Unit 5 - Pharm 2 Flashcards
What are the characteristics that differ among the axons of peripheral nerves?
Size, structure, speed of conduction, myelination, sensitivity to local anesthetic blockade
How does myelination and axon diameter affect conduction velocity?
Increased myelination and wider axon diameter increase conduction velocity
What are the three major classes of peripheral nerves based on diameter and myelination?
A, B, C
In what order do local anesthetics inhibit peripheral nerves based on speed of onset?
B fibers, C fibers, small diameter A fibers, large diameter A fibers
In what order does regression of blockade occur?
Opposite order of block onset
What do local anesthetics bind to in voltage-gated Na+ channels?
Alpha subunit
What are the three possible states of the Na+ channel?
Resting (Nonconducting), Active (Conducting), Inactive (Nonconducting)
According to the guarded receptor hypothesis, when can local anesthetics bind to Na+ channels?
When Na+ channels are in their active or inactive states
What is the resting membrane potential of a peripheral nerve?
-70 mV
What is the threshold potential for depolarization in a peripheral nerve?
-55 mV
What occurs during depolarization in a nerve?
Na+ enters the cell and an action potential is propagated
What restores the resting membrane potential after depolarization?
Increased K+ conductance and Na/K-ATPase activity
What effect do local anesthetics have on resting membrane potential and threshold potential?
They do NOT affect resting membrane potential or threshold potential
Fill in the blank: Hypocalcemia makes the threshold potential more ______.
negative
What are local anesthetics classified as in terms of their acidity?
Weak bases
What happens to local anesthetics when injected around a nerve?
They dissociate into an unchanged base and an ionized conjugated acid
How does pKa affect the onset of action of local anesthetics?
Closer pKa to blood pH leads to faster onset; further pKa leads to slower onset
How are ester local anesthetics metabolized?
In the plasma by pseudocholinesterase
How are amide local anesthetics metabolized?
In the liver by the P450 system
What is the significance of the number of ‘i’s in amide local anesthetics?
All amides have two ‘i’s in their name
What is the maximum dose of bupivacaine in Exparel?
266 mg (2 vials)
What is the recommended treatment for lidocaine toxicity?
100% FiO2, benzodiazepines for seizures
What is the primary cause of local anesthetic toxicity syndrome (LAST)?
Inadvertent IV injection during regional anesthesia
Which local anesthetic is associated with the highest difficulty of cardiac resuscitation?
Bupivacaine
What is the treatment for methemoglobinemia?
Methylene blue
What can lead to a false SpO2 reading in methemoglobinemia?
A significant concentration of methemoglobin
What is the effect of methemoglobin on oxygen carrying capacity?
Reduces ability to bind O2 and shifts the oxyhemoglobin dissociation curve left
Fill in the blank: The pH of blood is ______.
7.4
What is the recommended treatment dose for methylene blue?
1-2 mg/kg over 5 minutes (Max dose = 7-8 mg/kg)
Redosing may be necessary due to rebound methemoglobinemia.
What is a potential complication after methylene blue administration?
Rebound methemoglobinemia can occur up to 12 hours after administration
Hyperbaric O2 can be considered for treatment.
Which patients are at risk for methemoglobin toxicity?
Patients with Glucose-6-phosphate reductase deficiency
Methylene blue can precipitate hemolytic crisis in these patients.
What treatment is indicated for hemolytic crisis due to methylene blue?
Exchange transfusion
Why are neonates at higher risk for methemoglobinemia?
Fetal Hgb is deficient in methemoglobin reductase
What is EMLA cream composed of?
50/50 combination of 2.5% lidocaine & 2.5% prilocaine
How long does EMLA take to produce analgesia?
Produces analgesia within one hour, maximum effect after 2-3 hours
What should be applied after the topical application of EMLA?
Occlusive dressing
What can be applied simultaneously with EMLA to hasten absorption?
Nitroglycerine
Where should EMLA cream be applied?
Intact skin, never on mucus membranes
What skin conditions can alter EMLA pharmacokinetics?
Eczema, psoriasis, & skin wounds
What is the risk of applying EMLA over affected areas?
Increased risk of toxicity
What metabolite does prilocaine convert to that can oxidize Hgb?
o-toluidine
Which drugs prolong LA duration of action?
