Unit 1 bolded terms Flashcards
pharmaceutic phase
the drug becomes a solutation so that it can cross the biologic membrane
excipients
used in drug preparation to allow the drug to take on a particular size and shape to enhance dissolution
AKA fillers and intert substances
Some additives in drugs, such as the ions K and Na in penicillin potassium and penicillin sodium, increase the absorbability of the drug
disintegration
the breakdown of a tablet into smaller particles
dissolution
the dissolving of the smaller particles in the GI fluid before absorption
rate limiting
the time it takes the drug to disintegrate and dissolve to become available for the body to absorb it
generally, drugs are both disintegrated and absorved faster in acidic fluids with a pH of 1 or 2 rather than in alkaline fluids
both the very young and older adults have less gastric acidity; therefore drug absorption is generally slower for those drugs absorved primarily in the stomach
pharmacokinetics
the process of drug movement to achieve drug actions
4 process: absorption, distribution, metabolism (or biotransformation), and excretion (or elimination)
passive absorption
occurs mostly by diffusion (movement from higher concentration to lower concentration)
with diffusion, the drug does not require energy to move across the membrane
active absorption
requires a carrier such as an enzyme or protein to move the drug against a concentration gradient
energy is required
pinocytosis
process by which cells carry a drug across their membrane by enguling the drug particles
note on absorption:
remember: drugs tha are lipid soluble and nonionized are absorved faster than water-soluble and ionized drugs
first-pass effect
AKA hepatic first pass
the process in which the drug passes to the liver first
exampes of drugs with first-pass metabolism: warfarin (Coumadin) and morphine.
Lidocaine and some nitroglycerins are not given orally because they have extensive first-pass metabolism and therefore more of the dose would be destroyed
bioavailability
is a subcategory of absorption. It is the percentage of the administered rug dose that reaches the systemic circulation
oral dose: less than 100%
intravenous route: usually 100%
factors that alter bioavailability
1) drug form (tablet, capsule, sustained-release, liquid, transdermal pathc, rectal supossitory, inhalation
2) route of administration (oral, rectal, topical, parenteral)
3) GI mucosa and motility
4) food and other drugs
5) changes in liver metabolism caused by liver dysfunction or inadequate hepatic blood flow (but only if drug is metabolized in the liver)
distribution
the process by which the drug becomes available to body fluids and body tissues
influenced by blood flow, the drug’s affinity to the tissue, and the protein-binding effect
volume of distribution (Vd)
dependent on drug dose and its concentration in the body
drugs with larger volume of distribution have a longer half-life and stay in the body longer
protein-bind effect
as drugs are distributed in the plasma, many are bound to varying degrees (percentage) with protein (primarily albumin)
>89% bound to protein: highly protein-bound drugs
61%-89%: moderately highly protein bound
30%-60% moderately protein bound
<30%: low protein bound
Low protein level decreases the number of protein-bind sites, leading to more free drug in plasma. Clients with liver or kidney disease, or who are malnourished, may have abnormally low serum albumin
some drugs bind with specific protein compenent: most anticonvulsants bind primarily to albumin. Most antidysrhythmics (e.g., lidocaine and quinidine) bind mostly to globulins
free drugs
drugs not bound to protein
only free drugs are active and can cause pharmacologic response
metabolism
drugs can be metabolized in both the GI tract and the liver
liver is the primary site for metabolism
most drugs are inactivated by liver enzymes and are then converted or transformed by hepatic enzymes to inactive metabolites
half-life (t1/2)
of a drug is the time it takes for one half of the drug concentration to be eliminated
4-8 hr: short half-life
24 hours or longer: long half-life
administration of a drug for 3-5 half-lives saturates the bioligic system to the extent that intake of drug equals amt metabolized and excreted
elimination
main route is through the kidneys
other routes include: bile, feces, lungs, saliva, sweat, and breast milk
kidneys filter free unbound drugs, water-soluble drugs, and drugs that are unchanged
protein-bound drugs cannot be filtered through the kidneys
lungs eliminate volatile drug substances and products metabolized to CO2 and H2O
elimination and pH
Urine pH varies from 4.5-8
acidic urine promotes elimination of weak base drugs.
