Apex Unit 5 Pharm II Flashcards
Match each type of peripheral nerve with its function. A Alpha A delta B C
A alpha + Motor
A delta + Fast pain
B + Preganglionic SNS
C + Slow pain
Local anesthetics can bind to the voltage-gated sodium channel when it is in the: active state only. active and inactive states. resting and inactive states. resting and active states.
Active and inactive states
The sodium channel can exist in three states: resting, active, and inactive.
Local anesthetics preferentially bind to the alpha-subunit of the sodium channel in the active and inactive states.
Local anesthetics: (Select 2.)
increase threshold potential.
decrease resting membrane potential.
have no effect on threshold potential.
have no effect on resting membrane potential.
Have no effect on threshold potential
Have no effect on resting membrane potential
When a critical number of sodium channels are blocked by local anesthetic, sodium is unable to enter the neuron in sufficient quantity. This means the neuron can’t depolarize and the action potential can’t be propagated.
Local anesthetics do NOT affect resting membrane potential or threshold potential, but you should know what does:
Potassium regulates resting membrane potential.
Calcium regulates threshold potential.
Select the true statement regarding the primary mechanism of action of local anesthetics.
The uncharged base binds to the intracellular portion of the sodium channel.
The uncharged base binds to the extracellular portion of the sodium channel.
The conjugate acid binds to the intracellular portion of the sodium channel.
The conjugate acid binds to the extracellular portion of the sodium channel.
The conjugate acid binds to the intracellular portion of the sodium channel.
Local anesthetics are weak bases. When they are placed into solution, they dissociate into an uncharged base and its conjugate acid.
You may have been tempted to select the uncharged base. This form of the drug is required for it to gain entry inside the cell. Once inside, however, it’s actually the conjugate acid that binds to the sodium channel.
A patient states she experienced hypotension, tachycardia, and shortness of breath after receiving tetracaine during a previous surgery. Which drugs should be avoided in this patient? (Select 3.)
Chloroprocaine Mepivacaine Cocaine Articaine Benzocaine EMLA cream
Cocaine
Benzocaine
Chloroprocaine
There are two classes of local anesthetics: esters and amides.
Because there is no cross sensitivity between these classes, a patient with an ester allergy may safely receive an amide (and vice versa). Since the preservatives are often the cause of an alleged allergic reaction, a preservative free anesthetic should be selected.
Which characteristics correlate BEST with local anesthetic duration of action?
Protein binding
Lipid solubility
Concentration
pKa
Protein binding
For testing purposes, you should equate: Onset of action + pKa Potency + lipid solubility Duration of action + protein binding In real life, however, it's not this cut and dry. We hope the NCE isn't so picky as to ask you about the secondary variables that influence onset, potency, and duration of action. Just to be safe, we have a handy chart for you on the next page.
Match each local anesthetic with its pKa. Mepivacaine Lidocaine Ropivacaine Chloroprocaine
Mepivacaine + 7.6
Lidocaine + 7.9
Ropivacaine + 8.1
Chloroprocaine + 8.7
The pKa correlates with onset of action. The closer the pKa is to the pH of the blood, the faster the local anesthetic begins to take effect.
As you’ll see on the next page, chloroprocaine has a high pKa and a fast onset of action. Why is this?
Rank the speed of local anesthetic uptake after injection into each location. Intercostal Caudal Brachial plexus Sciatic
Intercostal + 1
Caudal + 2
Brachial plexus + 3
Sciatic + 4
The blood flow to the area where local anesthetic is injected affects duration of action. Furthermore, it affects the concentration of LA in the blood and the risk of systemic toxicity.
Match each local anesthetic with its MAXIMUM allowable dose in the adult. Bupivacaine Ropivacaine Lidocaine Mepivacaine
bupivacaine 175mg
ropivacaine 200mg
lidocaine 300mg
mepivacaine 400mg
At what plasma concentration would you expect lidocaine to produce seizures?
(Enter your answer as a whole number in mcg/mL)
10 – 15 mcg/mL
Lidocaine can cause cardiac and neurologic toxicity. Seizures are most likely to begin when Cp = 10 – 15 mcg/mL.
