Pharmacology Chapter 5 Quiz

General Pharmacology

• Pharmacology is the study of interactions between a living organism and external chemicals that alter normal biochemical functions.
• Pharmaceuticals are substances with medicinal properties.
• Drugs are chemical substances used to treat, diagnose, or prevent disease (prophylaxis).
• Pharmacology is a branch of chemical science practiced by pharmacologists.
• Sub-divisions of pharmacology include clinical pharmacology, neuro- and psychopharmacology, pharmacogenetics, pharmacogenomics, and pharmacoepidemiology.

Introduction

• Toxicology is the study of harmful drug effects, including diagnosing and treating exposures to toxins and toxicants.
• Pharmacology can be sub-divided into pharmacodynamics and pharmacokinetics.
• Pharmacokinetics describes what the body does to a drug, including absorption, distribution, metabolism, and excretion (ADME).
• Pharmacodynamics describes what the drug does to the body, including pharmacological actions and mechanisms.

Routes of Drug Administration

• Therapeutic objectives guide the choice of drug administration route, considering factors like rapid onset of action or localized delivery.
• Enteral Route (oral):
  • Most drugs absorbed through the gastrointestinal (GI) tract pass through the liver (first-pass metabolism) and then the general circulation.
  • First-pass metabolism in the liver often reduces the efficacy of oral drugs.
  • Food can affect the absorption of some drugs, like insulin and penicillin.
• Sublingual Route: Drugs placed under the tongue diffuse directly into capillaries and enter systemic circulation, bypassing the liver.
• Rectal Route: Fifty percent of blood draining from the rectum bypasses the liver, minimizing biotransformation. This route is used for anti-emetic agents.
• Parenteral Route: Used for drugs poorly absorbed by the gut or for those that are unstable in the GI tract, such as insulin.
  • Intravascular (IV): Provides the most control over drug delivery to the body. Avoids first-pass metabolism and has a rapid onset of action. However, it can be contaminated, and is painful.
  • Intramuscular (IM): Injection into muscle. Absorption from aqueous solutions is faster than from depot preparations.
  • Subcutaneous (SC): Minimizes intravascular injection risks. Epinephrine, a vasoconstrictor, can be used to slow drug absorption.
• Intradermal (ID): Injection into the dermis, commonly used for vaccines.
• Intraarticular: Injection into joints for local effects.
• Intrathecal/Intraventricular: Administration into cerebrospinal fluid (CSF), used in specific cases like leukemia.
• Inhalation: Used for drugs that are gases (e.g., anesthetics, bronchodilators). Absorption is rapid due to the large surface area of the lungs.
• Intranasal: Used for drugs such as desmopressin.
• Topical: Applied directly to the skin or mucous membranes, causing local effects (e.g., creams, eye drops).
• Transdermal: Applies drugs directly to the skin, often using a patch, achieving systemic effects.

Absorption of Drugs

• Absorption is the transfer of a drug from its site of administration into the bloodstream.
• Transport of drugs from the GI tract: Passive diffusion and active transport are the two mechanisms.
• Passive diffusion: Drugs move from high to low concentration due to the concentration gradient, not requiring a carrier protein.
• Active transport: Drugs move against the concentration gradient using carrier proteins and energy (ATP).
• pH effect on absorption: Weak acids and weak bases exist in both ionized and unionized states; their absorption is highly pH dependent; un-ionized forms are typically absorbed readily.
• Physical factors influencing absorption: Blood flow to the absorption site is a crucial factor. Greater absorption occurs in areas with higher blood flow and larger surface areas (e.g., small intestine).

Bioavailability

• Bioavailability is the fraction of a drug that reaches systemic circulation in a chemically unchanged form.
• Bioavailability is determined by comparing plasma concentrations achieved after oral administration with those after intravenous administration.
• Factors affecting bioavailability include first-pass hepatic metabolism, drug solubility, chemical instability, and drug formulation.
  • First-pass metabolism: Rapid liver metabolism after absorption decreases the amount of drug reaching the systemic circulation.

Drug Distribution

• Distribution is the process of transferring a drug from the bloodstream into the extracellular fluid and tissues.
• Factors influencing distribution include blood flow, capillary permeability, and drug binding to plasma proteins.
• Blood flow: The rate of blood flow to tissues influences drug distribution, with tissues receiving more blood flow receiving higher drug concentrations.
• Capillary permeability: Capillary structure, especially the presence of slit junctions, influences drug penetration into tissues. Lipid-soluble drugs pass through cell membranes easily, while water-soluble drugs are often impeded.
• Drug binding to plasma proteins: Reversible binding to plasma proteins like albumin reduces free drug levels and affects tissue distribution.

Volume of Distribution

• Volume of distribution (Vd) is a hypothetical volume of fluid in which the drug is distributed.
• Vd is calculated by dividing the administered dose by the plasma concentration at time zero.
• Drugs with high Vd are often found in tissues, while drugs with lower Vd remain primarily in plasma.
• Water compartments in the body (plasma, extracellular and intracellular) determine the distribution of a drug.

Drug Metabolism (Biotransformation)

• Metabolism involves the biotransformation of drugs into more polar molecules.
• The liver is the primary site of drug metabolism; however, other tissues can metabolize certain drugs.
• Drugs can be metabolized into inactive or active metabolites.
• Phase 1 metabolism often involves oxidation, reduction, or hydrolysis, increasing polarity.
• Phase 2 metabolism involves conjugation with endogenous substrates to form a more water-soluble form that can be excreted.
• Zero-order kinetics mean a constant amount of drug is metabolized per unit of time.
• Drugs with high concentrations saturate the enzyme, leading to zero-order kinetics.

Drug Elimination

• Elimination describes the removal of a drug from the body.
• The kidney is the primary organ for drug elimination.
• Elimination processes include glomerular filtration, proximal tubular secretion, and passive tubular reabsorption.
• Some drugs are excreted through the bile, lungs, or milk.
• Renal elimination, a key aspect of the overall body clearance, is affected by various factors such as plasma flow, extraction ratio and ionization.
• Total body clearance is the sum of clearance from the kidneys, liver, lungs and other organs.

Clinical Situations Affecting Drug Half-Life

• Certain situations can prolong drug half-life, requiring dosage adjustments.
  • Decreased renal function (reduced blood flow to the kidneys).
  • Binding competition of multiple drugs.
  • Decreased metabolic capacity.

Test your knowledge on key concepts of drug absorption and metabolism from Pharmacology Chapter 5. This quiz covers topics including bioavailability, hepatic metabolism, and the physical factors affecting drug absorption. Understand how these processes influence therapeutic outcomes in clinical practice.