Pharm Final Study Guide PDF

**Genetics, Protein Production, & Cell Communication** Explain DNA replication, transcription, and translation, and relate these to protein production\ \ Replication: cell makes copy of itself before cell division. Three parts to replication, initiation, priming, and elongation. \- Initiation us...

**Genetics, Protein Production, & Cell Communication** Explain DNA replication, transcription, and translation, and relate these to protein production\ \ Replication: cell makes copy of itself before cell division. Three parts to replication, initiation, priming, and elongation. \- Initiation uses an enzyme helicase to unwind the double helix of dna, making two single strands. - Priming: enzyme called primase adds short RNA primers to single stranded DNA templates to start replication process - Elongation: DNA polymerase adds new DNA nucleotides (ATCG) to strand using original strand as a template. - Termination: once DNA molecule is copied, process stops and is then proofread for errors. Transcription: Where information encoded in a DNA strand is copied into messenger RNA (mRNA). mRNA serves as a template for protein synthesis in the next stage. - Initiation: enzyme RNA polymerase binds to specific region of DNA and unwinds the DNA - Elongation: RNA polymerase moves along the DNA template, synthesizing an mRNA molecule that is complementary to DNA. In RNA, nucleotide uracil replaces thymine, so A = U, C=G - Termination: when RNA reaches terminator, transcription stops and newly formed RNA is released Translation: mRNA is used to build corresponding protein. Ribosome is where this happens, where it reads a set of three nucleotides (codons). Describe the functional and structural roles proteins play in cell, organ, and organ system function Cytoskeleton proteins: actin, tubulin, intermediate filaments all help hold the cells shape, mechanical support, and facilitate movement such as division, transport, and migration.\ \ Cell membrane proteins: integral and peripheral membrane proteins like integrins and cadherins play structural roles by anchoring cells to the extracellular matrix.\ \ Collagen: most abundant protein in the body, mostly found in connective tissues. Provides structural support.\ \ Extracellular Matrix: collagen, elastin, and fibronectin form the ECM\ \ Muscle proteins: actin and myosin are main components of muscle fibers and are responsible for muscle contraction and movement.\ \ \ Enzymes: proteins act as enzymes which are catalysts that speed up chemical reactions. Crucial in cellular metabolism and DNA replication, protein synthesis, energy production, breakdown of nutrients. Transport proteins: hemoglobin, ion channels and transporters in cell membrane- regulate the movement. Of ions and nutrients, maintaining, cellular homeostasis. Signaling proteins: g-protein coupled receptors- mediate the effect of hormones, neurotransmitters, growth factors, enabling cells to respond to changes in the environment. Gene regulation: proteins like transcription factors and repressors bind to DNA to control expression of genes, determines when and how much of a protein is produced in response to cellular needs. Compare and contrast the structure and function of ligand-gated ion channel receptors, G-protein coupled receptors, enzyme-linked protein receptors, and intracellular receptors Ligand-gated ion channel receptors (inotropic): - Structure: - Mult subunit complex: multiple subunits that channel in the cell membrane - Extracellular ligand binding site: ligand binds to specific site on the receptor located on the extracellular part of the protein - Transmembrane segments: protein spans the membrane with hydrophobic regions that form the channel. - Function: - Ion channel opening/closing: when it binds (ligand, usually neurotransmitter), the channel undergoes a conformational change that opens or closes, allowing ions to flow in or out of the cell. - Rapid response: involved in rapid, short lived signaling, synaptic transmission in neurons (acetylcholine, GABA) - Results in cellular response: flow of ions across membrane changes the membrane potential, leading to excitatory or inhibitory effects G Protein Coupled Receptors: - Structure: - Single polypeptide chain: crosses membrane seven times - Extracellular ligand binding site: ligands bind to extracellular region - Intracellular G protein binding site: intracellular domain interacts with g proteins which are activated by the receptor - Function: - Signal amplification: once ligand binds, the receptor undergoes a conformational change activating an associated g protein by exchanging GDP for GTP. - Second messenger: GPCR signaling often involves second messenger, which amplify the signal and lead to various cellular responses such as gene expression, metabolism, or ion channel modulation. - Longer lasting effects: slower, more sustained cellular responses compared to channels Identify the key ANS receptors and their effects in target organs/tissues **Pharmacokinetics** Describe common routes for drug administration - IV - IM - PO - Subq - Sublingual - Rectal - Vaginal Compare benefits and disadvantages associated with common routes of administration - Oral: - Easy to administer - Non invasive - Cost effective - Variable absorption - First pass effect - Delayed onset - GI issues - IV - Immediate effect - 100% bioavailability - Precise control - Invasive - Complications - IM - Faster than oral absorption - Larger volumes ok compared to subq - Less frequent dosing - Painful - Invasive - Tissue injury risk - Subq - Slow and steady absorption - Less invasive than IM/IV - No first pass effect - Variable absorption - Small volumes only - Topical - Localized action - Non invasive - Limited absorption - Skin irritation - Inhalation - Rapid onset - Localized effect - Non invasive - Limited to lung conditions - Rectal - Bypasses first pass effect - Useful for pt who are vomiting/unconscious - Localized effect - Pt discomfort - Absorption inconsistency Describe pharmacokinetic (PK) processes of absorption, distribution, metabolism, and excretion (ADME) - Absorption: - Drug enters blood stream after adminstation - Moves from site of admin to bloodsteam - Influencing factors: - Routes: - Oral - Iv - Im - Etc. - Drug formulation - Blood flow - Distribution: - Drug is transported throughout body via