextrose units from starch and highly water soluble
How does sugammadex work?
Taking advantage of intermolecular/thermodynamic bonds/forces and hydrophobic interactions, it encapsulates your paralytic drugs
List these drugs in increasing ability of sugammadex to nullify: Vecuronium, Pancuronium and Rocuronium
Pancuronium < Vecuronium < Rocuronium
What is the primary elimination method of sugammadex?
In the urine, 70% in 6 hours, 90% in 24 hours. Give with care in renal failure
What is the generic classification of sugammadex?
Selective relaxant-binding agent
What is the moderate block, deep block and extreme block dose of sugammadex?
Mod = 2 mg/kg
Deep = 4 mg/kg
Extreme = 8 - 16 mg/kg
S/e of sugammadex?
(all are dose related)
N/V, pruritus, Urticaria, anaphylaxis, bradycardia or just doesn’t work
If a dose of sugammadex is given, and you have already given a dose of Roc but need to give another dose of Roc (can’t use a different drug in this scenario) how long would it take for a 0.6 mg/kg dose vs a 1.2 mg/kg dose to kick in?
0.6 = 4 hours (this timeframe would still be the case if you gave 0.1mg/kg of Vec)
1.2 = 5 minutes
If you need to redose a paralytic after giving sugammadex, what paralytics could you give?
Sugammadex is used to reverse aminosteroids, so use benzylisoquinilones; atracurium, cisatracurium or mivacurium
What are some cautions to giving sugammadex?
Pt is on oral contraceptives (can bind to progesterone, contraceptive won’t work for 7 days), pt is on toremifene (displaces NMBD from sugammadex), if pt is bleeding (elevates coagulation labs) and recurarization at lower than recommended doses
What is recurarization?
Reparalyzation, s/sx = drop in O2 sats, unresponsive patient, appears “floppy” or uncoordinated and ineffective abdominal/intercostal activity
If you suspect recurarization, what are you treatment goals?
Re-sedate the patient and give additional reversal agents in divided doses (such as neostigmine of 0.05 mg/kg IV)
What was the first local anesthetic?
Cocaine
What are are some non-anesthesia related uses for LA drugs?
(think lidocaine), treat dysrhythmias (Sodium channel blocker), treat pain
What is the IV drip/dose of lidocaine?
Initial bolus: 1-2 mg /kg IV
Drip: 1-2 mg/kg/hour for 12 - 72 hours
List the plasma lidocaine concentration and their side effects (in mcg/ml)
1-5 = Analgesia
5-10 = Circum-oral numbness, tinnitus, skeletal muscle twitching, hypotension, myocardial depression
10-15 = seizures, unconsciousness
15-25 = apnea, coma
25 < cardiovascular depression
Describe the basic structure of an LA
A lipophilic portion connected by a hydrocarbon chain to the hydrophilic portion, bond between 1 (lipopholic) and 2 (intermediate chain) classifies it as an ester or amide
With the intermediate chain, what differentiates an ester vs amide?
Ester = COOR in the chain
Amide = NHCO in the chain
In general; the bond between the lipophilic portion and the intermediate chain creates the differentiation of LAs
What are most LAs classified as in terms of pH?
Weak bases
What are the ester LAs? Amide?
Ester = Procaine, chloroprocaine, tetracaine
Amides = lidocaine, prilocaine, mepivacaine, bupivacaine, levobupivacaine, ropivacaine
List the esters in terms of potency, onset, duration and max dose
Procaine (1), slow, 45-60 duration and max dose of 500 mg
Chloroprocaine (4), rapid, 30-45 duration and max dose of 600 mg
Tetracaine (16), slow, 60-180 duration and max dose of 100 mg
What is the trick to remember what is an amide vs an ester?
Amides have 2 “I’s” in the name
Esters have 1 “I”
What is the only rapid onset amide?
Lidocaine
What is the potency, onset, duration and max single dose of lidocaine
1, rapid, 60-120 minutes and 300 mg
What is the potency, onset, duration and max single dose of Bupivacaine
4, slow, 240-480 minutes and 175 mg
What LA has the highest fraction non-ionized?
Mepivacaine
What LA has the highest lipid solubility?
Tetracaine
What LA has the highest VD?
Prilocaine @ 191
What LA has the highest clearance?
Mepivacaine, 9.78
How do liposomes affect local anesthetics?
Uploads higher amount of LA into a molecule which causes more consistent release of LA into tissues
prolongs duration of action and decreases toxicity
Basic MOA of LAs?
Bind to voltage gated Na channels and block/inhibit Na passage in nerve membranes -> slows depolarization and APs can’t reach threshold
What are 3 factors affecting blockade with an LA?
