p.3
Mechanism of Action of Local Anesthetics
What is the primary action of local anesthetics on sodium channels?
They bind to specific receptors and block permeability to sodium ions.
p.9
Conceptual Definition of Epilepsy
What is required for a diagnosis of epilepsy?
The occurrence of at least one epileptic seizure.
p.7
Toxicity and Side Effects of Local Anesthetics
Which local anesthetics have negligible incidence of TNS?
Bupivacaine, prilocaine, and chloroprocaine.
p.11
Mechanism of Action of Local Anesthetics
What is the mechanism of action for anti-seizure drugs targeting presynaptic excitability?
They target neurotransmitter release.
p.13
Clinical Applications of Local Anesthetics
What are the clinical uses of Vigabatrin?
Partial seizures and WEST syndrome.
p.3
Mechanism of Action of Local Anesthetics
What theory explains how local anesthetics bind to sodium channels?
Specific Receptor Theory.
p.11
Pharmacokinetics of Local Anesthetics
What is the absorption rate of most anti-seizure drugs (AEDs)?
80-100% reaching circulation.
p.1
Pharmacokinetics of Local Anesthetics
How does potency correlate with local anesthetics?
Potency correlates with lipid solubility.
p.10
Classification of Local Anesthetics: Amides vs Esters
What are some types of generalized seizures?
Atonic, clonic, myoclonic, tonic, tonic-clonic, and epileptic spasms.
p.9
Conceptual Definition of Epilepsy
What characterizes epilepsy?
An enduring predisposition to generate epileptic seizures and the neurobiologic, cognitive, psychological, and social consequences of this condition.
p.3
Mechanism of Action of Local Anesthetics
What additional receptors do local anesthetics block?
Calcium, potassium, and NMDA receptors.
p.12
Classification of Seizure Types
What characterizes epilepsy?
A chronic disorder characterized by repeated seizures.
p.9
International Classification of Seizures
What are the types of partial seizures?
Simple, complex, and secondarily generalized seizures.
p.11
Mechanism of Action of Local Anesthetics
What is the mechanism of action of Phenytoin?
It alters Na, K, and Ca conductance and affects neurotransmitter concentrations.
p.2
Factors Affecting Local Anesthetic Efficacy
What factors influence the potency of local anesthetics?
Hydrogen ion balance, fiber size, type and myelination, vasodilator/vasoconstrictor properties, frequency of nerve stimulation, pH, and electrolyte concentration.
p.15
Pharmacokinetics of Local Anesthetics
When does the maximum plasma concentration occur after oral dosing of anti-seizure drugs?
1-4 hours after oral dosing.
p.10
Classification of Local Anesthetics: Amides vs Esters
What are some new focal seizure types?
Atonic, automatisms, clonic, hyperkinetic, myoclonic, tonic, and behavior arrest.
p.12
Classification of Seizure Types
What is a simple partial seizure?
A seizure where consciousness is preserved, such as jerking of a hand.
p.7
Commonly Used Local Anesthetics and Their Properties
What is the primary clinical use of cocaine?
Topical anesthesia for ear, nose, and throat procedures.
p.8
Toxicity and Side Effects of Local Anesthetics
What is the risk associated with prilocaine?
Prilocaine can induce methemoglobinemia due to the accumulation of ortho-toluidine.
p.7
Toxicity and Side Effects of Local Anesthetics
What are the consequences of membrane damage caused by local anesthetics?
Enzyme leakage, cytoskeletal disruption, accumulation of intracellular calcium, disruption of axonal transport, growth cone collapse, and apoptosis.
p.5
Pharmacokinetics of Local Anesthetics
What is the effect of strong plasma protein binding on local anesthetics?
It tends to retain anesthetic in the blood.
p.5
Pharmacokinetics of Local Anesthetics
How does high lipid solubility affect local anesthetics?
It facilitates tissue uptake.
p.7
Clinical Applications of Local Anesthetics
Why has lidocaine seen a decline in use as a spinal anesthetic?
Due to a high incidence of TNS leading to dissatisfaction.
p.7
Commonly Used Local Anesthetics and Their Properties
What is the primary use of chloroprocaine?