alkaline urine promotes elimination of weak acid drugs
Aspirin, a weak acid, is excreted rapidly in alkaline urine. If someone OD’s on aspirin, bicarbonate may be given to change urine pH to alkaline
Large quantities of cranberry juice can decrease urine pH, causing acidic urine and inhibiting the elimination of aspirin
creatinine clearance (CLcr)
most accurate test to determine renal function
compaires the level of creatinine in the urine with the level of creatinine in the blood
creatinine is a metabolic byproduct of muscle that is excreted in the kidneys
CLcr test consists of 12 or 24 hour urine collection and blood sample
normal CLcr is 85-135 mL/min
Older adult clients may have creatinine clearance of 60 mL/min due b/c aging decreases muscle mass and results in a decrease in functioning nephrons
creatinine clearance varies with age and gender: lower values are expected in older adult and female clients b/c of their decreased muscle mass
A decrease in GFR results in an increase in serum creatinne and a decrease in urine creatinine clearance
pharmacodynamics
the study of drug concentration and its effects on the body
drug response can cause a primary or secondary physiologic effect or both
primary effect is desirable, and the secondary effect may desirable or undesirable
dose response
the relationship b/w the minimal versus the maximum amount of drug dose needed to produce the desired drug response.
some clients respond to a lower drug dose, whereas others need a high drug dose to elicit the desired response
onset of action
is the time it takes to reach maximum effective concentration (MEC) after a drug is administered
peak action
occurs when the drug reaches its highest blood or plasma concentration
duration of action
is the length of time the drug has a pharmacologic effect
time-response curve
evaluates 3 paramaters of drug action
1) onset of drug action
2) peak action
3) duration of action
receptor families
1) kinase-linked receptors
2) ligand-gated ion channels
3) G proteincoupled receptor systems
4) nuclear receptors
ligand-binding domain
the site on the receptor at which drugs bind
kinase-linked receptors
the ligand-binding domain for drug binding on the cell surface.
The drug activates the enzyme (inside the cell), and a response is initiated
ligand-gated ion channels
the channel spans the cell membrane and, with this type of receptor, the channel opens, allowing for the flow of ions into and out of the cells. The ions are primarily Na and Ca
G-protein coupled receptor systems
there are 3 components to this receptor response
1) the receptor
2) the G protein that binds with guanosine triphosphate (GTP)
3) the effector that is either an enzyme or an ion channel
Drug activates the receptor. Receptor then activates G protein. G Protein then activates the effector
nuclear receptors
found in the cell nucleus (not on the surface) of the cell membrane. Activation of receptors through the transcription factors is prolonged.
With the first 3 receptor groups, activation of the receptors is rapid
agonists
drugs that produce a response
ex: Isoproterenol (Isuprel) stimulates beta1 and beta2 receptors, so it is anagonist
antagonists
drugs that block a response
ex: cimetidine (Tagamet) blocks the histamine (H2) receptor, thus preventing excess gastric acid secretion
The effects of an antagoist can be determined by the inhibitory (I) action of the drug concentration on the receptor site
IC50 is the antagonist drug concentration required to inhibit 50% of the maximum biological response
nonspecific drugs
drugs that affect various sites
occurs when drugs act on receptors that can be found throughout the body
nonselective drugs
drugs that affect various receptors
categories of drug action
1) stimulation or depression
(ex: drug stimulating or depressing the secretion of a gland)
2) replacement
(ex: insulin)
3) inhibition or killing of organisms
(ex: antibiotics)
4) irritation
(ex: laxatives irritate the inner wall of the colon, thus increasing peristalsis and defecation)
therpeutic index (TI)
estimates the margin of safety of a drug through the use of a ratio that measures the effective (therapeutic concentration) dose (ED) in 50% of persons or animals (ED50) and the lethal dose in 50% of animals (LD50)
The closer the ratio is to 1, the greater the danger of toxicity
TI = LD50/ED50
low therapeutic index
have a narrow margin of safety
high therapeutic index
wide margin of safety and less danger of producing toxic effects
Plasma drug levels do not need to be monitored routinely for drugs with a high TI
therapeutic range
(therapeutic window)
therapeutic range of a drug concentration in plasma should be between the minimum effective concentration in the plasma for obtaining desired action and the minimum toxic concentration
when the therapeutic range is given, it includes both protein-bound and unbound portions of the drug
peak drug level
the lowest plasma concentration of a drug
measures the rate at which the drug is eliminated
trough levels are drawnimmediately before the next dose of drug is given
peak drug level
the highest plasma concentration of a drug at a specific time
peak drug levels indicate the rate of absorption
if the drug is given orally,the peak time might be 1-3 hours after drug administration.