- Lipid solubility or non/ionized form
- repetitively simulated nerve
- diameter of the nerve
What is MEC?
Minimum effective concentration of an LA, 1 MEC = 2-3 nodes of Ranvier blocked (about 1 cm blocked)
What fibers block fastest? Slowest?
Fast = Preganglionic B fibers
Slow = C fibers
How does pregnancy affect MEC of LA’s?
Increased sensitivity d/t decreased amount of plasma cholinesterases
Which pKa’s have the most rapid onset?
Those closest to physiologic pH
What factors influence absorption of an LA?
- Site of injection
- dosage
- use of epinephrine
- pharmacologic characteristics of the drug
List the routes of LA administration from least amount uptaken in the blood to most
SubQ < Sciatic < Brachial < Epidural < Paracervical < Caudal < Tracheal < IV
What is the primary determinant of LA potency?
Solubility
What are the 2 primary factors that affect clearance of LAs?
CO and protein binding
List these LAs from least to most protein bound (Bupivacaine, mepivacaine and lidocaine)
Lidocaine < mepivacaine < bupivacaine (this is the MOST protein bound)
What metabolizes Amides?
Microsomal enzymes in the liver
What amide metabolizes fastest? Slowest?
Fast = prilocaine
Int= licocaine, mepivacaine
Slow = Bupivacaine, ropivacaine and etidocaine
What metabolite is formed from metabolism of esters?
para-aminobenzoic acid (PABA)
What metabolizes esters? General concern?
Hydrolysis by plasma cholinesterase, they have an a metabolite with an allergy concern: PABA
In general, what metabolize faster, amides or esters?
Esters
What LAs are subject to a first pass pulmonary effect?
Lidocaine, Bupivacaine and prilocaine
What LA class has pregnancy concerns?
Amides (they cross the placental barrier more than esters). Another concern is ion trapping of the fetus
The fetus is more acidic than mother, LA’s favor ionized form more in fetus
can cause fetal seizures, coma, bradycardia, asystole
List the amides from least to most protein bound
Prilocaine (55%) Lidocaine (70%) and Bupivacaine (95%)
Lidocaine metabolite?
Xylidide
What is the max dose of lidocaine with and without epi
Without = 300mg
With = 500 mg
What is the primary concern with Prilocaine?
Can convert Hgb into MetHgb doses >600mgs
Tx for MetHgb related to prilocaine?
Methylene blue 1-2 mg/kg IV over 5 min, max dose of 8 mg/kg
Why does mepivacaine have longer duration of action compared to lidocaine?
lacks vasodilator activity that lidocaine has
What LAs prefer to bind to a1-Acid glycoprotein?
Bupivicaine, Ropivacine
What plasma protein do local anesthetics bind to?
a1-acid glycoprotein
What esters are primarily broken down by hydrolysis? list them from fastest to slowest
chloroprocaine > procaine > tetracaine
Why is Dibucaine not used as a local anesthetic? What is it used for?
Inhibits the activity of plasma cholinesterases by more than 70%
Used to diagnose succinylcholine allergy
What LA is a weak acid?
Benzocaine
What is the dose of benzocaine?
brief spray (20%) 1 second = 200-300mg
Which populations are plasma and liver cholinesterases decreased in?
- Parturients
- neonates
- elderly
- severe hepatic disease
What is the peak duration and duration of topical cocaine?
peak = 30-45min
duration= 60min after peak
How does alkalization affect LAs?
Faster onset, enhances depth and increase the spread
Which type of injection would be contraindicated to use alkanilized LA solutions
Spinals, alkalinized will increase spread which we don’t want in a spinal
With a pH of 7.4, random drug is a weak acid with a pKa of 8.5, is it more ionized or non-ionized?
Non-ionized
With a pH of 7.4 random drug is a weak base with a pKa of 9.1, is it more ionized or non-ionized?
More ionized
What adjuvants can be mixed with LA’s? What do they do to the LA?
Dexmedetomidine IV, magnesium, chlonidine/ketamine and dexamethasone
all increase the duration of the block
Why do we use constrictors with LAs?
The duration of action of a LA is proportional to the time the drug is in contact with nerve fibers. So by using a constrictor, we can increase the length of the LA
What is the concentration of 1:200,000? 1:500,000?
(divide 1 mil/x) 5 mcg/ml and 2 mcg/ml
What is the concentration of 1:10,000 and 1:1,000
10k = 100 mcg/ml or 0.1 mg/ml
1k = 1000 mcg/ml or 1 mg/ml
What is 1% concentration? 2? 4?
1 = 10 mg/ml
2 = 20 mg/ml
4 = 40 mg/ml
What is the 0.25% concentration? 0.5?
