Apex Unit 5 Pharm II Flashcards

Question

``` The routine administration of succinylcholine is contraindicated in young children because of the possibility of: bradycardia. malignant hyperthermia. trismus. hyperkalemic rhabdomyolysis. ```

Answer 1

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.

Answer 2

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.

Answer 3

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.

Answer 4

Cisatracurium + 1 Pancuronium + 2 Atracurium + 3 Rocuronium + 4

Answer 5

Rocuronium + Biliary excretion Pancuronium + Renal excretion Atracurium + Non-specific ester hydrolysis Cisatracurium + Hofmann elimination

Answer 6

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

Answer 7

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.

Answer 8

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…

Answer 9

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.

Answer 10

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.

Answer 11

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.

Answer 12

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

Answer 13

Rocuronium Sugammadex is a gamma-cyclodextrin that encapsulates the aminosteroid neuromuscular blockers in the bloodstream. It has the greatest affinity for rocuronium.

Answer 14

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.

Answer 15

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.

Answer 16

Meperidine + 0.1 times Alfentanil + 10 times Remifentanil + 100 times Sufentanil + 1000 times

Answer 17

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.

Answer 18

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.

Answer 19

Low degree of ionization Alfentanil achieves effect site equilibration in ~ 1.4 min (compared to 6.8 min for fentanyl). You might be tempted to think that a higher degree of lipid solubility accounts for this, but you'd be mistaken. Instead, it's all about the pKa. Alfentanil’s pKa is 6.5, which is less than physiologic pH. This makes it 89% unionized at physiologic pH. This means that there are more molecules in the lipid soluble, non-ionized form to enter the CNS. Alfentanil's potency is about 10 times morphine, 1/10th of fentanyl, 1/10th of remifentanil, and 1/100th of sufentanil.

Answer 20

Ketamine Magnesium sulfate Remifentanil is associated with opioid induced hyperalgesia. This response can be attenuated by ketamine (NMDA receptor antagonist) or magnesium sulfate. At resting membrane potential, the NMDA receptor is plugged by Mg+2. It should make sense that increasing Mg+2 concentration near the receptor limits receptor activation.

Answer 21

Cholinergic receptor antagonism Among the opioids, methadone's mechanisms of action are unique. It works via three distinct mechanisms: Mu receptor agonism NMDA receptor antagonism Monoamine reuptake inhibition

Answer 22

Oxygen consumption Pulmonary vascular resistance Intracranial pressure Opioid induced skeletal muscle rigidity causes sustained muscular contraction of the muscles in the abdomen, thorax, and throat. Contraction is an ATP-dependent process, so oxygen consumption is increased. Increased VO2 reduces (not increases) mixed venous oxygen saturation. Decreased (not increased) chest wall compliance increases intrathoracic pressure. This can elevate ICP.

Answer 23

Bradycardia Naloxone is the prototype opioid antagonist. Acute reversal of analgesia activates the SNS (tachycardia and hypertension). A significant rise in afterload can precipitate cardiac failure and pulmonary edema. Naloxone also causes nausea and vomiting. Opioids cross the placenta, so the fetus of an opioid dependent mother is also dependent. Naloxone also crosses the placenta. It can cause a state of acute withdrawal in both mother and baby.

Answer 24

1 + B fibers 2 + C fibers 3 + A delta fibers 4 + A alpha fibers Differential blockade refers to how susceptible nerve fibers are to local anesthetic conduction block. Laboratory findings often differ from clinical experience. In vivo, local anesthetics inhibit peripheral nerves in the following order (first to last): B fibers C fibers A fibers (smaller diameter) A fibers (larger diameter) As a general rule, the fibers that are blocked first are the slowest to recover.

Answer 25

Voltage-gated sodium channels Local anesthetics reversibly bind to the alpha subunit of the voltage-gated sodium channel. Plugging the channel reduces sodium conductance and interrupts the creation and propagation of action potentials in the axon. The voltage-gated sodium channel contains 1 alpha subunit and several beta subunits. The alpha subunit forms the entire ion conduction pore.

Answer 26

C fibers Axons in the peripheral nerves differ in their size, structure, speed of conduction, myelination, and sensitivity to local anesthetic blockade. For example, conduction velocity is faster in axons with a wider diameter as well as those with myelination. Myelin insulates the axon and allows the electrical current to skip along only the uninsulated regions, known as the nodes of Ranvier. This process is called saltatory conduction. Critical to answering this question was also knowing which type of nerve fiber lacks myelination. It looks like you got this one right, so nice job!

