Basic Principles of Pharmacology

Basic Principles of Pharmacology

Author: Jennifer Baker, MSN-Ed, CNE, SANE, MLT-ASCP

Original Author: Joseph Doromal, DNP, AGACNP-BC

Course: NURS 3303 Clinical Pharmacology

Institution: Kennesaw State University

Introduction

• Welcome message: "Pharm Oh Yeah, you got this!"

Course Objectives

• Understand medication properties and factors that determine patient responses to medications.

• Describe the process of medication development and resources used to disseminate medication research and information.

• Discuss the processes of pharmacokinetics and pharmacodynamics.

• Understand the mechanisms and results of medication interactions.

• Identify the manifestations and diagnostics of medication adverse effects, and the nursing actions involved in managing adverse effects.

• Describe the etiology of medication errors and methods to reduce medication error occurrence.

• Apply nursing clinical judgement in the use of medications as part of the delivery of patient care.

Properties of an Ideal Drug

• Effective: Elicits the response for which it is given.

• Safe: Cannot produce harmful effects.

• Selective: Elicits only the response for which it is given.

• Objective of drug therapy: Provide maximum benefit with minimal harm.

Additional Properties of Ideal Drugs

• Reversibility: Effects can be reversed if needed.

• Predictability: Expected outcomes can be determined.

• Ease of Administration: Simple to administer.

• Freedom from Drug Interactions: Should not interact adversely with other medications.

• Low Cost: Should be affordable for patients.

• Chemical Stability: Should remain effective without degradation over time.

• Simple Generic Names: Easier to remember and prescribe.
  Special Note: Reversal agents for opioid (L) and benzodiazepine (R) overdose are important.

Medication Costs

• Medications can be very costly, which can be a barrier for patients to afford them.

Factors that Determine Intensity of Drug Responses

• Administration: Includes dosage, route, and time of administration.

• Pharmacokinetics (ADME): What the body does to the drug.

• Pharmacodynamics: What the drug does to the body.

• Individual Variation: Factors include drug interactions, physiological and pathological variables, and genetic variables.

Medication Administration & Patient Care

• Nurses are the last line of defense against medication errors and have a significant responsibility in medication management.

Pharmacology in Patient Care

• Pre-administration Assessment:

  • Collect baseline data.

  • Identify high-risk patients (e.g., drug allergies).

  • Drug allergies can place a patient at high risk. Assess for allergies of all types prior to administration of medications.

  • Assess patient capacity for self-care (e.g., allergies to medications).

  • Pre-administration data can determine appropriateness for medication use (e.g., checking blood pressure prior to antihypertensive agents).

  • Initial CBC (Complete Blood Count) for patients who initially presented with generalized pain who eventually received additional work up and treatment for leukemia.

  • The nursing process and clinical judgment model help to serve as frameworks to guide clinical decision-making.

The NCSBN Clinical Judgment Model

• Layer 0: Client Needs

• Layer 1: Clinical Judgment Not Satisfied

  • Form hypotheses, refine hypotheses, evaluation.

• Layer 2: Instances to recognize and analyze cues, prioritize hypotheses, generate solutions, take actions, and evaluate outcomes.

• Layer 3: Environmental and individual factors affecting decision-making (e.g., resources, cultural considerations).

• Layer 4: Nursing Process includes assessment, analysis, planning, implementation, and evaluation.

Patient Education

• Topics to include in patient education:

  • Drug name

  • Indication

  • Dosing

  • Drug schedule

  • Missed doses

  • Food-drug interactions

  • Special storage instructions

  • Pregnancy/lactation instructions

  • Importance of reading labels, potential costs, and periodic lab testing.

Drug Regulation, Development, Names, and Information

History of Drug Legislation

• Federal Pure Food and Drug Act ($1906$): Set standards for drug quality, purity, and strength.

• Food, Drug, & Cosmetic Act ($1938$): All medications must be tested for safety by the FDA.

• Harris-Kefauver Agreements ($1962$): Medications must be proven effective before marketing.

• Controlled Substance Act ($1970$): Established rules for categorizing medications with potential for abuse.

• BPCA & PREA ($2002$): Promotion of research in drug safety and efficacy in children with clinical trials.

• FDA Amendments Act ($2007$): Includes rigorous oversight of drug safety post-approval.

