NURS 365 Deck 2 Flashcards

Terms Definitions
randomized controlled trials most reliable to assess drug therapies 3 features: 1- use of controls 2- randomization 3 - blinding
preclinical test
animals test for: toxicity, pharmacokinetics, and useful effects bw 1-5 years
clinical testing
humans done in 4 phases (4th after on the market) bw 2-10 years
chemical vs generic vs trade names
chemical = chemistry generic= US adopted name less complex than chemical but more than trade trade = brand which drug is marketed, co make them easy to remember, say
4 processes ofpharmacokinetics
1- absorption 2-distribution 3-metabolism 4-excretion
mvmt of drug from site of admin into blood
mvmt from blood to interstitial space of tissues and from there into cells
biotransformation - enzymaticall mediated alteration of drug structure
mvmt of drugs and their metabolites out of the body
metabolism plus excretion
drug therapy
max effect min harm
pharmacokinetic factors used to determine
route, dose, and schedule
3 ways drugs cross cell membranes
1- through channels or pores 2- with aid of a transport system 3-direct penetration of membrane** **most common
channel and pore transport
only small molecules and must be right port ex: ions like K and NA
Transport system
*selective - depends on drug structure EX: P-Glycoprotein or "multi-drug transporter protein"> transports many drugs out of the cell
Direct penetration
most drugs too big for channels/pores and lack transport system *must be lipid soluble to pass membrane
non lipid soluble molecules
polar molecules - ex: h2o ions - have a charge, can NOT cross membrane
quaternary ammonium compounds
molecules with at least one nitrogen atom AND carry a POSITIVE charge always -unusual bc nitrogen has 4 chemical bonds unable to cross membranes
pH-dependent ionization
weak acids or weak bases charge determined by pH of medium (remember acid= proton donor) acids ionize in basic media bases ionize in acidic media
Ion trapping
pH partitioning when a pH gradient bw two sides of membrane.... acid drugs accumulate on alkaline side basic " " on the acidic side where pH favors ionization once ionized on the other side...can't move back
rate of dissolution of drug
bf absorption must dissolve can be formulated for fast or slow
surface area (rate)
surface area available for absorption determines rate larger = faster ex: most oral drugs absorbed in small intestine bc microvilli
blood flow (rate)
more rapidly where blood flow is high bc maintain gradient bw concentration of drug inside and outside blood
lipid solubility (rate)
bc lipid soluble drugs can cross membrane
pH partitioning (rate)
enhanced when diff bw pH of plasma and pH site of administration is such that drug molecules will have a greater tendency to be ionized in the plasma
Routes of administration
enteral = GI Parenteral = outside GI (IV, subcut, IM) all vary and will affect onset and intensity of effects
IV route
no barriers bc absorption is bypassed almost instant and complete absorption advantage = rapid onset complete control over levels in the blood permits large fluid volumes can give more toxic chemical bc constantly diluted in flowing blood PROBS = $,difficult, inconvenient, irreversible, fluid excess, embolism
IM route
barriers = capillary wall, drugs pass easily don't pass membrane can be fast or slow depending on water solubility and blood flow at site use when water solubility of drug is poor (bc those cant go in IV) ALSO good for DEPOT drugs to be absorbed over time BUT can cause discomfort, be inconvenient
subcut route
no significant barriers (like IM) similar drawbacks and advantages as IM
Oral route
absorbed from stomach or intestines, both must cross epithelial cells of GI tract AND capillary wall ALSO P-glycoprotein may pass back into intestinal lumen highly variable absorption bc: pH, solubility, gastric emptying time, food in gut, coadmin. with other drugs, coating on drug easy,convenient, safer
parenteral best when
emergency plasma drug levels must be tightly controlled when stomach acid would destroy drug (or liver or digestive) local injury could occur drugs can't cross membrane ptnt cant or wont take
chemical equivalent
drugs contain same amt of identical compounds
drugs are absorbed at same rate and same extent
coating to dissolve in intestines not stomach high variabiltiy
determined by blood flow to tissue, ability of drug to exit vascular system, ability of drug to enter cell
areas of limited blood flow include
abscess and tumors
exit vascular system happens at
capillary bed - bc little resistance bw cells most can't in brain bc BBB (only if lipid soluble or transported) drugs can form reversible bonds with proteins mostly ALBUMIN in blood but albumin never leaves blood stream
drug metabolism
aka biotransformation the enzymatic alteration of drug structure most takes place in liver
hepatic-drug metabolizing enzyme
P450 system cytochrome= key component group of enzyme families can catalyze wide variety of reactions using drugs as substrates
6 possible consequences of drug metabolism
accelerated renal excretion of drug drug inactivation increased therapeutic action activation of "prodrugs" increased toxicity decreased toxicity
compound that is inactive until administer and undergoes conversion in the body
factors influencing drug metabolism
age drug-metabolizing enzyme induction ex phenobarbital causes liver to synthesize drug-metabolizing enzyme drugs inactivated by liver when PO poor nutrition can compromise competition bw drugs
