Pharmacotherapeutics: Review and Core Concepts
Course Resources
Eclass: Primary platform for all course materials.
Announcements: Key updates and information.
Course outline: Detailed structure of the course.
Lecture materials: Includes learning outcomes and PowerPoint presentations.
Ask a question forum: For general queries.
Email: helenas@ualberta.ca for confidential information, allow 2 school days for response. Subject line must be N216A ….. (subject). University of Alberta email etiquette must be observed.
PowerPoint is a guideline ONLY: Supplement with your own notes.
Units/chapters resources are posted in the course outline.
Add/write your own notes during lecture time, focusing on key concepts rather than every word. Handwritten note-taking enhances learning and retention by intensifying CNS synapse junctions.
Add to your class notes during study time, including diagrams, tables, charts, and concept maps.
Avoid rewriting the textbook; highlight key points and integrate them into existing notes.
Self-directed and independent learning: You are responsible for your own work.
Recordings of class material are not permitted: As per the University of Alberta Student code of conduct.
Testable material: Includes lecture depth and critical thinking (linking knowledge together).
How to Use Concepts (Linking Knowledge)
Main concepts: (e.g., abdominal pain) are central topics.
Related concepts: (e.g., patient health/illness development) are results of critical thinking and linking knowledge.
Examples of Concepts:
Patient Health/Illness: Development, Fluid & Electrolyte, Nutrition, Mobility, Mood & Affect, Functional Ability, Acid-Base Balance, Perfusion, Tissue Integrity, Anxiety, Family Dynamics, Thermoregulation, Gas Exchange, Sensory Perception, Cognition, Culture, Sleep, Clotting, Pain, Psychosis, Spirituality, Cellular Regulation, Reproduction, Fatigue, Addiction, Adherence, Intracranial Regulation, Sexuality, Stress, Interpersonal Violence, Self-Management, Hormonal Regulation, Immunity, Coping, Glucose Regulation, Inflammation, Elimination, Infection.
Nursing/Health Care Professional Identity: Communication, Care Coordination, Health Care Organization, Clinical Judgement, Collaboration, Caregiving, Health Care Economics, Leadership, Safety, Palliative Care, Health Policy, Ethics, Technology & Informatics, Health Disparities, Health Care Law, Patient Education, Evidence, Health Promotion, Health Care Quality.
Pharmacotherapeutics: Drug Categories
Drug/Medication: A chemical agent, synthetically produced.
Biologic: A medication produced from living organisms or containing components of living organisms, such as proteins, cells, or tissues. Examples include antibodies (e.g., immunoglobulins), blood products (e.g., RBCs), and hormones (e.g., Insulin).
Natural Health Product (NHP): Sourced or derived from nature (e.g., plants). Examples include vitamins, minerals (e.g., Calcium), dietary supplements (e.g., whey protein), and dried herbs (e.g., echinacea).
Drug Names
Generic Name:
Describes the drug without a proprietary affiliation.
Assigned as an international non-proprietary name.
The same throughout the world; there is only 1 generic name per drug.
Used on the NCLEX exam.
Brand/Trade Name:
Named by the manufacturing company.
Many trade names can exist for one generic drug.
Often refers to the drug first to market, which is patent-protected for 20 years before other manufacturers can produce it.
Chemical Name:
The drug name based on its chemical composition.
Assigned by IUPAC (International Union of Pure and Applied Chemistry).
Example: Potassium Chloride.
Drug Schedules (Canada)
Table 2.4 Schedule System for Drugs Sold in Canada:
Schedule I: Available only by prescription and provided by a pharmacist. Includes all prescription drugs, drugs with no potential for abuse, controlled drugs, and narcotics.
Schedule II: Available only from a pharmacist (pharmacist Rx); must be retained in an area with no public access.
Schedule III: Available via open access in a pharmacy or pharmacy area (OTC - Over-The-Counter).
Nursing Process in Pharmacotherapeutics
Always use the Nursing Process, and always include patient education.
Assessment: Includes health history and chief concern assessment (signs and symptoms).
Planning: Developing a plan of care.
