NRS 321 Pathophysiology - Pharmacology 1 Class Notes: Introduction - Fall 2023 PDF

Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class notes: Introduction – Fall 2023 NRS 321 Pathophysiology – Pharmacology I Cellular pathophysiology Overview of pharmacology and nursing practice Pharmacokine...

Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class notes: Introduction – Fall 2023 NRS 321 Pathophysiology – Pharmacology I Cellular pathophysiology Overview of pharmacology and nursing practice Pharmacokinetics/dynamics Lifespan Pathophysiology - the physiology of altered health Terms Health Disease Etiology Biologic agents Physical forces Chemical agents Genetics Nutrition Pathogenesis – sequence or process Clinical Manifestations Signs - observed Symptoms – reported by the patient Epidemiology – study of disease occurrence in human populations Cell Physiology - Function Through differentiation – 8 major functions Movement Conductivity Metabolic absorption Secretion Excretion Respiration Reproduction Communication Group I Class discussion: Give examples of pathophysiology based on cellular function disruption. Cellular Responses and Adaptation Common reaction to disease Physiologic vs. pathogenic Atrophy  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class notes: Introduction – Fall 2023 Hypertrophy Hyperplasia Non - adaptive Metaplasia Dysplasia Physiologic vs Pathologic adaptation Cellular adaptation is a central theme to many disease states Atrophy – decrease in cell size. Physiologic – developmental (thymus gland atrophies); pathologic – disuse (muscle atrophy from immobilization), decrease blood supply, etc (aging causes brain cells and gonads to atrophy). Hypertrophy – increase in size and effect. Physiologic – skeletal muscles, pregnancy; pathologic – heart hypertrophies secondary to hypertension Hyperplasia – increase in number. Physiologic – after trauma (skin, liver, etc grows); pathology – endometrial hyperplasia Atrophy and Hypertrophy Atrophy Hypertrophy Non-Adaptive Responses Metaplasia – replacement of one mature cell with another (bronchial linings – ciliated columnar epithelial replaced with stratified squamous epithelial cells) can be changed if smoking ceases, otherwise may advance into malignancy. Dysplasia – abnormal changes in size, shape organization usually from a stimulus. Is NOT precancerous but frequently adjacent to cancerous tissue. Cellular injury Cells respond to injury Cells may Adapt and continue to function Be injured, but recover Be injured and not recover Cellular injury - Causes Injuries – Physical agents Mechanical forces  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class notes: Introduction – Fall 2023 Extreme temperature Electrical forces Radiation injury Chemical injury Biologic agents Nutritional imbalances Mechanisms of cellular injury/death Three major causes Free radicals and reactive oxygen species Hypoxic injury – most common cause Ischemia Anoxia ATP depletion Intracellular calcium and loss of calcium steady state Result: Injury or ineffective cellular function Defects in membrane permeability Common element is damage to the cellular membrane Cellular responses Intracellular accumulations Normal substances in abnormal amounts Abnormal products (endogenous) Abnormal products (exogenous) Pathologic Calcifications Dystrophic Metastatic Pharmacology and the nursing process The ideal medication Properties Effectiveness Safety Selectivity Additional properties: Reversible action, predictability, ease of administration, lack of drug interactions, cost  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class notes: Introduction – Fall 2023 Therapeutic objective “to provide maximum benefit with minimum harm” How do nurses help to meet this objective? How do nurses decide when to use prn medications? Medication administration safety Five/Six Rights of Medication Administration: Right drug Right patient Right dose Right route Right time Right documentation Beyond the six rights Right of refusal Right reason – demonstrated critical thinking Includes a careful preadmission assessment and evaluating therapeutic effects Affects your use of prn medications Nursing process – relate to medication therapy Assessment Analysis/Diagnosis Planning Implementation Evaluation Supplementing the nursing process Critical thinking Patient education Managing toxicity PRN administration Non-pharmaceutical measures Groups II Class discussion: Your patient has returned from surgery and will have an oral prn pain medication ordered. What do you anticipate assessing prior to giving their prn pain medication? What will you do to ensure safe medication delivery? What will you teach the patient about taking their pain medication when they go home?  