enterohepatic recirculation
drug transported from liver to duodenum via bile duct then back to liver **only certain drugs, usually drugs that have undergone glucuronidationd
removal of drug from body exits: urine, bile, sweat, saliva, breast milk, and expired air **kidney most important organ
renal drug excretion
3 steps 1- glomerular filtration - cap network and Bowmans capsule filter small molecules (some drugs) from blood to urine 2- passive tubular reabsorption - drugs that are lipid soluble reabsorb back into blood bc of concentration gradient 3 - active tubular secretion - active transport in kidney tubule that pump drugs from blood to urine
pH dependent ionization
altering urinary pH can promote ionization of a drug and decrease passive reabsorption into blood, quicker elimination
competition of active tubular transport
if multiple drugs compete for trans site then elimination delayed....can be used therapeutically by prescribing a drug to compete to sustain treatment
two plasma drug levels
1- min effective concentration 2-toxic concentration
minimum effective concentration
plasma drug level below which therapeutic effects will NOT occur
Toxic concentration
plasma drug level too high
therapeutic range
bw MEC and toxic narrow therapeutic range difficult to administer safely
drug half-life
the amount of time required for the amount of drug in the body to decrease by 50%
dose-response relationship
as dose increases response becomes larger 3 phases: 1- no curve , too low 2- increase dose, ^ response 3- flatten, ^ dose, same response
study of the biochemical and physiologic effects of drugs and molecular mechanisms by which those are produced
dose-response relationship
bw size of dose and intensity of response
dose-response 3 phases
phase 1 - low dose phase 2 - increase in dose elicits ^ response phase 3 - increased dose no ^ response
max efficacy
largest effect drug can produce
amount of drug given to elicit effect
any functional macromolecule in a cell to which a drug binds to produce its effects binding to receptor usually reversible binding sites intended for endogenous compounds (hormones, neurotransmitters, etC)
drugs and receptors
can mimic endogenous action or BLOCK sites
four families of receptors
1- cell-membrane-embedded enzymes 2-ligand-gated ion channels 3- G protein-coupled receptor system 4-transcription factors
cell membrane-embedded enzymes
-line cell membrane -ligand binding domain outside -enzyme's catalytic site inside -response to activation of these occur in seconds ex: insulin
ligand-gated ion channels
-span cell membrane -regulation ion flow in and out -each is specific for an ion -when agonist binds receptor, ion flow freely (concentration gradient) bc channel opened -response in millisec. ex: acetylcholine
G protein-coupled receptor system
3 components: receptor, G protein, effector agonist binds receptor >which activates G protein> which activates effector serpentine structure
transcription factors
WITHIN the cell on DNA delayed response hours-days regulate protein synthesis agonist stimulate transcription of RNA molecules agonist must be lipid soluble
selective drug action is possible bc
so many types of receptors in body, each regulating few processes
theories of drug receptor interaction (2)
simple occupancy theory modified occupancy theory
simple occupancy theory
-intensity of response to a drug is proportional to the numbe of receptors occupied by that drug -max response occurs when all available receptors occupied ***doesn't account for why some drugs are more potent
modified occupancy theory
includes quality of drug: affinity (attract bw drug and receptor) and intrinsic activity (ability of drug to activate)
drugs w high affinity effective in low doses are VERY POTENT
intrinsic activity
high intrinsic activity = cause intense receptor activation reflected in MAX EFFICACY
drugs that mimic body's own regulatory molecules
drugs that block body reg molecules
noncompetitive antagonists
bind irreversibly, basically reduces the # -reduce maximal response to agonist *rarely used bc can't reverse BUT cells don't last forever
competitive antagonist
bind reversibly compete with agonist for site, site occupied by whichever (agonist of antagonist) has highest concentration
partial agonist
max effect lower than a full agonist, less affinity can act as AGONIST and ANTAGONIST
receptor regulation
# of receptors can change depending on activation or inhibition continued agonist = desensitized antagonist = hypersensitive
average effective dose = dose at middle of frequency distribution curve effective dose in 50% of population
therapeutic index
measure of drug safety high therapeutic index = relative safety
outcomes when drugs interact (3)
intensification of one reduced effect of one response not seen in either drug alone
potentiative interaction
one drug increases effect of another can be good or bad
inhibitory effects
one drug reduces effects of another can be good or bad
mechanisms of drug interaction (4)
1-direct chemical or physical interaction 2-pharmacokinetic interaction 3- pharmacodynamic interaction 4-combined toxicity
ways drugs can alter absorption of another
alter pH - accelerating passage through intestines - depress peristalsis - increase vomiting - reduction of regional bloodflow
drugs can alter distribution of another by
competition for site alteration of extracellular pH
drug can alter metabolism of another by...