- Epi
- Dexamethasone
- Dextran
What does Epi do in the context of local anesthetics?
Reduces uptake and works best with LA with intermediate duration
What drugs provide supplemental analgesia?
- Epi
- Clonidine
- Opioids
What is the effect of chloroprocaine on opioids in the epidural space?
Reduces effectiveness of opioids
What can shorten the onset time of local anesthetics?
Sodium bicarbonate
What is the clinical relevance of sodium bicarbonate in LA?
Debatable
What enzyme terminates the effect of ACh at the neuromuscular junction?
Acetylcholinesterase
What is the structure of the postsynaptic nicotinic receptor?
Pentameric ligand-gated ion channel
What happens when two ACh molecules bind to the postsynaptic nicotinic receptor?
Ion-conducting pore opens, allowing Na+ & Ca++ to enter
What condition leads to the proliferation of extrajunctional receptors?
Denervation injury or prolonged immobility
What is the normal structure of the Nm receptor?
ααβδε
What variant of extrajunctional Nm receptors is depolarized by succinylcholine?
Variant #1: ααβδγ
What is the effect of succinylcholine on patients with extrajunctional receptors?
Predisposes to hyperkalemia
What is the treatment for succinylcholine-induced hyperkalemia?
- IV CaCl
- Hyperventilation
- Glucose + insulin
What is the mechanism of fade during TOF stimulation?
Antagonism of presynaptic Nn receptors
Why is fade not observed with succinylcholine?
It stimulates presynaptic Nn receptors, preserving ACh mobilization
What is needed to mobilize ACh for release during depolarization?
Ca++
What distinguishes phase 1 block from phase 2 block?
The presence or absence of fade
Phase 1 does not exhibit fade while phase 2 does exhibit fade.
What is the typical effect of succinylcholine under normal circumstances?
Produces a phase 1 block
A high dose or long IV infusion can produce a phase 2 block.
What is the dose threshold for succinylcholine to potentially produce a phase 2 block?
> 7-10 mg/kg
Also, greater than 30-60 minutes of IV infusion can lead to a phase 2 block.
Which muscle groups are more resistant to neuromuscular blockade?
More central muscles
They recover sooner than peripheral muscles.
Which muscle and nerve are best for measuring the onset of neuromuscular blockade?
Muscle: Orbicularis oculi; Nerve: Facial nerve (CN 7)
This muscle closes the eyelid.
What is the best muscle and nerve to assess recovery from neuromuscular blockade?
Muscle: Adductor pollicis; Nerve: Ulnar nerve
This muscle is responsible for thumb adduction.
What defines recovery from neuromuscular blockade?
TOF > 0.9 at the adductor pollicis
Previously, it was defined as TOF > 0.7.
What is the risk percentage of residual neuromuscular blockade despite best efforts?
20-40%
Highlights the inaccuracy of subjective bedside tests.
What are the best qualitative bedside tests of recovery from neuromuscular blockade?
- Sustained tetany > 5 seconds
- Sustained head lift > 5 seconds
- Inspiratory force better than -40 cm H2O
- Ability to hold a tongue blade in mouth against force
These tests account for 50% of receptors being occupied.
What are the side effects of succinylcholine related to bradycardia?
Stimulates M2 at the SA node
Succinylmonocholine may also be implicated.
What is the effect of succinylcholine on potassium levels?
Increased K+ (0.5-1.0 mEq/L for up to 10-15 min)
Severe sepsis increases the risk of hyperkalemia.
What is the black box warning for succinylcholine?
Risk of cardiac arrest & sudden death due to hyperkalemia in children with undiagnosed skeletal muscle myopathy
Most commonly associated with Duchenne muscular dystrophy.
What is the dibucaine test used for?
To diagnose atypical pseudocholinesterase
Atypical PChE is a qualitative defect where the enzyme produced is not functional.
What is a common cause of postoperative myalgia with succinylcholine?
Muscle soreness in neck, shoulders, subcostal region, upper abdominal muscles, & trunk muscles
May persist up to 24-48 hours.
Which conditions increase the risk of succinylcholine-induced hyperkalemia?
- Guillen-Barre
- Hyperkalemic periodic paralysis
- Malignant hyperthermia
- Multiple sclerosis
- Up-regulation of acetylcholine receptors
- Charcot-Marie-Tooth
These conditions affect potassium levels and neuromuscular responses.
