Test 1 Flashcards
drug
a chemical substance that interacts with a part of the body to alter an existing physiological or biochemical process
Food, Drug and Cosmetic act of 1938 a drug is
a natural or synthetic substance which affects its functioning structure, and is used in the diagnosis, mitigation, treatment or prevention of a disease or relief of discomfort
where do drugs come from
plants, animals, minerals or can be synthetic
synthetic drugs
are preferred bc of quality control , ease of preparation and they are not dependent on certain resources
dosage formulation
drug delivery system; final formulation of the drug in combination with one or more non medicinal agents
dosage formulations
important for accuracy, protection of a drug substance outside of the body, protection of a drug substance inside the body, optimization of delivery to its site of action or convenience
pharmacology
a drugs mechanism of action
toxicology
possible harmful side effects
medicinal chemistry
chemical structure and properties
pharmacotherapy
medicinal treatment by means of drugs
pharmacokinetics
what the body does to the drug
pharmacodynamics
what the drug does to the body
pharmaceutics is
all things related to drug formulations
the first pharmacists
were tribal people, sick ppl were those punished for their sins, evil spirts were tied to disease; v symbolic
hippocates
4 humors, rationalization of the source of illness; Hippocratic oath; father of medicine
dioscorides
1st century greek philosopher; wrote Materia Metica; developed the first pharmacopeia
Galen
2nd century greek philosopher; first cold creme; father of compounding
who split physicians and pharmacists why??
Frederick 2 of Germany; enforce ethics; too much knowledge for 1 person to know
Friedrich Wilhelm Adam serturner
specialized in removal of alkaloids and is credited with the discovery of morphine
Carl Wilhelm Scheele
discovery of oxygen; extracted and isolated chemicals
what is the USP
United States Pharmacopeia
what is the NF
National formulary
what is the timeline of USP and NF
USP originally run by physicians and only drugs of “therapeutic merit”; NF made their own with pharmacists; both were recognized by the pure food and drug act of 1906; USP became controlled by pharmacists; then USP bought NF
Pure Food and Drug Act of 1906
regulated drug production; standards for purity, strength, and quality
Sherley Amendment of 1912
regulated therapeutic benefit; and prohibited false claims
Food Drug and Cosmetic act of 1938
prohibit distribution of any drug without prior filing of a new drug application and approval by the FDA; ensured safety
Kefauver-Harris Amendment of 1962
added efficacy requirements
what are the 3 types of drug discoveries
serendipity; high throughput screening; molecular modeling
serendipity
good fortune
high throughput screening
a library of candidate compound is examined quickly using an applicable biologic assay to identify a lead compound that can be further tested
molecular modeling
computer aided evaluation of a target site receptor and design of a drug that can be synthesized to fit that target site
role of FDA in approval of dosage form
sponsor of a new drug must file and IND application with the FDA; institutional review board then evaluates the plan for safety; after 30 days human trials begin; three phrases of testing demonstrate drug safety and therapeutic effectiveness
Investigational New Drug
IND; identifications of phase, investigational plan with rationale for the study; brief summary of previous human experience, preclinical and clinical summary; protocol for each planned study
New Drug Application
NDA; names of drugs, statement as Rx; technical sections or human pharmacokinetics and bioavailability, clinical data, statistical methods, samples of the drug substance, drug product proposed for marketing; clinical case report forms
phase 1 of clinical trials
20-100; lasts several months, assess safety
phase 2 of clinical trials
up to several hundred patients with the condition; months - 2 years;
phase 3 of clinical trials
several hundred to several thousand patients with the condition for which the drug is intended; last 1- 4years
phase 4 of clinical trials
continued clinical study; drugs MOA, possible new therapeutic uses for drugs; dosage strengths, check for adverse rxn, side effects
what are functional groups & why are they important
a group of atoms responsible for the characteristic reactions of a particular compound; provide specific properties and behaviors that allow drug molecules to exert their desired pharmacokinetic and pharmacodynamic effects
solubility
the ability for a given substance to dissolve in another substance
saturation
when the max amount of solute is dissolved in the solvent
hydrophilicity
drugs ability to be dissolve in water
lipophilicity
drugs affinity to dissolve in lipids or other non polar solvents
intrinsic aqueous solubility
how inherently soluble a drug is in water; measured by the partition coefficient of the drug; determined after equilibrium is reached
P
the partition coefficient; equal to the partition solvent concentration divided by the concentration of dissolved water; solvent conc./conc. in H2O
the larger value of log P,
the more lipophilic the drug molecule is
polarity
used to describe the presence of a dipole moment
polar molecules
possess a dipole moment; meaning there is a partial charge separation between atoms due to the electronegativity of the atoms; dissolve in water