bloodstream to site of action - Influencing factors: - Cardiac output/bloodflow - Plasma protein binding - Lipid solubility - Tissue perfusion - Barriers like blood brain barrier - Volume of distribution - Metabolism: - Alteration of drug by enzymes, usually in liver. Processing of drug - Drug metabolite - Influencing factors: - Liver function - CPY450 - Genetic factors - Age, diet, comorbid conditions - Excretion: - Drugs and metabolites are eliminated from body - Eliminated usually through kidneys. Also can be through bile, sweat, saliva, exhaled air. - Influencing factors: - Kidney function - Liver function Identify common pharmacokinetic parameters associated with PK processes. (e.g., half-life, volume of distribution, etc.) - Half life - Time it takes for plasma concentration of a drug to reduce by half - Bioavailability: - Proportion of drug that reaches systemic circulation in an active form after administration - Volume of distribution (Vd) - Hypothetical volume that relates the amount of drug in the body to the concentration of the drug in the blood or plasma - Therapeutic window - Range of drug concentrations that are effective without being toxic - Steady state - Point where drugs intake and elimination are balanced and concentration stays the same over time - Protein binding - Percentage of drug bound to plasma proteins Describe factors that influence PK processes (ADME) See above\ - Compare how different drugs are handled by the body\ - Identify potential for drug interactions based on PK - Gastric pH - Motility - Competition for active transporters - Food/drug interactions - Plasma protein levels - Blood flow - CYP450 Describe how genetic variants can alter metabolism - CYP450 - Poor metabolizers - Intermediate metabolizers - Extensive metabolizers **Pharmacodynamics** Describe how regulations affect drug development and use in the United States - FDA - DEA Describe how drugs interact with receptors as to produce therapeutic & adverse effects - G protein coupled receptors (GPCRs) - Largest family of receptors - Activates a signaling cascade inside cell, needing secondary messengers - Beta-adrenergic receptors activated by norepinephrine. Beta agonists like albuterol activate receptors to cause bronchodilation in asthma - When overstimulated or blocked, side effects like tachycardia, hypotension, respiratory depression happen - Ion channel receptors - Control flow of ions in or out of the cell, affecting cell membrane potential and cellular activity - If channels are excessively activated or inhibited, side effects happen - Enzyme linked receptors - Cellular growth and metabolism. When drug binds, activates intracellular enzymatic pathways that influence cellular activity Define the terms agonist and antagonist 1/1 - Agonist - Bind to a receptor and active it - Mimic action of endogenous (naturally occurring) substances like neurotransmitters, hormones. - Ex: beta agonists like albuterol bind to beta-2 receptors to relax smooth muscle - Agonist activates receptors in an unintended organ, lead to adverse effects - Opiods causing respiratory depression - Antagonists - Bind to receptors but do not activate them - Block excessive activation of receptor - Ex: betablockers block beta-1 adrenergic receptors in heart, reducing HR and BP - When block receptors that are needed for normal function of bodies, can cause adverse reaction - Ex: antihistamines causing drowsiness - Partial agonists - Bind to receptors and activate them but only produce partial response - Great for when moderate response is needed - Can still cause side effects but usually less pronounced Describe characteristics of the doseresponse curve - Typically S shape curve - Relationship between drug concentration and effect - Therapeutic index Compare efficacy and potency for two drugs - Efficacy - Maximum effect a drug can produce regardless of dose - Potency - Amount of drug required to produce specific effect. - More potent drug will produce the same effect at a lower dose than a less potent drug Identify potential for drug interactions based on pharmacodynamics - Additive drug interactions (Synergistic effects) - Two drugs with similar actions are combined, the resulting effect is equal to the sum of the individual effects. - Called additive effect - Synergistic drug interaction - Two drugs with different mechanisms of actions produce a greater effect than the sum of individual effects - Antagonistic drug interactions - One drug reduces of blocks effect of another drug Contrast therapeutic, adverse, and side effects of drugs Describe how genetic variants can alter pharmacodynamic response - Variations in drug receptors - Alterations in receptor sensitivity - Signal ability/transporters - Enzyme function - Ion channels **ANS/Neurotransmitters** Describe the three parts of a neuron - Cell body: - Also called soma - Central part of neuron - Contains nucleus and most of the cells organelles - Responsible for basic metabolic activities of neuron including energy production and protein synthesis - Processing signals: receives incoming signals from dendrites and initiations an action potential if signals are strong enough. - Nucleus: contains neurons genetic material (DNA), involved in regulating cellular activities, such as protein synthesis - Dendrites: - Branch like extensions that project from cell body. Receives signals from other neurons or sensory receptors. Receiving these signals is called postsynaptic potentials. - Dendritic spines that are the branches. The more spines, the more chance of potential. - Axon: - Long, thin, cylindrical extension that conducts electrical impulses away from the cell body toward other neurons, muscles, or glands. - May have myelin sheath which is made of glial cells, helps speed up signal transmission - Action potentials: from cell body to axon terminals (synaptic terminals) Understand how neurotransmitters are released and bind in neuronal synapses - Action potential arrival: - Action potential travels down the axon to the axon terminal - Calcium influx: - Voltage gated calcium channels open, allowing calcium to enter the axon terminal. - Vesicle fusion: - Calcium triggers the fusion of synaptic vesicles with the presynaptic membrane. - Neurotransmitter release: - Neurotransmitters are released into the synaptic cleft by exocytosis. - Receptor binding: - Neurotransmitters bind to receptors on the postsynaptic membrane which triggers a cellular response - Postsynaptic response: - Binding leads to either excitation or inhibition of the postsynaptic cell - Neurotransmitter removal: - Neurotransmitters are removed via reuptake, enzymatic degration, or diffusion. - Vesicle recycling: - Vesicle membrane is recycled to reuse in future neurotransmitter release Discuss the effects of the following neurotransmitters: glutamate, serotonin, norepinephrine, epinephrine, GABA, dopamine, acetylcholine, oxytocin, histamine, substance P & nitric oxide - Glutamate: - Main excitatory neurotransmitter - Increases likelihood of firing a neuron - Serotonin: - Mood regulation, sleep - Norepinephrine: - Transmitter and hormone, mostly involved in response to stress - Fight or flight - Epinephrine: - Fight or flight response to stress - GABA - Primary inhibitory neurotransmitter - Counteracts glutamate - Produces calming effect (think gabapentin) - Dopamine: - Reward processing system - Mood regulation - Parkinson's - Acetycholine - Autonomic nervous system - Muscle control - Memory - Rest and digest - Oxytocin: - Bonding hormone/love hormone - Reproduction - Emotional regulation - Histamine: - Immune response - Sleep wake cycle - Promotes wakefulness - Substance P - Pain transmission - Inflammatory response - P is for pain - Nitric oxide: - Vasodilation - Remember nitro for angina - Learning and memory Understand the general role of neurotransmitters in movement arousal/sleep, appetite, cognition, mood/emotion, & pain **Pregnancy** Discuss hormone changes in pregnancy - Progesterone: - Managing uterine lining - Relaxes smooth muscles of uterus - Suppresses maternal immune response to prevent rejection of fetus - Stimulates breast tissue development in preparation for lactation - Estrogen: - Stimulates growth of uterine muscles - Increases blood flow to placenta - Regulate development of fetal organs - Promotes growth of mammary glands in breasts - Regulation of other pregnancy related hormones like hCG and progesterone. - hCG: - first hormones produced during pregnancy, primarily by placenta - levels rise rapidly in early pregnancy, peaking between 8-10 weeks and then stabilize - maintain corpus luteum, which produces progesterone during first trimester Understand the formation, function, and flow of blood through the placenta - trophoblast differentiation: - developing embryo undergoes blastocyst formation... one of the layers, the trophoblast, will become the placenta - Function of placenta: - Nutrient and gas exchange (oxygen, nutrients, waste removal) - Oxygen is transferred through fetal blood through diffusion - Placenta removes waste products like carbon dioxide, urea, and creatinine from fetal blood and transports them into the maternal circulation to be excreted by the mothers kidneys - Hormone production (hCG, progesterone, estrogen, hPL, relaxin) - Immunological protection - Protection from toxins - Blood flow through the placenta: - Maternal blood flow: - Uterine arteries carry oxygen rich blood from mothers heart and is delivered to placenta - Spiral arteries branch off uterine arteries and penetrate the decidua. Placenta hormones widen (remodeling) to allow for an increased blood volume - Once blood enters the placenta through the spiral arteries, it enters the intervillous space which is filled with maternal blood and surrounds the fetal chorionic villi. The villi is where exchange of gases, nutrients, and waste happens - Maternal venous return happens after nutrient and gas exchange. Deoxygenated blood flows out of the placenta through the endometrial veins and returns to maternal circulation. - Fetal blood flow: - Umbilical arteries have deoxygenated blood that flow through placenta through two umbilical arteries - Fetal blood circulated through the chorionic villi, exchanges gases and nutrients with maternal blood in the intervillous space via diffusion - Oxygen and nutrients in the maternal blood move into the fetal capillaries in the villi, while waste products move in the opposite direction to be eliminated from the fetal circulation - Oxygenated blood returns to the fetus through the umbilical vein which carried oxygen rich blood back to the fetus's liver and heart. Describe the response of the body to pregnancy - Increased blood volume - Rises by about 30% - Plasma volume increases more than red blood cell volume leading to dilutional anemia - Increased cardiac output: - Volume of blood the heart pumps per minute increases by 30-50% - Heart rate increases about 10-15 bpm - Stroke volume increases - Blood pressure - Systolic BP may remain the same or slightly decrease in early pregnancy - Diastolic blood pressure typically drops by 5-10 mmHg, peaking at around the 24-28 week mark and then gradually returns to baseline levels by term - Supine hypotension can occur due to pressure from uterus on inferior vena cava, reducing venous return to the heart - Vascular changes: - Vasodilation occurs to accommodate increased blood volume, especially in uterus, kidneys, and breasts. - Varicose veins and hemorrhoids are a result of increased blood volume and venous pressure - Increased tidal volume: - Increases by 30-40% - Increased RR - 20% increase in oxygen use by mother at term - Increased glomerular filtration rate: - Increases by 40-50% which helps eliminate waste products - Creatine and urea nitrogen levels decrease because of this Describe anatomical changes that contribute to common complaints during pregnancy - Weight gain when pregnant: - Average 25-25 pounds - Fetus: 7 lbs - Placenta and amniotic fluid: 4 lb - Uterus: 2 lbs - Breasts: 2 lbs - Plasma volume: 6 lbs - Fat: 3 lbs - Metabolism and nutrition: - Basic metabolic rate increases about 15% during later half of pregnancy - Placenta stores of nutrients are needed to sustain fetal growth during last months of pregnancy Describe the actions of specific vitamins, minerals, and dietary supplements to support pregnancy and fetal development - Folic acid: - Essential for DNA synthesis and cell division - Reduces risk of neural tube defects such as spina bifida and anencephaly when taken before conception and during the first trimester - 400-800 mcg of folic acid daily - Adverse effects: - Water soluble - May mask deficiency of vit b12 - Iron - Production of hemoglobin - Prevents iron deficiency anemia - Recommended to take 27 mg/day while pregnant - Vitamin C increases absorption - Ferrous is more easily absorbed compared to ferric - Taken with food lowers absorption - Adverse effects: - Nausea - Bloating - Constipation - Dark stools - Overdose can be fatal! - Calcium: - Bone - Neuronal excitability/neurotransmitter release - Muscle contraction - Cardiac action potential, contraction - Blood coagulation - Fetal skeletal development (mostly 3^rd^ trimester) - Maternal skeletal - Adverse effects include GI upset, especially constipation - Dose: - 1000mg elemental calcium/day (includes food intake!) Describe US regulation that addresses safety of drugs in pregnancy - Prior to 2015: - Cat A: drugs are safe, failed to demonstrate risk in 1^st^ trimester - Cat B: - animal: failed to demonstrate risk - Human: no studies - Cat C: - Animal: adverse effect on fetus or no studies done - Human: no controlled studies - Cat D: - Human: proof of human fetal damage - "WARNING" statement on drug label - Cat X: - Animal or human studies demonstrate definite risk of fetal abnormality - "CONTRAINDICATION" statement on drug label - After 2015: - Pregnancy - Labor and Delivery - Nursing mothers - Females and males of reproductive potential Define FDA pregnancy categories. - See above Identify nursing actions to support safe use of drugs in pregnancy - Education for women of childbearing age - Assume any rug will reach the embryo/fetus - Weigh risk vs benefit - Is a drug needed? - Avoid substances of abuse (before and during) - For known teratogens - Written informed consent - Multiple forms of contraception - Pregnancy test just prior to initiation **Fetal and Pediatric Development** Discuss the major events of basic embryology including:\ -- Embryonic Period (conception -- week 8), including tissue formation\ -- Fetal Period (weeks 9-40), including fetal lung & circulatory development - Week 1: Fertilization - Conception occurs when sperm fertilizes the egg (oocyte) in the fallopian tube, forming a zygote - Zygote undergoes cleavage (cell division without growth) to form a morula (ball of cells) which then develops into a blastocyst - Blastocyst implants into the uterine wall around 6-7 days post fertilization - Week 2: Three germ layers - Bilaminar disk differentiates into two layers: the epiblast and the hypoblast - Gastrulation occurs in week 3 which forms the three germ layers: - Ectoderm: skin, nervous system, and sensory organs - Mesoderm: muscles, bones, cardiovascular system, kidneys, connective tissues - Endoderm: internal structures such as digestive system, liver, pancreas, lungs - Week 3-4: neurulation - Ectoderm undergoes neurulation which forms neural tube which eventually will be the brain and spinal cord - Neural crest cells become peripheral nerves and other structures, such as parts of the face and heart - Week 3-8: Organogenesis - Organogenesis is when the primary organs and tissues begin to form - Week 3: heart tube begins to form, and embryo starts to develop basic circulatory system - Week 4-5: limb buds, facial features, formation of primitive gut - Week 6: neural tube differentiates into the brain (forebrain, midbrain, hindbrain) - Week 7: facial features take shape. Heart starts beating - Week 8: embryonic period ends, major organs are formed but not fully functional. Limbs are well formed. Embryo is now a fetus. - Weeks 9-12: - Growth and refinement - Organ development - Heart and circulatory system are well formed. Kidneys begin producing urine. - External genitalia differentiate but not distinguishable until later - Fetus begins making movements but not yet felt by mother - Fetal circulation - Ductus venosus (liver directly into the inferior vena cava) - Foramen ovale (hole between atria of heart that allows blood to bypass the lungs) - Ductus arteriosus (pulmonary artery to the aorta, also bypasses lungs) - Weeks 13-24 - Respiratory development - Surfactant production beings in alveoli - Nervous system - Reflexes - Skin and hair - Less transparent - Lanugo beings to grow on body - Fetal circulatory development - Weeks 25-40 - Lung maturation - More surfactants made - Fat accumulation - Subcutaneous fat for temperature regulation after birth - Bone growth and muscle development - Organ maturation - Liver starts to store iron - Gastrointestinal system can digest amniotic fluid - Neurodevelopment - Sleep wake cycles - Weeks 37-40 - Lung maturity - Ready for birth Understand the general patterns involved in pediatric growth and development - Physical growth - 0-2 years old: rapid growth. Double the birth weight by 6 months and triple by 1 year. - Head circumference - Growth slows down after 2 years old - 6-12 yrs old usually gains about 2 inches in height and 5-7 lbs per year - Cephalocaudal: - Head to tail - Proximodistal: - Closer to farther away Identify factors which influence pediatric growth and development - Critical/sensitive period - Genetics - Environment - Physical - Psychosocial - Culture - Health status - Family Describe the actions of specific vitamins, minerals, and dietary supplements to support pediatric development - Vitamin K - Fat soluble vitamin - Helps body make blood clots - Produced by bacteria in intestines - At birth, have very little in body so vit K shot is given - Vitamin D - Bone health - Prevents rickets - Immune system support - Linked to mental health - Low levels may be increased risk of depression - Calcium, magnesium, phosphorus - Accounts for 90% of body's mineral content by weight - Biochemical reactions at cellular level - Main components of skeleton - Magnesium: - Responsible for many metabolic functions - Iron - Hemoglobin Predict common age-related effects on PK process of absorption, distribution, metabolism, and excretion - Neonates and infants: - Absorption: - Prolonged and irregular gastric emptying time - Low gastric acidity - Low blood flow through muscles during first days of life - Very thin stratum corneum and greater blood flow to skin - Distribution: - Protein binding - Low serum albumin levels - Endogenous compounds (bilirubin) compete with drugs for available binding sites - Blood- brain barrier - Not fully developed at birth - Metabolism and Excretion: - Low drug metabolizing capacity - Low during infancy - Renal blood flow - Glomerular filtration - Active tubular secretion - Children over 1 - By age 1, most PK parameters = adult - Exceptions: - Drug metabolizing effects of the liver - Effects increased until about 2 yrs old - 2^nd^ sharp decline during puberty **Aging and Dying** Discuss the physiologic and psychosocial aspects of normal human development from transition to adulthood to healthy aging - Generativity vs stagnation - Social relationships - Integrity vs despair - Reflection and life review - Reduced mobility - Organ function declines - Sensory changes - Chronic diseases Relate the physiologic and psychosocial aspects of aging to health risks - Decreased immune function - Thymus gland decreases in size and function - Makes t cells for immune response - Autoimmune diseases - Cancer - Cardiovascular changes - Hypertension - Heart disease - Stroke - Musculoskeletal decline - Decline in bone density - fractures - Decline in muscle mass - Loss of mobility - Chronic pain - Endocrine changes - Decline in hormonal production - Lower levels of testosterone, estrogen, growth hormone, and insulin sensitivity - Neurological changes - Reduced gray matter - Slower processing speed - Changes in neurotransmitter levels - Cognitive decline + dementia - Parkinson's disease - Mental health disorders - Sensory decline - Hearing, vision, taste, smell - More falls and injuries - Isolation and depression due to sensory decline (such as hearing) Describe and identify nursing considerations associated with common physiologic changes that occur in a dying person - Decreased circulatory function - Heart becomes less efficient - Cooler skin esp in extremities - Skin care - Comfort measures - Observe for mottling - Positioning - Decreased respiratory function - Breathing becomes irregular - Signs of apnea - Cheyne-stokes respirations - Monitor breathing patterns - Oxygen therapy - Provide humidity - Suctioning - Changes in level of consciousness - Unresponsive - Delirious - Communication - Support the family - Monitor for agitation - Emotional support - Decreased renal function - Decreased urine output/cessation of urination - May be darker and more concentrated - Fluid balance - Skin care - Comfort - Decreased digestive function - Digestive system slows down - Pt may lose interest in food and fluids - May lead to constipation - Provide comfort - Monitor for nausea/vomiting - Avoid force feeding - Bowel management - Loss of muscle tone - Pt may have difficulty maintaining posture - Decrease in response to external stimuli - Positioning - Supportive care Predict common age-related effects on PK processes of absorption, distribution, metabolism, and excretion - Absorption: - Decreased absorption rate - May affect onset of action of oral medications - Increased gastric pH - Medications requiring acidic pH may have reduced bioavailability - Distribution: - Increased body fat - Alter volume of distribution for lipophilic drugs - Prolonged half-lives due to increased fat storage (diazepam) - Decreased lean body mass - Volume of distribution of hydrophilic drugs - May reach higher concentrations due to reduced volume of distribution (digoxin) - Decreased serum albumin - Reduced protein binding capacity due to lower levels of albumin and other plasma proteins - Free drug concentrations may increase for highly protein bound drugs (warfarin) - Metabolism: - Decreased liver size and hepatic blood flow - Liver size and blood flow decline with age which reduces drug metabolism (CYP450) - Drugs metabolized by liver may have prolonged effects - Decline in CP450 enzyme activity - Drugs metabolized by CYP450 enzymes may have prolonged half-lives - Excretion: - Decreased renal function - GFR is lower - Reduced renal function may lead to drug accumulation and toxicity for drugs metabolized by kidneys - Decreased renal size and number of nephrons - Longer half lives - Drug dosage may need to be altered - Decreased ability to concentrate urine - Drug excretion and hydration status - Fluid balance must be managed esp. for drugs that can cause electrolyte disturbances **Fluids, Electrolytes, Acid/Base Homeostasis** Describe homeostatic control of fluid balance - Total body water - Fluid intake - Fluid loss - Kidneys - Filter blood and adjust volume and composition of urine - Filtration - Glomerular filtrate - Glomeruli (makes GFR) nephrons (water nad solutes are reabsorbed or excreted) - Antidiuretic hormone (ADH) - Secreted by posterior pituitary gland - Increases water reabsorption in kidneys which reduces urine output and body will retain water - Aldosterone - Produced by adrenal glands - Released in response to low sodium or low blood pressure - Promotes sodium retention in kidneys - Increase blood volume and regulates blood pressure - Thirst mechanism - Thirst center is located in the hypothalamus - Monitors blood osmolarity (concentration of solutes) - When body is dehydrated or there is an increase in osmolarity, the hypothalamus triggers the sensation of thirst - Hormonal control of fluid balance - ADH - Increases water reabsorption - Aldosterone - Retain sodium and water - Atrial natriuretic peptide (ANP) - Released by the heart - Response to increased blood volume and pressure - Promotes natriuresis and water excretion - Renin-angiotensin-aldosterone system (RAAS) - In response to low blood pressure/volume - Kidneys release renin - Activates angiotensin system - Blood pressure and volume regulation - Baroreceptors - Identifies changes/pressure - Low blood volume - Triggers increased sympathetic nervous system - Releases renin - Together they conserve fluid and sodium and constrict blood vessels to raise BP - Negative feedback loop - Renal feedback - Blood volume low = renin released = triggers angiotensin Understand how fluids are distributed throughout the body - Intracellular fluid (ICF) - 60% of total body water is found inside the cells - Primary site of metabolic activity - High concentration of - Potassium - Phosphate - Magnesium - Low concentration of - Sodium - Extracellular fluid (ECF) - 40% of total body water found here - Fluid outside the cells divided into two categories - Interstitial fluid - Fluid between cells that fill spaces around tissues and organs - Accounts for 75% of ECF - Intravascular fluid (plasma) - Within blood vessels - 20% of ECF - Transcellular fluids - Cerebrospinal fluid - Synovial fluid - Fluids within the eyes and peritoneal