What is the pKa of Chloroprocaine?
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9.0
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What is the pKa of Chloroprocaine?
9.0
Which local anesthetic has the highest potency?
Tetracaine (Pontocaine)
What theory explains how local anesthetics bind to sodium channels?
Specific Receptor Theory.
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.
What is the primary action of local anesthetics on sodium channels?
They bind to specific receptors and block permeability to sodium ions.
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.
What is the difference between a seizure and epilepsy?
A seizure is an event, while epilepsy is a disease associated with spontaneously recurring seizures.
Which subunits of sodium channels do most local anesthetics bind to?
Alpha subunits.
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.
What characterizes epilepsy?
An enduring predisposition to generate epileptic seizures and the neurobiologic, cognitive, psychological, and social consequences of this condition.
What factors determine sensitivity to local anesthetic blocks?
Axonal diameter, degree of myelination, and other anatomical and physiological factors.
What are the two main types of seizure onset?
Focal and generalized.
What is the absorption rate of most anti-seizure drugs (AEDs)?
80-100% reaching circulation.
Which patient positions increase the risk of TNS during surgery?
Certain positions such as lithotomy.
What is required for a diagnosis of epilepsy?
The occurrence of at least one epileptic seizure.
What is the effect of strong plasma protein binding on local anesthetics?
It tends to retain anesthetic in the blood.
What is a seizure?
Finite episodes of brain dysfunction resulting from abnormal discharge of cerebral neurons.
What additional receptors do local anesthetics block?
Calcium, potassium, and NMDA receptors.
What is a characteristic of focal onset seizures?
They can involve awareness and may not always lead to loss of consciousness.
What is the therapeutic level range for anti-seizure drugs?
10-40 mcg/ml.
What do local anesthetics primarily block?
Voltage gated sodium channels.
How are most anti-seizure drugs cleared from the body?
Chiefly by the liver.
Which local anesthetics have negligible incidence of TNS?
Bupivacaine, prilocaine, and chloroprocaine.
What are the two main categories of seizures in the 1981 classification?
Partial seizures and generalized seizures.
How does high lipid solubility affect local anesthetics?
It facilitates tissue uptake.
What characterizes epilepsy?
A chronic disorder characterized by repeated seizures.
What are the therapeutic levels for valproate?
50-100 mcg/ml.
What is the pKa of Procaine?
8.9
What is a characteristic of generalized onset seizures?
They typically involve loss or impairment of consciousness.
What is the mechanism of action of Vigabatrin?
Irreversible inhibitor of GABA aminotransferase (GABA-T), responsible for GABA degradation.
How does potency correlate with local anesthetics?
Potency correlates with lipid solubility.
What is the mechanism of action for anti-seizure drugs targeting presynaptic excitability?
They target neurotransmitter release.
Which tissue serves as the greatest reservoir for local anesthetic agents?
Muscle.
Why has lidocaine seen a decline in use as a spinal anesthetic?
Due to a high incidence of TNS leading to dissatisfaction.
What is a limitation of local anesthetics in terms of block characteristics?
They have poor block characteristics and may produce an inverse differential block.
What are the types of partial seizures?
Simple, complex, and secondarily generalized seizures.
What are the most common causes of seizures in children?
Idiopathic causes, birth and neonatal injuries, congenital or metabolic disorders, infections, and neoplasia.
What is the typical dosage range for valproate?
25-60 mg/kg/d.
Which local anesthetic has a pKa of 8.7?
Cocaine.
What are some types of generalized seizures?
Atonic, clonic, myoclonic, tonic, tonic-clonic, and epileptic spasms.
What are the clinical uses of Vigabatrin?
Partial seizures and WEST syndrome.
What factors influence the onset of action of local anesthetics?
Many factors, including the site of injection and the specific anesthetic used.
What is the mechanism of action of Phenytoin?
It alters Na, K, and Ca conductance and affects neurotransmitter concentrations.
What are the two main classifications of local anesthetics?
Amides and Esters.
How are esters metabolized?
Through hydrolysis by plasma cholinesterase or butyrylcholinesterase.
What types of generalized seizures are recognized?
Absence, tonic-clonic, atonic, myoclonic, and other types.
What is the primary use of chloroprocaine?
As an alternative to lidocaine for short-duration spinal anesthesia.
How does levobupivacaine compare to bupivacaine in terms of cardiotoxicity?
Levobupivacaine is somewhat less cardiotoxic than the racemic mixture of bupivacaine.
What are the most common causes of seizures in adults?
Idiopathic causes, vascular lesions, head trauma, neoplasia, infections, metabolic issues, and heredity.
How does valproate interact with phenytoin?
It displaces phenytoin from proteins.
What is the half-life of Lamotrigine?
24 hours, but lowers to 13-25 hours with enzyme inducing drugs.
What are the elements of consciousness affected during seizures?
Awareness, memory for time, responsiveness to stimuli, and sense of self.
What is the absorption characteristic of anti-seizure drugs after oral intake?