0.25 = 2.5 mg/ml
0.5 = 5 mg/ml
Clinical Scenario: Your surgeon injected 20 mLs of Bupivacaine 0.25% with 1:200,000 of Epi.
What are the total mgs for Bupivacaine and the total mcgs for Epinephrine?
B: 0.25% = 2.5 mg/ml, 2.5 mg x 20 ml = 50 mg total
E: 1:200,000 = 5 mcg/ml x 20 = 100 mcg total
What is the normal and epi dose of lidocaine and bupivacaine?
L: 300 mg alone, 500 w/epi
B: 175 mg alone, 225 w/epi
Primary use for cocaine?
Nasal surgery
What is EMLA?
Eutectic mixture of LAs
What is the dose and onset of EMLA cream?
2.5% lido and 2.5% prilocaine, 1-2 gms per 10 cm sq of area, 45 minute onset
Cautions to use of EMLA cream?
MetHgb, skin wounds or amide allergies
When is subQ LA w/epi contraindicated?
Tissues with end arteries (digits, ears, nose, penis)
What is the general trend of numbing with an LA?
Proximal body parts numb first followed by distal, proximal recovers first followed by distal (core numbs first and recovers first)
What LAs is generally used in a Bier block?
Lidocaine is most commonly used (mepivacaine is the “better” choice per slide 66)
Describe the steps of a Bier block
Iv start -> exsanguination -> double cuff -> LA injection -> IV DC
With neuraxial anesthesia, list the systems of sensory, motor and SNS in correct sequence of blockade (first to blockade to last)
SNS then sensory then motor
With spinal anesthesia (direct injection) describe the level of sensory effect, SNS and motor effects via level of the spinal cord
Sensory = same level of denervation
SNS = 2 spinal segments cephalad (above) of sensory
Motor = 2 spinal segments below
What do we base the dosage of subarachnoid block on?
Height of patient (volume of subarachnoid space)
Segmental level of anesthesia desired
Duration of anesthesia desired
What is most important when giving a drug via the subarachnoid space: dose, concentration or volume of drug?
dose
Most common drug used in an epidural?
Lidocaine
Describe the differential zone of SNS, sensory and motor blockade with an epidural
No difference
Describe tumescent liposuction
SubQ infiltration of large volumes (5L) of dilute lidocaine (0.05% to 0.1%) with 1:100,000 (10 mcg/ml) of epi
How would you dose neuraxial anesthesia in terms of volume?
1 ml starting at 5 foot tall, then 0.1 ml per inch above 5 feet
PABA is a common source of allergic reactions with LAs, what is the other mentioned in lecture?
Methylparaben
Are allergies more common in esters or amides? Why?
Esters because they have PABA
LAST = LA systemic toxicity, what are 2 common reasons this can occur?
Entrance into the systemic circulation from inactive tissue redistribution and clearance metabolism or accidental direct IV injection
What does the magnitude of systemic absorption depend on with LAs?
Dose, Vascularity of site, epinephrine use and physiochemical properties
What lab value in conjunction with suspected toxic levels of lidocaine can promote seizures?
Hyperkalemia
What changes EKG changes are consistent with high plasma concentrations of lidocaine?
Slowed conduction: prolonged PR, QRS widening
IV bupivacaine is far more cardiotoxic than lidocaine, with toxic plasma levels, what EKG changes would you expect to see?
Precipitous hypotension, AV block, Cardiac dysrhythmias: SVTs, ST changes, PVCs, widening of QRS, V-tach
What can predispose you to LA CV toxicity?
Pregnant, hypoxic/acidotic/hyercarbic, on BBS/Dig/CCBs, epi or neo may prevent systemic toxicity
What is the most cardiotoxic amide?
Bupivacaine
What are the 3 goals with suspected systemic LA toxicity?
1) Prompt airway management
2) Circulatory support
3) Removal of LA from receptor sites
(in this order per the slide, from lecture, Castillo says he would do 3, 1, 2)
Basic interventions in CNS systemic toxicity?
100% O2, hyperventilate, barbiturates/benzos/propofol for seizures, epinephrine
What is the best pharmacologic treatment LA systemic toxicity?
Lipid rescue
What is the dose for lipid emulsion in lipid rescue? Adjunct medication? Last ditch effort if it doesn’t work?
Bolus: 1.5 ml/kg of 20% lipid emulsion
Infusion: 0.25 ml/kg/minute for 10 minutes
Adjunct: 10 - 100mcg of epi
Last ditch resort: CPB (cardiopulmonary bypass)
Max dose of lipid rescue?