**complex*** some increase others decrease by increasing or decreasing synthesis of hepatic drug-metabolizing enzyme
drug safety issues (2)
ADR or ADE adverse drug reaction/event medication errors
noxious, unintended, undesired effect at normal dose
side effect
nearly unavoidable secondary drug effect produced at therapeutic doses ex: drowsiness
drug reaction caused by excessive dosing
allergic recation
immune response immune system must have prior sensitization to drug re-exposure triggers immune response
idiosyncratic effect
uncommon drug response resulting from a genetic predisposition
iatrogenic disease
health care provider produced disease, or produced by drugs
physical dependence
body grows dependent on presence of drug abstinence syndrome develops if discont. usually CNS acting drugs but not always
hepatotoxic drugs
injury to liver
QT interval drugs
ability of some meds to prolong QT interval on electrocardiogram > risk for dysrhythmias QT interval is measure of time for ventricle to repolarize after contraction
boxed warnings
required for potentially dangerous drugs summarizes adverse effects
risk evaluation and mitigation strategies = plan to reduce drug induced harm
types of med errors (13)
wrong: ptnt, route, drug, time, dose, dosage form, diluent, strength/concentration, infusion rate, technique, duration omitted dose, deteriorated drug (expired
number of women taking med during pregnancy
2/3 take at least 1
challenge to prescribe to pregnant wmn bc
risks are unknown but health of fetus dependent on health of mother
physiologic changes that impact drug disposition and dosing
3rd trimester renal blood flow doubles = accelerated clearance of drug tone and motility of bowel decreases = increase transit time
production of birth defects less than 1% of birth defects from drugs
teratogenesis and stage of development
conception to 2 wks = all or nothing 3 to 8 wks = gross malformations fetal period (2nd and 3rd) = disruptions in function rather than anatomy
drug risk catergories
A = least dangerous X = most dangerous, known to harm fetus
pharmacokinetic in neonates and infants
-drug effects usually intense and prolonged
increased sensitivity in infants due to (6)
immaturity of 5 processes: drug absportion protein binding drugs exclusion of drugs from CNS by blood brain barrier hepatic drug metabolism renal drug excretion
infant absorption
Oral - gastric emptying prolonged and irregular IM - slow and erratic, low blood flow through muscles in 1st days, then becomes very rapid Transdermal - more rapid and complete, thin skin, greater blood flow to skin
infant distribution
protein binding to albumin is limited bc low albumin and competition from endogenous compounds
infant hepatic metabolism
low drug metabolism capability, increases after 1 month, completely mature 1 year
infant renal excretion
reduced at birth blood flow, glomerular filtration, active tubular secretion low
children 1+
metabolize fast than adults highest at age 2 then declines
child dose approximation equation
dose = body surface area x adult dose 1.73m^2
older patients
more sensitive to drugs more varied reactions multiple drugs multiple illnesses poor adherence
elder absorption
rate of absorption most effected = slowed gastric acidity reduced
elder distribution
4 factors: increased body fat (storage for lipid soluble drugs) decreased lean mass decreased body water reduced serum albumin
elder metabolism
rates of hepatic metabolism decline reduced hepatic blood flow
elder excretion
renal function decline **important cause of ADR*** causes accumulation of drug
Innate immunity
Natural barriers and inflammation
Inflammatory response
Broad and nonspecific - 2nd line initiated by trauma, burn, any antigen (ex:smoking, virus)
Adaptive immunity
3rd line of defense, slower, more specific ex infection
Epithelial cell chemical defenses.