Intervention: Involves pharmacotherapeutics and patient education.
Evaluation: Includes assessment of drug action, drug effects, and side effects.
Drug Formulations and Administration Routes
Reasons for various formulations and administration routes: Clinical setting, medical situation, and drug properties (stability, metabolism, and the drug's need to reach target tissues).
Clinical Example: A 72 year old patient with invasive malignancy experiencing pain, taking Hydromorphone (Dilaudid), 4 ext{ mg} PO, q4 ext{h}. With advancing disease, the patient becomes increasingly somnolent. The change that should be made to the drug order, in regards to formulation, would be to consider an alternative route of administration to oral, given the somnolence.
Administration Routes:
Oral (PO) + via inserted tubes (NG, NJ, etc.)
Sublingual (SL)
Intranasal (insufflation)
Inhalation + via ET tube
Topical
Intravenous (IV)
Intramuscular (IM)
Subcutaneous (SC)
Transdermal
Rectal (PR)
Implanted ports
Vaginal
Intraosseous
Epidural + Spinal (intrathecal)
Terminology: Parenteral (non-enteral routes, e.g., IV, IM) vs. Enteral (GI tract routes, e.g., PO, rectal).
Example: Sublingual (SL) Administration:
Placement is sublingual (under the tongue).
Capillary absorption directly into circulation (bypasses GI tract and first-pass effect).
Achieves systemic effect.
10 Rights of Drug Administration (Adam's text: pg. 86-94)
RIGHT:
Drug
Patient
Dose
Route
Time (delivery & frequency)
Documentation
History & Assessment
Informed consent (right to refuse)
Interactions evaluation
Education & Information
Pharmacokinetics (PK) and Pharmacodynamics (PD)
Pharmacokinetics ('PK'):
'pharma' = medicines & 'kinetics' = motion.
Refers to the movement of drugs across cell membranes via the lipid bilayer.
Involves ADME: Absorption, Distribution, Metabolism, Excretion.
Pharmacodynamics ('PD'):
Refers to receptor binding and affinity (saturable, competitive), e.g., G-protein receptor.
Increases OR suppresses existing physiological processes.
An antagonist only blocks the receptor and has no efficacy (does not produce a direct cellular response).
Factors Affecting Pharmacokinetics: Molecular Characteristics (MC)
Charge (ionization):
Neutral atoms or molecules can be converted to electrically charged ones, becoming 'ionized' (polar) with positive or negative charges.
'Non-ionized' means not charged (aka non-polar).
Lipophilicity vs. Hydrophilicity: Drug's affinity for lipids (fats) or water.
Size: The molecular size of the drug.
Membrane Transport:
Passive: Diffusion, osmosis, facilitated diffusion (does not require energy).
Active: Requires energy to move drugs against a concentration gradient.
ADME General Rule
Lipophilic, non-ionized, small: Generally leads to easy Absorption (A) & Distribution (D).
Hydrophilic, ionized: Generally leads to easy Excretion (E).
Absorption (A): The process of the drug entering into circulation (becoming bioavailable), influenced by administration route and molecular characteristics (MC).
Distribution (D): The transport of the drug through the body to target tissues, affected by blood flow, tissue size, molecular characteristics (MC), and Plasma Protein Binding (PPB).
Metabolism (M): Prepares the drug for excretion or activates prodrugs; the liver is the primary organ for metabolism.
Excretion (E): The elimination of the drug from the body, influenced by creatinine clearance (CrCl) and following either first-order or zero-order kinetics.
Metabolism: First-Pass Metabolism
First-Pass Metabolism: This phenomenon primarily affects orally administered drugs.
Drug is ingested and enters the Lumen of the GI Tract.
Absorbed drug travels via the Hepatic Portal Capillary Network System.
It then proceeds through the Hepatic Portal Vein.
The drug reaches the Liver, which metabolizes a significant portion of it.
The remaining drug (after first-pass metabolism) enters the General (Systemic) Circulation.
Therapeutic Range Graph
Single-dose drug administration example:
Onset of action = 2 hours.