nonpolar molecules
do not possess a dipole moment; dissolve in lipid solvents due to van der wals forces
hydrogen bonding
a special kind of dipole dipole attraction that occurs between molecules with specific structural features
dielectric constant
a measure of the ability of a molecule or solvent to separate charges
what type of functional groups increase partition coefficient
carbons; halogens,
what type of functional groups decrease the partition coefficient
anything that has oxygen or nitrogen
general trends for increasing water solubility of drug molecules
1) introduction of a polar functional group 2) branching of alkyl groups 3) decrease molecular weight
electrolyte
a compound that ionizes in solution; can conduct electricity
strong electrolytes
ionize completely
weak electrolytes
ionizable but only dissociate partially
non-electrolyte
does not ionize in water; remains neutral and uncharge
ionization
allows for more water solubility due to the formation of ion-dipole bonds
the pH scale
is a logarithmic quantification of the concentration of H+
a change in 1 number on the pH scale
represents a tenfold change in [H+]
as the pH decrease
[H+] increases
acids
donate or lose a hydrogen
bases
accept or gain a hydrogen
the strength of the acid
can be quantified by the acid dissociation constant; Ka
Ka
is the ratio of products to reactant
pka =
-logKa
strong acids have a ___ pka
lower
2 key features of an acidic functional group
1) presence of a liable proton 2) ability of the remaining atoms to delocalize the resulting negative charge via resonance
key structural feature of a basic functional group is
the presence of an atom with a lone pair of electrons
distribution coefficient
log D values for acidic and basic drugs will vary depending on the pH of the molecules environment; values for drugs without acidic or basic functional groups will remain constant
salt
an ionic compound that is formed when an acid reacts with a base; dissociate in water; salts of drugs are typically more stable and more water soluble
inorganic salts
the result of the reaction between a drug molecule and an inorganic acid or base
inorganic salts acidic
typically made with NaOH, KOH, Ca(OH)2
inorganic salts basic
typically made with HCl, HBr, H2SO4, H3PO4
organic salts
the result of the reaction between a drug molecule and an organic acid or base
processes for solid dosage form
- disintegration 2. dissolution 3. absorption
process for semi-solid dosage
- release 2. dissolution 3. absorption
process for liquid
- dissolution 2. absorption
solubility
the capacity of a solute to dissolve in a solvent
dissolution
the rate act which the dissolving occurs
dissolution is defined by the ____ equation
Noyes-Whitney
D =
diffusion coefficient; not easily manipulated
A =
surface area of a drug, greater SA = faster dissolution
S =
drug solubility, not easily manipulated
C
concentration of a drug in solvent
H
thickness of diffusion layer; thinner layer = faster
ficks law
flux = K * S * D (C1 - C2) / h
diffusion equation
dm/ dt = D * A(S-C) / h
transcellular
take molecules in one side of the cell and out the other
paracellular transport
occurs when a small molecule is able to pass between cells through tight junctions
pH =
pka + base / acid
OAT
organic anion transporter; influx transporters
OCT
organic cation transporter; influx but bidirectional
stomach
primary site for oral drug disintegration and dissolution, v acidic, little SA
small intestine
less mucous than stomach, rich blood supply, less acidic, large SA
a symporter is also called a
cotransporter
antiporter AKA
exchangers
efflux transporters
ABC (ATPase binding cassette) aka P-gp (P-glycoprotien) aka (multidrug resistant type 1); into the gut, urine, bile; out of brain, and other organs
influx tranporters
OATP (organic anion transporter polypeptide) mediates transport of organic anions expressed in BBB, liver, intestines, kidneys, absorptive membrane surfaces; OCT (organic cation transporter) mediates transport of organic cations, expressed in the BBB, liver, intestines, and kidneys
the first pass effect
describes hepatic metabolism of a drug when it is absorbed from the gut and delivered to the liver via the hepatic portal vein where some amount of the drug undergoes metabolism before entering into systemic circulation
IV administration
plasma concentration starts at its highest level and steadily decreases
other routes
plasma concentration starts at zero increase to a maximum then begins to decrease
bioavailability
the fraction of an administered dose of a drug or other substance that reaches systemic circulation an is available to reach the site of action
absolute bioavailability
compares bioavailability of a dosage form to that of intravenous administration
relative bioavailability
compares the bioavailability of a dosage form to another dosage form is specifically uses when an intravenous form of the drug does not exist or cannot be used
bioavailability
(area under curve for dosage form) / (area under curve for IV administration) then mult. by 100
extemporaneous pharmacy compounding
the preparation, mixing, assembling, packaging, or labeling of a drug or device as a default of a practitioners prescription drug order initiated based of the triad course of professional practice or for the purpose of research, testing, chemical analysis and not for resale or dispensing
compounding is regulated by
the state board of pharmacy; adhering to good practices set forth by USP 795 ad 797