Completely absorbed after oral intake.
How is the duration of action of local anesthetics correlated?
It is correlated with lipid solubility.
What is the therapeutic plasma level range for Phenytoin?
10-20 mcg/ml.
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.
What is the primary site of metabolism for amide local anesthetics?
The liver, using microsomal P-450 enzymes.
What is a significant disadvantage of benzocaine?
It has the potential to induce methemoglobinemia.
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.
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.
What type of seizure is limited to one area of the brain?
Partial seizure.
What is the mechanism of action of primidone?
Similar to phenytoin.
What adverse reactions are associated with Lamotrigine?
Dizziness, headache, diplopia, nausea, somnolence, and life-threatening dermatitis.
What is the best surrogate marker for seizure classification according to the 2017 Classification?
Awareness.
Where are local anesthetics typically injected or applied?
Very close to their intended site of action.
When does the maximum plasma concentration occur after oral dosing of anti-seizure drugs?
1-4 hours after oral dosing.
What is the half-life of Carbamazepine?
36 hours, reduced to 12 hours in continuous therapy.
What is the significance of lipophilic-hydrophobic balance in local anesthetics?
It affects potency, duration, and onset of action.
What is lidocaine known for in the context of local anesthetics?
Lidocaine is the reference standard against which most anesthetics are compared.
What are the signs and symptoms of seizures?
Varies by seizure type, including loss of consciousness, abnormal sensations, and motor activity.
What can cause methemoglobinemia when using local anesthetics?
Prilocaine and Benzocaine, especially in high doses.
What is the half-life of primidone?
6-8 hours.
What type of seizure affects the whole brain?
Generalized seizure.
What is bupivacaine commonly used for?
Prolonged peripheral anesthesia and analgesia for postoperative pain control.
What is the mechanism of action of Gabapentin and Pregabalin?
They bind to the alpha2delta subunit of voltage-gated calcium channels, modifying GABA release.
What are some new focal seizure types?
Atonic, automatisms, clonic, hyperkinetic, myoclonic, tonic, and behavior arrest.
What affects the rate of systemic absorption of local anesthetics?
The vascularity of the site of injection.
How does food affect the absorption of anti-seizure drugs?
Food does not affect the rate and extent of absorption.
What is the mechanism of action of Phenobarbital?
Enhances GABA receptor mediated current and blocks excitatory responses.
Which local anesthetic has the highest potency and lipid solubility?
Bupivacaine and Levobupivacaine.
What is a notable characteristic of mepivacaine compared to other local anesthetics?
Mepivacaine tends to cause vasoconstriction rather than vasodilation.
What is a key characteristic of chloroprocaine in obstetrical anesthesia?
Its rapid hydrolysis minimizes the risk of systemic toxicity or fetal exposure.
What is the effective plasma range for felbamate?
30-100 mcg/ml.
What is the treatment for methemoglobinemia?
IV administration of methylene blue.
What is an early symptom of systemic toxicity from local anesthetics?
Numbness of the tongue (metallic taste).
What is a simple partial seizure?
A seizure where consciousness is preserved, such as jerking of a hand.
What is the half-life of Pregabalin?
4.5-7 hours.
What are some new generalized seizure types?
Absence with eyelid myoclonia, myoclonic-atonic, and myoclonic-tonic-clonic.
How are ester local anesthetics predominantly metabolized?
By pseudocholinesterase.
What is the half-life (T1/2) of anti-seizure drugs?
13 hours.
How is Phenobarbital excreted from the body?
Unchanged in urine (20-30%).
What is the pKa of Bupivacaine?
8.1.
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.
Why is mepivacaine considered a poor choice for epidural anesthesia in parturients?
It is slowly metabolized by the fetus.
What is the mechanism of action of tiagabine?
Inhibitor of GABA intake in neurons and glia.
What is the primary clinical use of cocaine?
Topical anesthesia for ear, nose, and throat procedures.
What factors can affect the pharmacokinetics of local anesthetics?
Age and disease process.
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.
What characterizes a complex partial seizure?
Involves the limbic system and presents with automatisms like lip smacking.
What is the mechanism of action of Levetiracetam?
Binds to synaptic vesicular protein SV2A, modifying GABA and glutamate release.
What is a new combined seizure type?
Focal to bilateral tonic-clonic.
What is the site of premonitory signs of overdose from local anesthetics?
The central nervous system (CNS).
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.
What is the loading dose for Phenytoin?
10-20 mg/kg given orally and IV.
Which ester local anesthetic has the lowest potency?
Chloroprocaine.
What is the risk associated with prilocaine?
Prilocaine can induce methemoglobinemia due to the accumulation of ortho-toluidine.
What is the bioavailability of tiagabine?
90-100%.
What patient-related factors influence local anesthetic efficacy?
Age, cardiovascular status, and hepatic function.
How do vasoconstrictors affect local anesthetic activity?
They can enhance the duration and efficacy of the anesthetic.