How is the potency of neuromuscular blockers assessed?
By comparing dosages
Higher doses indicate lower potency.
What are the two classes of nondepolarizing neuromuscular blockers?
- Benzylisoquinolinium
- Aminosteroid
Examples include mivacurium, atracurium, pancuronium, rocuronium.
What is the primary metabolism method for benzylisoquinolinium compounds?
Spontaneous degradation in plasma
This includes Hofman elimination and non-specific plasma esterases.
What does the term ‘ED95’ refer to?
The dose at which there’s a 95% decrease in twitch height
It’s a measure of potency in neuromuscular blockers.
What are common cholinergic side effects of AChE inhibitors?
- Bradycardia
- Bronchoconstriction
- Nausea/Vomiting
Remember the acronym DUMBBELLS.
What is the efficacy of Precedex in relation to postoperative shivering?
It matches meperidine & clonidine
Precedex can also help with postoperative shivering.
What type of amine is Physostigmine and what is its significance?
Tertiary amine that allows it to penetrate the BBB
Physostigmine can cross the blood-brain barrier.
What are the quaternary amines that cannot cross the BBB?
Edrophonium, neostigmine, & pyridostigmine
These agents are unable to penetrate the blood-brain barrier.
What does the acronym DUMBBELLS represent in cholinergic side effects?
- Diarrhea
- Urination
- Miosis
- Bradycardia
- Bronchoconstriction
- Emesis
- Lacrimation
- Laxation
- Salivation
These are the common side effects of AChEi.
What is the primary effect of Atropine among muscarinic antagonists?
Increases heart rate the most
Atropine can cause paradoxical bradycardia in small doses.
What is the role of Glycopyrrolate in relation to the BBB?
It is ionized & does not cross the BBB
It does not prevent motion-induced nausea.
What is Sugammadex and its primary function?
A gamma-cyclodextrin that encapsulates aminosteroid NDNMBs
It provides swift reversal of neuromuscular blockade.
What is the effect of Sugammadex on rocuronium?
Increases the rate of transfer from NMJ to plasma
Sugammadex augments the concentration gradient.
Can Sugammadex be used with succinylcholine?
No, it has no effect on succinylcholine
Sugammadex is effective with rocuronium, vecuronium, & pancuronium.
What are the side effects of Sugammadex?
- Anaphylaxis (0.3% chance)
- Bradycardia
- Cardiac arrest
- Reduction in hormonal contraceptives effectiveness for 7 days
Backup birth control is advised for 7 days.
What are the four types of opioid receptors?
- Mu (MOP)
- Delta (DOP)
- Kappa (KOP)
- ORL1 (NOP)
All are G-protein coupled receptors.
What physiological effects are associated with Mu receptor stimulation?
- Analgesia
- Bradycardia
- Respiratory depression
- Euphoria
- Physical dependence
- Constipation
These effects are key to understanding opioid action.
What are the classifications of opioids?
- Naturally occurring
- Semisynthetic
- Synthetic
Each category includes various derivatives and compounds.
Define tolerance in the context of opioid usage.
Occurs when a patient requires higher doses to achieve a given effect
Tolerance develops to nearly all side effects except miosis & constipation.
What is the significance of active metabolites in opioid metabolism?
They may require dose adjustments in patients with impaired clearance mechanisms
Active metabolites can lead to increased effects or side effects.
What is the primary metabolic pathway for remifentanil?
Hydrolyzed in the plasma by erythrocyte & tissue esterase
It is highly lipophilic with a rapid rate of clearance.
What unique properties does methadone possess?
- Mu receptor agonist
- NMDA receptor antagonist
- Inhibits reuptake of monoamines
Useful in chronic treatment of opioid abuse and pain syndromes.
What defines a partial opioid agonist?
Can never achieve the same intensity of effect as a full agonist
They have a ceiling effect for analgesia.
What is naloxone and its primary use?
Prototype opioid antagonist that competitively antagonizes opioid receptors
It has the greatest affinity at the mu receptor.
What is the gold standard method of postoperative opioid delivery?
IV Patient Controlled Analgesia (PCA)
It offers better postoperative analgesia and improved patient satisfaction.