As an alternative to lidocaine for short-duration spinal anesthesia.
p.7
Clinical Applications of Local Anesthetics
What is a key characteristic of chloroprocaine in obstetrical anesthesia?
Its rapid hydrolysis minimizes the risk of systemic toxicity or fetal exposure.
p.1
Toxicity and Side Effects of Local Anesthetics
What is the site of premonitory signs of overdose from local anesthetics?
The central nervous system (CNS).
p.6
Toxicity and Side Effects of Local Anesthetics
What is a feared complication of local anesthetic administration related to the cardiovascular system?
Reduced myocardial contractile function and prolonged intracardiac function.
p.6
Toxicity and Side Effects of Local Anesthetics
How do local anesthetics affect the respiratory system?
They can depress hypoxic drive and cause apnea due to nerve paralysis.
p.12
Basic Pharmacology of AEDs
Name some anti-seizure drugs with different structures.
Carbamazepine, benzodiazepines, levetiracetam, and pregabalin.
p.14
Mechanism of Action of Local Anesthetics
What is the mechanism of action of lacosamide?
Enhances slow inactivation of voltage-gated sodium channels.
p.4
Pharmacokinetics of Local Anesthetics
How does tissue binding affect the absorption of local anesthetics?
Highly tissue-bound anesthetics are absorbed more slowly.
p.7
Toxicity and Side Effects of Local Anesthetics
What is Transient Neurologic Symptoms (TNS) and its incidence with lidocaine?
TNS occurs at modest doses of anesthetic and has been documented in as many as 1/3 of patients receiving lidocaine.
p.10
Classification of Local Anesthetics: Amides vs Esters
What is a characteristic of focal onset seizures?
They can involve awareness and may not always lead to loss of consciousness.
p.12
Important Causes of Seizures
What are the most common causes of seizures in children?
Idiopathic causes, birth and neonatal injuries, congenital or metabolic disorders, infections, and neoplasia.
p.8
Toxicity and Side Effects of Local Anesthetics
What advantage does levobupivacaine have over ropivacaine according to recent studies?
Levobupivacaine is more effectively sequestered into a lipid sink, implying greater ability to reverse toxic effects.
p.9
Key Seizure Signs & Symptoms
What are the signs and symptoms of seizures?
Varies by seizure type, including loss of consciousness, abnormal sensations, and motor activity.
p.2
Commonly Used Local Anesthetics and Their Properties
Which local anesthetic has the highest potency and lipid solubility?
Bupivacaine and Levobupivacaine.
p.13
Mechanism of Action of Local Anesthetics
What is the mechanism of action of Levetiracetam?
Binds to synaptic vesicular protein SV2A, modifying GABA and glutamate release.
p.6
Toxicity and Side Effects of Local Anesthetics
What medications can provide prophylaxis against local anesthetic-induced CNS toxicity?
Parenteral benzodiazepines like Diazepam or Midazolam.
p.14
Pharmacokinetics of Local Anesthetics
What is the primary route of elimination for tiagabine?
Primarily by feces (60-65%).
p.5
Toxicity and Side Effects of Local Anesthetics
What is a potential risk when using lidocaine with cimetidine or propranolol?
Decreased hepatic blood flow, increasing the risk of toxicity.
p.1
Mechanism of Action of Local Anesthetics
What do local anesthetics primarily block?
Voltage gated sodium channels.
p.13
Mechanism of Action of Local Anesthetics
What is the mechanism of action of Vigabatrin?
Irreversible inhibitor of GABA aminotransferase (GABA-T), responsible for GABA degradation.
p.5
Biotransformation and Excretion of Local Anesthetics
How are esters metabolized?
Through hydrolysis by plasma cholinesterase or butyrylcholinesterase.
p.13
Pharmacokinetics of Local Anesthetics
What is the half-life of Lamotrigine?
24 hours, but lowers to 13-25 hours with enzyme inducing drugs.
p.9
Seizure Classification
What is the criteria for resolving epilepsy?
Individuals who had an age-dependent epilepsy syndrome but are now past the applicable age or have remained seizure-free for the last 10 years without seizure medicines for the last 5 years.
p.8
Commonly Used Local Anesthetics and Their Properties
What is lidocaine known for in the context of local anesthetics?