Duration of action = 6 hours.
Termination of action = 8 hours after administration.
Peak plasma concentration = 10 ext{ mcg/ml} (maximum drug concentration reached in plasma).
Time to peak drug effect = 5 hours.
This graph illustrates the plasma concentration of a drug over time, showing when it reaches therapeutic levels, peaks, and declines.
Therapeutic Index (TI): How Safe is a Drug?
The Therapeutic Index is the ratio between the median toxicity dose (TD{50}) and the median therapeutic dose (ED{50}).
ED_{50} (Median Therapeutic Dose): The dose at which 50 ext{%} of patients will achieve the desired therapeutic effect.
TD{50} ('Median Toxicity Dose'): The dose at which 50 ext{%} of patients will experience a toxic response. It is often derived from LD{50} (Lethal Dose in lab trials).
TI = rac{TD{50}}{ED{50}}
A smaller TI number indicates a higher risk associated with the drug, meaning the margin between an effective dose and a toxic dose is narrow.
Narrow TI medications (require careful monitoring):
Digoxin (Lanoxin)
Warfarin (Coumadin)
Phenytoin (Dilantin)
Tacrolimus (Prograf, Astagraf)
Distribution: Plasma Protein Binding (PPB) Explained
PPB involves the cohesion ('binding') of drugs with plasma protein molecules.
Drugs have varying 'affinity' (strength of binding) for plasma carrier proteins.
Examples of plasma proteins:
Albumin: Primarily binds acidic drugs.
Alpha-1-acid glycoprotein: Primarily binds basic drugs.
Binding decreases distribution rates: Only unbound (free) drug can distribute to tissues, bind to receptors, and exert its pharmacological effect.
Characteristics of binding: Competitive, Reversible, Saturable.
Unbound drugs: Are effective and able to elicit a therapeutic response.
Bound drugs: Are NOT effective; they act as a circulating reservoir.
Recall the clinical example of PPB & 99 ext{%} PPB drug Warfarin (Coumadin):
Warfarin is an anticoagulant highly effective in reducing blood coagulation.
99 ext{%} PPB means that only 1 ext{%} of the drug is free (unbound) and active.
Why is PPB 'beneficial'? It provides a reservoir, allowing for a sustained release of free drug over time, thus prolonging its action and reducing fluctuations in active drug concentration.
If PPB decreases by as little as 1 ext{%} (e.g., from 99 ext{%} bound to 98 ext{%} bound), how much more Warfarin is free? The free drug concentration would double (from 1 ext{%} to 2 ext{%}), leading to a significant increase in active drug. This is technically an overdose due to increased free drug concentration.
What effect will this have on the patient? Increased risk of bleeding or hemorrhage due to enhanced anticoagulant effect.
Metabolism (aka Biotransformation)
Metabolism is an enzymatic chemical conversion process that prepares the drug/substance for excretion. It terminates drug action (by yielding metabolites for excretion) or activates prodrugs.
Liver: The primary metabolizing organ (other organs include lungs, kidneys, etc.). It 'ionizes' drugs to make them more hydrophilic for better excretion.
Phase I Metabolism:
Occurs via hepatic microsomal enzymes, collectively known as the 'CYP450 group'.
These enzymes are saturable and dynamic (meaning their activity can be changed by inducers and inhibitors).
Examples: CYP3A4, CYP1A2.
Phase II Metabolism:
Applies only to some drugs.
Involves conjugation, where a large, polar molecule is attached to the drug or its Phase I metabolite to make it more water-soluble for excretion.
Example: Glutathione conjugates Tylenol's toxic metabolite (n-acetyl-p-b).
Biotransformation outcomes:
Active drug to inactive metabolite (the most common outcome, terminating drug action).
Active drug to active metabolite (requires further metabolism to be eliminated).
Inactive drug to active metabolite ('prodrugs' require metabolism for activation).
Note: Orally administered (PO) drugs undergo a portion of 'First-pass' metabolism as described previously.
Note: Some drugs travel 'unchanged' and are excreted without significant metabolism (e.g., Amoxicillin).