cavity Describe how fluid moves in and out of a cell via osmosis - Water moves across cell membrane by osmosis - Low solute concentration to areas of high solute concentration - Direction of fluid movement depends on the relative concentrations of solutes inside and outside the cell - Hypotonic solution - Water moves INTO the cell - Isotonic solution - No net water movement - Hypertonic solution - Water moves OUT of the cell - Vital for maintaining proper cell volume and osmotic balance Describe the effects of isotonic, hypertonic, and hypotonic extracellular fluid states on intracellular fluid movement & cells - Hypotonic solution (SWELL) - Water moves INTO the cell - Isotonic solution - No net water movement - Hypertonic solution (SHRINK) - Water moves OUT of the cell Describe the forces involved in filtration and reabsorption - Filtration (OUT of CAPILLARIES) - Capillary hydrostatic pressure (CHP) - Pressure exerted by the fluid within the capillaries - Push fluid out of the capillaries and into the surrounding tissues - Interstitial fluid pressure (IFP) - Pressure exerted by the fluid in the interstitial space surrounding the capillaries - Push fluid back into the capillaries - Reabsorption (INTO CAPILLARIES) - Plasma oncotic pressure - Pressure exerted by proteins (albumin) in the plasma that cannot cross the capillary wall - Pulls water back into the capillaries to maintain blood volume/fluid balance - Capillary hydrostatic pressure (CHP) - Movement of fluid back into the capillaries - Interstitial fluid osmotic pressure (IFOP) - Pressure exerted by proteins in the interstitial fluid - Draws fluid from the capillaries into the interstitial space Understand the role and normal ranges of the following cellular electrolytes: sodium, potassium, calcium, magnesium, and phosphate - Sodium - Extracellular cation ( + charged ion) - Maintaining osmotic pressure and fluid balance - Generating and propagating action potentials in nerve and muscle cells - Regulating blood pressure - Active transport of nutrients into cells via sodium-potassium pumps - Normal range: - 135-145 mEq/L - Potassium - Intracellular cation - Maintaining membrane potential and electrical conductivity - Neurons, muscles, heart cells - Regulating cell volume and acid base balance - Protein synthesis and glycogen storage - Normal range: - 3.5-5.0 mEq/L - Calcium - Bone and teeth formation - Muscle contraction - Heart!! - Nerve transmission and synaptic transmission - Second messenger in cellular signaling pathways - Blood clotting - Normal range: - 8.5-10.5 mg/dL - Magnesium - Smooth muscle contraction and relaxation - Suppresses release of acetylcholine at neuromuscular junctions - Formation of bone and teeth - Normal range: - 1.5-2.3 mEq/L - Phosphorous/Phosphate - (phosphorus) Combines with oxygen in body to form phosphate - Intracellular anion and in the bone - Component of nucleic acids and cell membrane phospholipids (DNA!!!) - Aerobic and anaerobic energy metabolism - Role in oxygen delivery to tissues - Normal range: - 2.5-4.5 mg/dL Discuss how chemical, renal, and respiratory buffering systems maintain a constant pH of body fluids - Chemical buffering systems - Bicarbonate buffer system - Most important system in blood!! - Balance between carbonic acid and bicarbonate ion - When pH is too high (basic): - Carbonic acid will release H+ - = higher free H+ concentration - End results: - Higher free H+ - Lower in the pH - When pH is too low (acidic) - Bicarbonate ion will accept H+ - = lower free H+ concentration - End results: - Lower free H+ - Higher in the pH - CO₂ + H₂O ↔ H₂CO₃ ↔ H⁺ + HCO₃⁻. - Renal buffering system (slower system) - Kidneys secrete more or less H+ into the renal tubule (to pee out) - Phosphate and ammonia combine with H+ and are excreted - Secrete more H+ (increase pH) vs less (decrease pH) - Kidneys reabsorb more or less bicarbonate into the blood - CO₂ + H₂O ↔ H₂CO₃ ↔ H⁺ + HCO₃⁻. - Respiratory buffering system (Faster, minutes to hours) - Acidic (acidotic) - Breathe faster and deeper to fix it - Removes more CO2 gas from blood - Lower pCO2 in blood - End result: - Lower Free H+ - Higher in the pH - Basic (alkalotic) - Breathe slower and shallower to fix it - More CO2 gas remains in blood - Higher pCO2 in the blood - End result: - Higher free H+ - Lower in the pH - CO₂ + H₂O ↔ H₂CO₃ ↔ H⁺ + HCO₃⁻. Analyze simple blood gases to determine acidosis/alkalosis - Respiratory Acidosis - pH \< 7.35 - pCO2 \> 45 mmHg - HCO3- : Normal or high - Primary disorder: - CO2 retention (hypoventilation) - Respiratory alkalosis - pH \> 7.45 - pCO2 \< 35 mmHg - HCO3-: normal or low - Primary disorder: - CO2 loss (hyperventilation) - Metabolic acidosis - pH \< 7.35 - pCO2 \< 35 mmHg - HCO3-: \< 22 mEq/L - Primary disorder: - Low bicarbonate (kidney failure, diarrhea) - Metabolic alkalosis - pH \> 7.45 - pCO2 \> 45 mmHg - HCO3-: \> 26 mEq/L - Primary disorder: - High bicarbonate (vomiting, diuretics) **Inflammation & Immunity, Wound Healing** Describe the three lines of defense - 1^st^ line of defense: - Innate immunity - Physical barriers - Characteristics: - Constant presence - Epithelial cells - Non specific response - No memory - Examples: - Skin and mucous membranes - Cells and secretory molecules - Mucous, salvia, tears, earwax - Cilia - Normal flora on surface barriers - Skin, GI, GU - 2^nd^ line of defense: - Innate immunity: - Inflammation - Characteristics: - Nonspecific - In response to and usually in proportion to degree of injury - Immediate response - No memory - Examples: - - 3^rd^ line of defense: - Adaptive (acquired, specific) immunity - Characteristics: - Delayed response (4-7 days) - Specific process to eradicate "antigen" - Discriminatory and diverse - T and B lymphocytes, macrophages, dendritic cells - Has memory, quicker response in future - Examples: - Immunizations - Immunotherapy - Cell mediated ( T cells) - No antibodies involved - Humoral (B Cells) - Antibodies involved State the benefits of inflammation - Prevents infection and further injury/damage by microorganisms - Self-limiting through plasma protein systems - Interacts with components of adaptive immune system - Promotes and prepares injured site for healing Understand the three components of the inflammatory process - Vasodilation and vascular permeability - Chemokines activate mast cells - Histamines - Potent