Pure Food and Drug Act of 1906
development of the U.S. Pharmacopeia (USP)
required manufacturers to list the contents of medication
Food, Drug, and Cosmetic Act of 1938
Requires food and drug companies to test products for safety
1952 Durham-Humphrey Amendment of the 1938 Act
description of prescription and nonprescription drugs
1962: Kefauver-Harris Amendment to the 1938 Act
tightened controls on drug safety; required labels to contain adverse reactions and contraindications
required drugs to be tested for safety
required companies to wait for FDA approval prior to marketing product
Controlled Substance Act of 1970
designation of schedules or categories
increased research and education for prevention of drug dependence
strengthened enforcement authority over prescribing, manufacturing and regulating of drugs
Created the Drug Enforcement Agency (DEA)
Orphan Act of 1983
created to stimulate research of medications for rare diseases
Food and Drug Administration Modernization Act of 1997
accelerated the process for the review and use of new drugs
2003: Health Insurance Portability and Accountability Act (HIPPA)
set industry standards for privacy of health information
Five Rights
1. right patient
2. right drug/medication
3. right dose
4. right route of admin
5. right time
Five+ Rights
1. right assesment
2. right documentation
3. right evaluation
4. right education
5. right to refuse
Echinacea: Action
Immune builder
Echinacea: Use
upper respiratory and urinary infections
Garlic: Action
Inhibits platelet aggregation (blood thinner)
Heart health
Antibiotic properties
Garlic: Use
hypertension (HTN)
coronary artery disease (CAD)
low BP
Ginkgo Biloba: Action
improves blood flow
crosses blood-brain barrier
brain health
Ginkgo Biloba: Use
used for Alzheimer's, dementia, & peripheral vascular disease (PVD)
Ginseng: Action
sympathomimetic
neuro protection
not well understood
Ginseng: Use
used to relieve stress, decrease fatigue, and lower blood sugar
Saw Palmetto "plant catheter:" Action
not yet understood
Saw Palmetto "plant catheter": Use
decreases swelling of the prostate
used to treat benign prostatic hyperplasia (enlarged prostate)
aids in urination
hair loss
St. John's wort: Action
releases dopamine, norepinephrine, & serotonin
St. John's Wort: Use
happiness herb"
used to treat MILD depression and sleep disorders
controlled substances
broken into categories I-V; I having the highest likelihood of abuse and V having the least
Schedule I Drugs
highest abuse potential
no medical use/acceptance in the US
ex. ecstasy, marijuana, LSD
Schedule II Drugs
non-reffilable drugs
ordering requires a DEA 222 form
high abuse potential; may lead to physical or psychological dependence
ex. morphine, oxycodone, cocaine
Schedule III Drugs
may lead to moderate or low physical dependency or high psychological dependence
not given six months after prescription written
not refilled more than 5 times
ex. tylenol with codeine
Schedule IV Drugs
low potential for abuse
ex. Xanax, clonazepam, clorazepate
Schedule V Drugs
used for antitussive, antidiarrheal, and analgesic purposes
ex. cough medicine
Chemical Name
chemical composition of the drug (i.e. 2-(4-isobutylphenyl)propanoic acid)
Generic Name
universal name; not capitalized (i.e. ibuprofen)
Brand or Trade Name
commercial name; capitalized (i.e. Motrin, Advil)
Preclinical Research
tests human microbial cells and animals
always inconclusive
not regulated by FDA yet
Clincal Trial: Phase 1
small group of healthy volunteers
evaluates safe doses dosage range and side effects
Clinical Trial: Phase 2
small group with disease
determining drug effective
dosage ranges are set here
Clinical Trial: Phase 3
large study group
under New Drug Application review
drug's name is finalized
Clinical Trial: Phase 4
after market studies to determine long term effects
Pharmacological class
big picture
how the drug acts
mechanism of action and effect on the body
i.e. beta blocker
mechanism of action
explanation of how a drug produces its effect; specific
Therapeutic Classification
what's being treated by the drug
Pharmacokinetics
study of drug movement throughout the body (absorption, distribution, metabolism, excretion)
Pharmacodynamics
how medicine changes the body
action of a drug
Absorption
process of moving something in the body to circulating fluids (blood)
Distribution
movement through the body to reach target cell
Metabolism (biotransformation)
chemically converting a drug to a form that is more easily removed from the body
occurs in the LIVER
Excretion
process that removes waste from the body
Absorption is affected by
route of administration
blood flow
condition of the GI tract (oral med)
other food/drugs
size of drug
surface area
lipid solubility
topical administration
skin and mucous membranes
constant absorption
slow onset
ex. eye drops, ear drops, vaginal suppositories
inhalation administration
works quickly
nebulizers & metered dose inhalers (MDI)
goes straight to lungs
Enteral administration
oral
SL (DISSOLVE NOT SWALLOW)
buccal
NG
parenteral administration
IV (absorbed 100%; quick onset of action; fastest)
IM
SQ
Intradermal (slowest)
Pros of oral administration
easy, cheap, safer (bc it can be retrieved easily), self-admin
cons of oral administration
GI distress
less reliable
some enzymes can't be broken down (ex. insulin)
Rate Limiting
delaying of absorption
(ex. enteric coated drugs, capsules, drug fillers)
Greater Blood Flow
#NAME?