Answer 27

Regarding the structure of local anesthetics, match each molecular component with its medicinal chemistry. The local anesthetic molecule is constructed from 3 key components: ``` 1. Benzene Ring: Lipophilic (permits diffusion through lipid bilayers) 2. Intermediate Chain: Class - ester or amide Metabolism Allergic potential ``` 3. Tertiary Amine: Hydrophilic Accepts proton Makes molecule a weak base *Nagelhout says it's a quaternary amine, but this isn't right.

Answer 28

Lipid solubility As a general rule: Onset of action = pKa Potency = Lipid solubility Duration of action = Protein binding (receptor) Although this is a bit of an oversimplification, it is essential that you know this!

Answer 29

1 + Chloroprocaine 2 + Tetracaine 3 + Bupivacaine 4 + Lidocaine Remember that the pKa is the pH where 50% of a drug exists as the uncharged base (unionized) and 50% of the drug exists as the conjugate acid (ionized). ``` Acid in acid = unionized Base in base = unionized Acid in base = ionized Base in acid = ionized Since we are putting a base (local anesthetic) in a relatively acidic medium (blood), then the drugs with the highest pKa tend to ionize the most and the drugs with the lowest pKa tend to ionize the least. Let's look at those listed in the question. ``` Chloroprocaine pKa = 8.7-9.1 (most ionized) Tetracaine pKa = 8.4 Bupivacaine pKa = 8.1 Lidocaine pKa = 7.8 (least ionized) *Understand that pKa values are a little different in each book, however the ranking of agents is usually the same.

Answer 30

Benzocaine You already know that local anesthetics are weak bases that are ionized (charged) at physiologic pH, but did you also know that benzocaine is the odd man out? It’s the only clinically available local anesthetic with a pKa well below physiologic pH (benzocaine pKa = 3.5). What’s the significance of this? Benzocaine is unionized at physiologic pH, yet it possesses anesthetic activity. For all other local anesthetics, the charged species is required to produce the anesthetic effect. Benzocaine is useful for topical anesthesia of the mucus membranes during endoscopy, TEE placement, and bronchoscopy. Methemoglobinemia is a side effect of benzocaine. This risk greatly increases when the total dose exceeds 200-300 mg.

Answer 31

Tetracaine There are two parts to this question. 1. ) This patient has a sensitivity to bupivacaine, so you had to choose an ester. This narrowed your choices to tetracaine and chloroprocaine. Remember that the "i-caine" drugs belong to the class of amide agents. 2. ) You also had to know that chloroprocaine is NOT used for spinal anesthesia. Although the literature is unclear, neurotoxicity may be directly related to chloroprocaine or its preservative (bisulfite). Other data suggest that bisulfite may actually be protective! While you don't need to know these minutiae, you must know that subarachnoid chloroprocaine is associated with neurotoxicity.

Answer 32

Chloroprocaine Chloroprocaine is an ester local anesthetic that is rapidly metabolized from the plasma. Because of this, plasma protein binding with this drug is assumed to be nil. We've ranked the degree of plasma protein binding below: ``` Levo-bupivacaine = 98% Bupivacaine = 96% Ropivacaine = 94% Mepivacaine = 78% Tetracaine = 76% Lidocaine = 65% Prilocaine = 55% Procaine = 6% Chloroprocaine = 0% ```

Answer 33

1 + Intrapleural 2 + Intercostal 3 + Caudal 4 + Epidural For most drugs we administer, systemic absorption begins the process of delivering a drug to its site of action. Local anesthetics are different. We administer these drugs directly to their site of action. Absorption into the systemic circulation removes the LA from its site of action and contributes to the termination of its effect. At the same time, a higher amount of vascular uptake contributes to a higher plasma concentration. This may result in toxicity. You must know how fast LAs are transferred into the systemic circulation from a variety of sites. The most vascular site (fastest uptake) is listed first. ``` Interpleural Intercostal Caudal Epidural Brachial plexus Femoral Sciatic Subcutaneous The takeaway is that local anesthetic toxicity is greater after an interpleural block than with a sciatic block. ```

Answer 34

54 mL Local anesthetic systemic toxicity (LAST) is treated with 20 percent lipid emulsion at a dose of 1.5 mL/kg (lean body mass) over one minute. Follow with an infusion of 0.25 mL/kg/min. This patient weighed 36 kg, so the initial dose is 54 mL (36 kg x 1.5 mL/kg). If symptoms are slow to resolve, repeat bolus up to two more times and increase infusion to 0.5 mL/kg/min. Continue infusion for 10 minutes after achieving hemodynamic stability. The maximum recommended dose is 10 mL/kg in the first 30 minutes. Propofol is NOT a substitution for lipid emulsion therapy! This question could’ve asked you to calculate the dose in mg to be administered. Remember that this is a 20 percent lipid emulsion. Pay attention to what the question asks of you.

