N393 Final Flashcards
How do hormones change in pregnancy?
Every woman has cycle with variation; same hormones responsible play key role in maintaining pregnancies upon conception and fertilization
The corpus luteum is endocrine structure(produces hormones) or gland formed in ovary at site where egg is released
If egg not fertilized, the corpus luteum goes away
If egg is fertilized, the CL transforms into endocrine organ that helps maintain pregnancy
We think CL and hormones released is responsible for morning sickness
CL is responsible until placenta is large enough to take over
Hormones
HCG
Estrogen
Progesterone
HCG
(Human Chorionic Gonadotropin)
Produced by developing conceptus and placenta
Is a positive feedback mechanism; tells CL to release larger quantities of sex hormones (estrogen and testosterone)
Basis of many pregnancy tests and lab tests
Prevent involution of corpus luteum
Estrogen
Produced by CL and Placenta
Enlargement of uterus, breasts, and external genitalia
Relax pelvic ligaments so body can accommodate larger growing organ of uterus and baby inside
Progesterone
Produced by CL
Role in nutrition of early embryo
Decreases uterine contractility (tells body to “chill out”)
Helps estrogen prepare breasts for lactation
Shown in graph how it increases and then drops off completely to allow labor
Formation of placenta
Formed from trophoblast cells around the blastocyst (fetal development tissues)
Placenta thickness between mom and baby is about 1 layer of cells in some places - think about this small barrier with pharmacology
Function of placenta
Diffusion: Primary way placenta works
Higher concentration to lower
Flow of blood through placenta
Mom has uterine arteries and veins that empty into middle sides (maternal sinuses)
Baby side has umbilical vein and umbilical arteries, getting what they need from diffusion
Nutrients
Waste is exchanged
Gases (CO2 and O2)
Body’s response to pregnancy: weight
Weight gain- average total: 24 lbs (by end of pregnancy) Fetus: 7lbs Placenta, amniotic fluid: 4 lbs Uterus: 2 lbs Breasts: 2 lbs Plasma volume: 6 lbs Fat: 3 lbs
Body’s response to pregnancy: Metabolism & Nutrition
Metabolism & Nutrition*
Basic metabolic rate increases 15% during later half of pregnancy
Providing nutrients to help baby grow
Placental stores of nutrients are needed to sustain fetal grown during the last months of pregnancy (a lot of moms worry about weight)
Body’s response to pregnancy: Breast Development
Starts in first few weeks of gestation; they are enlarging but not working or prepared to do milk portion of it
Hormones
estrogen, progesterone, prolactin oxytocin
Breast development Hormones
Estrogen: stimulates tissue to grow
Progesterone: stimulates tissue to grow; the ductules, lobes in breasts
Prolactin: stimulated production with baby eating/suckling (baby eats = prolactin levels rise = nipple stimulated = milk produced)
Oxytocin: responsible for let down or milk ejection and responsible for uterine contractions
Will help uterus return to size while breastfeeding
Body’s response to pregnancy: Kidney Function
Increased renal plasma flow and glomerular filtration rate
More fluid that all must go through kidneys
Very little is related to waste of fetus; babies would produce urine and would be in amniotic fluid, it is sterile
Majority of this is mom with increased plasma and fluid she needs to process
Body’s response to pregnancy: Circulatory
Mom’s cardiac output will increase 30-40% by 27th week of pregnancy; By end of pregnancy, 30% greater blood volume
Less RBCs in relation to blood volume may see resulting in dilutional anemia; not anemic, not decrease in hematocrit; in relation to everything going on, she will have/experience decrease in hematocrit
Moms will be monitored closely but in greater context it is just because mom has more plasma volume
Heart working harder to maintain the new volume
Body’s response to pregnancy: Respiratory
Respiratory- increased RR
20% increase in oxygen use by mother at term
May see higher RR taking vitals
Progesterone increases minute ventilation
Uterus presses abdominal content up against the diaphragm
Common complaints during pregnancy and anatomical reason why
Spine
Back pain, displaced center of gravity back pain
Intestines
Constipation, organ moved around
Bladder
Constant urination, bladder squished
Stomach
Gastric reflux/indigestion, change in pressure, no room to expand
Can’t eat as much, get full fast
Lungs
Can’t take deep breaths
Sleeping changes Needing to pee Needing to sleep on side Edema Extra fluid
Breast tenderness
Colostrum can be excreted for weeks
Falls
Increased risk for falls
Massive stretching
Heart should not enlarge
What to avoid during pregnancy (don’t need to know specifics)
Cigarettes, alcohol, illicit drugs, stimulants, Vitamin A at doses higher than 5,000 IU, Liver(?), herbal products, Dieting and skipping meals, Iodine, Limit certain fish, undercooked or raw fish, meat, etc.
Prenatal vitamins
Various products may not be equivalent/interchangeable; Content not standardized
Regulation as “supplement”
Potential compliance issues- health individuals may not appreciate need - Education!
Adverse effects
Nausea, vomiting, constipation (especially Fe- containing)
Take with food or in evening to
Constipation- hydration, fiber intake activity
Notes
Recommend reputable brand if OTC (may have prescription)
Stress on body - need supplement
Folic Acid Function
Cell division, DNA synthesis (makes DNA)
Neurodevelopment
FA goes through reduction with dihydrofolate reductase reduced to tetrahydrofolic acid and goes on to make amino acids
Folic Acid Use in Pregnancy
Start preconception (preferably in months before) Neural tube closure @ 18-26 days post conception Populations at risk for deficient (e.g., epilepsy, family history neural tube defect, etc)
Folic Acid Dose
Decreased neural tube defects Preconception & 1st trimester 400-800 mcg daily Different doses for certain increased risk groups Adverse effects Water soluble-few AE May mask deficiency of Vitamin B12
Iron Function
HB (70-80% of total body Fe); myoglobin; iron-containing enzymes
Other
Transferrin
Ferritin (storage iron pool)
Fe from degraded RBCs recycles (120 days)
As you take iron in, some immediately stored, some go through life cycle, as RBC dies it releases iron again and it will keep going through cycle
Loss largely due to blood loss
Iron deficiency anemia
Fe requirements
Increased RBC production
Iron - Uses in pregnancy
Expansion of maternal RBC mass, blood volume
RBC production in fetus
Iron- Dose
Determined by Hb & iron status prior (highly variable)
General pregnancy RDA=27 mg/day (vs. 15-18 mb/d non-pregnant)
Iron- Adverse effects
GI
Nausea, bloating, constipation
Causes dark stools, be careful could be blood
Caution!! Overdose can be fatal; leading cause of death is poisonings
Want to make sure stored appropriately and not laying around (red tablets, yummy!)