Larger Surface Area
faster rate of absorption
GI motility
greater contact time = greater absorption rate
pH Partitioning (acid)
more FAT soluble in ACID environments
more WATER soluble in ALKALINE environments
pH Partitioning (alkaline)
more FAT soluble in ALKALINE environments
more WATER soluble in ACID environments
Bioavailability
the percentage of the administered drug dose that reaches the systemic circulation
drug/drug interactions
when two or more drugs that cause side effects when taken together are given at the same time
why it's important to know mech of action
Distribution factors: blood flow
more blood flow = more distribution
Distribution factors: polar drugs (solubility)
CAN'T cross plasma membrane
Distribution factors: nonpolar drugs (solubility)
lipid soluble
= more distribution
Distribution factors: protein binding
attachment of a drug molecule protein
drugs w/high affinity to protein will compete for binding sites (one will win) - leaves other drug to do all the work (must be given at different times)
inactivates drugs and blocks excretion (drug becomes too large t
Bound drugs
protein bound; inactive; cannot be excreted
Free drugs
not bound
goes to target organ/cell
eventually excreted
Distribution factors: tissue affinity (trapping)
when drugs accumulate in tissue until there's no room left
causes drug molecules to be unevenly distributed
be aware of side effects (i.e. shouldn't give tetracyclines to children with developing teeth)
tissue affinity: B-vitamins & water soluble
trapped in liver cells
tissue affinity: tetracyclines
trapped in bone and developing teeth
tissue affinity: iodine containing drugs
trapped in thyroid tissue
Distribution factors: barriers (blood brain)
water soluble can't cross, only fat soluble
most efficient
makes some diseases more difficult to treat (i.e. Parkinson's)
Distribution factors: barries (placental)
protects fetus from MOST harmful substances (not caffeine, cocaine, etc...)
Which trimester(s) do we worry about the most?
1st trimester: bc important organs are still forming
3rd trimester: bc placental barrier begins degrading; more susceptible to risks
METABOLISM (drug doses change depending on these factors)
diseased state (liver disease-toxicity; heart failure)
enzyme induction: drugs metabolize too fast
age: elderly - deteriorate; infant - immature liver
food/drug interactions
environment: i.e. smoking & stress
Pro-drug
inactive when taken, but activated by liver enzymes, then goes to target organ
When a drug is metabolized...
drug is de-activated by the liver for excretion (water soluble)
First Pass Effect (Metabolism)
when the drug passes to the liver first
metabolized and made inactive
applies only to med that goes through the stomach (ORAL, nasogastric)
drugs that are susceptible to FPE must be given in higher doses
ALL oral drugs are susceptible (why oral doses are
Where does excretion primarily occur?
KIDNEYS
Other sites for excretion
lungs (expelling CO2) - anesthetics
skin (sweating)
mammary glands (milk)
mouth (saliva)
eyes (tears)
rectum (feces)
bile
enterohepatic reticulation
when drugs accumulate in bile and are reabsorbed
Excretion Factors: kidney function
renal failure - low ability to excrete drugs; drug retention
why we do dialysis on kidney pat
Excretion Factors: pH of urine
BASIC (alkalinic) urine excretes more acidic drugs
ACIDIC urine excretes more basic drugs
affects reabsorption of electrolytes; body retains H2O
Excretion Factors: protein binding
only free drugs are excreted
substances are too large to be excreted
Excretion Factors: metabolism
more efficient metabolism = more efficient excretion
NOTE ON EXCRETION
medication that is not excreted will return to the blood, this increases blood-plasma levels of drugs & they may become toxic
Onset of action
once med is absorbed and starts having an effect
Minimal effective concentration (MEC)
smallest amount of drug that produces a therapeutic effect
after this: termination of effect
low MEC = little to no therapeutic effect
Peak Plasma effect
highest concentration
when the drug is most therapeutic
want peak to be in therapeutic range (don't want it to be above - toxicity)
middle of duration of action
duration of action
amount of time drug remains therapeutic
administer another dose when this is coming to an end
therapeutic range
plasma drug concentration between MEC and toxic concentration
Toxicity
level of drug that results in adverse effects
Termination of effects
below MEC
there may be some drug in circulation, but it no longer has a therapeutic effect
varies in every med; no standard
Summary of drug response
PEAK is in the middle of DURATION OF ACTION & it should be in THERAPEUTIC RANGE (NOT toxic)
Time course of drug response
admin of drug --> absorption (onset of action) --> peak (duration of action) --> elimination --> minimal effective range (termination of action)
half-life
time it takes for drug is plasma to be reduced by 50% determines dosing intervals
kidney function affects this
(i.e. if half-life is two hours: 0900 - 240 mg; 1100 - 120; 1300 - 60; 1500 - 30, etc...)