Answer 35

17.5 mL The maximum weight based dose for bupivacaine is 2.5 mg/kg. If epinephrine is added, then the dose can be increased to 3 mg/kg. 35 kg x 2.5 mg/kg = 87.5 mg Then you have to cross multiply… 5 mg / 1 mL = 87.5 mg / ? mL Maximum allowable volume of 0.5% bupivacaine = 17.5 mL

Answer 36

Local anesthetic potency Hypercarbia Higher potency local anesthetics are more likely to produce CNS toxicity. Hypercarbia/Acidosis: Increases cerebral blood flow, which increases drug delivery to the brain. Reduces protein binding, and this increases the free fraction available to the brain. Promotes ion trapping inside the brain. Lowers the seizure threshold. The clinical implications of this cannot be overemphasized! Seizures → hypoventilation → respiratory acidosis → ↑ CNS toxicity. Hyperkalemia: Raises resting membrane potential, making neurons more likely to fire.

Answer 37

Para-aminobenzoic acid A type I hypersensitivity reaction is another name for anaphylaxis. Although rare, this can occur in response to local anesthetic exposure. It is more common with ester-based local anesthetics. Ester-type local anesthetics undergo hydrolysis in the plasma, producing para-aminobenzoic acid (PABA). This compound is antigenic. Although true allergy to the amide-based local anesthetics is incredibly rare, many of these agents are prepared with methylparaben as a preservative. This compound is similar to PABA and can also precipitate an allergic response. Metabisulfite is another presevative that can cause an allergic response. There is no cross sensitivity between esters and amides, however it is best practice to give a preservative free amide to a patient with an ester allergy.

Answer 38

Compared to adults, infants are more susceptible to methemoglobinemia A dressing should be applied after EMLA is applied to the patient 5 percent EMLA cream is a 50/50 combination of 2.5 percent lidocaine and 2.5 percent prilocaine. It produces analgesia within 1 hour (not 15 minutes) and achieves maximum effect after 2-3 hours. A dressing should be applied after EMLA is applied to the patient. Prilocaine (not procaine) is metabolized to o-toluidine, which oxidizes hemoglobin to methemoglobin. Infants and small children are more likely to become toxic.

Answer 39

150 mg or 200 mg Barash says that the dose range for cocaine is 1.5 – 3.0 mg/kg, not to exceed 200 mg. Stoelting says that the maximum dose is 150 mg. We accepted both answers. Cocaine (an ester) is the only local anesthetic with vasoconstrictive properties. It inhibits NE reuptake into the presynaptic nerve terminal - it does NOT cause the release of endogenous NE. Cocaine should be avoided with MAOIs, TCAs, or sympathomimetic drugs. Beta-blockade in the setting of cocaine overdose is a questionable practice that allows for unopposed alpha-1 stimulation. High SVR (alpha-1 stimulation) and reduced inotropy (beta-1 antagonism) set the stage for cardiovascular collapse. A vasodilator such as nitroglycerine is best, but if you are given a list of beta-blockers, then labetalol (or another mixed alpha and beta antagonist) is the correct choice.

Answer 40

Which of the following illustrations best represents the mechanism of action of a local anesthetic? After you inject local anesthetic around a nerve, the local anesthetic rapidly dissociates into an uncharged base (LA) and an ionized, conjugate acid (LA+). The uncharged base (LA) enters the axon, and once inside the nerve, a new equilibrium is established Only the ionized, conjugate acid (LA+) binds to the local anesthetic binding site (alpha-subunit) on the inside of the voltage-gated sodium channel. The sodium channel remains in the closed, inactivated state until enough local anesthetic diffuses away.

Answer 41

Chloride The neuromuscular junction is populated by M-type nicotinic receptors (M = muscle). After two acetylcholine molecules bind to the two alpha subunits of the nicotinic receptor, the receptor opens allowing Na+ and Ca+2 to flow into the cell and K+ to flow out of the cell. Anions, such as Cl-, can’t pass through the nicotinic receptor. They are repelled by the strong negative charge inside the channel.