One minute following an interscalene block, a 62 kg patient has a seizure. How much 20 percent lipid emulsion should you administer?
(Enter your answer as a whole number in mL)
93 mL
Local anesthetic systemic toxicity (LAST) is treated with 20% lipid emulsion at an initial dose of 1.5 mL/kg.
62 kg x 1.5 mL/kg = 93 mL
What is the MAXIMUM recommended dose for lidocaine during tumescent anesthesia?
5 mg/kg
7 mg/kg
55 mg/kg
75 mg/kg
55 mg/kg
When used for tumescent anesthesia, the maximum dose of lidocaine should not exceed 55 mg/kg.
For all other applications, the maximum dose of lidocaine is:
4.5 mg/kg (some texts say 5 mg/kg)
7 mg/kg when epinephrine is added
Which local anesthetics are MOST likely to produce methemoglobinemia? (Select 3.) Ropivacaine Cetacaine Mepivacaine Benzocaine EMLA cream Etidocaine
Benzocaine
Cetacaine
EMLA cream
Methemoglobin is formed when the iron on the hemoglobin molecule becomes oxidized to its ferric form (Fe+3). It decreases oxygen carrying capacity and shifts the oxyhemoglobin dissociation curve to the left.
Benzocaine, cetacaine, and EMLA cream can induce methemoglobinemia.
What is the MAXIMUM dose of EMLA cream for a nine month old infant who weighs 8-kg?
(Enter your answer as a whole number in grams)
Two
EMLA cream contains a 50/50 percent mixture of lidocaine and prilocaine.
The max dose in this patient is 2 g.
All of the following additives prolong the duration of local anesthetics EXCEPT: hyaluronidase. dexamethasone. dextran. epinephrine.
Hyaluronidase
Hyaluronic acid is present in the interstitial matrix and basement membrane. It hinders the spread of substances through tissue.
Hyaluronidase hydrolyzes hyaluronic acid, which facilities diffusion of substances in the tissues.
All of the other answer choices prolong the duration of local anesthetics. These include dexamethasone, dextran, and epinephrine.
Which subunits MUST be occupied to open the nicotinic receptor at the motor end plate? Alpha and gamma Alpha and epsilon Alpha and alpha Alpha and delta
Alpha and alpha
The postsynaptic nicotinic receptor (Nm) is a pentameric ligand-gated ion channel located in the motor endplate at the neuromuscular junction. It is comprised of 5 subunits that align circumferentially around an ion conducting pore.
There are two alpha subunits on this receptor, and both must be occupied by an agonist (Ach or succinylcholine) for the channel to open.
All of the following statements regarding extrajunctional nicotinic receptors are true EXCEPT:
an epsilon subunit replaces a gamma subunit.
it opens for a longer period of time.
denervation allows for its proliferation.
it is opened by choline.
An epsilon subunit replaces a gamma subunit
The extrajunctional nicotinic receptor has a gamma subunit in lieu of an epsilon subunit (not the other way around). This structural change impacts how it responds to succinylcholine.
Fade during train-of-four stimulation is caused by:
impaired presynaptic acetylcholine reuptake.
agonism of presynaptic nicotinic receptors.
antagonism of presynaptic nicotinic receptors.
decreased acetylcholine synthesis.
Antagonism of presynaptic nicotinic receptors
Antagonism of the presynaptic Nn receptor produces fade during train-of-four stimulation. Indeed, this is how nondepolarizers produce fade.
By contrast, agonism of the presynaptic nicotinic receptor prevents fade. This explains why succinylcholine does not produce fade.
Identify the statements that BEST characterize a phase II block following succinylcholine. (Select 2.)
Fade with tetany
Post-tetanic potentiation is absent
Constant but diminished response to double burst stimulation
Prolonged duration
Fade with tetany
Prolonged duration
A phase I block is a normal response to succinylcholine. It is characterized by the absence of post-tetanic potentiation and demonstrates a constant but diminished response to double burst stimulation.
