Basics of Pharmacology: Chapter 2 Study Guide

Overview of Pharmacology and Pharmacokinetics

• Definition of Pharmacology: Pharmacology is the exploration of substances used to heal and comfort the sick, and to help individuals live longer, healthier lives.

• Goal of Study: The primary purpose of studying pharmacology is to discover the most effective medications that cause the minimum amount of problems for patients.

• Historical Context:

  • Early pharmacologists were pioneering individuals who experimented with substances such as maggots on necrotic wounds to promote clean tissue or brewing tea from the poisonous foxglove plant to treat heart failure.

  • Modern advances in pharmacology have increased life expectancy by eradicating childhood illnesses and producing antibiotics to cure infections.

• Pharmacokinetics: This is the scientific study of how the body absorbs, distributes, metabolizes, and excretes drugs (collectively known as the drug cycle). It examines what happens once medications are ingested, injected, or applied.

Key Terms and Definitions

• Absorption: The process by which a substance moves into the bloodstream from the site of administration.

• Adverse Reaction: A severe side effect that can cause significant harm or death (e.g., hallucinations, hypotension, or anaphylactic shock).

• Agonist: A drug that works together with another drug to provide a more potent effect.

• Antagonist: A drug that renders another drug less effective.

• Bioavailability: The specific amount of a drug that is actually absorbed and available for use by the body.

• Biotransformation / Metabolism: The chemical transformation of a medication into usable components or inactive waste products (metabolites).

• Distribution: The delivery of a drug to the appropriate site after it has been absorbed into the bloodstream.

• Excretion: The process of eliminating extra medication and waste products from the body.

• Half-life: The length of time required for the concentration of a drug in the blood plasma to decrease by one-half ($50\%$).

• Idiosyncratic: A unique, rare, or unexpected reaction to a drug specific to an individual.

• Pharmacokinetics: The study of the drug cycle (absorption, distribution, metabolism, excretion).

• Receptors: Specific sites on cells (described as "locks") that are activated or blocked by a medication ("key").

• Side Effects: Mild and often predictable effects of a drug that are not the primary intended therapeutic effect.

• Synergism: A drug combination that provides a more potent effect than when each drug is taken separately.

• Teratogenic: Interferes with normal fetal development; substances that cause harm to a fetus.

• Toxic: Poisonous or harmful to the patient; refers to drug levels that exceed the therapeutic range.

The Drug Cycle: Phase 1 – Absorption

• The Process: Medication enters the bloodstream from its site of administration. The duration of the entire drug cycle varies based on the drug, route, and organ health, ranging from $15\,\text{minutes}$ to several days.

• Routes of Administration:

  • Enteral: Given directly into the gastrointestinal (GI) system (orally, rectally, or via tube).

  • Parenteral: All other routes that do not involve the GI system (e.g., injections, topical applications).

• Topical vs. Systemic:

  • Topical: Acts locally at the site of concern. Examples include Desitin or Balmex for rashes and EMLA cream or Lidocaine for local numbing.

  • Systemic: Circulates throughout the body. Administered via mouth, IV, IM, or transdermal patches.

• Speed of Absorption:

  • Intravenous (IV): The fastest route because the drug is injected directly into a vein.

  • Intramuscular (IM): Fairly quick due to rich blood supply in muscle tissue.

  • Oral (Liquid): Faster than pills because pills must be mechanically broken down first.

• Factors Influencing Absorption and Bioavailability:

  • Fat/Lipid Solubility: Higher solubility allows easier absorption through the stomach into the bloodstream.

  • pH Levels: Acidic medications ($\text{low pH}$) are absorbed easily in the stomach; alkalotic medications ($\text{high pH}$) are less effective.

  • Concentration: Higher concentrations are absorbed more easily.

  • Length of Contact: Longer contact (e.g., sucking on a lozenge vs. swallowing) increases absorption.

  • Age: Children and the elderly absorb more topical medication through the skin than healthy adults; thin layers are required.

  • Food: Large amounts of food slow absorption, but stomach acid can facilitate the absorption of certain systemic medications.

  • Depth of Breathing: For inhalants, deeper breaths increase the amount of medication received (crucial for asthma treatments).

The Drug Cycle: Phase 2 – Distribution

• The Process: Delivery of the drug via the circulatory system to the point of action. Initially, well-perfused organs (brain, heart, kidneys, lungs) receive the majority of the drug.

• Permeability:

  • Lipid-soluble drugs: Can pass through lipid layers of membranes due to small molecular size.

  • Water-soluble drugs: Have Difficulty passing through tissues.

• Physiological Barriers: Specialized densely packed cells that filter substances.

  • Blood-placental Barrier: Protects the fetus but can be crossed by alcohol, cocaine, and lipid-soluble drugs.

  • Blood-brain Barrier: Allows psychotropic drugs but blocks many antibiotics and water-soluble drugs.

  • Blood-testicular Barrier: Protects male reproductive organs from toxins; makes treating certain diseases difficult.

The Drug Cycle: Phase 3 – Metabolism (Biotransformation)

• The Process: The drug is chemically transformed into a less active or inactive form called a metabolite. This is necessary to remove foreign substances from the body.

• Primary Organs: The liver does most of the work through enzymes. The kidneys and intestines also participate.

• Prodrugs: Medications administered in an inactive form that only become active after metabolism. Example: fosamprenavir (Lexiva) used for HIV.

• Factors Affecting Metabolism:

  • Age: Elderly patients have decreased liver blood flow, leading to slower metabolism.

  • Genetics: Determine levels of specific enzymes.

  • Disease: Liver diseases can cause drugs to build up to toxic levels.