Recall the clinical example of Grapefruit juice & Lovastatin:
Lovastatin is a cholesterol-reducing drug.
Lovastatin is primarily metabolized by CYP3A4.
Grapefruit juice is a known CYP3A4 inhibitor.
What does 'inhibition' of a metabolizing enzyme mean? It means the enzyme's activity is reduced or blocked, slowing down the metabolism of its substrate drugs.
What will happen to the metabolism of Lovastatin if its metabolizing enzyme is inhibited? The metabolism of Lovastatin will be slowed down or reduced.
What will this cause in the patient? Lovastatin will accumulate in the plasma, leading to higher drug levels, potentially increasing its cholesterol-reducing effect but also the risk of dose-dependent side effects like myopathy or rhabdomyolysis.
Factors Affecting Renal Excretion
Molecular characteristics: Ionization, hydrophilicity, small size promote renal excretion.
Plasma Protein Binding (PPB): Highly protein-bound drugs are generally not freely filtered by the glomerulus and thus less readily excreted by the kidneys.
Metabolized state: Drugs that have been metabolized (especially becoming more polar/ionized) are typically more easily excreted by the kidneys.
Urinary pH: The pH of the urine can be medically altered to ionize specific drugs, thereby enhancing their excretion (e.g., alkalization of urine to excrete acidic drugs like ASA in overdose).
Cardiac Output: Affects renal blood flow, which in turn influences glomerular filtration and drug delivery to the kidneys for excretion.
Renal function:
A decline of approximately 1 ext{%} per year in the elderly population affects drug excretion.
Neonates and young infants have immature renal function, leading to slower drug excretion.
The integrity of the glomerulus: Renal disease can significantly impair drug excretion.
Clearance (Cl): 'RATE OF ELIMINATION of drug in an hour'
First-order elimination kinetics:
Elimination is proportionate to the drug serum concentration.
A constant fraction of the drug is eliminated per unit time.
Calculated as: Cl = rac{ ext{elimination}}{ ext{peak plasma concentration}}, where elimination is the total amount of drug voided in urine in an hour. Units: ext{mg/dL/hr} or ext{mg/L/hr}.
Zero-order elimination kinetics:
The rate of elimination or 'clearance' is constant, regardless of drug concentration.
A constant amount of the drug is eliminated per unit time, regardless of how much drug is in the body.
Examples: Ethanol, aspirin (ASA) at high doses, phenytoin (Dilantin).
Excretion: Renal Function in Clinical Practice
GFR (Glomerular Filtration Rate) calculation: Normal is >59 ext{ ml/min}.
Creatinine: Measured via bloodwork lab results and used to estimate GFR.
Clearance: Requires calculation, often using formulas involving creatinine levels to estimate kidney function and drug elimination capacity.
Case: ETOH (Alcohol) Poisoning
Why 10 shooters within 1 hour can cause ETOH poisoning:
CNS effects: Drug-dose dependent. Ethanol acts as a GABA agonist and Glutamate inhibitor, leading to calming effects initially.
1-2 drinks can result in blood alcohol levels of 20-30 ext{ mg/dL} (in serum).
Metabolism: Primarily metabolized by alcohol dehydrogenase in the liver and GI tract.
Clearance rate: The liver metabolizes alcohol at a relatively constant rate of approximately 20 ext{ mg/dL/hr} (zero-order kinetics).
Diuresis: ETOH inhibits Antidiuretic Hormone (ADH), leading to increased diuresis, dehydration, and electrolyte imbalances.
ETOH poisoning: Emergency Room admissions typically have blood alcohol levels averaging >295 ext{ mg/dL}, far exceeding the body's elimination capacity, especially with rapid consumption.
Note: Breathalyzer results are typically converted by multiplying by 1000 to express in ext{mg/dL}.
Half-Life (t ½)
Definition: The time required for a drug plasma concentration to decrease by one half (by 50 ext{%}).
Continuous Processes:
Circulating drug is continuously biotransformed for excretion.
If a drug is 'unchanged' (not metabolized), biotransformation is not required for its elimination.