Answer 42

Butyrylcholinesterase Plasma cholinesterase We hope you're already familiar with acetylcholinesterase and plasma cholinesterase, but each one has a bunch of synonyms. Enzymes that metabolize succinylcholine and mivacurium: ``` Type 2 cholinesterase False cholinesterase Butyrylcholinesterase Plasma cholinesterase Pseudocholinesterase Enzymes that metabolize acetylcholine: ``` ``` Type 1 cholinesterase Genuine cholinesterase Specific cholinesterase True cholinesterase Acetylcholinesterase ```

Answer 43

Metoclopramide Pseudocholinesterase is synthesized by the liver. Elimination half-time = 8 - 16 hours Succinylcholine is prolonged when serum concentration is less than 75 percent of normal Anything that impairs the ability of pseudocholinesterase to hydrolyze succinylcholine will increase the duration of action for succinylcholine. Of course this assumes that all other factors remain unchanged. Examples include: ``` PChE inhibitors (echothiopate, neostigmine, pyridostigmine) Metoclopramide Monoamine oxidase inhibitors Cyclophosphamide Esmolol (this is very short lived) Severe liver disease Malnutrition Although pregnancy is associated with increased estrogen, succinylcholine’s duration of action is not prolonged. This is best explained by an increased Vd. ```

Answer 44

80 + Homozygous typical plasma cholinesterase 50 + Heterozygous atypical plasma cholinesterase 20 + Homozygous atypical plasma cholinesterase Dibucaine is an amide local anesthetic that inhibits normal plasma cholinesterase. It has no effect on atypical PChE. The number reflects the percentage of normal enzyme that is inhibited by dibucaine. Homozygous typical = 70 - 80% Heterozygous atypical = 50 - 60% Homozygous atypical = 20 - 30% Duration of action for succinylcholine: Homozygous typical = 5 - 10 minutes Heterozygous atypical = 20 - 30 minutes Homozygous atypical = 4 - 8 hours

Answer 45

Fentanyl The incidence of myalgia can be minimized, but not entirely eliminated, by pretreatment with a nondepolarizing neuromuscular blocker. The dose is 1/10th of the ED95. Other methods that may reduce the risk of myalgia include: NSAIDs Lidocaine 1.5 mg/kg Use of a higher dose rather than a lower dose of succinylcholine Opioids do not decrease the incidence of myalgia. Patients at the greatest risk of myalgia include young adults undergoing ambulatory surgery (women > men) and those that do not routinely engage in strenuous activity. Children, the elderly, and pregnant patients seem to have the lowest rate of occurrence.

Answer 46

Vecuronium Pancuronium Neuromuscular blockers are classified as depolarizing or non-depolarizing. Succinylcholine is the only clinically used depolarizing NMB. Non-depolarizing NMBs are classified as aminosteroid or benzylisoquinolinium compounds. Aminosteroids = rocuronium, vecuronium, pancuronium Benzylisoquinoliniums = atracurium, cisatracurium, mivacurium

Answer 47

Succinylcholine + 0.30 mg/kg Atracurium + 0.21 mg/kg Vecuronium + 0.04 mg/kg When thinking about the potency of any drug, all you have to do is compare the dosages. The higher the dose you have to give to achieve a given effect, the lower its potency. The ED95 is a Measure of Potency - They are inversely related In the context of neuromuscular blockers, the ED95 is the dose at which there is a 95% decrease in twitch height. This is different than the intubating dose! ``` The dose required to provide optimal conditions for tracheal intubation is ~ 2 – 3 times the ED95. ED95 of all of the clinically used NMBs (most potent to least potent): Cisatracurium = 0.04 mg/kg Vecuronium = 0.043 mg/kg Mivacurium = 0.067 mg/kg Pancuronium = 0.067 mg/kg Atracurium = 0.21 mg/kg Succinylcholine = 0.30 mg/kg Rocuronium = 0.305 mg/kg ```

Answer 48

Hypothermia Atracurium and cisatracurium undergo organ independent elimination. ``` Atracurium = non-specific plasma esterases > Hofmann elimination Cisatracurium = Hofmann elimination ``` Hoffman elimination is dependent on pH and temperature. Hypothermia and metabolic acidosis prolong duration of action. Hyperthermia and metabolic alkalosis shorten duration of action. Both produce laudanosine as a metabolite (atracurium produces more). Laudanosine is a CNS stimulant that can theoretically produces seizures. This is not a problem with routine dosing in the OR.

Answer 49

Cisatracurium Vecuronium Obstructive cardiomyopathy (idiopathic hypertrophic subaortic stenosis) causes left ventricular outflow tract obstruction. This is the result of: Congenital hypertrophy of the intraventricular septum. Systolic anterior motion (SAM) of the anterior leaflet of the mitral valve. ``` The obstruction is made worse by any condition that causes narrowing of the LVOT. This includes a/an: Increased heart rate Increased contractility Decreased preload Decreased aortic pressure Decreased afterload ``` Pancuronium is a vagolytic that increases heart rate. Atracurium and mivacurium release histamine, which increases heart rate and reduces afterload. * Hines p. 137 states incorrectly that a reduced afterload improves LVOT obstruction.