Lidocaine is the reference standard against which most anesthetics are compared.
p.11
Mechanism of Action of Local Anesthetics
What is the mechanism of action of Phenobarbital?
Enhances GABA receptor mediated current and blocks excitatory responses.
p.12
Classification of Seizure Types
What characterizes a complex partial seizure?
Involves the limbic system and presents with automatisms like lip smacking.
p.5
Factors Affecting Local Anesthetic Efficacy
How do vasoconstrictors affect local anesthetic activity?
They can enhance the duration and efficacy of the anesthetic.
p.4
Drug Interactions with Local Anesthetics
What role do vasoconstrictors play in local anesthesia?
They prolong analgesia by causing vasoconstriction at the injection site.
p.3
Factors Affecting Local Anesthetic Efficacy
What factors determine sensitivity to local anesthetic blocks?
Axonal diameter, degree of myelination, and other anatomical and physiological factors.
p.10
Classification of Local Anesthetics: Amides vs Esters
What is a characteristic of generalized onset seizures?
They typically involve loss or impairment of consciousness.
p.7
Toxicity and Side Effects of Local Anesthetics
What is a significant disadvantage of benzocaine?
It has the potential to induce methemoglobinemia.
p.2
Mechanism of Action of Local Anesthetics
What is the significance of lipophilic-hydrophobic balance in local anesthetics?
It affects potency, duration, and onset of action.
p.15
Pharmacokinetics of Local Anesthetics
How does food affect the absorption of anti-seizure drugs?
Food does not affect the rate and extent of absorption.
p.10
Classification of Local Anesthetics: Amides vs Esters
What are some new generalized seizure types?
Absence with eyelid myoclonia, myoclonic-atonic, and myoclonic-tonic-clonic.
p.6
Toxicity and Side Effects of Local Anesthetics
What are some signs of central nervous system toxicity from local anesthetics?
Lightheadedness, tinnitus, visual disturbance, slurring of speech, muscle twitching, irrational conversation, unconsciousness, grand mal convulsion, coma, and death.
p.4
Patient-Related Factors Influencing Anesthetic Activity
What patient-related factors influence local anesthetic efficacy?
Age, cardiovascular status, and hepatic function.
p.4
Pharmacokinetics of Local Anesthetics
How does the site of injection affect systemic absorption of local anesthetics?
It influences the rate and extent of absorption into the bloodstream.
p.13
Mechanism of Action of Local Anesthetics
What is the mechanism of action of Ethosuximide?
Reduces low-threshold (T-type) calcium current in thalamic neurons.
p.14
Pharmacokinetics of Local Anesthetics
How is perampanel absorbed in the body?
Rapidly absorbed from the GI tract with close to 100% oral bioavailability.
p.6
Toxicity and Side Effects of Local Anesthetics
What is the myotoxic effect of local anesthetics?
They can cause myofibril hypercontraction, degeneration, edema, and necrosis.
What is the difference between a seizure and epilepsy?
A seizure is an event, while epilepsy is a disease associated with spontaneously recurring seizures.
p.12
Classification of Seizure Types
What is a seizure?
Finite episodes of brain dysfunction resulting from abnormal discharge of cerebral neurons.
p.8
Clinical Applications of Local Anesthetics
What is a limitation of local anesthetics in terms of block characteristics?
They have poor block characteristics and may produce an inverse differential block.
p.1
Factors Affecting Local Anesthetic Efficacy
What factors influence the onset of action of local anesthetics?
Many factors, including the site of injection and the specific anesthetic used.
p.12
Important Causes of Seizures
What are the most common causes of seizures in adults?
Idiopathic causes, vascular lesions, head trauma, neoplasia, infections, metabolic issues, and heredity.
p.1
Clinical Applications of Local Anesthetics
Where are local anesthetics typically injected or applied?
Very close to their intended site of action.
p.13
Mechanism of Action of Local Anesthetics
What is the mechanism of action of Gabapentin and Pregabalin?
They bind to the alpha2delta subunit of voltage-gated calcium channels, modifying GABA release.
p.6
Toxicity and Side Effects of Local Anesthetics
What is an early symptom of systemic toxicity from local anesthetics?
Numbness of the tongue (metallic taste).
p.14
Mechanism of Action of Local Anesthetics
What is the mechanism of action of tiagabine?
