Epilepsy treatments and Antidysrhythmics

Question 1

What is epilepsy?

Answer 1

Epilepsy is a group of diseases affecting 1-3% of the population, characterized by recurring unprovoked and provoked seizures. Seizures involve hypersynchronous hyperexcitability of neuron groups and are diagnosed by EEG (electroencephalography).

Question 2

What is an EEG, and how does it relate to epilepsy?

Answer 2

Electroencephalography (EEG) records electrical activity between two electrodes, capturing the potential difference between points. It measures the summated activity of neuron groups and is used to diagnose epilepsy.

Question 3

What are the three main types of seizures?

Answer 3

The main seizure types are:
- Focal onset (awareness can be intact or impaired).
- Generalized onset (involves loss of awareness).
- Unknown onset (when the origin isn’t clear).

Question 4

What are the types of generalized seizures?

Answer 4

Generalized seizures include Absence, Tonic-Clonic, Myoclonic, and Atonic seizures, each with distinct appearances based on which neurons are excessively firing.

Question 5

Describe Tonic-Clonic seizures and their characteristics.

Answer 5

Tonic-Clonic seizures involve:
- Tonic phase: muscles stiffen, loss of awareness, possible groaning, stopped breathing (cyanosis), foaming, and loss of bladder control.
- Clonic phase: violent jerking that can last minutes.
Both types may cause injuries, slow recovery, confusion, and drowsiness.

Question 6

What are absence seizures, and how are they treated?

Answer 6

Absence seizures, common in children, cause sudden loss of awareness with retained motor function. They may involve staring or eye fluttering and are associated with T-type calcium channel abnormalities. Treated with valproate (calcium channel blockers).

Question 7

What is the genetic basis of epilepsy?

Answer 7

Over 30% of epilepsy cases have a genetic component, with certain single-gene mutations identified in rare syndromes. Most epilepsies involve multiple genes.

Question 8

Describe focal seizures.

Answer 8

Focal seizures originate from a specific neuron group firing simultaneously. Symptoms depend on the brain area affected (e.g., motor or sensory cortex). Causes include anoxia, infections, trauma, tumors, and flashing lights.

Question 9

What is temporal lobe epilepsy, and how is it treated?

Answer 9

Temporal lobe epilepsy is a focal seizure type originating in the temporal lobe. It often involves strong emotions or dream-like states and is difficult to treat with drugs, leading some patients to opt for surgery.

Question 10

What is status epilepticus?

Answer 10

Status epilepticus is life-threatening, defined as a seizure lasting 5 minutes or more or two or more seizures without recovery between them. It’s a medical emergency with high mortality risk.

Question 11

What are some consequences for patients with epilepsy?

Answer 11

Patients may experience anxiety, depression, social discrimination, lifestyle restrictions (e.g., no driving), limited alcohol, and often require lifelong antiepileptic drug treatment, with fetal risks for women.

Question 12

What is the mechanism of action for antiepileptic drugs (AEDs)?

Answer 12

AEDs work by:
1. Enhancing inhibitory (GABAergic) input.
2. Blocking sodium channels to reduce impulse transmission.
3. Blocking calcium channels to prevent neurotransmitter release.
4. Blocking excitatory (glutamatergic) input.

Question 13

What are the pharmacodynamic properties of classical AEDs?

Answer 13

Classical AEDs have:
- Narrow therapeutic index.
- CNS depression (neurotoxicity) with effects like sleepiness, dizziness, and ataxia.
- Rare but severe hypersensitivity reactions.
- Teratogenic risks (e.g., valproic acid, phenytoin, carbamazepine).
- Long half-lives and potential for drug interactions (e.g., P-450 modulation).
- Poor compliance due to complex dosing.

Question 14

Describe benzodiazepines and their use in epilepsy.

Answer 14

Benzodiazepines are allosteric modulators of GABA𝐴 receptors, increasing GABA action by enhancing the opening probability of the GABA receptor. They are used for status epilepticus and long-term treatment in certain seizure disorders. Side effects include sedation, lethargy, and ataxia.

Question 15

What are barbiturates, specifically phenobarbital, and how are they used in epilepsy?

Answer 15

Phenobarbital is an allosteric modulator of GABA𝐴 receptors, increasing pore opening time. It’s used for neonatal seizures and as a last-resort AED, with side effects like strong sedation and CYP-related interactions.

Question 16

Describe valproic acid/valproate and its mechanism.

Answer 16

Valproic acid treats various focal and generalized epilepsies, including absences. It inhibits GABA breakdown, blocks T-type Ca channels, and Na channels. Highly protein-bound, it also inhibits P-450 enzymes.

Question 17

What are the conformational states of sodium channels, and how do AEDs interact with them?

Answer 17

Sodium channels have closed, open, and inactivated states. AEDs preferentially bind to the inactivated state, inhibiting rapid firing without affecting normal Na channel function.

Question 18

How do calcium channel blockers help in treating epilepsy?

Answer 18

Calcium channel blockers like valproate and ethosuximide target T-type channels for absence seizures, while gabapentin and pregabalin target P/Q-type channels, reducing neurotransmitter release.

Question 19

Summarize the progress with new AEDs.

Answer 19

New AEDs have similar effectiveness as older AEDs, with fewer sedative effects, lower teratogenic risks, and improved pharmacokinetics, with fewer interactions with the cytochrome P-450 system.

Question 20

What is the ketogenic diet, and how does it relate to epilepsy?