Mucus, perspiration, saliva, tears, earwax.
In tears, sweat, saliva. Kills gram + bacteria
Sebaceous glands secrete
Fatty acids and lactic acid kill bacteria And fungi
make enviro. inhospitable by creating acidic environment
anitmicrobial peptides
secreted by epithelial cells can kill fungi, bacteria, viruses more than 1000 discovered
two best studied antimicrobial peptides are
cathelicidins and defensins
many kinds exist grouped as a types and B types
a-type defensins
require activation by proteollytic enzymes in granules of neutrophil, may help killing bacteria, also found in Paneth cell of intestine
B-type defensins
synthesized in active form found in variety of epithelial cells antibacterial AND help protect surfaces from infection from adenovirus and HIV
glycoproteins in lungs
normal flora
nonpatho. microorganisms in body "commensal" relationship but really "mutualistic" relation with humans contribute to innate protection against pathogens ASLO help train adaptive immune system by inducing growth of gut associated lymphoid tissue
opportunistic microorganisms
normal flora but will cause disease if unchecked
what is the 2nd line of defense
innate immune systems
responds to damage to body this response initiates an interactive system of humoral and cellular systems called INFLAMMATION
first response to injury 1-tissue has to have blood supply VASCULARIZED 2- activates RAPIDLY after damage 3-dependent on CELLULAR and CHEMICAL components 4-NONSPECIFIC
symptoms of inflammation
red, swelling, pain, loss of function
process of inflammation:
VASODILATION - slows blood velocity and increases blood flow to injured site INCREASED vascular permeability and leakage of fluid out of the vessel> SWELL WBC ADHERENCE to inner walls of vessels and migrate through enlarged junctions of endothelial cells
loss of function from
tissue injury, pain, swelling
benefits of inflammation
1-prevents infection/more damage by diluting toxins produced by bacteria, destroying debris, clotting 2-limits inflammatory process through influx of plasma proteins, enzymes, and cells to prevent spread to healthy tissue 3-interacts with adaptive immune system to elicit more specific response through influx of macrophages and lymphocytes 4-drains byproduct to prepare for healing and repair through lymphatic vessels
inflammation kicks on acquired immunity bc
microbial antigens found in lymphatic fluid pass lymph nodes where they encounter lymphocytes
3 key plasma protein systems essential to inflammatory response are
complement system clotting system kinin system bc they set off biologic functions, sometimes called "cascades"
Complement system
proteins aka "complement factors" that equal about 10% of serum proteins -activation can destroy pathogens and activate other components of immune response -factors produced are some of most potent against bacterial invasion **activates C3 and C5 resulting in OPSONINS, CHEMOTATIC FACTORS< and ANAPHYLATOXINS
coat surface of bacteria to "tag" them to be eaten by neutrophil or macrophages
chemotatic factors
away from the site to attract phagocytic cells to site "SMOKE SIGNAL"
induce rapid degranulation of mast cells
C5b and C9 complement components
MAC = membrane attack complex makes pores in cell outer membrane> water rushes in and it explodes
pathways that control activation of complement (3)
classical pathway = activated by antibodies alternative pathway= activated by substances on surface of infectious organism lectin pathway = activated by plasma proteins, esp. mannose-binding lectin
clotting system
forms blood clot "barrier" activated by chemicals released in tissue injury activated through: tissue factor pathway AND contact activation pathway
Kinin system
interacts with coagulation system system results in bradykinin molecule which causes DILATION of blood vessel, acts with prostaglandins to INDUCE PAIN, smooth muscle contractions, INCREASE vascular PERMEABILITY
plasma protein system regulation
mechanisms to activate and deactivate are built into system
wbc includes: basophils, neutrophils, eosinophils
wbcs precursors of macrophages
wbcs in immune response as NK cells (innate) B and T cells (acquired)
Pattern recognition receptors
receptors on cells of innate immune resp. can recognize: molecules from infectious agents (PAMP) OR molecules from cell damage (DAMP)
toll-like receptors
example of PRR recognizes PAMPs
complement receptors
recognize molecules produced by activation of plasma protein systems
