Neuroscience of Seizures and Treatment

Action Potentials and Seizures

• Sodium (Na+) channels are crucial for action potentials. Slowing Na+ channels slows action potential transmission and can suppress seizures.
• Calcium (Ca+) channels are implicated in absence seizures. Blocking Ca+ channels in the hypothalamus can prevent these seizures.

Antiepileptic Drugs (AEDs)

• AEDs can have adverse effects, including increased suicidal thoughts, fetal abnormalities, and dermatological reactions like rashes and Stevens-Johnson syndrome.

Types of Seizures

• Focal onset seizures stay confined to one hemisphere of the brain. Impaired awareness can occur, but isn't always present.
• Generalized onset seizures are more problematic as they originate in core brain areas (thalamus or brainstem) and spread.
• Absence seizures are characterized by brief lapses of awareness (seconds) without loss of posture. They are common in childhood, typically resolving by adulthood.
• Tonic-clonic seizures involve muscle stiffness and rhythmic jerking.
• Atonic seizures involve rapid loss of muscle tone.
• Myoclonic seizures involve sudden, brief muscle contractions.

Seizure Characteristics

• Seizures are not typically life-threatening.
• The brain usually stops a seizure.
• Breathing may stop for seconds during a seizure.
• Patients do not feel pain during seizures.
• Post-seizure effects can include altered behavior.
• Seizures involve irregular electrical activity in the brain.
• Localized seizures involve high-rate firing in one hemisphere.
• Generalized seizures involve irregular firing throughout the brain.

Seizure Treatment

• Treatment aims to identify and address the cause and control seizures.
• AEDs suppress seizure frequency, not cure them.
• Therapy supports seizure management and prevention.

Specific AEDs and Mechanisms of Action

• Phenytoin: Na+ channel inhibitor, slows repetitive firing, treats tonic-clonic and focal onset seizures. Adverse effects include gingival hyperplasia and drug metabolism interaction.
• Carbamazepine: Na+ channel inhibitor, slows neuron firing; treats focal, focal bilateral, and tonic-clonic seizures. Adverse effects include hyponatremia, dermatological toxicity (Stevens-Johnson syndrome), and drug interactions.
• Oxcarbazepine: Similar to carbamazepine, primarily for focal seizures, has a slightly reduced risk of drug interactions. Adverse effect risk increased for hyponatremia.
• Lamotrigine: Na+ channel inhibitor, effective for focal, generalized, and tonic-clonic seizures. Adverse effects include suicidal ideation and Stevens-Johnson syndrome.
• Levetiracetam: Mechanism unknown, used for various seizure types (focal, tonic-clonic, generalized, and myoclonic). Adverse effects include mood and behavior changes.
• Valproic acid: Na+ and Ca+ channel blocker, GABA synthesis stimulant; treats generalized, tonic-clonic, and myoclonic seizures. Potential adverse effects include toxicity, hepatotoxicity, pancreatitis, and potential pregnancy and drug interaction concerns.
• Ethosuximide: Ca+ channel inhibitor; first-line treatment for absence seizures. Relatively well-tolerated.
• Gabapentin: Ca+ and K+ channel blocker; used for focal and tonic seizures, neuropathic pain, and migraine.
• Pregabalin: Similar to Gabapentin, potentially greater adverse effect risk. (weight gain, xerostomia)

Benzodiazepines

• Positive allosteric modulators of GABA receptors and can be used in status epilepticus.
• Adverse effects include sedation, anesthesia, lethargy, behavioral changes, GI upset, and increased risk of status epilepticus during sudden withdrawal.
• Includes PAMs for status epilepticus management.

Local Anesthetics

• Classified as amino esters and amino amides based on their chemical structure and metabolism in the body.
• Local anesthetics work by blocking pain perception, have high affinity for areas with high pain stimuli.
• Important factors include water solubility for injection, becoming lipophilic for membrane crossing, and the need for vasoconstriction (often with epinephrine) to limit systemic absorption.
• Some specific examples include: Cocaine, Procaine, Chloroprocaine, Benzocaine, Tetracaine, Lidocaine, Mepivacaine, Bupivacaine, Ropivacaine.
• Their use is directly related to the desired outcome in terms of onset, duration, systemic toxicity and the route of administration. pH can also play a role in drug concentration.

Other CNS Stimulants

• Malignant Hyperthermia: Characterized by a dangerously high body temperature. Treatment includes dantrolene.
• Proprofol, Etomidate: General anesthetics with different properties; Propophol is a GABA receptor modulator (increasing sensitivity), while etomidate is selected for use in hypertensive patients.
• Methylxanthines (caffeine, chocolate, tea): Block phosphodiesterase (increasing cAMP), block adenosine; used to treat airflow obstruction, bradycardia, and acute cardiac decompensation.
• Amphetamines, Lisdexamfetamine, Methamphetamine, Methylphenidate (Ritalin), Atomoxetine: Used to treat ADHD, narcolepsy, and obesity. Amphetamines are reuptake blockers of NE and dopamine.
• Ephedrine: Mixed-acting monoamine release; stimulates presynaptic NE release, used in anesthesia-induced hypertension, cardiogenic shock, and nasal congestion.
• Modafinil: With an unknown mechanism, used to treat narcolepsy and sleep apnea.

CNS Stimulant Dependence

• CNS stimulant dependence includes extensive psychological dependence and is a scheduled drug.
• Physical withdrawal is often mild.

CNS Stimulant Adverse Effects

• Common adverse effects include headaches, dizziness, tremors, irritability, insomnia, and appetite suppression.
• These can lead to weight loss, stunted growth in children/adolescents, and xerostomia (dry mouth), which can increase risk of tooth decay.
• Cardiovascular effects include palpitations, chills, and potential arrhythmias, chest pain, and increased HR/BP at high doses.
• Drug holidays can help with adverse effects regarding appetite.

This quiz explores the mechanisms of action potentials and the role of antiepileptic drugs (AEDs) in managing seizures. It also covers different types of seizures, including focal, generalized, absence, and tonic-clonic seizures. Dive into the critical aspects of neurological function and therapeutic interventions.