A phase II block occurs with an excessive dose of succinylcholine. It is characterized by fade with tetany as well as a prolonged duration.
Identify the MOST sensitive indicator of recovery from neuromuscular blockade.
Nerve stimulator shows 4/4 twitches with no fade
Tidal volume 6 mL/kg
Vital capacity > 20 mL/kg
Inspiratory force better than – 40 cm H20
Inspiratory force better than – 40 cm H2O
You should be able to match the bedside test of recovery to the maximum percentage of post junctional nAChRs that can remain occupied by the NMB.
A tidal volume of 6 mL/kg is possible when no more than 80% of the receptors are blocked.
A vital capacity that exceeds 20 mL/kg is possible when no more than 70% of the receptors are blocked.
4/4 twitches without fade is possible when no more than 70 – 75% of the receptors are blocked.
An inspiratory force better than – 40 cm H20 is possible when no more than 50% of the receptors are blocked.
Identify the statement that demonstrates the MOST accurate understanding of succinylcholine. (Select 2.)
It is an absolute contraindication with an open globe injury.
Masseter spasm warrants cancellation of the planned procedure.
Severe sepsis increases the risk of hyperkalemia.
Hypertension is a normal side effect.
Hypertension is a normal side effect
Severe sepsis increases the risk of hyperkalemia
Why where the other answers wrong?
Succinylcholine is not absolutely contraindicated with an open globe injury. The risk of eye injury in this context is low, and securing the airway is the top priority.
Masseter spasm may be a warning sign of malignant hyperthermia. It is also a normal effect of succinylcholin
Which enzymes hydrolyze succinylcholine? (Select 3.) True cholinesterase Pseudocholinesterase Type 1 cholinesterase Butyrylcholinesterase Acetylcholinesterase Plasma cholinesterase
Pseudocholinesterase
Butyrylcholinesterase
Plasma cholinesterase
Succinylcholine is metabolized by one enzyme that happens to go by several different names. type 2, butrl, false, plasma and pseudo cholinesterase
Acetylcholine is metabolized by one enzyme that also goes by several different names.Type 1, acetylcholinestersa, true, spcific, genuine
Which factors are associated with a reduction in pseudocholinesterase activity? (Select 3.)
Obesity Myasthenia gravis Esmolol Metoclopramide Edrophonium Late stage pregnancy
Esmolol
Metoclopramide
Late stage pregnancy
You should be familiar with the drugs that reduce pseudocholinesterase activity. Some examples include: metoclopramide, esmolol, echothiophate, oral contraceptives, cyclophosphamide, and neostigmine (not edrophonium).
Late stage pregnancy reduces PChE activity.
Obesity increases PChE activity.
Myasthenia gravis is associated with a resistance to succinylcholine, but this is a pharmacodynamic effect related to a reduced number of nicotinic receptors at the neuromuscular junction (not PChE activity).
A patient with a dibucaine number of 20 received succinylcholine. This patient:
fails to produce pseudocholinesterase in sufficient quantity.
is heterozygous for pseudocholinesterase.
should receive fresh frozen plasma.
will be paralyzed for eight hours.
Will be paralyzed for eight hours
Atypical PChE is a qualitative defect. Pseudocholinesterase is produced in sufficient quantity, however the enzyme that is produced is not functional.
This patient is homozygous (not hetero) for atypical PChE, so he’ll remain paralyzed for 4 – 8 hours.
Although whole blood, fresh frozen plasma, or purified human cholinesterase will restore plasma pseudocholinesterase levels in a patient with an atypical variant, postoperative mechanical ventilation and sedation is the treatment of choice. It is the safest and least expensive option.
The routine administration of succinylcholine is contraindicated in young children because of the possibility of: bradycardia. malignant hyperthermia. trismus. hyperkalemic rhabdomyolysis.
Hyperkalemic rhabdomyolysis
Succinylcholine is contraindicated in young children because of the possibility of hyperkalemic rhabdomyolysis in patients with undiagnosed muscular dystrophy.