Answer 50

Desflurane Inhalation anesthetics work in the ventral horn of the spinal cord to produce immobility. Therefore, it should make sense that the inhaled agents potentiate the neuromuscular blocking effects of nondepolarizing NMBs. This means that, in the presence of an inhaled anesthetic, the level of blockade is deeper and duration of action is longer for a given dose of NMB. The inhaled anesthetics are ordered from most potentiation to least potentiation (propofol is added for comparison): Des > Sevo > Iso > N2O > Propofol There are several possible explanations for this including: A central effect on alpha motor neurons and their synaptic connections. Inhibition of postjunctional nicotinic receptors at the NMJ. Increased NMB affinity at the postjunctional nicotinic receptors at the NMJ.

Answer 51

Gentamycin Clindamycin Some antibiotics potentiate neuromuscular blockade. Agents that inhibit Ach release and reduce the sensitivity of the postjunctional nicotinic receptor to the effect of Ach: Aminoglycosides (gentamycin, streptomycin) Clindamycin Lincomycin Polymyxins Agents that reduce the sensitivity of the postjunctional nicotinic receptor to the effect of Ach: Tetracycline

Answer 52

Mivacurium Atracurium and mivacurium stimulate histamine release from mast cells. Physiologic effects of histamine release include: ``` Increased airway resistance Increased heart rate Decreased systemic vascular resistance Decreased blood pressure Skin flushing It is best to avoid atracurium or mivacurium in patients who are sensitive to a/an: ``` Increased heart rate (hypertrophic cardiomyopathy) Decreased afterload (aortic stenosis) Increased airway resistance (asthma)

Answer 53

Tryptase Anaphylaxis is the result of mast cell activation. An elevated tryptase level is consistent with mast cell degranulation. The serum tryptase concentration peaks between 15 – 120 minutes. An elevated serum histamine concentration peaks at 60 – 90 minutes. Intradermal skin testing is used to diagnose the allergic potential of a given drug in a particular patient, however it isn’t helpful in determining if a reaction has already occurred. An elevated homocysteine level is associated with vascular inflammation and may increase the risk of cardiovascular disease.

Answer 54

Facial nerve When using a nerve stimulator, observe the following rules: Best location to monitor onset: ``` Nerve = facial Muscle = orbicularis oculi or corrugator supercilii ``` Best location to monitor recovery: Nerve = ulnar Muscle = adductor pollicis

Answer 55

Corrugator supercilii + Moves the eyebrow Orbicularis oculi + Closes the eyelid Medial rectus + Adducts the eyeball Adductor pollicis + Adducts the thumb The corrugator supercilii moves the eyebrow. It is innervated by the facial nerve (CN VII). The orbicularis oculi closes the eyelid. It is innervated by the facial nerve (CN VII). The adductor pollicis adducts the thumb. It is innervated by the ulnar nerve. The medial rectus adducts the eyeball. It is innervated by the oculomotor nerve (CN III).

Answer 56

B C Stimulation of the ulnar nerve results in contraction of the adductor pollicis muscle. Visually this appears as thumb ADDuction; not pinky finger ADDuction or flexion. The adductor pollicis recovers later than the diaphragm, laryngeal adductors, and abdominal muscles, however it recovers at the same time as the geniohyoid. The take away is that if the adductor pollicis is not recovered, then the geniohyoid probably isn’t either and this increases the risk of upper airway obstruction. Stimulation of the ulnar nerve at the wrist: Negative electrode = C Positive electrode = D Stimulation over the adductor pollicis muscle: Negative electrode = B Positive electrode = A Remember the red wire of the nerve stimulator is Positive and placed Proximal. The black wire is distal and black.

Answer 57

0.9 A train-of-four ratio less than 0.9 at the adductor pollicis is associated with: Impaired pharyngeal function and swallowing Decreased upper esophageal sphincter tone Taken together, these consequences increase the risk of pulmonary aspiration. The patient may appear to be strong enough to maintain ventilation, however once the endotracheal tube is removed, the upper airway and pharyngeal musculature may not be strong enough to maintain upper airway patency or protect the airway.