Oral Iron
(ferrous is most easily absorbed/common)
With adequate stores, Fe absorption is decreased
Dietary- heme form best
Various (ferrous sulfate, gluconate, fumarate, etc.(solid or liquid)
~10% absorbed- body knows it doesn’t need it
Vitamin C increases absorption
Food decreased absorption (but may help with GI Distress initially… nausea and constipation)
Compare mg “elemental iron” in products
Iron- what to know
Different formulations
Different between salt and elemental
Ferrous sulfate (salt form) = 65 mg of elemental iron
When talking about how much iron is in something, focus on ELEMENTAL IRON
Same with calcium
Calcium
Functions- need for everything Bone Neuronal excitability/NT release Muscle contraction Cardiac action potential, contraction Blood coagulation
Pregnancy
Fetal skeletal development (mostly 3rd trimester)-Forming baby, need to supplement their development
Maternal skeletal
RDA- pregnancy /lactation
1000 mg elemental Ca++/day (19-50 years) this includes food intake
Calcium salts- oral
Forms vary & have differing Ca++ content
Calcium carbonate, citrate, etc.
Common adverse effects include (not many)
GI (especially constipation)
Drugs in pregnancy
~⅔ of pregnant females take ≥1 med
Both pregnancy & non-pregnancy related conditions
Drugs of abuse (e.g., alcohol, caffeine, etc.)
Safety testing cannot be done in pregnancy women- requires retrospective approach (registries)
Adverse consequences may occur with just 1 dose!
Effects are relative to period of pregnancy
Very early -death
3-8 weeks- major morphologic malformation
9-term -physiologic defect/minor morphologic
Risk vs. benefit approach to taking medication
Consequences of leaving condition untreated may be more harmful to embryo/fetus
Physiologic changes in pregnancy- GI
GI tract- impact on tone and motility of bowel (would impact absorption)
Prolongation of intestinal transit time– everything is moving through pretty slowly
Increased absorption potential- can’t predict how slow and may lead to continuous absorption
Potential impact on enterohepatic recirculation
Increased potential
Physiologic changes in pregnancy- Kidney
By 3rd trimester, renal blood flow is doubled
Results in large increase in glomerular filtration rate-
Excretion impacted- decreased drug concentration excreting out more
Physiologic changes in pregnancy- Liver
For some drugs, hepatic metabolism increase
Embryo/Fetal Development
1-2 week exposure to teratogens
3-8 week: Embryonic period
Organogenesis- making the organs
Exposure to teratogens during this time may cause malformation
I.e., cleft palate, neural tube defect,
9- 38 week: Fetal period
Exposure to teratogens during this time may impact function of the organs
Types of effects
Teratogenic
Behavioral- neurocognitive
Pharmacological or toxic effects in fetus
Teratogen
an agent/factor that causes a malformation of an embryo
Fetal structural malformation; or
Other- miscarriage, stillbirth, etc.
Exposure to medication within 1-2 weeks, pregnancy will terminate
Pharmacological or toxic effects in fetus
Pharmacologic effect: respiratory depression with opioid
Example: baby would have depressed breathing if it is taken right before delivery
Delayed toxicity
Example: Diethylstilbestrol (DES): estrogenic substance- causes vaginal cancer in female offspring 18 years or so after they were born
Physiologic dependence-infant
Prototype example: Thalidomide- treating morning sickness in 1950s-1960s, children born with “seal limbs”
New Labels for Pregnancy
- 1 Pregnancy: Includes labor and delivery
- 2: Lactation: Includes nursing mothers
- 3 Females and Males of Reproductive Potential (new)
Old Labeling
- 1 Pregnancy
- 2 Labor and Delivery
- 3 Nursing Mothers
FDA Pregnancy Categories
A:
Controlled human studies fail to demonstrate risk in 1st trimester; no evidence of risk in later trimesters
B:
Animal- failure to demonstrate risk (or do show risk, but controlled human studies do not)
Human- no controlled studies
C:
Animal- adverse effect on fetus - or - no studies done
Human- no controlled studies
D:
Human- proof of human fetal damage
“WARNING” statement on drug label
X:
Animal or human studies demonstrate definite risk of fetal abnormality
“CONTRADICTION” statement of drug label
Lack of teratogenic effect in animals ≉ safety in humans
FDA drug approvals are based on animal testing
Nursing agents to support safe drug use in pregnancy
Problematic Agents (not an all-inclusive list)
Considerations to minimize risks
Drug therapy during breastfeeding
Considerations to minimize risk of drug use during pregnancy
Educate women of childbearing age
Assume any drug will reach the embryo/fetus (some drugs won’t cross but don’t assume)
Weigh risk vs. benefit
Is a drug needed?
Eliminate unnecessary drugs
Avoid certain drugs, if drug therapy is necessary
If necessary, use drugs with better safety profile
Avoid substances of abuse (before & during)
For known teratogens (e.g., isotretinoin, Retin-A)
Written informed consent
Multiple forms of contraception
Pregnancy test just prior to initiation
Problematic agents
Drugs with hormonal effects Anticancer (Ex: cytotoxic) Antiseizure Drugs that affect thyroid Ethanol Drugs of abuse Mercury Drugs that affect cell development/differentiation (ex: Vitamin A derivatives-isotretinoin) Antimicrobial Drugs that affect RAAS Warfarin (anticoagulant) New: analgesics-insufficient data for FDA action NSAID-miscarriage; opioids-birth defects; Tylenol- ADHD
Drug therapy during pregnancy
Large number of drugs can be excreted in breastmilk
Extent of excretion and infant exposure is based on medication absorption factors- think about factors that determine whether a drug can pass through a membrane
Factors determining if it will enter breast milk:
Lipophilic
Small in size
Ionized vs non
Is it compatible with breastfeeding? Look for diarrhea in infant
Don’t always have a lot of data to understand clinical effects
Always look it up
How would you counsel a patient?