Although the rest of the answer choices are troubling events that can occur with the use of succinylcholine, they are not the origin of the black box warning.
Identify the patient at the HIGHEST risk for developing postoperative myalgia following succinylcholine.
6 year old boy for strabismus correction
24 year old female for umbilical hernia repair
86 year old male for total hip arthroplasty
35 year old pregnant patient for appendectomy
24 year old female for umbilical hernia repair
Muscle pain is a side effect of succinylcholine. Young adults (women > men) undergoing ambulatory surgery have the highest incidence of myalgia, while children, the elderly, and pregnant patients seem to have the lowest incidence.
Which diseases are associated with hyperkalemia following succinylcholine administration? (Select 3.) Guillain-Barre Hypokalemic periodic paralysis Myotonic Dystrophy Multiple sclerosis Hyperkalemic periodic paralysis Huntington chorea
Guillain-Barre
Multiple sclerosis
Hyperkalemic periodic paralysis
Succinylcholine can cause hyperkalemia in patients with Guillain-Barre, multiple sclerosis, and hyperkalemic (not hypokalemic) periodic paralysis.
In patients with myotonic dystrophy, succinylcholine can cause muscle contractures that may interfere with ventilation and intubation. There is no risk of hyperkalemia.
Patients with Huntington chorea are sensitive to succinylcholine. There is no risk of hyperkalemia.
Rank the nondepolarizing neuromuscular blockers in terms of potency.
(One is the most potent and four is the least potent) Cisatracurium Rocuronium Atracurium Pancuronium
Cisatracurium + 1
Pancuronium + 2
Atracurium + 3
Rocuronium + 4
Match each drug with the primary event that terminates its effect. Rocuronium Pancuronium Atracurium Cisatracurium
Rocuronium + Biliary excretion
Pancuronium + Renal excretion
Atracurium + Non-specific ester hydrolysis
Cisatracurium + Hofmann elimination
Which drugs potentiate neuromuscular blockade? (Select 3.)
Gentamycin Hydrocortisone Phenytoin Mannitol Desflurane Dantrolene
Desflurane
Gentamycin
Dantrolene
You should know how other drugs affect the duration of action of neuromuscular blockers.
Duration can be prolonged by: volatile anesthetics, aminoglycosides, and dantrolene
Duration can be shorted by: phenytoin
Duration is unaffected by: mannitol and hydrocortisone
Which condition precludes the use of pancuronium? Aortic regurgitation Hypertrophic cardiomyopathy Bradycardia First degree AV block
Hypertrophic cardiomyopathy
Pancuronium is a vagolytic (it increases heart rate). Depending on the patient’s co-morbidities, this can be helpful or harmful.
The vagolytic effect is beneficial in the patient with aortic regurgitation and bradycardia.
In the patient with hypertrophic cardiomyopathy, tachycardia reduces blood flow through the left ventricular outflow tract, ultimately reducing cardiac output.
Which neuromuscular blocker is MOST likely to cause anaphylaxis? Rocuronium Succinylcholine Cisatracurium Atracurium
Succinylcholine
Contrary to some teachings, anaphylaxis is most common with succinylcholine (when compared to the other neuromuscular blockers). Read on for our analysis of this controversial subject…
What type of bond is formed when edrophonium binds to the anionic site on acetylcholinesterase?
Ester
Covalent
Hydrogen
Electrostatic
Electrostatic
Acetylcholinesterase hydrolyzes Ach into choline and acetate. This enzyme can be inhibited at the anionic site and/or the esteratic site, and the type of bond that is formed at these sites determines the drug’s duration of action.
Edrophonium forms an electrostatic bond at the anionic site and a hydrogen bond at the esteratic site. These are weak bonds, which explains its short duration of action.
Neostigmine, pyridostigmine, and physostigmine form a carbamyl ester at the esteratic site. These are stronger bonds, which explains why these drugs have a longer duration of action.
Which statements regarding anticholinesterase drugs are true? (Select 2.)
50 percent of neostigmine is metabolized by the liver.