Answer 58

Patient holds tongue blade in mouth against force The upper airway is the most sensitive component of the respiratory system. Indeed, upper airway tone is impaired and aspiration is a risk when the TOF ratio is < 0.9. Most sensitive bedside assessments of recovery: Head lift > 5 seconds Leg lift > 5 seconds Holding tongue depressor between teeth against force (of these, Barash thinks this is the best)

Answer 59

Neostigmine Many books say that neostigmine adequately reverses a block with 90 percent twitch suppression, however this is a function of how we define full recovery. Older data suggests that full respiratory recovery occurs at a TOF ratio of 0.6 at the adductor pollicis. Newer data suggests that upper airway dilator tone and hypoxic ventilatory drive are impaired up to a TOF ratio of 0.9! For this reason, we recommend that you wait to reverse until you have a minimum of two twitches. Although edrophonium is as effective as neostigmine in reversing mild to moderate neuromuscular blockade (2 – 4 twitches), it fails to adequately reverse profound relaxation (90 percent twitch depression or one twitch). Physostigmine has a prolonged onset, making it less attractive. Also, it is the only acetylcholinesterase inhibitor that diffuses across the blood-brain barrier. CNS side effects limit its utility as a reversal agent.

Answer 60

Decreasing acetylcholine hydrolysis Neostigmine is a cholinesterase inhibitor that reversibly binds to the enzyme acetylcholinesterase at the NMJ. This process inhibits acetylcholine hydrolysis, thus allowing more acetylcholine to compete with the NMBA at the nicotinic receptors. This is an example of competitive antagonism. The offset of NMBAs is also influenced by its diffusion away from the NMJ, redistribution, metabolism, and excretion. Butyrylcholinesterase, (another name for plasma cholinesterase or pseudocholinesterase) is concentrated in the plasma. It, too, is inhibited by neostigmine. Butyrylcholinesterase metabolizes succinylcholine, mivacurium, and local anesthetics.

Answer 61

Neostigmine + 0.05 mg/kg Edrophonium + 1 mg/kg Pyridostigmine + 0.3 mg/kg If you were asked to line these up according to potency, the drug with the smallest dose (neostigmine) is the most potent and the one with the largest dose is the least potent (edrophonium).

Answer 62

Physostigmine Scopolamine crosses the BBB and may cause central anticholinergic syndrome. The elderly are particularly vulnerable. Symptoms include confusion, agitation, hallucinations, somnolence, and unconsciousness. Physostigmine (15 - 60 mcg/kg) is the only AchE inhibitor that crosses the BBB. It is the antidote for antimuscarinic overdose. It is dosed q1-2 hr. Central anticholinergic syndrome is often mistaken for slow emergence from anesthesia. Pyridostigmine does not cross the BBB, so it won't benefit this patient. Midazolam does not reverse the etiology of this patient's confusion, so it's not the best choice. Reducing environmental stimuli can also be useful, but again it doesn't reverse the cause of confusion, so it's not the best option.

Answer 63

Neostigmine Pyridostigmine Succinylcholine is hydrolyzed by pseudocholinesterase in the plasma. AchE inhibitors inhibit acetylcholinesterase at the NMJ and neostigmine and pyridostigmine (not edrophonium) inhibit pseudocholinesterase in the plasma. If succinylcholine is administered shortly after neostigmine or pyridostigmine, then succinylcholine's duration of action will be prolonged. Physostigmine crosses the BBB, so its CNS side effects limit its utility as a reversal agent.

Answer 64

Edrophonium + 1 minutes Neostigmine + 10 minutes Pyridostigmine + 15 minutes At a steady state concentration of NMBA in the plasma, the onset of action for the AchE inhibitors is: Edrophonium: 1 min Neostigmine: 7 - 11 min Pyridostigmine: Up to 16 min

Answer 65

Atropine pairs better than glycopyrolate This question deals with the pharmacokinetics of antimuscarinics. Since the onsets and durations are similar, atropine can be mixed with edrophonium and glycopyrrolate can be mixed with neostigmine. This explains why atropine is "better" than glycopyrrolate when edrophonium is selected. You should've been able to exclude the rest of the answer choices to arrive at this answer. Mixing glycopyrrolate and edrophonium in the same syringe will cause profound bradycardia. The same complication can occur if you administer atropine after edrophonium. While atropine does cross the BBB, it remains an acceptable choice when it is paired with edrophonium. Correct Answer: Edrophonium + 1 minutes Neostigmine + 10 minutes Pyridostigmine + 15 minutes At a steady state concentration of NMBA in the plasma, the onset of action for the AchE inhibitors is: Edrophonium: 1 min Neostigmine: 7 - 11 min Pyridostigmine: Up to 16 min

Answer 66

Glycopyrrolate Atropine and scopolamine are naturally occurring tertiary amines, which makes them lipophilic. These drugs easily diffuse through lipid membranes like the blood-brain barrier, GI tract, and placenta. Pyridostigmine is the longest acting AchE inhibitor. It's a first-line medical therapy for myasthenia gravis. Glycopyrrolate is different. It has a quaternary ammonium that ionizes in the plasma. This limits its ability to cross cell membranes, which explains why it doesn't pass through the BBB, GI tract, or placenta.