Age related effects on PK processes
Immature organs, alterations in binding, alterations in # of receptors (increases and decreases)
May show greater variability patient to patient (vs.geriatrics and adults)
Lack of safety or efficacy data- not used in studies (patients excluded under 18 years of age typically, may not have data on younger people with medication)- may be dosing guesses early on
Neonates & Infants
Kinetic differences in kids- longer time above MEC
With appropriate weight based dose, adults decrease faster than children; we have a longer period of time above MEC
Neonates & Infants: Absorption
Not good predictability;
Prolonged & irregular gastric emptying time
Reach adult levels at 6-8 mo
Increase in absorption
Low gastric acidity
Reach adult levels at about 2 years
Ionization- GI absorption
Low blood flow through muscles in first days of life
Slower absorption in muscles (IM route)-(infants better than neonate/adults)
Slow and erratic in neonates
Give a lot this way for infants
Very thin stratum corneum and greater blood flow to skin
Topical is FAST; worried about toxicity
Very thin skin with a lot of blood flow
Neonates & Infants: Distribution
Protein bending
Low serum albumin levels
Increased free drug- risk of toxicity or increased clinical effect
Adult levels in 10-12 months
Endogenous compounds (bilirubin) compete with drugs for available binding sites
Blood brain barrier
May need decreased dosing if it has increased CNS potential or toxicities
Worry about stuff getting in there
Not fully developed at birth; it protects your brain so stuff doesn’t get in
Neonates & Infants: Metabolism
Low drug-metabolizing capacity
Increased risk of toxicity because not metabolizing like need to
Liver maturation at about 1 year
Neonates & Infants: Excretion
Low during infancy (below) resulting in increased drug levels…Decreased renal excretion means increased drug levels
Renal blood flow
Glomerular filtration
Active tubular secretion
Children 1 year & older: PK processes
By age 1, most PK parameters = adults
Exceptions:
Drug metabolism continues until about 2 year of age (then gradually declines)
Excretion of some drugs can increase tremendously
BBB is fully developed about a year or older
Factors Affecting Medication Complications in the Elderly
Alterations in pharmacokinetics
Multiple and severe illnesses
Multidrug therapy
Different prescriber
Poor adherence
Cost, forget to take, dementia, trouble swallowing, have to take a lot/can’t keep straight, don’t want to, etc.
How can we help geriatric patients?
Technological strategies, pill boxes, pill packs (send prescriptions and they send pill packs), community outreach programs, routes of administration, simplifying regimen, does every provider know everything the patient is on
Geriatric patients: Absorption
Rate affected, not really sure how much; can lead to delayed response Increased gastric Decreased absorptive surface area Decreased splanchnic blood flow Decreased GI motility Delayed gastric emptying
Geriatric patients: Distribution
Several things can happen:
Increased body fat
Lipophilic drugs will have increased distribution into fatty areas; can lead to decreased plasma concentration levels of these drugs because they are hanging out in the fat
Decreased lean body mass
Decreased muscle mass, not a lot going out to muscles
Decreased total body water
Increase concentration if drugs are water soluble (hydrophilic drugs)- smaller pool for them to play in
If same amount given as someone with normal water, it could increased risk of toxicity
Decreased serum albumin
Decreased protein binding = increase in free drug
Decreased cardiac output
Geriatric Patients: Metabolism
Decreased metabolism
Decreased hepatic blood flow
Decreased hepatic mass
Decreased activity of hepatic enzymes
Geriatric Patients: Excretion
MOST important part!! This will be the most concerning outcomes, biggest toxicity
Decreased renal blood flow
Decreased glomerular filtration rate
Decreased tubular secretion
Decreased number of nephrons
PK Geriatric Patients: Overall
A- increased, D- all over the place, M- won’t happen as good as it should
Geriatric Patients & Kidneys
Important to understand that how well kidneys work as geriatric patient we know what labs to look at
Lab to look at: Creatinine; Creatinine clearance is estimate of glomerular filtration rate
It is a protein> proteins come from muscle> geriatric patients have decrease in muscle mass
Ex: 80 year old with creatinine clearance may look good but doesn’t mean same as someone that is younger; if there albumin is 2.4, their muscle will look super small … the number doesn’t mean much
Normal creatinine is 120. Clearance calculation example: (140-age/serum creatinine) That would put an 80 year old 60 versus 20 year old would be at 120. This would tell a nurse how to adjust dosage for clearance
PD changes in elderly
May have significant alterations in receptor activity but is difficult to predict
Reduction in number of receptors
Reduction in receptor affinity
We know very little about how this actually applies to clinical practice
Can’t adjust for this
Adverse Drug Reactions: Geriatric Patients
7 times more common in the elderly vs. younger patients
Accounts for 16% of hospital admission in older patients and 50% of all medication related deaths
Why?