Answer 20

The ketogenic diet, effective for certain childhood epilepsy types, is high in fat (80-90% of calories), low in protein, and low in carbohydrates, providing 75-100% of recommended calories through fats.

Question 21

How is heart rhythm controlled?

Answer 21

The pacemaker generates a wave of signals to contract, signals are delayed at the AV node, then pass to the heart apex and spread throughout the ventricles.

Question 22

What is membrane potential, and what ions contribute to it?

Answer 22

Membrane potential depends on ion distribution and open channels.

Intracellular: Na+ (12 mmol/l), K+ (150 mmol/l), Ca2+ (0.1 µmol/l), Cl- (5 mmol/l)

Extracellular: Na+ (145 mmol/l), K+ (2.4 mmol/l), Ca2+ (2 mmol/l), Cl- (125 mmol/l)

Question 23

What are pacemaker cells, and how do they differ by heart location?

Answer 23

Pacemaker cells in different heart areas fire at different rates:

• SA node: 70-80 ap/min
• AV node: 40-60 ap/min
• Purkinje fibers: 20-40 ap/min
• Non-SA node pacemaker cells are latent pacemakers.

Question 24

What is the effect of beta and muscarinic receptors on the heart?

Answer 24

Beta receptors: Activated by adrenaline/noradrenaline, increasing cAMP and calcium influx, leading to an increased heart rate.

Muscarinic receptors: Activated by acetylcholine, blocking cAMP formation, which decreases heart rate.

Question 25

How does an ectopic focus lead to tachycardia?

Answer 25

An ectopic focus, encouraged by sympathetic activity and partial depolarization, increases depolarization rate during phase 4 due to beta1-adrenoceptor activation, leading to tachycardia.

Question 26

What are re-entrant circuits, and how do they form?

Answer 26

Re-entrant circuits cause clinical arrhythmias by depolarizing in a continuous loop. Conditions for formation include:

• An area of unidirectional block.
• An alternate conduction pathway around the block.
• Conduction time through the alternate pathway must exceed the refractory period of adjacent tissue.

Question 27

What are afterdepolarizations, and what can they cause?

Answer 27

Afterdepolarizations, often due to high intracellular calcium, can lead to cardiac arrhythmias.

Question 28

What is heart block?

Answer 28

Heart block occurs from damage to the conducting system, ranging from slowed conduction (long PR interval) to complete block. Artificial pacemakers may be used for treatment.

Question 29

What is bradyarrhythmia?

Answer 29

Bradyarrhythmia includes heart block and asystolic arrest, with a heart rate <60 BPM (100 BPM for infants). Symptoms include fatigue, dizziness, and fainting due to cerebral hypoperfusion.

Question 30

Describe the Vaughn Williams classification of anti-dysrhythmic drugs.

Answer 30

Class I: Na+ channel blockers (use-dependent).
Class II: β-adrenoceptor antagonists.
Class III: Drugs prolonging the cardiac action potential.
Class IV: Calcium channel antagonists.

Question 31

What are the functional states of Na+ channels?

Answer 31

Na+ channels exist in resting, activated, and refractory states. They rapidly switch from resting to activated during depolarization, and maintained depolarization moves them to refractory. Membrane repolarization restores channels to resting.

Question 32

What are Class I Na+ channel blockers?

Answer 32

Class I Na+ channel blockers (e.g., lidocaine) preferentially block frequently activated Na+ channels, slowing conduction velocity and treating ventricular and atrial tachyarrhythmias. Side effects include bradycardia and potential worsening of arrhythmias.

Question 33

What are Class II β-adrenoceptor antagonists, and how do they work?

Answer 33

β-blockers reduce calcium influx, slowing pacemaker potentials at the SA and AV nodes. They reduce the probability of funny Na+ channels opening. Side effects include bradycardia, bronchospasm, and hypotension.

Question 34

What is Ivabradine (Coralan) used for, and how does it function?

Answer 34

Ivabradine is a cardiotonic agent used to manage angina and chronic heart failure by affecting pacemaker cells without impacting contractile cells.

Question 35

What are Class III drugs, and how do they affect the action potential?

Answer 35

Class III drugs prolong the action potential, increasing Na+ channel refractory periods to prevent reentrant tachycardia and ectopic activity. Side effects include potential worsening of dysrhythmias.

Question 36

What is the mechanism of Class IV calcium channel antagonists?

Answer 36

Class IV drugs block L-type calcium channels, slowing AV and SA node conduction and reducing contractile force (e.g., verapamil, diltiazem). Side effects include a shortened plateau phase and reduced contractile force.

Question 37

What is adenosine, and how is it used in tachycardia treatment?

Answer 37

Adenosine, an endogenous compound from ATP/ADP, activates cardiac A1 adenosine receptors to block calcium channels. It’s administered IV for tachycardia and is short-lived due to rapid metabolism.

Question 38

What drugs are used to treat bradyarrhythmia?

Answer 38

Atropine: Muscarinic antagonist used to increase heart rate by removing “brake” on the heart.

Isoprenaline: Beta-agonist that has positive inotropic effects, used for heart block or bradycardia.

Question 39

What are the main drug classes used to treat tachycardia?

Answer 39

Drugs used for tachycardia include:
- Voltage-sensitive Na+ channel blockers.
- Beta-blockers.
- Drugs prolonging cardiac action potential.
- L-type calcium channel blockers.
- Adenosine.

Question 40

What drugs are used to treat bradycardia?

Answer 40

Bradycardia is treated with:
- Atropine (muscarinic antagonist).
- Isoprenaline (beta-agonist).