Circulating biotransformed drug is continuously excreted with each cardiac output (CO).
Characteristics of t_{1/2}:
Calculated and known for each specific drug.
Serves as a broad guideline to estimate the frequency of drug administration needed to maintain therapeutic levels.
Elimination Rule: Approximately 4 imes t_{1/2} is the time required for 90 ext{%} of the drug to be cleared from the body, leading to clinical elimination.
Pharmacodynamics: Terminology
Receptor Affinity:
Refers to the 'strength' or 'length' of binding between a drug and its receptor.
Characteristics: Specific (binds to particular receptors), Saturable (finite number of receptors), Reversible (bound drugs can dissociate).
Drug Efficacy:
The effectiveness of a drug.
The degree to which a drug induces a maximum therapeutic effect.
Example: For motion sickness nausea, Gravol might be effective; for chemo-induced nausea, Ondansetron has higher efficacy.
Note: Antagonists have no efficacy themselves; they only block receptors and do not produce a direct cellular effect.
Potency:
Refers to the strength of a drug, specifically how much of the drug is required to produce a given effect.
A drug with higher potency produces a therapeutic effect at a lower dose.
Example: If Drug A requires 20 ext{ mg} to achieve an effect and Drug B requires 10 ext{ mg} for the same effect, then Drug B has higher potency.
Drug-Receptor Interactions
Agonist: 'Primary' or 'Full' Agonist
Binds readily to a receptor and mimics an endogenous substance, producing a full biological response.
Example: Morphine, which binds to opioid receptors to produce pain relief.
Partial Agonist
Binds to a receptor but produces a maximum response that is smaller than that of a full agonist, even if all receptors are occupied.
Has lower efficacy compared to a full agonist.
Note: Can interfere with full agonists' binding by competing for the same receptor, potentially reducing the effect of a full agonist.
Example: Buprenorphine.
Inverse Agonist
Induces the OPPOSITE effect of the naturally binding substance (e.g., adenosine).
Works by binding to the same receptor as an agonist but stabilizing the receptor in an inactive conformation, thereby reducing constitutive (basal) receptor activity.
Example: Caffeine, which acts as an inverse agonist at adenosine receptors.
Antagonist
'Blocks' the receptor to prevent endogenous substances or other agonists from binding.
Requires higher affinity than the agonist to effectively block the receptor.
Has no therapeutic effect other than to block the receptor; it does not produce a direct cellular response itself.
Example: Naloxone (Narcan), which blocks opioid receptors to reverse opioid effects.
Pharmacotherapy Effects on Populations
Older Adult Population:
Decreased peristalsis (affecting absorption), acidity (affecting drug dissolution), elimination (due to reduced kidney and liver function), and Glomerular Filtration Rate (GFR).
Decreased liver function (affecting metabolism).
Lower albumin levels (affecting plasma protein binding, leading to more free drug).
Decreased Cardiac Output (CO) (affecting drug distribution).
Higher incidence of polypharmacy (use of multiple medications, increasing risk of drug-drug interactions and adverse effects).
Pediatric Population:
Drug dosing is typically 'per kg' due to weight variations.
May have more adipose tissue per kg, which can affect the distribution of lipophilic drugs.
Immature liver function until later teens, impacting drug metabolism.
Pregnancy:
Most drugs cross the placenta, posing potential risks to the fetus.
The maternal drug concentration often determines the degree of effect on the fetus.
Pharmacodynamics (PD) & Drug Tolerance
Tolerance (aka Down-regulation):
The most common form of tolerance.
Characterized by receptor desensitization (receptors become less responsive) OR a decreased number of viable (functional) receptors available for a substance.
Result: More drug is required for the same response to be achieved.
Examples: Addictive substances such as opioids, benzodiazepines, and alcohol.
Other kinetic alterations leading to resistance:
Increased drug metabolism due to consistent demand for the drug, causing the drug to be metabolized too fast and thus become less effective.
Factors Influencing Patient Response
Drug-related Factors:
Pharmacokinetics:
Absorption (how drug enters circulation).