Drug accumulation -(poor D/M/E and erratic A)
Polypharmacy- all drugs and doctors and pharmacies don’t know
Greater severity illness
Multiple pathologies
Greater use of NTI drugs- effective/toxic concentration is narrow
Alterations in pharmacokinetics
Inadequate supervision of long-term therapy
Poor adherence
Basic events of embryology
Conception: fertilization of egg with sperm
Approximately two week difference between gestational age and conception
Conception
Occurs in fallopian tubes
Embryonic Period
First 8 weeks post conception *think malformations
All major organs are formed
Three primary germ layers
Basic body plan emerges
Week 1- travel
Week 2- implantation
*says embryo not susceptible to teratogens because there is no blood supply from mom supplying baby; doesn’t mean whatever mom is exposed to doesn’t change environment or make it optimal for implantation
It would be spontaneous abortion, women don’t even know they are pregnant
Blastocyst
Cleavage: Journey of 6 days to travel to uterus; cells are dividing and then implanting
Two distinct types of cells
Inner cell mass: forms the embryo
Trophoblast: layer of cells surrounding the cavity which helps form the placenta
Float for about 3 days
Implantation on about 6 days pays conception
Trophoblast erodes uterine wall
Takes 1 week to complete
Implantation
Adherence of the trophoblast to the uterine wall
Inner cell mass divides into epiblast and hypoblast
2 fluid filled sacs
Amniotic sac from epiblast
Yolk sac from hypoblast- nutrition, primitive digestive system
3 primary layers of tissue formation
Ectoderm
Mesoderm
Endoderm
Ectoderm
Interactions with external environment; CNS; External affairs
Nervous Tissue:
Epidermis
Nervous tissue
Neural tube CNS Retina Posterior pituitary Pineal gland Neural crest Pigment cells Adrenal medulla Cranial and sensory nn Cranial and sensory ganglia
Epidermis
Hair Nails Mammary glands Cutaneous glands Anterior pituitary Teeth enamel Inner ear Eye lens
Mesoderm
Structure & organization; Architect & engineers; skeletal system
Skeleton (head and body) Muscle Connective Tissue Circulatory sys (Cardiovascular & Lymphatic) Spleen Adrenal cortex Genital system: (Gonads, ducts, accessory glands) Dermis Dentine of teeth
Endoderm
Metabolism & homeostasis; chemist Epithelium of GI tract Liver Pancreas Urachus Urinary bladder
Epithelial portions Pharynx Thyroid Trachea, bronchi, lungs Tympanic cavity Pharyngotympanic tube Tonsils Parathyroids
Fetal period
(weeks 9-40) including fetal lung & circulatory development
Remaining 30 weeks (+2 weeks of conception = 40 weeks) *think function
Organs grow larger and become more complex
Overview of organ development
By 1st month, gross characteristics of all different organ systems have already begun to develop
By 4th month, organs are grossly the same as neonate
By birth, nervous system, kidney, and liver are not fully developed
Organogenesis
up until week 16
Differentiation
week 16 > birth
Ex: jaundice, liver is not fully developed
Gastrointestinal development
Midpregancy- ingest and absorb large amounts of amniotic fluid
Last 2-3 months- small quantities of meconium formed
Shouldn’t have much or would be indication of distress in baby
Kidney development
Begin to excrete urine during second trimester
Fetal urine = most of amniotic fluid
If not developing properly, ultrasound will show less fluid
Fetal blood
By 3 months, bone marrow is producing most of RBC
Even at low PO levels, fetal hemoglobin can carry
20-50% more oxygen than maternal hemoglobin
Hemoglobin concentration of fetal blood is about 50% greater than that of the mother
Lung Development
Surfactant is detectable at about 24 weeks in amniotic fluid
Is a phospholipid, produced inside lungs
Decreases surface tension (alveoli sticking together)
It is important in lung development and alveoli
Makes work of breathing easier
Lung function is not fully formed until 36-38 weeks
Fetal Circulation
Heart begins to beat at week 4
3 major structures: don’t need liver or lungs
ductus venosus
Ductus Arteriosis
Foramen ovale
1 Factor
High Pulmonary Vascular resistance
Ductus Venosus
Shunts blood to skip liver
Liver isn’t fully functional until after birth (some blood gets in to make sure that it is developing) but mom and placenta do the work of the liver
Ductus Arteriosis
Shunts blood into aorta which takes out of body
Blood shunted due to high pressure in lungs
Foramen ovale
Shunt/hole between right and left atrium
High Pulmonary Vascular Resistance
Lungs are high pressure, filled with fluid, blood doesn’t want to go there so two other structures are created to avoid
Growth & Development
Growth:
Increase in physical size (height, weight, head circumference)
Development:
Continuous, orderly series
Increase in function and complexity
Increase in capabilities
Patterns of G & D
Pace
Rapid from birth to 2 and puberty to ~15 years
Slower from 2 to puberty and 16-24 years
Cephalocaudal
Head to toe
Ex: Can sit up before walking
Proximodistal
Middle to outside
Ex: Sitting before fine motor
Simple to complex
Fine motor development
Factors that influence G&D
*Always give ranges
Critical/sensitive period
Genetics
Environment
physical and psychosocial (prenatal exposure/SES/access)(toxins/lead/pollution/etc.)