Answer 67

Scopolamine +++ Atropine ++ Glycopyrolate 0 Cycloplegia is paralysis of the ciliary muscle in the eye, resulting in loss of accommodation. Remember the comparison list we gave you in the corresponding tutorial? You'd be wise to memorize it.

Answer 68

Aminosteroids Sugammadex is a cyclodextrin that encapsulates all aminosteroids, however it is most selective for rocuronium. Its affinity for the aminosteroids is: rocuronium > vecuronium > pancuronium Sugammadex does not reverse benzylisoquinolines or succinylcholine.

Answer 69

Fentanyl + Phenylpiperidine Morphine + Phenanthrene Methadone + Diphenylpropylamine Opioid agonists and antagonists are classified as naturally occurring, semisynthetic, and synthetic. Naturally Occurring: Phenanthrene derivatives (morphine, codeine) Semisynthetic: Morphine derivatives (hydromorphone, heroin, naloxone, naltrexone) Thebaine derivatives (oxycodone) Synthetic: Phenylpiperidines (meperidine, fentanyl, sufentanil, remifentanil, alfentanil) Phenylheptylamines (methadone)

Answer 70

Bradycardia Respiratory depression Pruritus Opioid receptors are divided into three categories: Mu, Delta, and Kappa. Mu Receptor: There is no evidence to support the existence of separate mu1 and mu-2 receptors. Key effects of mu stimulation include supraspinal and spinal anesthesia, euphoria, sedation, respiratory depression, bradycardia, pruritus, miosis, constipation, N/V, increased biliary pressure, and urinary retention. Kappa Receptor: Key effects of kappa stimulation include dysphoria, antishivering effect, and diuresis. Delta Receptor If you understand mu and kappa effects, then you can probably get by not knowing much about the delta receptor. Know that delta receptors do not mediate bradycardia or sedation.

Answer 71

Miosis Constipation Tolerance occurs when a patient requires higher doses of a drug to achieve a given effect. It can occur without physical dependence, however the opposite isn't usually true. Tolerance and physical dependence are most likely due to receptor desensitization and increased synthesis of cAMP. These phenomena are not due to enzyme induction. There is cross-tolerance among the opioid antagonists. The time table for tolerance is dependent on the particular drug; it tends to occur faster with the more potent agents. Tolerance develops to nearly all of the side effects associated with opioids. This includes analgesia, sedation, euphoria, respiratory depression, and emetic effects. There are 2 exceptions to this rule. Tolerance does NOT develop to miosis and constipation.

Answer 72

Myocardial depression As a general rule, opioids don't cause myocardial depression. Meperidine is the exception to the rule (usually with higher doses). Cardiovascular side effects of opioids include: ↓ SNS tone → venous pooling → ↓ preload → ↓ CO → ↓ BP ↓ SNS tone → orthostatic hypotension Histamine release → ↓ BP (only morphine and meperidine)

Answer 73

Morphine has a greater analgesic potency Gender plays a role in the PK/PD differences among opioid agonists. In women, morphine is associated with a: ``` Greater analgesic potency Slower onset of action Longer duration of action Lower post-operative opioid consumption ```

Answer 74

Bronchospasm Be careful with questions that try to lead you down a particular path. Rapid IV administration of opioids can cause skeletal muscle rigidity. This condition is more common with the potent (lipophilic) compounds, such as sufentanil, fentanyl remifentanil, and alfentanil. Historically, this complication has been described as chest wall rigidity or stiff chest syndrome, however current evidence suggests that the greatest resistance to ventilation occurs at the larynx. This patient became difficult to ventilate after receiving succinylcholine. If skeletal muscle rigidity was the cause, then succinylcholine would’ve improved ventilation. Indeed, NMBs are the primary treatment for opioid-induced skeletal muscle rigidity, although naloxone works as well. What else could’ve caused this situation? Succinylcholine releases histamine. This can cause bronchospasm, making mask ventilation difficult or even impossible. As an aside, don’t forget that NMBs only relax skeletal muscle and not smooth muscle – they do not treat bronchospasm! Pulmonary embolism causes hypoxemia, however ventilation would remain possible. Malignant hyperthermia does not make sense in this context.