8 ml/kg
What are the 3 categories of neural tissue toxicity (make sure to say toxicity in your best Serj Tankian voice)?
Transient Neurologic Symptoms (TNS)
Cauda Equina Syndrome
Anterior Spinal Artery Syndrome
Describe the pathophysiology of transient neurologic symptoms (TNS)
Moderate to severe pain (lower back, buttocks & posterior thighs) within 6 to 36 hours after uneventful single-shot SAB
Cause = unknown, seen more often with lidocaine
Tx = Trigger point injection and NSAIDs
Generally recover in 1-7 days
Describe the pathophysiology of cauda equina syndrome
Diffuse injury @ lumbosacral plexus varying degrees of sensory anesthesia, bowel & bladder sphincter dysfunction, & paraplegia
Associated: large lumbar disc herniation, prolapse or sequestration with urinary retention.
Cause = unknown
Describe the pathophysiology of anterior spinal artery syndrome
Lower extremity paresis with a variable sensory deficit.
Cause: uncertain if its thrombosis or spasm of the bilateral anterior spinal artery
Other etiologies = effects of hypotension or vasoconstrictors drugs; PVD, spinal cord compression d/t epidural abscess or hematoma
Prilocaine and benzocaine are the 2 LAs most likely to have MetHgb issues, what 4 other drugs may also create MetHgb?
Lidocaine, nitroglycerine, phenytoin and sulfonamides
Lidocaine toxicity effect on respirations?
Lidocaine depresses the ventilatory response to arterial hypoxemia, making this condition particularly dangerous in COPD patients
What is the common cause of hepatotoxicity related to LA use?
Treatment of post-herpetic neuralgia using bupivacaine
What parturient effects does cocaine have?
Decreased uterine blood flow = fetal hypoxemia
What intermediate-acting NMBD has the longest time to maximal block?
Cisatracurium
What are the anti-cholinergics paired with our AChE inhibitors?
Atropine and glycopyrrolate
What organ primarily clears pyridostigmine and edrophonium?
The kidneys, around 75%
What twitches constitute a moderate block? Deep block?
Mod = the 2nd twitch appears during a TOF
Deep = if twitch recovery requires 1-2 post-tetanic counts
What amide must be avoided if pregnant?
Mepivacaine (prolonged elimination in the fetus/newborn)
What is the extended release name of bupivacaine?
Exparel
What ester LA is the most protein bound?
Tetracaine
What is the dose of lidocaine in tumescent LA?
35 - 55 mg/kg
How much lidocaine can each gram of subQ tissue absorb?
1 mg
What preservative is found in both esters and amides?
Methylparaben
What is the max dose of glycopyrrolate?
1 mg
In order for sugammadex to exert it’s effect, what state must the drug be in?
Unbound or free drug in plasma
When does recurarization occur with sugammadex?
With too low of a dose
What amide is the most protein bound? least?
Most = levobupivacaine
Least = prilocaine
What amide is closest to physiologic pH?
Mepivacaine
What LA has the highest lipid solubility?
Tetracaine
What fast ester and slow amide may be combined?
Chloroprocaine and bupivacaine
Generic name of Sux?
Anectine
Generic name of Cisatracurium?
Nimbex
Generic name of Vecuronium?
Norcuron
Generic name of Rocuronium?
Zemuron
Generic name of Pancuronium?
Pavulon
What ester has the shortest duration? Longest?
Short = Chloroprocaine
Long = Tetracaine
What amides have the shortest duration (2 of them)?
Lidocaine and prilocaine
What amides have the longest duration (3 of them)?
Bupivacaine, levobupivacaine and ropivacaine
What amide is broken down by CYP450?
Ropivacaine
What amide LA administration is not improved with concomitant administration of epi?
Bupivacaine
Do motor or sensory fibers need a higher concentration of LA? Why?
Motor; because they have 2x the diameter they need more LA to anesthetize
If the pKa of a weak base is 9.1 is it more ionized or non-ionized?
Ionized
If the pKa of a weak base is 4.5 is it more ionized or non-ionized?
Non-ionized
Describe the concentration of tumescent liposuction solution
Lidocaine 0.05 - 0.1%
Epi at 1:100,000 or 10 mcg/ml
What esters are not effective as topical agents?
Procaine and chloroprocaine
What esters may be used topically?
Cocaine and tetracaine
What amide has the highest possible dose you can give?
Prilocaine
What ester has the highest possible dose you can give?
Chloroprocaine
What amide has the highest lipid solubility?
Bupivacaine
What amide is metabolized the fastest?
Prilocaine
1st synthetic ester and amide LA?
Synthetic ester = Procaine
Synthetic amide = Lidocaine