\Culture
Health status
Family
Response of the body to pregnancy
Average weight gain 24 lbs 15% increase in basal metabolic rate 20% increase in respiratory rate 30-40% increase in cardiac output 30% increase in blood volume
Increased renal plasma flow and glomerular filtration rate
Breast development
Pace
Rapid from birth to 2 and puberty to ~15 years
Slower from 2 to puberty and 16-24 years
Cephalacaudal
Head to toe
Ex: Can sit up before walking
Proximodistal
Middle to outside
Ex: Sitting before fine motor
Simple to complex
Fine motor development
Factors that influence pediatric development
*Always give ranges Critical/sensitive period Genetics Environment physical and psychosocial (prenatal exposure/SES/access)(toxins/lead/pollution/etc.) Culture Health status Family
Aging
Is a normal physiologic process- universal and inevitable
Time dependent loss of structure and function
Cellular and molecular level
Not a disease
Three theories of aging
Gene Regulation Theory
Programmed Senescence Theory
Neuorendocrine
Programmed Senescence Theory
Cell senescence
Limits the number of cell divisions that humans can undergo
Genetically programmed (small amount of DNA is lost with each cell division)
Cell damage
Telomeres
Caps at the end of chormosones that protect, they shorten and eventually cell division stops
Reactive Oxygen Species
The formation of free radicals that triggers cell damage/DNA/RNA/Proteins/Cell death (UV light, metabolism, inflammation, ionizing radiation, smoking, air pollution)
Systemic
Neuroendrine- decreasing ability to survive stress; diminished ability to coordinate communication, program physiological response, maintain optimal functional state
HPA axis forever overwhelmed
Immunity decreased
TBW (Total Body of Water)
Newborn/Infant = 70-80%
Adult = 50-60%
Older/Aging Adult = 55%
Trends: decreasing over lifespan
in 2 compartments: extracellular (1/3) or intracellular (2/3)
Extracellular fluid is plasma and interstitial fluid
4 forces move
Cell membrane is permeable to water but not electrolytes, those need active transports
Filtration, Reabsorption, Oncotic, Hydrostatic
Osmosis vs. Filtration & Reabsoprtion
Osmosis- btw intracellular and extracellular
Filtration & Reabsorption - capillary membrane
Extracellular
A lot of Na+ (sodium) & Cl- (chloride)
Less of K (Potassium), Mg (Magnesium), Ca (Calcium) and Protein
Intracellular
A lot of K, Protein
Less of Na, Cl, Mg, Ca
Osmotic pressure
is force that attempts to balance the concentration of solute and water between intracellular and extracellular fluids
Water follows higher concentration of solutes in an attempt to balance
Isotonic
solute and water concentration is the same on both sides
hypertonic
solute concentration is higher on outside than inside
ex: osmolality 300, water goes out, cell shrinks
hypotonic
solute concentration is lower outside the cell than inside the cell
ex: osmolality: 200, water goes in, cell swells
Osmolity
is the number that reflects amount of solutes per kilogram
Top 5 fluids
Hypotonic: D5W
Hypertonic: D5 1/2 NS, D5NS
Isotonic: Lactated Ringers, NS .9% NaCl
Hypertonic Fluids
when you need sodium and fluid volume replacement and monitoring hydration, lung sounds, electrolytes
D5 ½ NS: used for Na and volume replacement; CAUTION, go slow, monitor BP, pulse rate, and quality of lung sounds & serum Na and urine output
and
D5NS
Hypotonic Fluids
D5W: isotonic until inside then body then metabolize glucose and become hypotonic; for when you need sugar, glucose
Don’t give to infants ore head injury patients! May cause cerebral edema
Isotonic fluids
same osmolarity as body fluid, used for fluid replacement in safe way; monitoring I&O’s,, skin turgor, mucous membranes, electrolytes (secondary)
NS 0.9% NaCl: used to expand volume, dilute medications and keep vein open
Lactated Ringers: used for fluid resuscitation
Normal Serum Electrolyte Concentrations
Calcium 9-11mg/dl
Magnesium 1.5-2.5 mEq/L
Potassium 3.5-5 mEq/L
Sodium 135-145 mEq/L
Labs drawn from extracellular space, it will show reflection of whats happening on inside
Na
135-145 mEq/L
Major extracellular fluid cation
Regulates osmotic forces & water balance (pull water one way or another)
Regulates acid-base balance
Facilitates nerve conduction and neuromuscular function
Transport of substances across cellular membrane
K
Range: 3.5-5.0 mEq/L
Major intracellular fluid cation
Maintains cell electrical neutrality
Facilitates cardiac muscle contraction and electrical conductivity
Facilitates neuromuscular transmission of nerve impulses
Maintains acid-base balance
Ca
Range 9-11 mg/dL
Vital for cell permeability, bone and teeth formation, blood coagulation, nerve impulse transmission, and normal muscle contraction
Plays important role in cardiac action potential and is essential for cardiac pacemaker automaticity
Mg
Range: 1.5-2.5 mEq/L
Role in smooth muscle contraction relaxation
Suppresses release of acetylcholine at neuromuscular junctions
Low Mg = increased acetylcholine = too much movement
High Mg = decreased acetylcholine = too little movement
Filtration
movement of ECF from intravascular space to interstitial space
Forces that favor filtration: Water moving from capillaries to interstitial Capillary hydrostatic (push force) Interstitial oncotic (pull force)
reabsorption
movement of ECF from interstitial space to intravascular space
Forces that favor reabsorption: Moving from interstitial to vascular Capillary osmotic (pull force) Interstitial hydrostatic (push force)
Oncotic pressure
osmotic pressure exerted by proteins pulling
Capillary (plasma) oncotic pressure
Osmotically attracts water from the interstitial space back into the capillary
Pulls water back into vascular space
Interstitial oncotic pressure
Attracts water from capillary into the interstitial space
Hydrostatic pressure
force generated by pressure of fluid on capillary walls pushing
Capillary hydrostatic pressure (blood pressure)
Facilitates the outward movement of water from the capillary to the interstitial space
Capillary hydrostatic pressure is primary force that pushes water out of vascular space
Interstitial hydrostatic pressure
Facilitates the inward movement water from the interstitial space into the capillary
Acid-Base Balance
pH normal range = 7.35-7.45
Acid: contribute or donate H+
Base: absorb an H+ ion
Inverse relationship: increased H+ = decreased pH #, decreased H+ = increased pH #
Acidosis
pH below 7.4 (↑H+)
Alkalosis
pH above 7.4 (↓H+)
1st line buffer: 3 chemicals
Bicarbonate-Carbonic Acid buffer (ECF)
H2CO3 (Carbonic acid) ⇄ H+ + HCO3 (Bicarbonate ion)
Protein buffer (ICF) - Hemoglobin absorbs/liberate H+
Phosphate buffer (CF) - Sodium Phosphate can absorb/liberate H
If the pH is alkalosis- carbonic acid will contribute its H+… end result is:
Increase H+ & decrease in the pH