Answer 75

Methadone + QT interval prolongation Codeine + Metabolized to morphine Sufentanil + Most potent opioid Alfentanil + pKa is less than physiologic pH Codeine is metabolized to morphine by CYP2D6. Asians tend to have lower CYP2D6 activity, making this population resistant to codeine therapy. Conversely, Ethiopians have significant CYP2D6 activity, making this population sensitive to codeine therapy. Sufentanil is the most potent opioid agonist. It is 1000 times the potency of morphine and 10 times the potency of fentanyl. Alfentanil is the only opioid with a pKa (6.5) that is lower than physiologic pH (7.4). Because most of the drug exists in the nonionized form (~90%), more of it is available to penetrate the blood-brain-barrier. This explains why it is the fastest acting opioid agonist. Methadone delays the inward K+ rectifier, and this can prolong the QT interval and increase the risk of Torsades de pointes.

Answer 76

Ketamine Magnesium Remifentanil is associated with acute opioid-induced hyperalgesia (OIH) following discontinuation. This phenomenon can be thought of as acute opioid tolerance that develops early in the post-operative period. These patients tend to consume more opioids during this time. The most likely explanation for OIH involves the NMDA receptor and its second messenger systems. NMDA receptor antagonists, such as ketamine and magnesium, have been shown to reduce or eliminate OIH after remifentanil.

Answer 77

Fentanyl Patients who are physically dependent on opioid agonists will experience s/sx of withdrawal upon discontinuation of these drugs. Early s/sx: diaphoresis, insomnia, restlessness Later s/sx: abdominal cramping and N/V The time course of opioid withdrawal is a function of the drug's half-life. Withdrawal s/sx occur as follows: Fentanyl and meperidine: Onset 2-6 hrs - Peak 6-12 hrs - Duration 4-5 days Morphine and heroin: Onset 6-18 hrs - Peak 36-72 hrs - Duration 7-10 days Methadone: Onset 24-48 hrs - Peak 3-21 days - Duration 6-7 weeks

Answer 78

Meperidine Meperidine exhibits a structural resemblance to local anesthetics as well as atropine. By inhibiting sodium channels in the axon, it inhibits nerve conduction. This can be useful for spinal anesthesia. Meperidine also resembles atropine. This explains why it increases heart rate and causes mydriasis.

Answer 79

Substantia gelatinosa The endogenous pain modulation pathway (descending inhibitory pain pathway) is a critical component of pain modulation. The periaqueductal grey communicates with the ventrolateral medulla to indirectly influence pain transmission in the substantia gelatinosa (Rexed lamina II and III) in the dorsal horn of the spinal cord. Periaqueductal grey → Rostroventral medulla → Substantia gelatinosa

Answer 80

Morphine Rostral spread describes the cephalad migration of a drug after injection into the CSF. This concept helps us understand why some opioids produce a late respiratory depression. Indeed, respiratory depression is the most common serious complication of intrathecal opioids. As an aside, pruritus is the most common side effect. Morphine is the least lipophilic opioid that is used for spinal anesthesia. Since morphine is less likely to diffuse out of the intrathecal space, more of the drug is available to ascend towards the brain. Early phase respiratory depression results from systemic absorption. This occurs at < 6 hours. Late phase respiratory depression results from rostral spread and inhibition of the respiratory center in the brainstem. This occurs between 6 and 12 hours

Answer 81

Epidural Epidural morphine can reactivate herpes simplex labialis virus, usually in obstetric patients. It tends to occur 2-5 days after the dose is administered. External symptoms tend to occur along the same dermatome as the initial infection. This is usually along the trigeminal nerve distribution on the face (cold sores).

Answer 82

Kappa receptor agonism Shivering increases whole body oxygen consumption, and this can lead to myocardial ischemia in susceptible patients. Stimulation of the kappa opioid receptor as well as the alpha-2 receptor reduces post-operative shivering. There are three drugs that are used to treat post-operative shivering: Meperidine: kappa and alpha-2 stimulation Butorphanol: kappa stimulation Clonidine: alpha-2 stimulation

Answer 83

Bradycardia Naloxone is an opioid antagonist used to treat opioid overdose. It reverses respiratory depression at the expense of reversing analgesia. It should be titrated slowly in increments of 1-4 mcg/kg q 2-3 minutes. In our experience, titrating 40 mcg at a time effectively reverses respiratory depression without significantly reversing analgesia. Acute analgesic reversal activates the sympathetic nervous system, which can manifest as tachycardia and hypertension. These sequelae can precipitate myocardial ischemia and pulmonary edema. Naloxone can also increase the incidence of N/V. Slower titration reduces the incidence.