Pharmacology Quiz: Key Concepts

General Pharmacology

• Pharmacology is the study of interactions between living organisms and external chemicals that alter natural biochemical processes.
• If a substance has medicinal properties, it's considered a pharmaceutical.
• A drug is a chemical substance used to treat, diagnose, or prevent (prophylaxis) diseases.
• Pharmacology is a branch of chemical science practiced by pharmacologists.
• It's subdivided into several subfields.
• Clinical pharmacology examines the effects of medications on humans.
• Neuro- and psychopharmacology studies the effects of medication on behavior and nervous system functioning.
• Pharmacogenetics involves clinical testing of genes for therapeutic purposes.
• Pharmacogenomics applies genomic technologies to new drug discovery.
• Pharmacoepidemiology studies drug effects on large populations.
• Toxicology examines the harmful effects of drugs, including adverse effects and treatments for toxin exposures.
• Pharmacology can also be broken down into pharmacodynamics and pharmacokinetics.
• Pharmacokinetics describes how the body processes a drug, encompassing absorption, distribution, metabolism, and excretion (ADME).
• Pharmacodynamics details the effect of a drug on the body and its mechanism of action.

Routes of Drug Administration

• Drug administration routes are selected based on therapeutic objectives, such as rapid onset or local action.

• Enteral Routes:

  • Oral: The most common route; drugs absorbed from the GI tract often go to the liver before general circulation. First-pass metabolism via the liver can significantly reduce drug efficacy. Food can affect absorption as well, some drugs are unabsorbable in the presence of food (insulin, penicillin).
  • Sublingual: Placing medications under the tongue allows direct absorption into capillaries, bypassing the liver and intestines.
  • Rectal: 50% of rectal drainage bypasses the liver, thus minimizing hepatic metabolism. This route is often used to administer antiemetics.

• Parenteral Routes:

  • Intravenous (IV): Direct injection into a vein, delivering drugs quickly into the blood, avoiding first-pass metabolism, and offering high drug concentration. High drug concentration, rapid onset, avoid gastric secretions and first pass metabolism are advantages; however, contamination and pain are disadvantages.
  • Intramuscular (IM): Injection into muscle tissue; drugs in solution are absorbed quickly, while drugs in depot preparations (suspension form) have slower absorption. The absorption of a drug in solution is faster compared to the depot preparations. Pain is a disadvantage
  • Subcutaneous (SC): Injection under the skin; absorption of drugs is generally slower than IM injections. Epinephrine is sometimes added to the solution to minimize the removal of the drug.

• Other Routes:

  • Inhalation: Absorption through the lungs is rapid due to the large surface area. Gasses like anesthetics and bronchodilators are often administered this way.
  • Intranasal: Drugs delivered through the nasal passages, often as nasal sprays (e.g., desmopressin).
  • Intrathecal/Intraventricular: Injection directly into cerebrospinal fluid, used for substances like methotrexate in specific cases.
  • Topical: Application to the skin or other surfaces.
  • Transdermal: Application via patches to achieve systemic effects, often used for sustained-release drugs like nitroglycerin.

Absorption of Drugs

• Absorption is the movement of a drug from the site of administration into the bloodstream.
• Absorption depends on drug transport across membranes.
• Passive diffusion: drugs move down a concentration gradient (high to low).
• Active transport: energy-dependent process; drugs move against the concentration gradient.
• Effect of pH: Acidic drugs are better absorbed in acidic environments (uncharged), while basic drugs are better absorbed in alkaline environments.
• Other factors influencing absorption include:
  • Blood flow to the absorption site, since high blood flow means faster absorption. Surface area also plays a role (intestine has a much greater surface area compared to the stomach). The presence of food often slows gastric emptying and thus drug absorption. The solubility of the drug is a major factor, for example, very hydrophilic drugs are poorly absorbed. Sometimes, drugs are unstable in the gut's acidic environment, which could hinder absorption. Some drugs could interact with other compounds or substances to hinder absorption (e.g., other foods).

Bioavailability

• Bioavailability is the fraction of an administered drug that reaches systemic circulation in unchanged form.

• Determination of bioavailability involves comparing plasma drug levels after different administration routes (e.g., oral vs. intravenous). The area under the curve (AUC) is often used.

• Factors influencing bioavailability include:

  • First-pass hepatic metabolism, the degree of drug metabolism in the liver.
  • Drug's solubility; very hydrophobic drugs are often poorly absorbed.
  • Chemical instability, some drugs are liable to degrading/transforming before absorption, therefore, lower bioavailability.
  • Nature of the drug formulation, particle size, salt form, crystal polymorphism; some of these can directly influence the absorption rate.

• Bioequivalence means that two drugs have comparable bioavailability and similar peak blood concentrations.

• Therapeutic equivalence means that two drugs have similar efficacy and safety, although they might have different pharmacokinetic profiles.

Drug Distribution

• Distribution is the process of drug movement from the bloodstream into the tissues and other organs.
• Factors affecting distribution include:
  • Blood flow to tissues, capillary permeability. Capillary structure can affect drug distribution; some drugs can pass through the capillary slits in some places (e.g., brain). The lipid solubility of the drug can affect its distribution.
  • Drug binding to plasma proteins, this can greatly affect distribution rate; bound drugs circulate without exerting effects.
• Blood-brain barrier: the tightly connected endothelial cells in the brain limit the passage of many drugs into the brain; lipid soluble substances can readily cross.
• Volume of distribution is a hypothetical volume that drug is distributed into to reflect its extent of distribution.

Drug Metabolism

• Metabolism involves the biotransformation of drugs in the body, typically in the liver, but other tissues can also participate (e.g., intestinal walls).
• Metabolism can either inactivate or activate a drug
• Types of reactions:
  • Phase I reactions (oxidation, reduction, hydrolysis) increase polarity, often to make them more readily eliminated.
  • Phase II reactions (conjugation) usually produce more water-soluble compounds that are more readily excreted.
• Rate of metabolism can be zero order or first order.
• This system is mainly conducted by the P-450 system

Drug Elimination

• Elimination is the removal of drugs from the body.
• Renal elimination: Most important pathway, involving glomerular filtration, tubular secretion, and tubular reabsorption. Urine is important for removing the drug and thus it is the major route for elimination.
• Other elimination methods include:
• Hepatic (bile) elimination: Substances eliminated through bile, frequently metabolized in the liver first.
• Pulmonary elimination: some drugs are exhaled in the form of gases.
• Other routes: milk, etc.
• Total clearance: is the sum of clearances from all the elimination pathways. Total clearance is often important to determining the half life of drugs in consideration.