Inhibitor of GABA intake in neurons and glia.
p.15
Mechanism of Action of Local Anesthetics
What is the mechanism of action of benzodiazepines in seizure management?
Potentiates GABAergic inhibition at all levels of the neuroaxis.
p.9
Seizure Classification
What defines epilepsy according to the ILAE 2017 classification?
At least two unprovoked seizures occurring >24 hours apart, one unprovoked seizure with a probability of further seizures, or a diagnosis of an epilepsy syndrome.
p.7
Patient-Related Factors Influencing Anesthetic Activity
Which patient positions increase the risk of TNS during surgery?
Certain positions such as lithotomy.
p.9
International Classification of Seizures
What are the two main categories of seizures in the 1981 classification?
Partial seizures and generalized seizures.
p.15
Pharmacokinetics of Local Anesthetics
What is the absorption characteristic of anti-seizure drugs after oral intake?
Completely absorbed after oral intake.
p.13
Toxicity and Side Effects of Local Anesthetics
What adverse reactions are associated with Lamotrigine?
Dizziness, headache, diplopia, nausea, somnolence, and life-threatening dermatitis.
p.5
Toxicity and Side Effects of Local Anesthetics
What is the treatment for methemoglobinemia?
IV administration of methylene blue.
p.8
Patient-Related Factors Influencing Anesthetic Activity
Why is mepivacaine considered a poor choice for epidural anesthesia in parturients?
It is slowly metabolized by the fetus.
p.11
Pharmacokinetics of Local Anesthetics
What is the loading dose for Phenytoin?
10-20 mg/kg given orally and IV.
p.15
Toxicity and Side Effects of Local Anesthetics
What are some side effects reported for anti-seizure drugs?
Agranulocytosis, hallucinations, agitation, SJS, TEN, rash, insomnia.
p.1
History and Development of Local Anesthetics
What is the historical significance of cocaine in local anesthetics?
Cocaine was first used in 1860 as a local anesthetic.
p.15
Mechanism of Action of Local Anesthetics
What is the mechanism of action of acetazolamide?
Inhibits carbonic anhydrase, making the brain acidic, leading to antiseizure activity.
p.6
Toxicity and Side Effects of Local Anesthetics
How does lidocaine affect coagulation?
It decreases coagulation, preventing thrombosis and decreasing platelet aggregation.
p.9
International Classification of Seizures
What types of generalized seizures are recognized?
Absence, tonic-clonic, atonic, myoclonic, and other types.
p.10
Classification of Local Anesthetics: Amides vs Esters
What are the elements of consciousness affected during seizures?
Awareness, memory for time, responsiveness to stimuli, and sense of self.
p.5
Toxicity and Side Effects of Local Anesthetics
What can cause methemoglobinemia when using local anesthetics?
Prilocaine and Benzocaine, especially in high doses.
p.8
Pharmacokinetics of Local Anesthetics
What is a notable characteristic of mepivacaine compared to other local anesthetics?
Mepivacaine tends to cause vasoconstriction rather than vasodilation.
p.11
Pharmacokinetics of Local Anesthetics
How is Phenobarbital excreted from the body?
Unchanged in urine (20-30%).
p.10
Classification of Local Anesthetics: Amides vs Esters
What is a new combined seizure type?
Focal to bilateral tonic-clonic.
p.12
Classification of Seizure Types
What is a generalized tonic-clonic seizure?
Also known as grand mal, it often involves incontinence.
p.6
Toxicity and Side Effects of Local Anesthetics
Which local anesthetic is more likely to cause allergic reactions?
Esters, due to their derivative of PABA.
p.8
Toxicity and Side Effects of Local Anesthetics
How does levobupivacaine compare to bupivacaine in terms of cardiotoxicity?
Levobupivacaine is somewhat less cardiotoxic than the racemic mixture of bupivacaine.
p.1
Pharmacokinetics of Local Anesthetics
How is the duration of action of local anesthetics correlated?
It is correlated with lipid solubility.
p.7
Clinical Applications of Local Anesthetics
What is bupivacaine commonly used for?