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class notes: Introduction – Fall 2023 Pharmacology and Legislation Select legislation for drug regulation Federal Food and Drug Act 1906 – drugs free of ‘adulterants’ Pure Food, Drug, and Cosmetic Act 1938 – safety Harris-Kefauver Amendment 1962 – effectiveness and new drug development (2007 – safety after marketing) Controlled Substances Act 1970 – abuse potential Accelerated approval process in 1992 1962: Thalidomide - Pharcomelia Drug development - process Preclinical – animal trials Phase I – safety on healthy volunteers Phase II – patients – varying doses, effectiveness, safety Phase III – larger trial numbers Phase IV- post marketing surveillance Nomenclature Chemical name: N-acetyl-para-aminophenol Generic name: Acetaminophen Trade/proprietary name: Tylenol, Acephen, APAP, Children’s ElixSure……. The NCLEX uses generic nomenclature only Sources of medication information People Published reputable sources Newsletters References Medication Administration Record (MAR) The internet Electronic Health record Digital chart Evidence-based Real time Patient centered Improved outcomes  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class notes: Introduction – Fall 2023 Group III Class discussion: What are the benefits of EHR and how is patient care improved using EHR? https://www.healthit.gov/faq/what-electronic-health-record-ehr Pharmacokinetics and Pharmacodynamics Pharmacokinetics The movement of drug through the body Four processes: Absorption Distribution Metabolism Excretion Pharmacokinetics processes Absorption – routes advantages/disadvantages Enteral (GI tract) Parenteral Intravenous Intramuscular Subcutaneous Distribution Drug delivery via blood flow through tissue Factors: The ability of the drug to leave the vascular system The ability of the drug to enter cells Considerations Blood brain barrier Placental drug transfer Metabolism Biotransformation Typically enzymatically mediated Liver: P450 system (hepatic microsomal enzyme system) Metabolism - considerations  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class notes: Introduction – Fall 2023 Age Induction – stimulating metabolism First pass Nutrition Competition (for metabolic pathways) Excretion Renal – majority of medications Age considerations Other Breast milk Bile Lungs Pharmacokinetics - terms Therapeutic range Half – life Loading dose Maintenance dose Pharmacodynamics Biochemical and physiological effect(s) of the drug Terms Agonist Antagonist Partial agonist Pharmacodynamics Dose – response relationship What is the minimum amount of drug needed to elicit a response What is the maximum response that can be elicited How much dosage is needed to produce the desired response. Pharmacogenomics and Individual variation Image from Forbes Pharmacogenomics – ‘the study of how genetic variations can affect individual responses to drugs’ Individual variation in drug responses Body weight and composition Age  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class notes: Introduction – Fall 2023 Disease processes Placebo effect Genetics Gender/Race Group IV Class discussion: Why is individual variation important to consider for your patient? Genetics and Pharmacogenomics Pharmacogenomics – ‘the study of how genetic variations can affect individual responses to drugs’ Required for several drugs prior to prescribing; recommended for others Genetic variants can alter Drug metabolism Drug targets Immune responses to drugs Genetic variants that alter drug metabolism Increase or decrease the activation or metabolism of certain drugs Examples: Reduced therapeutic effect of clopidogrel in individuals with a variant that does not allow drug activation Increased toxicity (elevated levels) of warfarin in individuals with a variant that slows metabolism of the drug Genetic variants that alter Drug targets (on normal cells) Genetic changes in drug targets (receptors) affect the drug responses Examples: Normal cells: Beta1 adrenergic receptors that are hyperresponsive produce a better response to beta blocking medications for hypertension. Cancer cells: Herceptin acts on breast cancers with overexpressed HER2 receptors Genetic variants that alter immune responses to drugs Genetic variation can increase the risk of hypersensitivity reactions to drugs Example: Carbamazepine can produce life threatening skin reactions in patients of Asian descent. Medication Interactions Drug – Drug Intensify effects (medications affecting clotting) Reduce effects (Propranolol and albuterol) Mechanisms Pharmacokinetic (absorption, distribution, metabolism, excretion)  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class notes: Introduction – Fall 2023 Pharmacodynamics (receptor competition) Basic Mechanisms of Drug-Drug Interactions Pharmacokinetic interactions Altered absorption Altered distribution Altered metabolism Altered renal excretion P Glycoprotein Pharmacokinetic Interactions Altered absorption Elevated gastric pH Laxatives Drugs that depress peristalsis Drugs that induce vomiting Adsorbent drugs Drugs that reduce regional blood flow Altered distribution Competition for protein binding Alteration of extracellular pH Altered renal excretion Drugs can alter: Filtration Reabsorption Active secretion Altered metabolism Most important and most complex mechanism in which drugs interact Cytochrome P450 (CYP) group of enzymes Inducing agents: Phenobarbital Increase rate of metabolism two- to three-fold over 7 to 10 days Resolve over 7 to 10 days after withdrawal Inhibition of CYP isoenzymes Usually undesired Clinical Significance of Drug-Drug Interactions Drug interactions have the potential to significantly affect the outcome