What medications can provide prophylaxis against local anesthetic-induced CNS toxicity?
Parenteral benzodiazepines like Diazepam or Midazolam.
What is a generalized tonic-clonic seizure?
Also known as grand mal, it often involves incontinence.
What is the half-life of Topiramate?
1-3 days.
What is a major cardiovascular toxicity concern with local anesthetics?
It requires about three times the concentration in the blood.
What are some side effects reported for anti-seizure drugs?
Agranulocytosis, hallucinations, agitation, SJS, TEN, rash, insomnia.
What is the duration of action for Lidocaine?
Moderate duration.
What drug interactions does Carbamazepine have?
Increases metabolism of Phenytoin, Ethosuximide, Valproic acid, and Clonazepam.
What is ropivacaine's distinguishing feature compared to bupivacaine and mepivacaine?
Ropivacaine is an S(–) enantiomer with reduced cardiotoxicity.
How does the site of injection affect systemic absorption of local anesthetics?
It influences the rate and extent of absorption into the bloodstream.
What medication can potentiate the effects of ester local anesthetics?
Succinylcholine.
What is the primary route of elimination for tiagabine?
Primarily by feces (60-65%).
What is a feared complication of local anesthetic administration related to the cardiovascular system?
Reduced myocardial contractile function and prolonged intracardiac function.
What is the EEG pattern associated with absence seizures?
A 3 hertz/sec spike and wave pattern.
What is the historical significance of cocaine in local anesthetics?
Cocaine was first used in 1860 as a local anesthetic.
What is the mechanism of action of benzodiazepines in seizure management?
Potentiates GABAergic inhibition at all levels of the neuroaxis.
How does hydrogen ion concentration affect local anesthetics?
It influences their potency and effectiveness.
What is EMLA and what is its composition?
EMLA is a eutectic mixture of local anesthetics, specifically 2.5% lidocaine and 2.5% prilocaine.
What is the mechanism of action of Ethosuximide?
Reduces low-threshold (T-type) calcium current in thalamic neurons.
What role do vasoconstrictors play in local anesthesia?
They prolong analgesia by causing vasoconstriction at the injection site.
What is a potential risk when using lidocaine with cimetidine or propranolol?
Decreased hepatic blood flow, increasing the risk of toxicity.
What type of receptor does perampanel antagonize?
AMPA receptor.
How do local anesthetics affect the respiratory system?
They can depress hypoxic drive and cause apnea due to nerve paralysis.
What are hydantoin derivatives?
A class of anti-seizure drugs including barbiturates, oxazolidinediones, and succinamides.
What are the two main chemical structures of local anesthetics?
Ester or amide links.
What is the half-life of benzodiazepines?
20-40 hours.
What is the relationship between protein binding and duration of action in local anesthetics?
Higher protein binding generally correlates with longer duration of action.
What is a common use for EMLA in pediatrics?
It is used to anesthetize the skin prior to venipuncture for intravenous catheter placement.
How is perampanel absorbed in the body?
Rapidly absorbed from the GI tract with close to 100% oral bioavailability.
What is the therapeutic level range for Ethosuximide?
60-100 mcg/ml.
What is the effect of epinephrine when added to local anesthetics?
It activates α2-adrenergic receptors to prolong analgesia.
Which local anesthetic is more likely to cause allergic reactions?
Esters, due to their derivative of PABA.
Name some anti-seizure drugs with different structures.
Carbamazepine, benzodiazepines, levetiracetam, and pregabalin.
What is the pKa range for most local anesthetics?
7.5 to 9.0.
What is the mechanism of action of acetazolamide?
Inhibits carbonic anhydrase, making the brain acidic, leading to antiseizure activity.
What is the binding percentage of perampanel to plasma proteins?
Approximately 95%.
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.
What are the two phases of distribution for local anesthetics?
Alpha phase and beta phase.
What is the myotoxic effect of local anesthetics?
They can cause myofibril hypercontraction, degeneration, edema, and necrosis.
What form do local anesthetics exist in the body?
As charged base or as a cation.
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.
What is the half-life of Valproic Acid?
9-18 hours.
What is the mechanism of action of lacosamide?
Enhances slow inactivation of voltage-gated sodium channels.
Which organs are highly perfused and affect the alpha phase of local anesthetic distribution?
Brain, lung, liver, kidney, and heart.
How does lidocaine affect coagulation?
It decreases coagulation, preventing thrombosis and decreasing platelet aggregation.
What can happen if anti-seizure drugs are withdrawn abruptly?
Can cause status epilepticus.
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.
What is Cauda equina syndrome associated with?
Continuous spinal anesthesia (CSA) involving repetitive dosing in the subarachnoid space.
What is the most dangerous side effect of AED overdose?
Respiratory depression.
How does tissue binding affect the absorption of local anesthetics?
Highly tissue-bound anesthetics are absorbed more slowly.
Which local anesthetic is considered the least toxic?
Lidocaine.