USP 795
NON-STERILE COMPOUNDING includes regulations for the environment, stability,, ingredient, strength, quality and pretty, process, records, quality control counseling
USP 797
STERILE COMPOUDING; describes conditions and practice to prevent harm, including death to patients that could result from contamination, endotoxins, variability, contaminants, inappropriate quality
manufacturing is regulated by
food and drug administration
cGMP
current good manufacturing processes
failure to meet cGMPs usually result in
voluntary recall of the drug
API
active pharmaceutical ingredient; furnishes pharmacologic activity
batch
specific quantity of drug of uniform specified quality produced according to a single manufacturing order during the same cycle of manufacture
lot
a beach or any portion of a batch having uniform quality and a distinctive identifying lot number
lot number
combination of letters which completed history of the manufacturer, processing, packaging, holding and distribution of a batch or lot of a drug product
drug product
a finished form that contains an active drug and inactive ingredients
compliance
determination through inspection of the extent to which a manufacturer s acting in accordance with prescribed regulations, standards, and practices
master record
record containing the formulation, specifications, manufacturing procedures, quality assurance requirements, and labeling of a finished product
validation
documented evidence that a system does what is should do
added substances
inactive ingredients
beyond use date
the date after which a compounded preparation should not be used
component
any ingredient necessary for the compounding of a preparation
compounded
a professional authorized by the appropriate jurisdiction to perform compounding
compounding
the preparation, mixing, assembling, altering, packaging, and labeling of a drug or drug delivery device in accordance wit a a licensed practitioners prescription within the triad relationship
hazardous drug
any drug that can cause cancer, reproductive toxicity, organ toxicity or gentoxicity
preparation
a compound drug dosage form which ac compounder has introduced a drug
3 categories of compounding by USP
simple, moderate, complex
simple
using a recipe that lists specific components, compounding procedure and equipment, and stability data from a manufacturer or peer reviewed journal
moderate
making a preparation that requires special calculations or procedures or making a preparation for which stability data is not available
complex
making a preparation that requires special training, facilities, equipment, and procedures to ensure appropriate therapeutic outcomes
responsibilities of a compounder
addresses the following areas of concern: appropriate ingredients, packing and beyond use dating, training of compounders, patient counseling
formulation record
recipe; step by step instructions
compounding record
what actually happened; specific to patient
SOPs
standard operation procedures; maintaining consistency
Materials safety data sheets
documentation of the chemical and physical properties of a chemical as well as safety information
aqueous for oral use
no later than 14 days
aqueous for topical use
no later than 30 days
non aqueous formulation
not later than the time remaining until the earlier expiration date of any API or 6 months
employee compounding procedure
the pharmacist demonstrates then employee does it; they will be monitored and be responsible for the finished preparation
patient counseling
proper use, storage, handling, disposal, physical changes, adverse event
micromeritics
field of science devoted to the study of the behavior and characteristics of small particles
why is micromeritics important
influences a large number of parameters in research development, manufacturing of dosage forms such as amount of water needed, uniformity, efficacy
powder
a solid consisting of v small particles; can refer to pharmaceutical ingredients or dosage formulation
desirable qualities of powders
ability to flow, higher degree of circularity, larger particle size low angle of repose
granules
specifically agglomerations of powders with desirable properties
utility of formatting drugs into pharmaceutical powders and granules
fast acting, easier administration of doses involving large portions of drugs, easier administration of doses to patient populations that have difficulty swallowing
most powders and granules are through what route
oral, topical, inhalation, and vaginal
ingredients needed to make a pharmaceutical powder and granule
drug API to treat disease, diluent, lubricants, anti adherents, miscellaneous ingredients (to make powders easier to work with)
general preparation of compounding pharmaceutical powders involves 2 processes:
reduction of particle size and blending of components
___ has the slowest onset of actions
tablets
which are faster granules or powders
powders
advantages for using pharmaceutical powders / granules
more stable, more convient, faster onset of action, good for patients who have difficulty swallowing
disadvantages for using pharmaceutical powders / granules
less convient to carry around than a small container of tablets, not good for drugs with unpleasant tastes, difficult to measure accurate doses, hygroscopic
the more round the powder,
the better it will flow
granules are preferred to powders due to the following
better flow, more stable, wetted better, better content uniformity