vasodilator - Prostaglandins - Vasodilation - Chemotactic factors - Pain sensation - Leukotrienes - Chemotaxis - Increased permeability - Vasodilation = greater blood volume to area - Cells of capillary walls = increased permeability - Recruitment and emigration of leukocytes - Chemotaxis - Cells migrate toward higher concentrations of chemotactic factors - Margination - Neutrophils get sticky - Then stick/roll along vessel wall - Pavementing - Emigration/diapedesis - Neutrophils exit blood vessels - Squeeze through and enter surrounding tissues - Phagocytosis - Digestion - Pus - Dead neutrophils, bacteria, cellular debris - Macrophages - Cleaning and healing - Dendritic cells - Present antigens - B Cells and T cells also arriving - \*\*opsonization\*\* - "tagging" so phagocytes know substance should be removed Describe the end effects of complement, kinin, and clotting plasma protein systems - Complement system - Responsible for: - destroying pathogens either directly or indirectly, recruiting others to help - Activated by: - Antibodies (classical pathway) - Infectious organisms (alternate pathway) - Other plasma proteins (lectin pathway) - Results in: - Opsonization - Tagging so phagocytes can recognize and destroy antigens - Degranulation of mast cells - "spit out" contents inflammatory mediators prostaglandins, histamines, leukotrienes - Direct lysis of pathogens - Membrane attack complex (MAC) forms on surface of pathogen transmembrane channels cause lysis - Chemotaxis - Phagocytes attracted to that area - Kinin system - Works closely with coag/clotting system - Triggered by activation of Factor XII factor XIIa - Final product: - Bradykinin - Increased vasodilation - Increased vascular permeability - Induces pain - Coagulation/clotting system - Responsible for: - Clot formation - Migration of leukocytes - Chemotaxis - Increased permeability - Activated by: - Tissue injury (extrinsic) - Damaged vessel wall (intrinsic... eg heart disease) - Components of the kinin system Relate the inflammatory process to physical examination findings - Redness (rubor) - Heat - Swelling - Pain Understand the role of histamines, prostaglandins, leukotrienes, bradykinin, cytokines, and leukocytes in the inflammatory process - Histamines - Function: - Released by mast cells and basophils - First mediators released in the inflammatory process - Vasodilation which increases blood flow to area - Prostaglandins - Function: - Vasodilation - Chemotactic factors - Pain sensation - Sensitize pain receptors to other inflammatory mediators (bradykinin), which amplifies the pain - Fever - Increased permeability - Contributes to swelling - Leukotrienes - Produced by mast cells, basophils, eosinophils, neutrophils - Function: - Recruitment of immune cells to site of inflammation - Bronchoconstriction - Vascular permeability - Mechanisms: - Chemotaxis - Attract immune cells to site of inflammation - Bronchoconstriction - Smooth muscle contraction in airways - Contributes to asthma and allergic reactions - Increased vascular permeability - Bradykinin - Plasma protein made from kininogen - Function: - Pain associated with inflammation - Contributes to vasodilation - Increased vascular permeability - Mechanisms: - Pain mediator, directly stimulating pain receptors - Blood vessels to dilate allowing more blood flow and redness seen in inflammation - Increases permeability of capillaries, allowing immune cells and proteins to reach inflamed tissue - Cytokines - Small signaling proteins - Secreted by macrophages, T cells, and endothelial cells - Function: - Regulates intensity and duration of inflammation - Mechanisms - Chemotaxis - Systemic effects - Fever - Acute phase response (C reactive protein) - Activation of hypothalamic pituitary axis - Leukocytes (WBC) - Made in bone marrow - Recruited to inflammation site by action of chemical mediators - Types: - Neutrophils - First responders to inflammation - Macrophages - Early and later stages of inflammation - Eosinophils - Inflammation associated with allergic reactions and parasitic infections - Lymphocytes - Chronic inflammation mostly in viral infections, autoimmune diseases and adaptive immune response Describe systemic manifestations of inflammation - Fever - Induced by cytokines - \*\*does not always mean infection!! - Leukocytosis - Increase in circulating WBC - Increased levels of circulating plasma proteins - "acute phase reactants" - Produced by liver - Lab values will change here - Erythrocyte sedimentation rate "ESR" - Increased fibrinogen = increased adhesion RBC/density=increase sed rate - C reactive protein - Increases with inflammation Describe the three phases of wound healing - Inflammation - Coagulation/hemostasis - Clotting system stops bleeding - Brings needed cells to the area - Platelets, neutrophils, macrophages - Fibrin mesh of blood clot - Creates scaffolding needed to create new tissue - Degranulating platelets - Release growth factor - Stimulates new tissue growth - Macrophages - Clean debris - Release growth factor - Recruit fibroblasts - Proliferation/new tissue - Begins 3-4 days after injury - Continues for up to 2 weeks - Wound is sealed, fibrin clot replaced by either normal or scar tissue - Granulation tissue = new lymphatic vessels and new capillaries - Red, granular appearance - Wound contraction begins - Myofibroblasts connect with neighboring cells - Contract and pull wound edges together - Remodeling/maturation - Begins several weeks after injury - Normally complete within 2 years - Fibroblasts - Deposit collagen - Tissue continues to regenerate - Wound continues to contract Describe the use of immunizations to prevent disease - Short term goal - Prevention in specific individual, population - Long term - Disease eradication - Active immunity - Via natural disease or vaccine - Biological response - Antibodies and memory B cells - Cytotoxic and memory T cells - Several weeks to full response - Passive immunity - Administration of antibody - Immediate protection - Duration: - Few weeks to months - Examples: - Breastfeeding - Immunoglobulin administration - Hep b - Tetanus - Rabies - Herd immunity - Non immunized individual protected - High vax rates = protection for unvaxxed - If only some vaccinated, illness will spread **Pain & Analgesics** Understand the 4 phases of nociception: transduction, transmission, perception, and