NOTE: half-life
if medication has short half life, we can expect that the dosage time frame will be more frequent
long half-life (long time to get out of the body), assume you won't give as many doses
Onset, duration, termination
allows you to safely guess when you can give next dose
also depends on pharmacokinetics factors
e.x: PO tylenol
onset: 30 min
duration: 3 hrs
termination: 30 minutes; give another dose 3.5-4 hrs post admin, therefore if given at 0900, give again at 1300
e.x: SL nitroglycerin - NTG
onset: 30 sec
duration: 4 min
termination: 30 sec; give 4.5-5 min post admin
How many half lives does it take to reach steady state?
approx 4 or 5
Loading dose
given as a LARGE initial dose; INCREASES blood plasma levels
used when a drug has a long half-life
given IV
gets therapeutic faster
Maintenance dose
given as a smaller dose to maintain blood plasma
follows loading dose
uses alternate route (i.e. oral)
loading dose vs. maintenance dose
Lanoxin 0.5 mg IV push now in 6 hours (loading dose) then 0.25 PO every day (maintenance dose)
local effect
drug that affects ONE body system/organ
typically skin (ex. eye drop; suturing; local anesthetics)
has the potential to go systemic (giving too much, wrong route, etc)
systemic effect
drugs that affect the whole body
Therapeutic Index (TI)
LD50/ED50
measurement of drugs toxicity/safety
LD50
lethal dose (of a toxin) for 50% of the test population
ED50
avg adult dose that produces desired response in 50% of pop
Low therapeutic index
narrow margin of safety (high risk of toxicity)
High therapeutic index
wide margin of safety (low risk of toxicity)
drug accumulation
what we want; not toxicity
certain amount of drug in the body at all times
provides effect in therapeutic range
plateau
multiple doses allow drug to accumulate in the blood until steady state is reached
steady state
the amount of drug that is eliminated (excreted) = the amount of drug administered
Reducing Complications in Drug Accumulation
continuous infusions
reduce half-life (long half life=long wait for steady state)
alter (increase or decrease) dosage size and intervals
GIVE IV (most controlled)
Peak and trough
gives titer control
gives dosage ranges
Peak
associated with DOSAGE/amount
usually done 1.5 hrs post admin (adults)
drawn when medication is at its highest
looking for therapeutic range
Trough
TIME for another dose
therapeutic effect at its lowest
where you decide time frame for admin
usually drawn 30 min prior to NEXT dose (adult)
Random Level
for pat who are on long term MEC med at home
checks for how much is in circulation at any given time
Potency
potency: (ex) drug X & Y produce 20-mm drop in BP. X produces this effect at 10 mg and Y produces it at 60 mg: X IS MORE POTENT
(smaller dose with greater effect)
most dangerous
Efficacy
max response that can be produced from particular drug
Receptor theory
drugs produce their effect by blocking or binding to a receptor (pharmacological response)
receptors are protein in nature (attract to things)
found in cell membranes
receptors usually bind to endogenous substance (i.e. hormones, neurotransmitters, etc)
Agonist
drugs that mimic a response to bind to a receptor & produce therapeutic effect
stronger binding/agonist=stronger response
Antagonist
drug that blocks response/neurotransmitter
prevents endogenous chemical from acting
NO pharmacological response
takes up binding space
Example: why we need antagonists
drugs that lower HR: beta BLOCKERS
blocks b1 and/or b2 to lower HR
Side effect vs adverse effect
side effect: all drugs have side effects; occurs with therapeutic dose; expected
adverse effects: severe; undesirable; occurs at NORMAL doses
toxicity
poisonous
black box warning
put on box when there is reasonable evidence of serious hazard w/drug
teratogans
substances that can cause birth defects/pregnancy malfunctions
i.e. epilepsy drug: may cause cleft pallet
i.e. accutane: may cause heart defect (vessels reversed O2 can't be oxygenated)
photosensitivity
skin rxn to sunlight
incompatibility
2 or more drugs; cant give drugs in same solution (IV)
i.e. lasix
sometimes causes crystallization
Polypharmacy
8-15 medications administered together
Placebo
harmless pill Rx for psychological benefits
Tachyphylaxis
rapid decrease in response to drug; "acute tolerance
Tolerance
body requires more of a drug for same effect
over long period of time
i.e pain med will eventually need higher dose (takes more to illicit response) if taking chronically; receptors become "immune
Pathway of drug through the body: oral med
stomach --> liver --> blood --> target site --> liver --> kidney --> excretion
MED THAT GOES THROUGH THE STOMACH 1st GOES THROUGH THE LIVER TWICE (first pass effect)
Pathway of drug through the body: IM
bloodstream --> target organ --> liver --> kidney --> excretion
Pathway of drug through the body: inhalant
bloodstream --> target organ --> liver --> kidney --> excretion
Pathway of drug through the body: SL
bloodstream --> target organ --> liver --> kidney --> excretion
Pathway of drug through the body: IV
bloodstream --> target organ --> liver --> kidney --> excretion