If the pH is acidosis - H+ will wimbine with bicarbonate… end result is:
Decrease H+ & increase in the pH
2nd line buffer: respiratory
If acidosis, breathe faster and deeper = removes CO2 gas from the blood = lower pCO2 of the blood … end result is:
Decrease in H+ = increase in pH
If alkalosis, breathe slower and shallower = adds more CO2 gas to the blood = Higher pCO2 of the blood
Increase H+ & decrease in the pH
2nd line buffer: renal
Secrete more or less H+ into the renal tubule and take out in urine
Phosphate
Ammonia
Secrete more H+ → ↓H+ → ↑pH
Secrete less H+ → ↑H+ → ↓pH
Respiratory acidosis/alkalosis
High or low pCO2 value
Metabolic acidosis/alkalosis
High or low HC03 value
Normal arterial values
pH: 7.35-7.45
pCO2: 35-45 mmHg
HC03: 22-26 mmHG
pO2: 80-100 mmHg
compensation
With partial compensation = buffer system activated but pH still high
With full compensation = buffer system activated and pH is normal
Hypoxemia
O2 values is off
1st line of Immunity
Physical barriers Characteristics: Innate Constant presence Epithelial cells Not very specific response No memory Examples: skin and mucous membranes, cells and secretory molecules, cilia, normal flora
2nd line of Immunity
Innate immunity- inflammation Characteristics: Not specific In response to (and usually in proportion to degree of) injury Immediate response No memory
3rd line of Immunity
Adaptive Characteristics: Delayed response Very specific toward “antigen’ Discriminatory & diverse T & B lymphocytes, macrophages, dendrite cells Specific memory Examples Antigens: infection diseases, environmental substances Humoral (b cell): antibodies Cell mediated (t cell): crafted cells in lymphocytes Immunizations Immunotherapy
Benefits of Inflammation
Prevents infection and further damage by microorganisms
Self limiting through plasma protein systems
Interacts with components of adaptive immune system so a more specific response can occur
Prepares the area for healing
3 phases of wound healing: inflammation is first
Components of Inflammation
- increased vascular permeability
- recruitment and emigration of leukocytes
- phagocytosis
Inflammation part 1: increased vascular permeability
(Get extra blood and cells to that area of body)
Mast cells releases- 3 key players
Histamines: potent vasodilator
Ex: targeting effects of this histamine? Give antihistamine to down inflammation response
Prostaglandins: vasodilate, chemotic factor (cells), pain
Leukotrienes: chemotaxis calling), inflammation > asthma
Vasodilation
Greater blood volume & hydrostatic pressure
Pushes fluid into surrounding tissue, the more fluid in vessels create push out into surrounding tissue to get specific type of cells where they need to go
Inflammation Part 2: recruitment and emigration of leukocytes
(Get from vascular to interstitial space)… 3 set stages:
Margination: neutrophils stick to the vessel wall, lining up; “pavementing”
Emigration/Diapedesis: neutrophils exits vessel
Chemotaxis (calling): tissues release chemotaxins (cells), migration toward higher concentration of chemotactic factors (prostaglandin, leukotrienes)
Inflammation Part 3: phagocytosis
(Doing its job of phagocytosis- digestion of things that should not be there)
Digestion; Results in:
By products- oxygen radicals which can cause cell damage
Pus- collection of dead neutrophils, bacteria, and cellular debris
Macrophages - cleaning
Kinins
Can activate itself
Works closely with clotting system
Initiated by activation of Factor XII to Factor XIIa
Results in: Bradykinin- chemical responsible
Pain
Vasodilation
Increased vascular permeability
Coagulation
at same time but different pathway to do some of same functions Activated by: Extrinsic- tissue injury Intrinsic- abnormal vessel wall & Factor XII Components of kinin system Responsible for: Clot formation Migration of leukocytes Chemotaxis Increased permeability
Compliment
“the one responsible for direction traffic”
Destroy pathogens direct or indirectly by recruiting others
Activated by:
Classical pathway- antibodies
Alternate- infectious organisms
Lectin- other plasma proteins
Results in:
Chemotaxis- calling, phagocytes attracted to area
Opsonization- tags/coats surface of bacteria; play come in & destroy
Direct lysis of pathogens- destroying pathogens
Degranulation of mast cells- inflammatory mediators (histmine, prostaglandin, leukotrienes, others)
Cascade systems
compliment, kinins, coagulation
Physical findings of inflammation
Pain (prostaglandin) Heat (vasodilation) Redness (vasodilation) Swelling (vasodilation) May have loss of function depending on what is going on
who is involved in the inflammatory process
Histamine, prostaglandin, leukotrienes
Bradykinin
Cytokinins
Leukocytes (WBCs)
cytokines and chemokines
Signaling molecules
Other names: monokinens, lymphokines, interleukins, tumor necrosis factor
Produced primarily by macrophages and T helper cells
Involved in: chemotaxis, recruitment, stimulation of leukocytes
Leukocytes
(*capable of phagocytosis)-formed in bone marrow with specific jobs to do
neutrophils* eosinophils* basophils* monocyte*s lymphocytes
Neutrophils
Early responder (6-12 hours) Polymorphonuclear leukocytes PMN Phagocytosis Release toxins Bands are immature neutrophils Destroy bacteria, remote debris & dead cells, short lived
eosinophils
Noted in allergic reactions and parasitic infections
Regulate inflammatory response “fumigation”
basophils
Mast cell Pro Inflammatory chemicals Allergic reactions Acute and chronic inflammation Wound healing
monocytes
Macrophages Longer living Phagocytosis Secrete cytokines (signaling molecules) Present antigens to activate T cells Clean up (disaster response team) (mononuclear)
lymphocytes
B&T longest to mobilize, trained for specific things) (mononuclear)
B-Cells
Able to produce antibodies
Have antibody like receptors on their surfaces (immunoglobulins)
T-Cells T-4 (CD4) cells Helper cells T-8 (CD8) cells No antibody circulating in order to work
Natural Killer cells
Nonspecific- innate
systemic manifestations of inflammation
Fever: cytokines released from neutrophils & macrophages that are pyrogens (fever causing)
Leukocytosis- increase in circulating WBCs
Lab changes- acute phase reactants (plasma proteins produced by liver, increased during inflammation)
Erythrocyte sedimentation rate- ESR = inc. sed = inc. inf
C-reactive protein
3 phases of inflammation
inflammation, proliferation, remodeling and maturation
inflammation
(Fill)
Coagulation/hemostasis
Bring cells that are needed to area
Fibrin mesh of blood clot = scaffold for healing
Degranulating platelets = growth factors
Macrophages = clear debris (can’t heal while old stuff there)
proliferation
Begins 3-4 days after injury
Continues for up to 2 weeks
Wound is sealed, fibrin clot replace scaffold by normal or scar tissue