If given IV, peak time might occur in 10 minutes
a blood sample should be drawn at the proposed peak time, according to the route of administration
loading dose
given when immediate drug response is desired
large initial dose
given to achieve a rapid minimum effective concentration in plasma
after a large initial dose, a prescribed dosage per day is ordered
bolus
adminstering drug by IV push
drop factor
number of drops per Ml
macrodrip set
delivers large drops per mL
(10-20 gtt/mL)
If infusion rate is 100mL/h or more, macrodrip set is preferred
microdrip set
small drops per mL
60 gtts/mL
if infusion rate is < 100 mL/h or client is a child, the microdrip set is preferred
Keep vein open
(KVO)
AKA to keep open (TKO)
when IV fluids are given at a slow rate to keep the vein open
reasons for ordering KVO: suspected or potential emergency situation for rapid administration of fluids and drugs and the need for an open line to give IV drugs at specified hours
For KVO, a micro drip set (60gtt/mL) and 250 mL IV bag may be used.
KVO is usually regulated to deliver 10mL/hr
secondary IV line set
inserted into primary IV line set through a rubber port
usually used when drugs are Rx to be administered 3-6 times a day in a small volume of IV fluid (50-100 mL)
drug solution is usually infused over a period of 15 minutes to 1 hour
This is called intermittent IV therapy
IV push
meds that are given by IV injection route are calculated in the same manner as meds for IM injection
clinically, it is the preferred route for clients with poor muscle mass or decreased circulation, or for a drug that is poorly absorbed from the tissues
electronic intravenous (IV) regulators
pumps
set to deliver Rx rate of IV solution
if flow rate is obstructed, an alarm sounds
flow rate set at mL/h
pumps do not recognize infiltration
the alarm does not sound until the pump has exerted its maximum pressure to overcome resistance
volumtric regulator
delivers a specific volume of fluid at a specific rate, in mL per hour
nonvolumetric regulator
designed to infuse at a drop rate in drops per minute
common progems associated with IV infusions
kinked tubing- if tubing kinks, the flow is interrupted and the Rx amt of fluid will not be given. The access site can clot
infiltration- fluid extravasates into the tissues and not into the vascular space. Trauma occurs to the tissues at the IV site
“free flow”- refers to rapid infusion of IV fluids. faster than Rx. causes fluid overload. B/c of possiblity of “free flow,” electronic infusion pumps are commonly used today
patient-controlled analgesia (PCA)
objective of PCA: to provide a uniform serum concentration of the durg, avoiding peaks and valleys
method designed to meet the needs of clients who require at least 24-48 hours of regular IM narcotic injections
reasons to use PCA:
1) effective pain control w/o the cl feeling oversedated
2) considerable reduction in the amount of narcotic used (approx. 1/2 that of IM delivery)
3) cleints’ feelings of having greater control over their pain
pediatric drug dosages differ b/c:
neonates and infants have immature kidney and liver function, which delays metabolism and excretion of many drugs
in neonates, drug absorption is different as a result of slow gastric emptying time
decreased gastric acid secretion in children under 3 contributes to altered drug absorption
neonates and infants have lower concentration of plasma proteins, which can cause toxicity with drugs that are highly protein bound
young children have less total body fat and more body water; therefore lipid soluble drugs require smaller doses when less-than-normal fat is present
water soluble drugs can require large doses b/c of a greater percentage of water
two methods considered safe in administration of drugs to children:
(calculating dose)
1) body weight
2) body surface area (BSA) or m2
dosage per body weight
usually done in kg
divide weight in lbs by 2.2 to get weight in kg
calculate pediatric dosage per body surface area
Need the child’s height and weigh
nomogram can be used (specialized chart)
the square root formula and be used
BSA= (square root of) height (inches) x weight (lbs)
3131 (constant)
injection sites for peds
vastus lateralis: safe for neonates to adolescents (varying amount of meds can be injected, depending on age)
rectus femoris: NOT safe for neonates and infants