Controlled Substances

Table $1.2$ - DEA Schedule of Controlled Substances

Randomized Controlled Trials

• RCTs are the most reliable way to objectively assess drug therapies. Key features include:

  • Use of controls.

  • Randomization.

  • Blinding.

  • A control group usually receives the placebo, not receiving that drug that is being investigated.

Steps in New Drug Development

1. Preclinical Testing: Toxicity, pharmacokinetics, possible useful effects.

2. Investigational New Drug (IND) Status: Begin clinical testing in humans.

3. Clinical Testing (Phases I-III): Evaluate safety and efficacy.

4. Post marketing Surveillance (Phase IV): Continued monitoring of safety and adverse effects post-approval.
   Despite all of the steps, there is:

5. Still very limited information on medication safety in women and children and possibility of undetected adverse effects after going to market

⭐Medication Nomenclature⭐

• Chemical Name: Describes medication using chemistry nomenclature.

  • Example: N-acetyl-para-aminophenol.

• Generic Name: Name of drug assigned by U.S. Adopted Names Council that is less complex than chemical name

  • Example: acetaminophen.

• Trade Name: Name under which a drug is marketed under for ease of use and recall

  • Example: Tylenol, Ofirmev, APAP.

Pharmacokinetics

Overview

• Pharmacokinetics: What the body does to the medication.

Key Processes (ADME)

1. Absorption: Movement from site of administration to bloodstream.

   • Rate determines speed of effects; amount determines intensity.

2. Distribution: Movement of drugs throughout the body to the sites of action.

   • Blood Flow to Tissues: Drugs are delivered rapidly to well-perfused organs (heart, liver, kidneys). Distribution to abscesses and tumors is limited by low blood flow.

   • Exiting the Vascular System:

     • Blood-Brain Barrier (BBB): Tight junctions prevent drug passage; only lipid-soluble drugs or those with transport systems can enter the CNS.

     • Protein Binding: Drugs can bind to Albumin. Only unbound ("free") drug molecules can leave the blood to reach sites of action.

     • Placental Transfer: Not an absolute barrier; lipid-soluble compounds cross easily to the fetus.

   • Entering Cells: Many drugs must enter cells to interact with receptors or undergo metabolism.

3. Metabolism: Conversion of drugs into another form (biotransformation).

   1. Accelerated renal excretion of drugs

   2. Drug inactivation

   3. Increased therapeutic action

   4. Activation of prodrugs

   5. Increase toxicity levels

   6. Decreased toxicity

   7. Consider age, nutritional status, and competition

4. Excretion: Removal of drug from the body.

Half-Life ($t_{1/2}$)

• Definition: The time it takes for the drug concentration to decrease by $50\%$.

• Dosing frequency: Short half-life requires more frequent dosing.

• Time to steady state: Usually takes about $4-5$ half-lives.

• Time for elimination: About $4-5$ half-lives to remove approximately $95-97\%$ of the drug.

Plasma Drug Levels

• Cannot directly measure drug concentration at site of action

• Direct correlation between therapeutic and toxic response and amount of drug present in plasma

• Drug concentration can help determine appropriate dosages, routes, and therapeutic effectiveness

First pass Effect

• Drugs that are highly metabolized lose much of their effectiveness due to first pass effect.

• May need higher doses or be administered via a different route to achieve therapeutic effect

Routes of Administration

Most common routes for drug administration includes IV, IM, SQ, and PO.

• Intravenous (IV): Instantaneous absorption; no barriers.

  • Advantages: Rapid onset, large volumes.

  • Disadvantages: Irreversible, risk of overload/infection.

• Intramuscular (IM) & Subcutaneous (SQ): Barrier is the capillary wall.

  • Advantages: Good for poorly soluble drugs.

  • Disadvantages: Painful, inconvenient.

• Oral (PO): Barriers include GI epithelium and capillary walls.

  • Advantages: Easy, safe, reversible.

  • Disadvantages: Variable absorption, inactivation by GI acids.

Pharmacodynamics

Overview

• Pharmacodynamics: What the drug does to the body.

• Efficacy: The largest effect a drug can produce. Increased height in the dose-response curve indicates more efficacy.

• Potency: The amount of drug needed to elicit a response. Potency is rarely an important characteristic of a drug, and potency does not imply anything about the drugs maximal efficacy.