Renal failure necessitates a second dose.
Edrophonium + neostigmine has a synergistic effect.
Neostigmine is more potent than pyridostigmine.
Neostigmine is more potent than pyridostigmine.
50 percent of neostigmine is metabolized by the liver.
Why were the other answers wrong?
Mixing AchE inhibitors yields an additive (not synergistic) effect.
Renal failure prolongs the duration of action for both AchE inhibitors and NMBs. Since both drugs remain in the body for a longer period of time, there is no need to adjust the dose of the AchE inhibitor or to re-dose it.
Which side effect is LEAST likely to occur following administration of neostigmine? Mydriasis Nausea Bronchospasm Prolonged QT interval
Mydriasis
If you already understand the autonomic nervous system (and you should if you’ve been through our tutorials), you quickly identified that neostigmine causes miosis – not mydriasis.
Compared to atropine, glycopyrrolate is MORE likely to cause: sedation. mydriasis. xerostomia. tachycardia.
Xerostomia
Compared to atropine, glycopyrrolate is more likely to cause xerostomia (dry mouth). This makes it particularly useful for awake fiberoptic intubation as well as oral surgery.
Additionally, glycopyrrolate is a quaternary ammonium and this prevents it from crossing the blood brain barrier.
By contrast, atropine is a tertiary ammonium (it crosses the BBB), so it produces sedation and mydriasis. It’s also associated with a more significant tachycardia
Which neuromuscular blocker is MOST effectively antagonized by sugammadex? Pancuronium Rocuronium Succinylcholine Cisatracurium
Rocuronium
Sugammadex is a gamma-cyclodextrin that encapsulates the aminosteroid neuromuscular blockers in the bloodstream. It has the greatest affinity for rocuronium.
Molecular mechanisms of opioid receptor stimulation include: (Select 2.) increased adenylate cyclase activity. increased potassium conductance. increased calcium conductance. decreased cAMP production.
Increased potassium conductance
Decreased cAMP production
Opioid receptors are linked to G proteins. When an opioid binds to its receptor, several events transpire:
Adenylate cyclase activity is decreased (not increased).
cAMP production is decreased.
Calcium conductance is decreased (not increased). This reduces neurotransmitter release.
Potassium conductance is increased. This hyperpolarizes the nerve, so it’s less responsive to stimulation.
Mu receptor stimulation contributes to all of the following EXCEPT: antishivering effect. bradycardia. miosis. increased biliary pressure.
Antishivering effect
There are three types of opioid receptors: mu, delta, and kappa
From this question, the mu receptor mediates bradycardia, miosis, and increased biliary pressure by constricting the sphincter of Oddi.
An antishivering effect is mediated by kappa stimulation. This explains why meperidine is the only clinically used opioid that is used to reduce shivering.
You’ll absolutely want to know which receptors mediate which side effects.
Match each drug to its potency relative to morphine. Remifentanil Alfentanil Meperidine Sufentanil
Meperidine + 0.1 times
Alfentanil + 10 times
Remifentanil + 100 times
Sufentanil + 1000 times
Which opioid produces an active metabolite? (Select 2.)
Remifentanil
Morphine
Meperidine
Alfentanil
Morphine
Meperidine
In the liver, morphine is conjugated to morphine-3- and morphine-6-glucuronide. M6G is an active metabolite that accumulates with renal failure and chronic morphine administration.
Meperidine is demethylated in the liver to its active metabolite - normeperidine. This metabolite is half as potent as its parent compound and accumulation in patients with renal failure or the elderly increases the risk of seizures.
Remifentanil and alfentanil do not produce active metabolites.
Which drug is associated with anticholinergic side effects?
meperidine.
methadone.
naloxone.
remifentanil.
Meperidine
Meperidine is unique in that is constructed from an atropine-like ring. This explains why meperidine causes mydriasis and elevates heart rate.
The rest of the opioids tend to cause bradycardia and miosis. Miosis is the result of stimulation of the Edinger-Westphal nucleus, which increases PNS tone to the oculomotor nerve and constricts the pupil.
