Concept summary Flashcards
Epilepsy and Seizure Types
Epilepsy: A neurological disorder marked by recurring seizures (1-3% prevalence). It involves abnormal electrical activity in neurons, often diagnosed by EEG.
EEG: Measures electrical activity in the brain, aiding in epilepsy diagnosis.
Seizure Classifications:
Generalized Seizures: Affect both brain hemispheres, usually with loss of consciousness. Includes Tonic-Clonic (muscle stiffness, then jerking) and Absence Seizures (brief loss of awareness, often treated with valproate).
Focal Seizures: Originate from a specific brain area, symptoms vary by affected region, often caused by anoxia, trauma, or infection.
Anti-Epileptic Drugs (AEDs)
Mechanisms of AEDs:
Enhance GABAergic inhibition.
Block sodium/calcium channels to control neural excitability.
Inhibit excitatory input.
Common AED Classes:
Benzodiazepines and Barbiturates: Enhance GABA activity, used in status epilepticus.
Valproate: Inhibits GABA breakdown, blocks Ca and Na channels, suitable for various epilepsies.
New AEDs: Fewer sedative effects, improved pharmacokinetics.
Status Epilepticus
A prolonged seizure lasting over 5 minutes, considered a medical emergency due to high mortality risk, often requiring immediate intervention.
Mechanism of Antiepileptic Drugs (AEDs)
AED Mechanisms: Work by enhancing inhibitory signals (GABA), blocking excitatory channels (sodium or calcium), or reducing neuron excitability.
Classical AED Properties: Narrow therapeutic range, CNS depression, potential for drug interactions, and teratogenic risks.
Arrhythmias and Heart Rhythm Control
Heart Rhythm: Controlled by pacemaker cells (SA node), regulated by both sympathetic and parasympathetic influences.
Arrhythmia Types:
Tachyarrhythmias (fast heart rate): Caused by ectopic foci, re-entrant circuits, or afterdepolarizations.
Bradyarrhythmias (slow heart rate): Include heart blocks, treated with medications like atropine or isoprenaline.
Antiarrhythmic Drug Classification (Vaughn Williams)
Class I: Sodium channel blockers (e.g., lidocaine) for atrial and ventricular tachyarrhythmias.
Class II: β-blockers reduce calcium influx to slow heart rate.
Class III: Drugs that prolong the action potential to prevent re-entrant tachycardia.
Class IV: Calcium channel blockers (e.g., verapamil) slow SA and AV node conduction.
Mechanisms of Blood Coagulation and Haemostasis
Haemostasis: The process of stopping blood loss after vessel injury, involving:
- Vasoconstriction
- Platelet Plug Formation: Platelets adhere, activate, and aggregate at the injury site.
- Coagulation Cascade: Fibrin stabilizes the platelet plug to form a clot.
Thrombin: A central enzyme in coagulation, converting fibrinogen to fibrin and activating platelets.
Thrombosis and Virchow’s Triad
Thrombosis: Formation of a clot within blood vessels without injury, influenced by Virchow’s Triad:
- Endothelial Injury
- Stasis or Altered Blood Flow
- Hypercoagulability: Increased clotting tendency (e.g., due to thrombophilia).
Antiplatelet Agents
Aspirin: Irreversibly blocks COX-1, reducing thromboxane A₂ production, thereby reducing platelet activation.
ADP Receptor Inhibitors (e.g., clopidogrel): Block P2Y₁₂ receptor to prevent platelet aggregation.
GP IIb/IIIa Inhibitors (e.g., abciximab): Block fibrinogen binding to platelets, preventing aggregation.
Anticoagulants and Direct Thrombin Inhibitors
Heparin: Enhances antithrombin’s activity, indirectly inhibiting thrombin and factor Xa.
Direct Thrombin Inhibitors (e.g., dabigatran): Block thrombin directly, preventing clot formation without relying on endogenous pathways.
Vitamin K and Warfarin in Coagulation
Vitamin K: Essential for synthesizing factors II, VII, IX, and X, critical for blood coagulation.
Warfarin: Competes with Vitamin K, inhibiting clotting factor synthesis. Requires regular monitoring due to narrow safety margins.
Fibrinolysis and Fibrinolytic Agents
Fibrinolysis: The breakdown of clots by plasmin, activated from plasminogen. Used therapeutically in acute myocardial infarction.
tPA Derivatives (e.g., alteplase): Enhance clot selectivity and effectively dissolve clots in a controlled manner.
Role of Eicosanoids in Platelet Function
Arachidonic Acid Pathways: COX-1 pathway produces thromboxane A₂ (promotes aggregation) and prostacyclin (inhibits aggregation).
Aspirin’s Selective Action: Irreversibly blocks platelet COX-1, reducing thromboxane without significantly affecting prostacyclin production in endothelial cells.
Cardiovascular Pacemakers and Beta/Muscarinic Receptors
SA Node: Primary pacemaker (70-80 bpm), with AV node and Purkinje fibers acting as latent pacemakers.
Receptor Influence:
Beta Receptors (adrenergic): Increase heart rate via cAMP and calcium influx.
Muscarinic Receptors (cholinergic): Decrease heart rate by inhibiting cAMP formation.
Mechanism of Re-entrant Circuits in Arrhythmias
Re-entrant Circuits: Cause sustained depolarization by looping through alternate pathways, often leading to tachycardia if not broken.
Ketogenic Diet for Epilepsy
Ketogenic Diet: High-fat, low-carbohydrate regimen that effectively controls seizures in some childhood epilepsy cases by altering energy metabolism in the brain.
Mechanism of Platelet Plug Formation in Haemostasis
Adhesion: Platelets attach to exposed collagen.
Activation: Platelets release ADP and thromboxane to recruit more platelets.
Aggregation: GPIIb/IIIa receptors link platelets, forming a stable plug.
Effects of Aspirin on Platelets and GI Health
Antiplatelet Action: Aspirin irreversibly inhibits COX-1 in platelets, reducing thromboxane and prolonging bleeding time.
GI Side Effects: Reduced protective prostaglandins (PGI₂, PGE₂, PGF₂α) in the stomach can lead to irritation, ulceration, and hemorrhage.
Impact of Calcium and Sodium Channels in Cardiac and Neuronal Excitability
Sodium Channels: AEDs target inactivated states to block excessive neuron firing.
Calcium Channels: Specific blockers help manage seizures and control heart rate in arrhythmias by reducing excitability.
Clopidogrel and CYP Enzyme Interaction
Clopidogrel Activation: Converted to active form by CYP enzymes (e.g., CYP2C19). Genetic variants or inhibitors can reduce its effectiveness.
Key Zymogens in Coagulation Cascade
Zymogens: Inactive enzyme precursors (e.g., prothrombin) that are sequentially activated to propagate and amplify the clotting response.
Thrombin’s Role Beyond Fibrin Formation
Thrombin: Converts fibrinogen to fibrin, stimulates platelet aggregation, and activates Factor XIII, which cross-links fibrin, stabilizing the clot.
Heart Block Types and Treatments
Heart Block: Slowed or blocked conduction, may lead to bradyarrhythmias. Treatment often includes pacemakers or medications like atropine.
Role of Platelet Factor 3 (PF3) in Clotting
PF3: Released by aggregated platelets to stimulate further coagulation, amplifying thrombin production.