of therapy  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class notes: Introduction – Fall 2023 Responses may be increased or reduced The risk for serious drug interaction is directly proportionate to the number of drugs a patient is taking Interactions are especially important for drugs with low therapeutic indices Many interactions are yet to be identified Minimizing Adverse Drug-Drug Interactions Minimize the number of drugs a patient receives Take a thorough drug history Be aware of the possibility of illicit drug use Adjust the dosage when metabolizing inducers are added or deleted Adjust the timing of administration to minimize interference with absorption Monitor the patient for early signs of toxicity Be especially vigilant when a patient is taking a drug with a low therapeutic index Medication interactions Drug - Food Absorption: decreased (tetracycline and milk, high fiber foods), increased Grapefruit Juice! Inhibits drug metabolism (CYP3A4 Isoenzymes) Drug-Food Interactions Impact of food on: Drug toxicity Theophylline and caffeine Potassium-sparing diuretics and salt substitutes Drug action Warfarin and foods rich in vitamin K Timing of drug administration Some drugs are better tolerated on an empty stomach Others should be taken with food, especially for nausea Adverse Drug Reactions and Medication errors Side effects vs. Adverse drug reactions Side effects – most likely to occur (mild) Adverse effect - unintended effect occurring at normal drug doses Most susceptible Comorbidities  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class notes: Introduction – Fall 2023 Genetics Age Diet Additional Terms Allergic reaction Toxicity Iatrogenic disease Physical dependence Carcinogenesis Teratogenesis Adverse drug reactions Symptoms temporally related (time) Symptoms subside when drug held Symptoms reappear when drug restarted Are other drugs possible Is the actual illness responsible for the reaction Medication errors Who makes errors Types of medication errors (Table 7-3) Reducing errors (causes – people, communication, drug naming, labeling and packaging) Medication reconciliation – Joint Commission requirement. Compares medications through transitions. Box 7-1 Group V Class discussion: What is medication reconciliation and why is it important? Drug therapy – Life span Pregnancy/breastfeeding, Pediatrics, Older adults Drug Therapy During Pregnancy Two thirds of pregnant patients take at least one medication; most take more For pregnancy-related problems such as nausea, constipation, and preeclampsia For chronic disorders such as hypertension, diabetes, and epilepsy For infectious diseases or cancer Drugs of abuse such as alcohol, cocaine, and heroin Physiologic changes during pregnancy and their impact on drug disposition and dosing  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class notes: Introduction – Fall 2023 Third trimester: Renal blood flow is doubled and renal excretion is accelerated Tone and mobility of bowel decrease Prolongation of drug effects Placental drug transfer All drugs can cross the placenta Some can cross more easily than others Adverse reactions during pregnancy Can adversely affect both pregnant patient and fetus Some unique effects: Heparin causes osteoporosis Prostaglandins stimulate uterine contraction Certain pain relievers used during delivery can depress respiration in the neonate Teratogenesis Incidence and causes of congenital anomalies Less than 1% of all birth defects caused by drugs Identification of teratogens very difficult As a result, only a few drugs are considered proven teratogens Minimizing the risk for teratogenesis Pregnant patients should avoid unnecessary drug use (for example, alcohol, cocaine) Responding to teratogen exposure Identifying details of exposure Ultrasound scans FDA Pregnancy Risk Factors A: Safest B: More dangerous than A C: More dangerous than A and B D: More dangerous than A, B, and C X: Most dangerous; known to cause fetal harm Drug Therapy During Breast-Feeding Drugs can be excreted in breast milk, and effects can occur in the infant How to decrease risk to the infant: Take drugs immediately after breast-feeding Avoid drugs that have long half-lives  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class notes: Introduction – Fall 2023 Choose drugs that tend to be excluded from milk and that are least likely to affect the infant Avoid drugs that are known to be hazardous Pediatric Patients Drug Therapy in Neonates and Infants Increased sensitivity in infants Caused by immature state of five pharmacokinetic processes: Absorption Protein binding of drugs Blood-brain barrier Hepatic metabolism Renal drug excretion Absorption Oral administration Gastric emptying time Prolonged and irregular Adult function at 6 to 8 months Gastric acidity Very low 24 hours after birth Does not reach adult values for 2 years Low acidity: Absorption of acid-labile drugs is increased Intramuscular administration Slow Erratic Delayed absorption as a result of low blood flow during the first few days of life During early infancy, absorption of intramuscular drugs more rapid than in neonates and adults Distribution Protein binding Binding of drugs to albumin and other plasma