modulation - Nociception: - Type of sensory nerve receptors for painful stimuli - Transduction - Tissue damaging stimuli activate nerve endings - Tissue damage: - Injury - Exposure - Illness - Infection - Trauma - Chemical mediators: - Histamine - Bradykinin - Prostaglandins - Leukotrienes - Lactate - Nociceptors excited: - Alters membrane potential - Transmission - Impulses carried from one site of tissue injury to (dorsal horn of) spinal cord and brain - Primary sensory fibers involved: - Alpha delta fibers - Size: - Medium sized - Myelinated: - Yes, thinly - Speed of transmission: - rapid - Type of sensation transmitted: - Sharp sensation, well localized - Primary neurotransmitter involved: - glutamate - C-fibers - Size: - Smaller and more numerous - Myelinated: - No - Speed of transmission: - Slower - Type of sensation transmitted: - Dull, aching, burning, poorly localized - Primary neurotransmitter involved: - Substance P - Perception - Conscious awareness of pain - Sensory: - Character, location, intensity (rate pain 1-10) - Affective - emotional - cognitive - learned behavior - Won't touch stove again! - Influenced by: - Pain threshold - Level of painful stimulation that is required to be perceived as pain -- similar among individuals - Pain tolerance - Greatest intensity of pain a person can endure - Different among individuals - Modulation - Can occur at various sites along the pain pathway - Increase or decrease the transmission of pain signals - Excitatory neuromodulators/neurotransmitters (increase pain) - Substance P - Histamine - Glutamate - Inhibitory neuromodulators (decrease pain) - GABA - Serotonin - Norepinephrine - Endogenous opioids - (enkephalins, endorphins, dynorphins) Discuss the role of the following neurotransmitters in nociception: glutamate, GABA, substance P, endogenous opioids - Glutamate - Primary excitatory neurotransmitter in CNS - Released from afferent pain fibers (C fibers and A Delta fibers) - Binds to glutamate receptors in the dorsal horn of spinal cord - NMDA - AMPA - Contributes to excitability of neurons in pain pathway - GABA - Primary inhibitory neurotransmitter in CNS - Modulating pain transmission by inhibiting the activity of pain conducting neurons - GABA opens chloride channels letting chloride ions in, making more negatively charged and less likely to fire - Controls magnitude and duration of pain signaling - Reduces pain perception - Substance P - Released by C fibers - Promotes release of other mediators - Histamine - Prostaglandins - Vasodilation and increased vascular permeability - Sensitivity of pain receptors increased - Endogenous opioids - Inhibit pain - Modulate pain perception - Inhibit pain transmission - Emotional regulation of pain - Bodies natural pain relief system Differentiate between the following types of pain: acute, chronic, neuropathic, ischemic, and referred - Physiologic - Acute - Duration: - \ 3 months or \> 6 months - Results from: - Peripheral and central NS sensitization - Reduction of threshold - Increase in sensitivity - Changes cause dysregulation of nociception and pain modulation process - Clinical manifestations: - Characteristics of pain, psychological and psychosocial components - Treatment: - Pain clinics, multimodal therapies - Examples: - Fibromyalgia - Low back pain - Neuropathic - Duration - Results from: - Nerves that have been damaged - Dysfunctional d/t tissue injury/chronic disease process, longer term changes in pain pathway structure, abnormal processing of sensory information - Clinical manifestations: - Constant aching with intermittent sharp, shoot, burning r/t reduction in GABA secreting neurons - Treatment: - Antidepressants or anticonvulsants - Examples: - Surgical sites - Diabetic neuropathy - Cancer treatments - trauma Describe treatment modalities that target specific phases of nociception - interrupt peripheral transduction/transmission of nociception - Non pharm: - Heat - Cold - Splint/minimize usage - Pharm: - NSAIDS - Inhibit prostaglandin production - Local anesthetics - Block sodium channel (EMLA) - Block the conduction of nociceptor impulse - modulate pain transmission at spinal cord level "The Gate" - Non pharm: - Heat/cold - Massage - Therapeutic touch - Acupuncture - TENS unit - Pharm: - Epidural - Intrathecal analgesics - alter the perception and integration of nociceptive impulses in the brain - Non pharm: - Imagery - Distraction - Hypnosis - biofeedback - Pharm: - opioids Relate the physiology of drug dependence, tolerance, and addiction to the signs and symptoms of each - Drug dependence - State in which an abstinence syndrome will occur if drug use is abruptly stopped (physiologic) - Tolerance - Larger dose is required to produce same response as before on smaller dose - Addiction - Uncontrollable cravings, inability to control drug use, compulsive drug use, use despite doing harm to oneself or others (behavioral) Describe the mechanism of action, effects of, and uses for major classes of OTC analgesics - Ibuprofen (Motrin, advil) - First gen NSAID - MOA: inhibition of COX I and II enzymes - Effects of: - Upper GI - Bleeding, ulcer formation, perforation, bowel obstruction - Use of \> 4 weeks increases risk of ulcer development - Renal injuries - Impairs renal blood flow - Problematic in elderly - Also when used and exercising excessively - Acute liver injury - General edema - Heart failure - Accelerate symptoms of disease - Uses: analgesia, inflammation, antipyretic - Acetaminophen (Tylenol) - MOA: honestly unknown,. Metabolized in liver - Effects of: - Liver toxicity - Do not take w alcohol - Conscious of combo prescription/OTC meds that also contain acetaminophen - Uses: reduces fever and pain but not inflammation - Naproxen (aleve) - MOA: - Effects of: - Uses: Predict common adverse effects associated with OTC analgesics See above Identify prototype drug(s) for categories of OTC analgesics See above Describe nursing considerations related to the appropriate and safe use of analgesic medications: - Acetaminophen - Liver issues - Alcohol use - Other medication - Ibuprofen - GI bleeds/ulcers - Renal injuries - Liver injuries - Other medications - Morphine - Respiratory status - Orthostatic hypotension/BP in general - Sedation risk - Other medication - Oxycodone - Respiratory status - BP - HR - Sedation risk - Other medications