Granulation tissue - new lymphatic vessels & new capillaries
Contraction begins
remodeling and maturation
Begins several weeks after injury Normally complete within 2 years Fibroblast- deposit collagen Tissue continues to regenerate Wound continues to contract
dysfunctional wound healing
Ischemia
Obesity- impaired leukocyte function, predisposition to infection
Diabetes- impaired circulation, increased risk for infection
Infection
Malnutrition- risk for infection, delayed healing, reduced tensile strength
Medications- delay healing, prevent macrophages from migrating inhibit fibroblasts
goals of immunization
Short term: prevention in specific individual; population
Long term: disease eradication & eradicate in US (polio, smallpox, diphtheria)
toxoid
Weakened bacterial toxin
vaccine
Killed vaccine (whole, killed microbe) Attenuated, live vaccine (risk to immunocompromised) Cell parts (mount response to part of cell)
active immunity
Via natural disease or vaccine Biological response Antibodies & Memory B cells Cytotoxic & Memory T cells Several weeks to full response Boosters
passive immunity
Administration of antibody Immediate protection Duration: few weeks or months Examples Breastfeeding Immunoglobulin administration (Hep B, Tetanus, Rabies)
herd immunity
Non-immunized individual protected
High vaccination rates protect unvaccinated
If only some get vaccinated- illness spreads
childhood immunization concerns
Minor illness or local reaction No OTC analgesics (dec immune response) Febrile seizures Autoimmune disease Autism Thimerosal Aluminum as an adjuvant
true contraindication
Anaphylactic reactions to specific vaccine: should not get further doses of THAT vaccine
Anaphylactic reaction to a vaccine component: should not get further vaccines with THAT component
Moderate or severe illnesses with or without a fever
not contraindication
Mild to moderate local reaction following a dose
Mild acute illness w/ or w/o low grade fever
Diarrhea
Current antimicrobial therapy
Convalescent phase of illnesses
Prematurity
Recent exposure to an infectious disease
Personal or family history of penicillin allergy or nonspecific allergies
regulation & logistics of immunizations
National Childhood Vaccine Injury Act- 1986
Details vaccine, vaccine information sheets
Reporting of Adverse Effects
VAERS VAE Reporting System
Storage & Handling
Storage, Reconstitution, Expiration Dates
Who can administer
vaccine information sheets
Requirement of National Childhood Vaccine Injury act Sheets must be given to all vaccines Produced by the CDC Benefits and risk Given before each dose Available in >30 languages
nocieptive pain
type of sensory nerve receptors that respond to pain (different receptors for different things)
afferent pathways
sensory - PNS → Dorsal horn & spinal cord → CNS
interpretive center
brainstem, midbrain, diencephalon, cerebral cortex
Location, ,characteristics, emotional response, meaning
efferent pathways
motivation - CNS → dorsal horn → motor area
4 stages of nociception
transduction, transmission, perception, modulation
transduction
Tissue Damage from exposure>
Release of that area of Chemical Mediators > Histamine, bradykinin, prostaglandin → inflammation >
Nociceptors receptors excited- A delta, C fibers
transmission
Impulses conducted centrally into the dorsal horn of spinal cord
Continue carrying impulse to CNS
Transmitting different types of sensations
Primary sensory fibers involved:
A delta fibers- medium sized, thinly myelinated (travels fast); well localized, reflex control; neurotransmitter: Glutamate
C fibers: unmyelinated, slow transmission; slow, dull, achy, burning pain; neurotransmitter substance P
perception
Conscious awareness of pain
Sensory- presence, location, characteristics, intensity
Affective- emotional response
Cognitive- learning
Influenced by
Pain threshold: level of painful stimuli required to be perceived as pain- similar among people
Pain tolerance: degree of pain one is willing to bear before seeking relief
modulation
(change or inhibition of transmission of pain) Occurs at multiple sites along the pain pathway Excitatory neuromodulators(makes pain worse) or Inhibitory neuromodulators (tone down pain
excitatory neuromodulators
(makes pain worse)
Substance P, histamine, glutamate
inhibitory neuromodulators
(tone down pain)
GABA, serotonin, norepinephrine, endogenous opioids
physiologic pain
tissue injury
Acute, Ischemic, Referred
chronic pain
long term changes within CNS/PNS; pain without purpose
Chronic, Neuropathic
Acute
Sympathetic Nervous System Resolves when injury heals ~3 months Signs & Symptoms: Increased HR, BP, RR Dilated pupils Pallor and perspiration Nausea and vomiting Urine retention Physiologic response Blood shunts from superficial vessels to muscles, heart, lungs, and brain Bronchioles dilate Decreased gastric secretions, GI motility Increased blood glucose Hypomotility of bladder and ureters Therapy Short term Opioid & nonopioid Safe short term, if better managed- no chronic
Chronic
Longer then expected healing time; ~6mo<
Results from:
Peripheral sensitization: reduction pain threshold
Central sensitization: increased responsiveness & sensitivity
Clinical manifestations: some acute, usually psychosocial (irritability, depression)
Treatment: multimodal, pain clinic
Examples: Fibromyalgia
Neuropathic
Results from injury to nerves themselves (chemo,surgery, radiation, trauma, diabetic hemopathy)
Clinical manifestations: constant ache wither intermittent sharp pain
Treatment: difficult to manage, doesn’t respond well to opioids/pharmacology; antidepressants/anticonvulsants do work well
Ischemic
Results from no blood flow to tissue; inflammatory process → release chemicals
Clinical manifestations depends on the site (aching, burning, tingling)
Treatment: improve blood supply (nitroglycerin - powerful vasodilator, could increase BP, headache)
Referred pain
Interrupting peripheral transmission of noception
Modulating pain transmission at the spinal cord level
Pain perceived in area other than injury
Consider signs and symptoms different between m/f
Treatment Modalities
Altering the perception and integration of nociceptive impulses in the brain
Altering the perception and integration of nociceptive impulses in the brain
Non-pharmacologic: distraction, imagery, hypnosis, biofeedback
Pharmacologic: opioids
Take home messages
As a nurse, working with a patient and their pain management needs to be both pharmacologic & non
You can do peripheral and spinal cord/brain and have multiple combinations for the most effective pain relief
Modulating pain transmission at the spinal cord level
Non-pharmacologic: cutaneous stimuli (massage, therapeutic touch, nerve stimulation, acupuncture, heat & cold)
Best way for a nurse to help modulate pain at spinal cord level: therapeutic touch, massage, etc.