proteins is limited in the infant Amount of serum albumin is relatively low Blood-brain barrier Not fully developed at birth Drugs and other chemicals have relatively easy access to the central nervous system (CNS) Infants especially sensitive to drugs that affect CNS function  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class notes: Introduction – Fall 2023 Dosage should also be reduced for drugs used for actions outside the CNS if those drugs are capable of producing CNS toxicity as a side effect Hepatic metabolism Metabolizing capacity of newborns is low Neonates are especially sensitive to drugs that are eliminated primarily by hepatic metabolism The liver’s capacity to metabolize many drugs increases rapidly about 1 month after birth Complete liver maturation occurs by 1 year of age Renal excretion Significantly reduced at birth Low renal blood flow, glomerular filtration, and active tubular secretion Drugs eliminated primarily by renal excretion must be given in reduced dosage and/ or at longer dosing intervals Adult levels of renal function achieved by 1 year Pharmacokinetics: Children Age 1 Year and Older Most pharmacokinetic parameters are similar to those of adults Drug sensitivity more like that of adults than for children younger than 1 year old One important difference: Children in this age group metabolize drugs faster than adults Markedly faster until the age of 2 years, then a gradual decline Sharp decline at puberty May need to increase dosage or decrease interval between doses Adverse Drug Reactions Children are vulnerable to unique adverse effects related to organ immaturity and ongoing growth and development Age-related effects: Growth suppression (caused by glucocorticoids) Discoloration of developing teeth (tetracyclines) Kernicterus (sulfonamides) Dosage Determination Dosing is most commonly based on body surface area Initial pediatric dosing is, at best, an approximation Subsequent doses need to be adjusted  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class notes: Introduction – Fall 2023 Older Adult Patients Altered pharmacokinetics More sensitive to drugs than younger adults and with greater variation in pharmacokinetics Multiple and severe illnesses Severity of illness, multiple pathologies Multiple-drug therapy Excessive prescribing Adherence Older Adult Patients Individualization of treatment is essential Each patient must be monitored for desired and adverse responses Regimen must be adhered to Group VI Class discussion: What factors affect an individual’s adherence to their medication therapy? What suggestions do you have to assist your patient to adhere to their therapy. Goals of treatment: Reduce symptoms and improve quality of life Pharmacokinetics: Absorption The rate of absorption may slow with age Delayed gastric emptying and reduced splanchnic blood flow also occur Pharmacokinetics: Distribution Increased percentage of body fat and decrease percentage of lean body mass Storage depot for lipid-soluble drugs Decreased total body water Concentration increased and effects more intense Reduced concentration of serum albumin May be significantly reduced in malnourished patients Causes decreased protein binding of drugs and increased levels of free drugs Pharmacokinetics: Metabolism Hepatic metabolism declines with age  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class notes: Introduction – Fall 2023 Reduced hepatic blood flow, reduced liver mass, and decreased activity of some hepatic enzymes occur Responses to oral drugs (for example, those that undergo extensive first-pass effect) may be enhanced Pharmacokinetics: Excretion Renal function undergoes progressive decline beginning in early adulthood Reductions in renal blood flow, glomerular filtration rate, active tubular secretion, and number of nephrons Drug accumulation as a result of reduced renal excretion is the most important cause of adverse drug reactions in older adults Pharmacokinetics: Excretion Renal function should be assessed with drugs that are eliminated primarily by the kidneys In patients who are older adults: Use creatinine clearance rather than serum creatinine to assess this, because lean muscle mass (source of creatinine) declines in parallel with kidney function Creatinine levels may be normal even though kidney function is greatly reduced Adverse Drug Reactions (ADRs) Seven times more likely in the elderly Account for 16% of hospital admissions Account for 50% of all medication-related deaths Majority are dose related rather than idiosyncratic Symptoms in older adults often nonspecific May include dizziness and cognitive impairment Measures to Reduce ADRs Obtain a thorough drug history that includes over-the-counter medications Consider pharmacokinetic and pharmacodynamic changes due to age Monitor the patient’s clinical response and plasma drug levels Use the simplest regimen possible Monitor for drug-drug interactions Periodically review the need for continued drug therapy Encourage the patient to dispose of old medications Take steps to promote adherence and to avoid the Beers criteria medication (Adult Geriatric Society)  Departments of Nursing NRS 321 Pathophysiology – Pharmacology I Class notes: Introduction – Fall 2023