Distribution (including Plasma Protein Binding (PPB)).
Metabolism (including half-life (t_{1/2})).
Excretion (how drug leaves the body).
Pharmacodynamics:
Onset, peak, and duration of action.
Therapeutic range (the desired concentration range).
Side effects and adverse reactions.
Clinical Factors:
Age and weight of the patient.
Present health disorder and other disease entities.
Client drug compliance.
Administration Factors:
Drug form (e.g., tablet, liquid, injection).
Route of drug administration.
Multiple drug therapy and potential drug interactions.
Drug Effects: Toxicity
Drug effects can be categorized as undesirable or therapeutic.
Undesirable effects:
Non-deleterious (Side effects): Minor, often predictable, and tolerable effects.
Deleterious (TOXIC): Harmful, potentially life-threatening effects indicating an overdose or extreme adverse reaction.
Therapeutic effects: The desired and beneficial outcomes of drug administration.
Common Toxicities
ASA (Aspirin)
Tylenol (Acetaminophen)
Opioids: Oxycodone, Fentanyl
Benzodiazepines: Xanax (alprazolam), Valium (diazepam)
Alcohol (ETOH)
THC (Cannabis)
Cocaine
Medication errors! (A significant cause of toxicity)
Clinical Procedure in Toxicity (Overdose): 'Stabilize & Analyze'
A (Airway) & B (Breathing):
Assess airway patency, respiratory effort, rate, and skin color.
Interventions: Consider ET tube insertion if airway compromised, administer oxygen if needed.
C (Circulation):
Assess perfusion quality: Level of Consciousness (LOC), pulses, skin condition, Blood Pressure (BP).
Interventions: Administer IV fluids, consider sympathomimetics for hypotension.
D (Dysfunctions):
Assess for dysfunctions and treat as needed.
Examples: Apnea, seizures, cardiac arrhythmias, hyperthermia.
E (Identify & Initiate Treatment):
Identify the drug/substance involved.
Initiate specific treatment based on the identified substance.
Identifying Drug/Substance in Toxicity: Toxidromes
Approach: Identify the drug/substance by reviewing the patient’s Health History, conducting a physical assessment of signs and symptoms using clinical tools called 'toxidromes'. Do not make assumptions; always assess the patient! Lab toxicology (urine, serum) can confirm.
ASA (Aspirin) Toxidrome: Confusion, Tachycardia, Tachypnea, Hyperthermia, Diaphoresis, Vomiting, Abdominal pain.
Acetaminophen Toxidrome: Abdominal pain, Loss of appetite, Nausea/vomiting, Diaphoresis, Somnolence (tend to occur later in the course).
Opioids Toxidrome (Fentanyl, Codeine, Morphine, Oxycodone, Heroin, etc.): Bradypnea/Apnea, Bradycardia, Somnolence/Coma, Pupils constricted (miosis).
Cocaine (& other stimulants) Toxidrome: Agitation, tremors, Tachycardia, Tachypnea, Hyperthermia, Diaphoresis, Pupils dilated (mydriasis).
Cannabis Toxicity & Toxidrome
Neurocognitive effects: Variable presentation.
Signs & Symptoms: Vital signs changes (tachycardia, hypertension), seizures, nausea/vomiting, acute psychosis, changes in Level of Consciousness (agitation; coma).
Route of administration considerations:
Inhalation: Onset of effect typically 15-30 minutes, with a bioavailability of approximately 50 ext{%}.
Oral (PO): Onset is 1-2 hours (highly variable), with a lower bioavailability of approximately 20 ext{%}.
Components:
THC (Tetrahydrocannabinol): Primarily causes CNS and vital signs instability.
CBD (Cannabidiol): Modulates the effect of THC at receptors, often by mitigating some of the adverse effects.
Treatment: Primarily supportive care (addressing symptoms).
Review of ADME as Treatment of Common Toxicities
General Principle: Stabilize the patient with supportive treatment first.
Adsorption: 'Binding of drug, to decrease its absorption'.
Tx for: Tylenol, ASA, Benzodiazepine toxicities.