Prolonged peripheral anesthesia and analgesia for postoperative pain control.
p.4
Pharmacokinetics of Local Anesthetics
What factors determine the pharmacokinetics of local anesthetics?
Amount injected, absorption rate, site of injection, rate of tissue distribution, rate of biotransformation, and excretion rate.
p.15
Clinical Applications of Local Anesthetics
What is the recommended dose for partial onset seizure monotherapy?
100 mg twice a day, increasing by 50 mg per week to a maintenance dose of 300-400 mg a day.
p.1
Toxicity and Side Effects of Local Anesthetics
What is a major cardiovascular toxicity concern with local anesthetics?
It requires about three times the concentration in the blood.
p.12
Classification of Seizure Types
What is the EEG pattern associated with absence seizures?
A 3 hertz/sec spike and wave pattern.
p.12
Basic Pharmacology of AEDs
What are hydantoin derivatives?
A class of anti-seizure drugs including barbiturates, oxazolidinediones, and succinamides.
p.4
Pharmacokinetics of Local Anesthetics
Which organs are highly perfused and affect the alpha phase of local anesthetic distribution?
Brain, lung, liver, kidney, and heart.
p.14
Drug Interactions with Local Anesthetics
How does valproate interact with phenytoin?
It displaces phenytoin from proteins.
p.5
Biotransformation and Excretion of Local Anesthetics
What is the primary site of metabolism for amide local anesthetics?
The liver, using microsomal P-450 enzymes.
p.11
Pharmacokinetics of Local Anesthetics
What is the half-life of Carbamazepine?
36 hours, reduced to 12 hours in continuous therapy.
p.1
Pharmacokinetics of Local Anesthetics
What affects the rate of systemic absorption of local anesthetics?
The vascularity of the site of injection.
p.8
Classification of Local Anesthetics: Amides vs Esters
What is ropivacaine's distinguishing feature compared to bupivacaine and mepivacaine?
Ropivacaine is an S(–) enantiomer with reduced cardiotoxicity.
p.8
Commonly Used Local Anesthetics and Their Properties
What is EMLA and what is its composition?
EMLA is a eutectic mixture of local anesthetics, specifically 2.5% lidocaine and 2.5% prilocaine.
p.8
Clinical Applications of Local Anesthetics
What is a common use for EMLA in pediatrics?
It is used to anesthetize the skin prior to venipuncture for intravenous catheter placement.
p.4
Pharmacokinetics of Local Anesthetics
What are the two phases of distribution for local anesthetics?
Alpha phase and beta phase.
p.11
Drug Interactions with Local Anesthetics
What drug interactions does Carbamazepine have?
Increases metabolism of Phenytoin, Ethosuximide, Valproic acid, and Clonazepam.
p.2
Factors Affecting Local Anesthetic Efficacy
How does hydrogen ion concentration affect local anesthetics?
It influences their potency and effectiveness.
p.2
Pharmacokinetics of Local Anesthetics
What is the relationship between protein binding and duration of action in local anesthetics?
Higher protein binding generally correlates with longer duration of action.
p.13
Mechanism of Action of Local Anesthetics
What is the mechanism of action of Valproic Acid?
Inhibits Na channels and has an inhibitory effect on GABA transporter GAT-1 and GABA transaminase.
p.15
Clinical Applications of Local Anesthetics
What can happen if anti-seizure drugs are withdrawn abruptly?
Can cause status epilepticus.
p.4
Drug Interactions with Local Anesthetics
What is the effect of epinephrine when added to local anesthetics?
It activates α2-adrenergic receptors to prolong analgesia.
p.15
Toxicity and Side Effects of Local Anesthetics
What is the teratogenic risk associated with anti-seizure drugs?
4-6% of fetuses exposed to AEDs may have major malformations compared to 2-3% in the general population.
p.6
Toxicity and Side Effects of Local Anesthetics
What is Cauda equina syndrome associated with?
Continuous spinal anesthesia (CSA) involving repetitive dosing in the subarachnoid space.
p.1
Chemistry of Local Anesthetics
What form do local anesthetics exist in the body?
As charged base or as a cation.
p.4
Pharmacokinetics of Local Anesthetics
What is the significance of the tissue/blood partition coefficient in local anesthetics?
It affects the distribution and absorption of the anesthetic in different tissues.