pro or anti inflammatory molecules secreted by cells to affect other cells "cooperation" of cells in immune response affect other cells through cell surface receptor activation
classification of cytokines (2)
interleukins and interferons
produced primarily by macrophages and lymphcytes in response to PRR stimulation most important: IL-1 and IL-6
cytokines that protect against viral infections macrophages and viral infected cells create them to warn other cells
special cytokines that attract leukocytes to site of inflammation different kinds exist
mast cells
most important in inflammatory response close to blood vessels near outside surfaces of body, filled with granules "hot head" easy to set off
found in blood, similar function to mast cells
release molecules like histamine and chemotactic factors
causes increased blood flow into microcirculation also increase WBC adherence to endothelium **antihistames - block binding of histamine to its receptors
mediators of inflammation (mast cell products)
leukotrienes - histamine like response only later prostaglandins - pain bc acts on nerves, synthesis blocked by asprin (ex) platelet-activating factors - similar to leukotrines
cytoplasmic fragments, circulate until vascular injury occurs when activated: 1- interact w coagulation cascade to stop bleeding 2- degranulation
primary phagocyte in early response respond w/in 6-12 hours of injury short lived, becomes pus removal of debris or bacteria
immature WBC in blood
mature wbc in tissue monocytes develop from bone marrow>travel to injury> become macrophages have larger lysosomes enter site after 24 hours survive for longer bc hand acid enviro better than neutrophils "direct" wound healing process
mildly phagocytic main functions: 1- defend against parasites 2 -regulate vascular mediators released by mast cells (LIMITS AND CONTROLS INFLAMMATION) by degrading vasoactive molecules ex: histamine
dendritic cells and t lymph
dendritic cells link innate and acquired immune response> contact with t lymph in nodes when travel through lymph system
2 important phagocytes
neutrophils and macrophages only phagocytosis once leave blood stream
aka emigration cells through inter-endothelial junctions which are loose due to inflammatory response
enhances adherence of target cell to phagocyte
acute inflammation is
self limiting, continues until threat to host is gone usually 8-10 days
serous exudate
watery, early and mild inflammation few plasma proteins or luekocytes
fibrinous exudates
more advanced, thick, clotted ex: lung infection in pneumonia
suppurative exudate
purulent, contains pus, large leukocyte accumulation ex: cysts or absesses
hemorrhagic exudate
bleeding occurs, filled with erythrocytes
systemic responses to acute inflammation (30
fever - endogenous pyrogens act on the hypothalamus leukocytosis - increase in circ. WBC, "left shift" may occur (more immature) increased plasma proteins - mostly ^ by liver, can be pro or anti inflammatory called "acute phase reactants" reach max w/in 10-40 hours
red blood cell sedimentation rate
an increase isconsidered good indicator of acute inflammatory response
chronic inflammation lasts
2 weeks or longer can occur w/o acute response chara: dense infiltration of macrophages and lymphocytes
attempt to wall off area when unable to protect body from tissue damage begins w macrophage differentiate into EPITHELIOID CELLS the form multinucleated GIANT CELLS (can engulf large particles) surrounded by a wall of lymphcytes -> leads to necrosis in center
restoration of tissue in healing
= replacement of destroyed tissue with scar tissue (collagen to provide strength but NOT function of replaced tissue)
primary intention
healing of wound with min tissue loss
secondary intention
ex: pressure ulcer takes longer at best 80% tensile strength restored
compensatory hyperplasia
complete restoration of tissue ONLY by liver, bone marrow, and epithelial cells
3 phases of wound healing:
phase I: inflammation 1-2 days, cleaned and clot forms phase II: proliferation, 3-4 days - 2 wks, wound sealed, clot replaced by normal tissue, granulation tissue grows phase III: several weeks to 2 year, remodeling
specialized cells for wound contraction contain smooth muscle cells and fibroblasts (secrete collagen)
sutured wounds pull apart usually 5 - 12 days later prompt surgical attention needs heralded by serous fluid
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