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.
CYP Enzyme Interactions with Warfarin and Aspirin
Warfarin Interactions: Metabolized by CYP2C9, making it sensitive to genetic differences and drug interactions.
Aspirin in Low Doses: Reduces GI side effects by minimizing prostaglandin inhibition but prolongs antiplatelet effects.
Direct vs. Indirect Thrombin Inhibitors
Heparin: Enhances antithrombin’s activity (indirect).
Direct Thrombin Inhibitors: Block thrombin directly, effective in preventing thrombus without needing antithrombin.
Fibrinolytic Drugs and Clot Selectivity
tPA-based Drugs (e.g., tenecteplase): Target fibrin-bound plasminogen, increasing clot selectivity to reduce bleeding risks.
Adverse Drug Reactions (ADRs)
Definition: Harmful, unintended drug effects that vary by dose, time course, and patient susceptibility.
Types:
Type A (Predictable): Dose-related, e.g., bleeding from high-dose warfarin.
Type B (Unpredictable): Idiosyncratic or immune-related, e.g., hypersensitivity to paracetamol.
Type C: Dose-dependent, related to long-term effects like carcinogenicity.
Overdose & Pharmacokinetics Variability: Factors like genetic differences or liver/kidney function can alter ADR risk.
Toxicity
Acute vs. Chronic: Acute toxicity occurs immediately after exposure; chronic toxicity arises from long-term exposure.
Organ-Specific Toxicity:
Liver: Can be hepatotoxic (e.g., paracetamol) or cause immune reactions (e.g., halothane).
Kidneys: Nephrotoxic drugs concentrate in renal tubules (e.g., NSAIDs).
Neurotoxicity: Certain drugs (e.g., MPTP) can cross the blood-brain barrier, causing neurotoxic effects.
Haematotoxicity: Substances like benzene can cause blood disorders.
Carcinogens & Mutagens: Substances that can cause cancer or genetic mutations.
Mechanisms of Cell Damage:
Non-Covalent Interactions: Lipid peroxidation, ROS, GSH depletion.
Covalent Interactions: DNA/protein binding, mutagenesis.
Pharmacodynamics & Pharmacokinetics
Therapeutic Window: Safe plasma concentration range for efficacy without toxicity.
Therapeutic Index (TI): Safety margin; calculated as LD50/ED50.
Drug Interactions:
Pharmacodynamic: Includes additive (1 + 1 = 2), synergistic (1 + 1 > 2), potentiation, and antagonism.
Pharmacokinetic: Competition for metabolism (e.g., P450 enzyme competition).
Enzyme Interactions:
P450 Inhibition & Induction: Influences drug metabolism and potential for toxicity.
Hormones & Endocrine Regulation
Gonadal Hormones:
GnRH, FSH, LH: Key in reproductive cycle regulation.
Estrogen & Progesterone: Estrogen supports endometrial growth; progesterone stabilizes it.
Inhibin: Inhibits FSH secretion.
Menstrual Cycle:
Follicular Phase: Dominant follicle matures; estrogen levels rise.
Luteal Phase: Corpus luteum forms and secretes progesterone.
Hormone Replacement & Contraception:
Estrogen Replacement: Used to manage menopause symptoms.
Progestin: Used alone (e.g., in progestin-only pills) or with estrogen (combined pills) to prevent endometrial hyperplasia.
Nervous System & CNS Pharmacology
Neurotransmitters:
Classes: Amino acids (e.g., glutamate), peptides, and monoamines (e.g., dopamine, serotonin).
Glutamate: Major excitatory NT; NMDA receptor activity modulated by drugs like ketamine.
GABA: Inhibitory NT; benzodiazepines and barbiturates enhance GABA effects.
Blood-Brain Barrier (BBB): Protects CNS, presenting challenges for drug delivery.
Opioid System:
Opioids: Bind to receptors (MOP, DOP, KOP) to manage pain; effects include respiratory depression and euphoria.
Pain Pathways: Involves descending control pathways rich in opioid receptors, contributing to analgesia.
Analgesics & Pain Management
Opioids: Used for severe pain (e.g., morphine, fentanyl); risk of tolerance, dependence, and respiratory depression.
NSAIDs:
Mechanism: Inhibit COX enzymes, reducing prostaglandins.
Effects: Anti-inflammatory, analgesic, and antipyretic.
Risks: GI irritation, renal effects, and cardiovascular risks.
Local Anaesthetics:
Mechanism: Block Na+ channels, preventing nerve impulse transmission.
Types: Esters (e.g., procaine) and amides (e.g., lidocaine) with differing properties.
General Anaesthesia: Involves induction (e.g., propofol), maintenance (e.g., sevoflurane), and analgesic components (e.g., opioids).
Inflammation & Immune System
Innate Immunity: Activated by DAMPs/PAMPs, leading to inflammation.
Cardinal Signs of Inflammation: Redness, heat, swelling, pain, and reduced function.
Phases of Inflammation:
Vascular Phase: Vasodilation and plasma protein influx.
Cellular Phase: Neutrophils and macrophages phagocytose pathogens and release cytokines.
Anti-inflammatory Drugs:
SAIDs (e.g., corticosteroids): Reduce phospholipase A2 activity.
NSAIDs: Inhibit COX enzymes, reducing prostaglandin synthesis.
Addiction & Substance Use Disorders
Mechanisms:
Reward Pathways: Dopamine release in the nucleus accumbens plays a key role.
Dependence: Can be physical (tolerance and withdrawal) or psychological (compulsive use).
Substance Classes:
Stimulants: Increase dopamine (e.g., cocaine blocks reuptake).
Cannabis: Alters perception and mood; mediated by CB1 and CB2 receptors.
Opioids: High potential for tolerance and dependence, managed with treatments like methadone.
Treatment of Addiction:
Methadone for opioids, Bupropion for nicotine, Naltrexone for alcohol.