The Drug Cycle: Phase 4 – Excretion

• The Process: Removal of drugs and waste products to prevent cumulation (buildup).

• Routes of Excretion:

  • Kidneys: Primary route for most medications.

  • Lungs: Released as a gas.

  • Other: Bile, saliva, sweat glands, and breast milk.

• Clinical Implications:

  • Decreased kidney/liver function leads to toxicity. For example, morphine buildup can cause respiratory arrest.

  • Methotrexate Therapy: Used for leukemia; can starve healthy cells of folic acid if left in the system too long. Leucovorin is used as an antidote/rescue drug to stop its effects at a specific interval.

Therapeutic Levels, Potency, and Interactions

• Therapeutic Level: The point at which the drug has the optimum desired effect. Blood levels may be monitored to keep the drug within the therapeutic range and avoid toxicity.

• Toxicity Example: Gentamicin (Garamycin) is nephrotoxic (kidneys) and ototoxic (ears).

• Potency: The strength of a drug. Higher potency means a smaller dose is required for the desired effect.

• Half-life ($t_{1/2}$): Determines frequency of dosing. Drugs with long half-lives are taken less frequently. For example, an anesthetic with a short half-life is preferred for patients who need to drive home soon after treatment.

• Drug-Drug Interactions:

  • Synergism: Drugs work together (e.g., Acetaminophen with Codeine).

  • Antagonism: One drug weakens another. Example: Birth control pills are less effective when taken with certain antibiotics; Tetracycline is ineffective when taken with Penicillin.

Side Effects and Adverse Reactions

• Classification: Usually classified by body system or organ.

• Mechanism: Drugs affect nontargeted cells via receptors. Metaphor: The receptor is the "lock," and the medication is the "key."

• Systemic Side Effects:

  • Central Nervous System (CNS): Agitation, hallucinations, confusion, depression, drowsiness, coma. Muscle relaxants like Flexeril (cyclobenzaprine) cause dizziness.

  • Liver: Damage (hepatotoxicity) can lead to jaundice (yellowing of skin/eyes). Associated with alcohol, acetaminophen, isoniazid, and aspirin.

  • Gastrointestinal (GI): Most common; include nausea, vomiting, constipation, and diarrhea. Long-term NSAID use can cause ulcers; misoprostol (Cytotec) may be given to prevent this.

  • Kidneys: Nephrotoxicity from drugs like ibuprofen can cause electrolyte imbalance and high potassium levels. Kidneys are monitored via Blood Urea Nitrogen (BUN) levels.

  • Ears: Ototoxicity (hearing/balance loss). Example: Vancomycin (Vancocin) can cause tinnitus and permanent hearing loss.

  • Eyes: High doses of oxygen are toxic to an infant's eyes.

  • Hematological System: Anticancer drugs can cause immunosuppression (loss of white blood cells), anemia (loss of red blood cells), and bleeding (loss of platelets). Warfarin (Coumadin) must be monitored for signs of bleeding, such as dark, tarry stools.

Drug Resources for Information

• Comprehensive Resources (Depth focus, usually print):

  • United States Pharmacopoeial National Formulary (USP/NF): Official source for FDA-approved drugs; provides standards for purity and quality.

  • United States Pharmacopoeial Dispensing Information (USP/DI): Volume 1 for prescribers; Volume 2 for patients (lay terms).

  • Physicians’ Desk Reference (PDR): Indexed by trade name, generic name, classification, and manufacturer. Includes color photographs for identification.

• Organization of the PDR:

  • Section 1 (White): Manufacturer's Index.

  • Section 2 (Pink): Brand and Generic Name Index.

  • Section 3 (Blue): Classification Index.

  • Section 4 (Gray): Product Identification Guide (Photographs).

  • Section 5 (White): Detailed Product Information (Package Inserts).

  • Section 6 (White): Catch-all (Pregnancy ratings, Poison control, etc.).

• Clinically Based Resources (Access focus):

  • Drug Handbooks / Pocket Guides: Portable and user-friendly.

  • Manufacturer’s Package Insert: Accompanies the drug from the pharmacy.

  • Pharmacists: Valuable resource for both professionals and patients.

Questions & Discussion

• Critical Thinking: Inhalation Issues: If a patient is taking shallow breaths and cannot follow directions to "breathe deeply" to increase bioavailability, alternate delivery methods or the use of a spacer might be necessary to ensure the drug reaches the lungs.

• Critical Thinking: Blood-brain Barrier Effects: Drugs crossing the blood-brain barrier often have strong effects because they directly alter the neurochemistry or environment of the central nervous system.

• Critical Thinking: Pregnancy and OTC Meds: A woman trying to conceive should consult a physician because many over-the-counter drugs are lipid-soluble and can cross the blood-placental barrier, potentially causing teratogenic effects even before she knows she is pregnant.

• Critical Thinking: Alcoholism and Metabolism: Chronic alcohol use can damage the liver, leading to reduced enzyme production and slower biotransformation, which increases the risk of drug toxicity.

• Critical Thinking: PDR Advantages/Disadvantages: Benefits include comprehensive data and visual ID; drawbacks include being bulky and requiring frequent updates to stay current with new drug releases.

• Self-Assessment/True or False Clarifications:

  • Cumulation does not mean a drug causes disease; it means the drug is building up in the body.

  • Ototoxicity damages the ears, not the eyes.

  • Idiosyncratic does not mean safe for children; it means a unique or rare reaction.

  • The primary organ of metabolism is the liver, not the kidneys.

  • BUN (Blood Urea Nitrogen) is a blood test used to evaluate kidney function.