ventrogluteal: NOT safe for neonates, infants, or toddlers
dorsal gluteal: NOT safe for neonates, infants, toddlers
gluteus maximus: NOT safe for neonates, infants, toddlers
deltoid: NOT safe for neonates and infants
The United States Pharmacopeia National Formulary (USP-NF)
the current 3 volume authoritative source for drug standards
an annual publication
U.S> Food and Drug Administration (FDA)
empowered by The Food, Drug, and Cosmetic Act of 1938 to monitor and regulate the manufacture and marketing of drugs
FDA is responsible for ensuring that all drugs are tested for harmful effects, have labels with accurate info, and enclose with the drug packaging detailed literature that explains adverse effects
Only drugs considered safe by the FDA are approved for marketing
Durham- Humphrey Amendment to teh 1938 Act
Passed in 1952
distinguished b/w drugs that can be sold with or without a Rx and those that should not be refilled w/o a new Rx
drugs that should not be refilled w/o a new Rx: narcotics, hypnotics, transquilizers
Kefauver-Harris Amendment to the 1938 Act
passed in 1962
resulted from widely publicized thalidomide tragedy of the 1950’s in which pregnant European women who took the sedative-hypnotic thalidomide during the first trimester of pregnancy gave birth to infants with extreme limb deformities
tightened controls on drug safety, especially experimental drugs, and required that adverse reactions and contraindications be labeled and included in the literatue
Also included provisions for the evaluation of testing methods used by manufacturers, the precess for withdrawal of approved drugs when safety and effectiveness were in doubt, and establishment of effectiveness of new drug before marketing
The Controlled Substances Act
passed in 1970
designed to remedy problem of drug abuse
several provisions:
1) the promotion of drug education and research into the prevention and tx of drug dependence
2) the strengthening of teh enforcement authority
3) the establishment of treatment and rehab facilities
4) designation of schedules, or categories, for controlled substances acordding to abuse liability
controlled substances
are described in 5 schedules:
schedule I:
not approved for medical use
ex: heroin, LSD, mescaline
schedule II
accepted medical use, high potential for drug abuse
es: meperidine (Demerol), morphine, pentobarbital
schedule III
accepted medical use, may cause dependence, less abuse potential than II
ex: codeine preparations, paregoric, nonnacotic drugs (pentazocine propoxyphene)
schedule IV
medically accepted, may cause dependence
es: phenobarbital, benzodiazepines
schedule V
medically accepted drugs. very limited potential for dependence. Labeled C-V
opioid controlled substances for diarrhea and cough (e.g., codeine in cough preparations)
Drug Enforcement Administration DEA
became the nation’s sole legal drug enforcement agency in 1983
Drug REgulation Reform Act
passed in 1978
shortened the time in which a new drug could be developed and marketed. Protects pt rights and at the same time facilitates the investigational process and promotes research
The Food and Drug Administration Modernization Act
passed in 1997
5 provisions:
1) review and use of new drugs is accelerated
2) drugs can be tested in children before marketing
3) clinical trial data are necessary for experimental drug use for serious or life-threatening health conditions
4) drug companies are required to give info on “off-label” drugs (non-FDA approved drugs) and their uses and costs
5) drug companies that plan to discontinue drugs must inform health professionals and clients at least 6 months before stopping production
Health Insurance Portability and Accountability Act (HIPAA)
passed in 2003
sets the standards for the privacy of individually identifiable health info as of 2003.
gives client more control over their health information
Pediatric Research Equity Act
2003
FDA is authorized to require testing by drug manufacturers of the drugs and bioligc products for their safety and effectiveness in children
One must not assume that children are small adults
Medicare Prescription Drug Improvement and Modernization Act
2003
provides financial assistance to seniors to purchase needed Rx meds
Cl responsible for monthly premium of $35 and $250 annual deductible.
This benefit will pay 75% of total cost of Rx drugs up to a max of0