Pharmacologic: epidurals, intrathecal anesthesia
Interrupting peripheral perception of nocicpetion
Non-pharmacologic (ice, heat vs cold, stabilize, splint, minimize use)
Pharmacologic (both should happen)
NSAIDS - inhibit prostaglandin production
Local anesthetics - block sodium channel (stop conduction of impulses)
Oxycodone
Therapeutic uses = relief of pain
MOA: mimic action of endogenous opioid peptides primarily at mu receptor
Drug interactions: CNS depressants, anticholinergic drugs, hypotensive drugs
AE: respiratory depression, constipation, orthostatic hypotension, urinary retention, sedation, euphoria, cough suppression, biliary colic, emesis
Morphine
Prototypical opioid analgesic
Therapeutic uses = relief of pain
MOA: mimic action of endogenous opioid peptides primarily at mu receptor
Drug interactions: CNS depressants, anticholinergic drugs, hypotensive drugs
Blocks muscarinic receptor = dry
AE: respiratory depression, constipation, orthostatic hypotension, urinary retention, sedation, euphoria, cough suppression, biliary colic, emesis
Ibuprofen
Ibuprofen
MOA: inhibit Cox 1 and 2 enzymes
Therapeutic uses: analgesia, inflammation, antipyretic
Generally well tolerated
Upper GI complaints
Bleeding, ulcer formation and perforation, bowel obstruction
Use of >4 weeks increases risk of ulcer development
Renal injuries
Impairs renal blood flow
Can be a problem when in combination with exhaustive exercise
Can be problematic in the elderly
Acute liver injury
Unusual event
<5/100,000 cases per year)
More likely to occur in conjunction with hepatotoxic agents
General edema or swelling
Heart failure
Elderly with heart failure at risk
Can accelerate symptoms of the disease
Acetaminophen
Don’t take more than 4 grams in 24 hours
Worry about potential for liver toxicity
Don’t take if consume alcohol
Be conscious of combination prescription and OTC medications
Combination products (cough and cold, headache products, sleep aids, prescription pain relievers)
Opioid analgesics
Act on Opioid receptors Mu, Kappa, Delta
Mu: analgesia, sedation, decreased GI motility, AND respiratory depression, euphoria, physical dependence
Kappa: analgesia, sedation, decreased GI motility
Delta: learning more about this receptor, may be a novel target for pain and depression treatments
Pure Opioid Agonists
(turns on receptors)
Mu: Agonist
Kappa: Agonist
Norpine, oxycodone, hydrocodone, fentanyl, etc
Agonist-Antagonist Opioids
Mu: Antagonist & Kappa: Agonist
Pentazocine, malbuphine, butorphanol
Mu: Partial agonist (little Mu) & Kappa: Antagonist
Buprenorphine
Pure Opioid Antagonists
Mu: antagonist
Kappa: antagonist
Naloxone, naltrexone
Reverses effects of opioids*
How does acetominaphen work
Selective COX inhibition in the CNS - reduces fever and pain (not inflammation)
Metabolized in the liver (knocks it out)
CYP450 - drug interactions
NAPQI toxic metabolite becomes inactive by glutathione
Give glutathione in overdose situation
Do not exceed 4 grams in 24 hours
Pain relief similar to NSAID but no anti-inflammatory activity
Know if patient has multiple drugs with acetaminophen
2nd generation NSAID
Celecoxib (Celebrex)
MOA: Cox 2 Inhibitors
Advantages: Less GI toxicity
Disadvantages: Expensive, Increased cardiovascular risks
1st generation NSAID
Ibuprofen
MOA: inhibit Cox 1 and 2 enzymes
Therapeutic uses: analgesia, inflammation, antipyretic
NSAID
Non-Steroidal Anti Inflammatory Drug
Indirect simulation of nociceptors (Cyclooxygenase pathways - COX 1 & 2)
Cox 1: protective prostaglandins (stomach mucosa, platelet stickiness)
Found in most tissues
Responsible for synthesizing the prostaglandins that maintain gastric mucosa and renal function
Cox 2: Inflammatory prostaglandins (pain, fever, inflammation)
Normally not present in healthy cells
Produced by presence of inflammation
NSAIDS will work by inhibiting Cox 1 & Cox 2
Common AE with OTC analgesics
Analgesic: drug to reduce pain by acting in the CNS or on peripheral pain mechanisms; Generally well tolerated
Upper GI complaints
Bleeding, ulcer formation and perforation, bowel obstruction
Use of >4 weeks increases risk of ulcer development
Renal injuries
Impairs renal blood flow
Can be a problem when in combination with exhaustive exercise
Can be problematic in the elderly
Acute liver injury
Unusual event
<5/100,000 cases per year)
More likely to occur in conjunction with hepatotoxic agents
General edema or swelling
Heart failure
Elderly with heart failure at risk
Can accelerate symptoms of the disease
If someone was taking this for several weeks, we would worry about ulcer, we would ask about stomach pain, blood in stool, etc.
