28-48 Flashcards
The science concerned with drugs, their sources, appearance,
chemistry, actions and uses. It includes the biochemical and
physiologic effects, mechanism of action, absorption,
distribution, biotransformation, and excretion
Pharmacology
is the science that analyzes how the human body interacts with a drug.
Pharmacokinetics
examines how the drug is absorbed, distributed, metabolized, and excreted
by the body.
Pharmacokinetics
is the science that studies the biochemical and physiologic effects of a drug and its organ- specific mechanism of action, including effects on the cellular level.
Pharmacodynamics
“what the body does to the
drug,”
Pharmacokinetics
“what the drug does to
the body.”
Pharmacodynamics
are used to evaluate the pharmacologic effects of the agent on
specific organ system.
Whole animal studies
define further the
compound’s activity and selectivity.
Studies with isolated animal tissues
are then performed to detect evidence of efficacy and to determine
whether the compound is an agonist or antagonist.
Compounds effect on the cell function
for various receptors and its activity against select enzyme
systems.
Compound’s selectivity
is to obtain basic information on the drugs effects that maybe safe and effective use in humans.
Animal Studies
Hypertensive studies-
Dogs and rats
Respiratory effects studies-
Dogs and Guinea pigs
Diuretic activities-
Dogs
Blood coagulation
Rabbits
Central Nervous system studies-
Mice and rats
involves those chemical process
within living organism to maintain life.
Drug metabolism
Series of animal studies of a proposed drugs ADME are
undertaken to determine the following:
Extent and rate of drug absorption from various route of
administration
Rate of distribution of the drug through the body and the
site and duration of drug’s residence
Rate, primary and secondary sites, mechanism of the
drug’s metabolism in the body
Proportion of administered dose eliminated from the
body
Participate in drug metabolism (liver, kidneys, lung & git)
Specific & non-specific enzymes
What happens to Drugs following oral adm. that enter the hepatic
circulation after absorption from gut
Exposed to rapid drug metabolism
transit through the liver & exposure to the
hepatic enzyme system
1st pass effect
what route of adm is used for the systemic cirulation through blood bessels other than hepatic
Adm of buccal and rectal
performed through the collection &
analysis of urine, blood & feces samples, & careful exam. Of animal tissues & organs upon autopsy
ADME studies
Deals with the adverse or undesired effects of drugs
Toxicology
Preclinical safety evaluation or toxicity studies
toxicology
enumerate what to determine in toxicology
Substance’s potential for toxicity with short-term or long-
term use
Substance’s potential for specific organ toxicity
Mode, site and degree of toxicity
Dose-response relationships over time
Gender, Reproductive or teratogenic toxicities
Substance’s carcinogenic and genotoxic potential
toxic effect of a test compound when administered in single
dose and/or multiple doses over short period, usually a single
day.
Acute or short-term toxicity studies
find doses that do not to produce toxic
effect, severe toxic effect & intermediate toxic level
doses are ranged
The relationship to projected human clinical studies
for safety
Subacute or subchronic studies
how much is the minimum of drug administration of aniaml toxicity studies and dosage level
two weeks daily and 3 or more dosage levels
drugs intended to be given to humans for a week or more, animal studies of 90 to 180 days in length must demonstrate safety
Chronic toxicity studies
How long is the animal studies for chronic human illness
1 year or longer
For limited no. of rat & mouse strains
Carcinogenicity studies
with surviving animals killed
& studied at defined weeks during the test period
Long term studies
how long does long term studies last?
18-24 months
undertaken when the
compound has shown sufficient promise as a drug to enter
human clinical trials.
Component of chronic testing
reveals any effect of an active ingredient on mammalian
reproduction
Reproduction studies
Evaluated for anatomical abnormalities, growth &
development: maternal parent, fetus, neonates & weaning
offspring
Reproduction studies
Fertility & mating behavior, mutagenicity, teratology
Reproduction studies
Determines whether test compd affects gene mutation or
cause chromosome or DNA damage
Genotoxicity or Mutagenicity Studies
Used in assays to detect mutations: Strains of Salmonella
typhimurium
Genotoxicity or Mutagenicity Studies
Each drug substance has intrinsic chemical and physical characteristics that must be considered
before the development of a pharmaceutical
formulation
Preformulation studies
Enumerate what are studied at preformulation studies
Drug solubility
Partition Coefficient
Dissolution Rate
Physical Form
Stability
A drug substance administered by any route must possess some aqueous solubility for
systemic absorption and therapeutic response
Drug Solubility
may exhibit incomplete,
erratic, and/or slow absorption thus produce
minimal response at desired dosage
Poor soluble compounds
is a measure of its distribution in a lipophilic- hydrophilic
phase system and indicates its ability to
penetrate biologic multiphase system
Drug’s Partition Coefficient
It is the speed at which a drug substance dissolves
in a medium
Dissolution Rate
The crystal or amorphous forms and/ or the particle size of a powdered drug can affect the dissolution rate, thus the rate and extent of absorption, for a number of drugs
Physical Form
testing at various temperature,
conditions of relative humidity (RH), durations, and
environments of light, air and packaging is
essential in assessing drug and drug product
stability
Stability
