Pharmacology: Basic Principles

Pharmacology Overview

• Pharmacology studies the effects of drugs on biological systems and vice versa.
• The discipline includes understanding drug sources, chemical attributes, biological impacts, and how drugs are used therapeutically.
• Drug action mechanisms, interactions, and metabolism fall under pharmacological examination.
• Pharmacology provides a basis for grasping drug development and clinical applications.

Basic Principles

• Pharmacokinetics is how the body affects the drug, including absorption, distribution, metabolism, and excretion.
• Pharmacodynamics is how the drug affects the body, focusing on mechanisms, therapeutic outcomes, and adverse effects.

Pharmacokinetics

• Absorption describes a drug's entry into the bloodstream from the administration site.
• Distribution is a drug's reversible movement from the bloodstream into tissues.
• Metabolism, or biotransformation, is the body's chemical modification of a drug.
• Excretion is the removal of a drug from the body.

Absorption Routes

• Oral administration involves drug absorption from the gastrointestinal tract after swallowing.
• Intravenous (IV) administration introduces drugs directly into a vein, resulting in 100% bioavailability.
• Intramuscular (IM) administration involves injecting drugs into muscle tissue.
• Subcutaneous (SC) administration involves injecting drugs under the skin.
• Inhalation allows drug absorption from the lungs via breathing.
• Transdermal administration delivers drugs into the bloodstream through skin application.
• Bioavailability is the fraction of a drug dose reaching systemic circulation.
• First-pass metabolism is the drug metabolism occurring before systemic circulation, largely in the liver.

Distribution Factors

• Volume of distribution (Vd) reflects the extent of a drug's distribution in the body.
• Plasma protein binding affects drug distribution; only unbound drugs produce effects.
• The blood-brain barrier (BBB) limits the entry of numerous drugs into the brain.
• Tissue binding can extend a drug's duration of action.

Metabolic Processes

• Phase I reactions modify a drug's structure via oxidation, reduction, or hydrolysis.
• Cytochrome P450 (CYP) enzymes are key players in Phase I metabolism.
• Phase II reactions attach polar molecules to drugs to enhance water solubility through conjugation.
• Glucuronidation, sulfation, and acetylation represent typical Phase II reactions.
• Prodrugs need to be metabolized into active forms to exert effects.
• Enzyme induction boosts drug-metabolizing enzyme production or activity.
• Enzyme inhibition reduces drug-metabolizing enzyme activity.

Excretion Mechanisms

• Renal excretion involves the kidneys filtering, secreting, and reabsorbing drugs.
• Glomerular filtration rate (GFR) reflects kidney function and affects drug excretion rates.
• Biliary excretion eliminates drugs via bile.
• Drugs can also be excreted through sweat, saliva, and breast milk.
• Clearance measures the volume of plasma cleared of a drug per unit of time.
• Half-life (t1/2) indicates the time for a drug's plasma concentration to halve.

Pharmacodynamics

• Receptors are drug-binding proteins that mediate drug actions.
• Agonists activate receptors upon binding, triggering a biological response.
• Antagonists block agonists by binding to receptors, preventing biological responses.
• Competitive antagonists reversibly bind to the same site as agonists.
• Non-competitive antagonists bind irreversibly or to a different receptor site.
• Partial agonists elicit submaximal responses, even at full receptor occupancy.
• Inverse agonists produce effects opposite to those of agonists upon receptor binding.
• The dose-response relationship links drug dosage to effect magnitude.
• Efficacy represents the maximum effect a drug can achieve.
• Potency refers to the drug amount needed for a specific effect.
• ED50 is the drug dose that yields 50% of the maximal effect.
• TD50 is the dose at which 50% of the population experiences a toxic effect.
• Therapeutic index (TI) is the TD50/ED50 ratio, indicating drug safety.
• Tolerance is the diminished drug response from repeated use.
• Tachyphylaxis is a rapid decline in drug response after repeated doses.
• Sensitization represents an increased drug response with repeated use.

Drug Interactions

• Pharmacokinetic interactions arise when one drug alters another's absorption, distribution, metabolism, or excretion.
• Pharmacodynamic interactions involve additive, synergistic, or antagonistic effects of drugs on the same target or pathway.

Adverse Drug Reactions

• Side effects are predictable and often unavoidable drug effects.
• Toxic effects are adverse effects from excessive doses or prolonged use.
• Allergic reactions are immune responses to a drug.
• Idiosyncratic reactions are rare, unpredictable adverse effects.
• Teratogenic effects are drug-induced fetal harm during pregnancy.

Drug Development Phases

• Preclinical studies involve in vitro and animal drug testing.
• Phase I clinical trials assess drug safety and tolerability in healthy volunteers.
• Phase II clinical trials gauge drug efficacy in patients with the target illness.
• Phase III clinical trials compare the drug against existing treatments in larger patient groups.
• Phase IV clinical trials are post-market studies monitoring long-term drug safety and efficacy.