Pharmacodynamics & Nursing

By knowing how drugs affect the body, nurses can:

1. Provide patient education in medications

2. Make decisions with PRN medications

3. Evaluate patients for drug responses

4. Collaborate with prescribers regarding medication therapy

Drug-Receptor Interactions

Drugs are simple chemicals. Most drugs work in the body by interacting with other chemicals and receptor site to produce an effect.

• Four Primary Receptor Families:

  1. Cell membrane-embedded enzymes.

  2. Ligand-gated ion channels.

  3. G protein-coupled receptor systems.

  4. Transcription factors.

Agonists, Antagonists, & Partial Agonists

The type of action a medication will have at the receptor site will affect the responses seen in patients.

a = agonist alone

b = agonist + antagonist (low dose)

c = agonist + antagonist (higher dose)

d = antagonist alone

Drug Interactions

Overview

Occur whenever a patient take two or more drugs and can be either intended or unintended and include

• Prescription drugs

• OTC drugs

• Caffeine, nicotine, alcohol, and illicit drugs

Interaction Consequences

• Intensification of therapeutic and adverse effects

• Reduction of therapeutic and adverse effects

• Creation of unique responses

Some patients benefit from medication interactions that result from intensification of effects, such as multiple medications used to lower blood pressure.

Minimizing Drug-Drug Interactions

Nurses can help minimize adverse interactions by:

• Minimizing number of drugs patient receives

• Take thorough drug history, including OTC and illicit drugs

• Adjust dosage with inducers of metabolism

• Monitor for s/s toxicity

Drug-Food Interactions

Calcium from dairy products can reduce absorption of tetracycline

• It important that you education patients on this interaction because children consume dairy products around this time.

Consuming food with saquinavir (type of antiviral for HIV), can increase adsorption of the medication.

Grapefruit Juice Effect

• Furanocoumarins and flavonoids can inhibit CYP3A4 metabolism, and increase blood levels of certain medications.

Medication Instructions

• “With food”: Take with or shortly after meals

• “On an empty stomach”: 1 hour before meals or 2 hours after meals

Adverse Drug Reactions (ADRs)

• Common ADRs: These may include nausea, dizziness, or rashes that can occur as a reaction to a medication.

• Serious ADRs: Initially present as rare but can lead to severe effects such as liver damage or anaphylaxis, requiring immediate medical attention.

• Adverse Effect: Noxious, unintended effect at normal doses.

• Side Effect: Unavoidable secondary effect at therapeutic doses.

• Toxicity: Organ-specific damage (e.g., nephrotoxicity).

Organ-Specific Toxicity

Nephrotoxicity: Amphotericin B (antifungal) and Vancomycin (antibiotic)

• Medications are leading cause of acute liver failure due to metabolism converting drugs to toxic products.

• Monitor liver enzymes (ALT & AST)

• Assess for s/s liver injury (jaundice, abdominal pain, and elevated bilirubin levels)

Pulmonary Toxicity: Amiodarone (Antidysrhythmic)

Ototoxicity: Aminoglycoside antibiotics

QT Interval Drugs

• Prolonged QT intervals creates a risk for dysrhythmias

• Must monitor patients on QT intervals drugs with telemetry

Minimize Adverse Drug Reactions

• Pharmaceutical Industry: Produce safest medications possible

• Prescriber: Select least harmful drugs, balance risks and benefits

• Nurses: Evaluate patients for ADR, educate patient and families

Medication Guides

1. Patient adherence to directions for drug use is essential for efficacy

2. Patients need to know about potentially serious effects when deciding to use a drug

U.S. Boxed (Black Box) Warnings

Strongest warning on drugs that can on the market. Alerts prescribers and patients to potentially severe side effects (dysrhythmias, suicidal thoughts, fetal harm)

Risk Evaluation & Mitigation Strategies

• Plan designed to minimize drug induced harm

• May have extra provisions, such as with iPLEDGE and isotretinoin

Medication Errors

• Any preventable event that may cause or lead to inappropriate medication use or patient harm.

• Human factors, communication mistake, and name confusion account for 90% of all errors.

• Nurses can reduce the risk of med errors by:

1.   Administer meds at the right time

2. Verify patients allergies and contraindications

3. Administer med consistent with standard safety protocol

4. Monitor patient and trend labs

5. Communicate findings consistent with ADR

6. Perform assessments as needed

Conclusion

• Pharmacology principles are essential for safe nursing practice and effective patient care.