Pharmacology: Drug Effects on Living Systems

• Pharmacology is the study of drugs and their effects on living systems
• It encompasses how drugs are absorbed, distributed, metabolized, and excreted (ADME), as well as their mechanisms of action and therapeutic uses
• Clinical pharmacology is the branch of pharmacology specifically focused on the effects of drugs in humans
• It involves studying drug responses in patients, optimizing drug therapy, and understanding individual variations in drug effects

Pharmacodynamics

• Pharmacodynamics describes what the drug does to the body
• It examines the relationship between drug concentration and its effect
• Key concepts include receptors, drug-receptor interactions, signal transduction, and dose-response relationships
• Agonists activate receptors to produce a response
• Antagonists block receptors, preventing agonist binding and reducing the response
• Partial agonists produce a submaximal response even when fully occupying the receptor
• Efficacy refers to the maximum effect a drug can produce
• Potency refers to the amount of drug needed to produce a given effect
• The therapeutic index is a measure of drug safety, comparing the dose that produces a therapeutic effect to the dose that produces toxicity

Drug Mechanisms

• Drugs produce effects by interacting with specific molecular targets in the body
• These targets are most commonly receptors, enzymes, ion channels, and transporters
• Receptor-mediated mechanisms involve drug binding to receptors, triggering a cascade of intracellular events
• Enzyme-mediated mechanisms involve drugs inhibiting or activating specific enzymes, altering their activity
• Ion channel-mediated mechanisms involve drugs blocking or modulating ion channels, affecting ion flow
• Transporter-mediated mechanisms involve drugs inhibiting or enhancing the activity of specific transporters, affecting the movement of molecules across cell membranes

Pharmacokinetics

• Pharmacokinetics describes what the body does to the drug
• It encompasses the processes of absorption, distribution, metabolism, and excretion (ADME)
• Absorption is the process by which a drug enters the bloodstream
• Factors affecting absorption include route of administration, drug formulation, and gastrointestinal factors
• Distribution is the process by which a drug moves from the bloodstream to various tissues and organs
• Factors affecting distribution include blood flow, tissue binding, and physiological barriers like the blood-brain barrier
• Metabolism, also known as biotransformation, is the process by which the body chemically modifies a drug
• The liver is the primary site of drug metabolism, involving enzymes like cytochrome P450s (CYPs)
• Excretion is the process by which the body eliminates a drug
• The kidneys are the primary site of drug excretion, involving glomerular filtration, tubular secretion, and tubular reabsorption
• Drug half-life (t1/2) is the time it takes for the plasma concentration of a drug to decrease by half
• Bioavailability refers to the fraction of an administered dose of drug that reaches the systemic circulation unchanged

Toxicology

• Toxicology is the study of the adverse effects of drugs and other chemicals on living organisms
• It encompasses the mechanisms, diagnosis, and treatment of drug-induced toxicity
• Dose-response relationships are critical in toxicology, as the severity of toxic effects often depends on the dose
• Acute toxicity refers to adverse effects that occur shortly after a single exposure or a few exposures to a substance
• Chronic toxicity refers to adverse effects that occur after prolonged or repeated exposure to a substance
• Carcinogenicity is the ability of a substance to cause cancer
• Mutagenicity is the ability of a substance to cause mutations in DNA
• Teratogenicity is the ability of a substance to cause birth defects
• Risk assessment is the process of evaluating the likelihood that exposure to a substance will cause harm to human health
• Toxicokinetics is the study of how the body processes a toxic substance, including its absorption, distribution, metabolism, and excretion
• Common mechanisms of toxic action include:
  • Oxidative stress, where an imbalance between the production of reactive oxygen species (ROS) and the body's ability to detoxify them leads to cellular damage
  • Disruption of cellular respiration, particularly within mitochondria, leading to energy depletion and cell death
  • Interference with DNA replication or repair, resulting in mutations and potentially cancer
  • Disruption of cell membrane integrity, leading to leakage of cellular contents and cell death
  • Disruption of intracellular signaling pathways, affecting various cellular functions
• Factors influencing toxicity:
  • Dosage, as the amount of substance directly correlates with the magnitude of the toxic effect
  • Route of exposure, affecting the rate and extent of absorption
  • Duration of exposure
  • Individual physiological factors
  • Genetic predispositions can make certain individuals more susceptible to toxic effects
  • Age
  • Pre-existing health conditions
• Treatment strategies for toxicological emergencies:
  • Supportive care: Maintaining vital functions such as respiration, circulation, and neurological function
  • Decontamination: Reducing absorption of the toxic substance through methods like induced vomiting, gastric lavage, activated charcoal, or dermal irrigation
  • Use of antidotes: Administering specific agents that counteract the toxic effects of the substance
  • Enhanced elimination: Employing techniques like hemodialysis or hemoperfusion to remove the substance from the body more rapidly