Treatment drug: Activated Charcoal, administered enterally.
Mechanism: Binds the drug to its surface carbons in the GI tract, preventing absorption, and the charcoal-drug complex is then eliminated via stool.
Metabolism: Induction of metabolism
Tx for Tylenol toxicity: Tylenol overdose depletes the liver enzyme Glutathione, causing low Phase II metabolism and accumulation of the hepatotoxic Phase I product, NAPB.
Treatment drug: NAC (n-acetylcysteine / acetylcysteine), administered IV or PO.
Mechanism: NAC is a Glutathione enzyme precursor, which enhances Phase II metabolism, replenishing glutathione stores and detoxifying NAPB.
Tx for ETOH intoxication: ETOH intoxication can be associated with depleted alcohol dehydrogenase.
Treatment drug: Metadoxine, administered IV.
Mechanism: Metadoxine induces alcohol dehydrogenase activity, aiding in faster alcohol metabolism.
Distribution: Blocking the tissue receptor
Tx for opioid toxicity: Achieved through antagonism at mu ($ ext{\mu}$) and kappa ($ ext{\kappa}$) opioid receptors.
Treatment drug: Naloxone (Narcan).
Characteristics: Onset 2-4 minutes, duration of action approximately 45 minutes.
Tx for benzodiazepine toxicity: Achieved through antagonism at the GABA receptor.
Treatment drug: Flumazenil, administered IV.
Elimination: Stool, urine, blood
In the GI tract: Activated Charcoal increases GI elimination of the charcoal-bound drug.
In the kidneys: Alkalization of urine can be medically induced to enhance acidic drug excretion.
Treatment drug: Sodium Bicarbonate.
Mechanism: Ionizes an acidic substance (e.g., ASA), making it less lipid-soluble and trapping it in the urine for faster excretion.
Example: Treatment of ASA toxicity.
In the blood: Hemodialysis.
Mechanism: Actively removes drugs or toxins from the blood by filtering it through an external machine.
Brainstorming from Clinical Scenarios
What would the effects of administering Narcan to a patient receiving opioids for therapeutic reasons be? It would reverse the opioid's therapeutic effects, leading to acute pain, potential opioid withdrawal symptoms, and possibly increased vital signs (e.g., heart rate, blood pressure) due to sympathetic activation.
Why is the duration of action of drugs so important? It dictates the frequency of administration and the need for repeat doses, especially in overdose situations. For example, Narcan's 45 minute duration means it might wear off before a longer-acting opioid, necessitating repeat Narcan doses.
What could decrease the efficacy of Narcan? Extremely high opioid doses, certain synthetic opioids (e.g., some fentanyl analogs) which may have very high receptor affinity, or issues with the chosen administration route (e.g., poor absorption).
An apneic patient is given Narcan, IN (intranasal). Will it be effective? It may not be as effective as other routes (IM/IV) in an apneic patient. Intranasal absorption relies on respiratory effort to draw the drug into the nasal passages and across the mucous membranes. Lack of breathing can severely impair drug delivery and absorption, leading to delayed or insufficient effect.
Homework, Testable Concepts
Review the main functions of the liver: E.g., metabolism of drugs/toxins, bile production for fat digestion, synthesis of plasma proteins (e.g., albumin, clotting factors), glucose regulation, detoxification of ammonia.
List 5 major issues if the liver is compromised:
Impaired drug metabolism, leading to drug accumulation and toxicity.
Decreased synthesis of albumin, leading to reduced plasma protein binding and increased free drug levels.
Decreased synthesis of clotting factors, leading to coagulopathy and increased bleeding risk.
Impaired bile production, leading to malabsorption of fats and fat-soluble vitamins.
Accumulation of toxins (e.g., ammonia), leading to hepatic encephalopathy and altered mental status.
What would you note on patient assessment (with compromised liver function)? Jaundice (yellowing of skin/eyes), ascites (fluid accumulation in abdomen), easy bruising or bleeding, fatigue, nausea, dark urine, pale stools, altered mental status (confusion, lethargy), spider angiomas, palmar erythema.