Lecture 1: Nature of Drugs & Drug Development Flashcards
Pharmacology definition
the study of substances that interact with living systems through chemical process, especially by binding to regulatory molecules and improving or impressing normal function
define medical pharmacology
the science of substances uses to prevent, diagnose and treat disease
define toxicology
the branch of pharmacology that deal with undesirable effects of chemicals on living things
pharmacodynamics
describes the action of the drug on the body (physical, molecular, and biochemical level)
pharmacokinetics
investigates the effects of the body drugs (ADME)
drug
any substance that causes alteration in cellular / biopic effect
therapeutic agent
a drug used to treat a medical condition or disease
prophylactic agent
a drug used to prevent a medical condition or disease
pharmacy
the profession of preparing, compounding, and dispensing chemicals for medical use
pharmacogenetics/genomics
examines the role of genetics on different drug responses
medicinal chemistry
design and synthesis of drug compounds
pharmaceutics
design and synthesis of drug formulations (ex: extended release)
there is evidence of natural remedies in the earliest writings of ancient ___, ___ , and ___
Egypt, china, greece
what was the start of early drug development in the 1800s
isolation of natural products
morphine is purified from ___
opium found in products
who was credited with developing early experimental physiology and pharmacology?
Francois magendie and Claude Bernard
the ingredients were not required to be disclosed until the ___ act in the US in __ and the ____ act in Canada in __
pure food and drug act, 1906; Food and Drugs 1920
what is the drug regulatory body in the US
FDA
what is the drug regulatory body in Canada
health Canada
what is the drug regulatory body in Europe?
European Medicines Act
section 9(1) of the health Canada food & drugs act prohibits advertising which is __, __, __, or is likely to create ___ impression regarding its character, value, quantity, composition, merit or safety
false, misleading, deceptive, erroneous
section 9(1) of the health food & drug act prohibits messages which emphasize only __ without including information on __
benefits; safety
section C 01. 044 of the Canada Food and Drug regulations prohibits consumer-directed ___ advertising beyond what 3 things? No reference can be made to its therapeutic ___ or __
Rx; Name, quality and price; use or benefits
health Canada prohibits the ____ of drugs which have not been authorized for sale by Health Canada
advertising
what is a serendipitous drug discovery?
drug found by accident or when trying to accomplish something different
give an example of serendipitous discovery
Alexander Flemming discovering penicillin in the 1920’s
what is intelligent (rational) drug design?
identifying the target and designing a drug to modulate this target
give an example of a drug therapy that is the result of intelligent (rational) drug development
reverse transcriptase inhibitors (HIV therapy)
what is high throughput screening?
testing large libraries of compounds to determine “hits”
what are “me-too” drugs?
additional related drugs that are produced after the discovery of the first
what are the main goals of the pre-clinical phase?
identify target, determine mechanism of action
what are the goals of phase 1 of clinical trial?
determine limits of safe dosing, predict toxicity, discover pharmacokinetic measurements
who are then volunteers in phase 1 of a clinical trial?
healthy volunteers (do not have disease of interest)
who are the volunteers in phase 2 of a clinical trial?
volunteers with the disease of interest
which phase of a clinical trial has the highest rate of failure?
phase 2
what are the goals of phase 2 of a clinical trial
determine efficacy of drug in diseased patients and continue determining toxicity and dosage
what are the goal of phase 3 clinical trial?
confirm safety and efficacy and minimize placebo effects
what happens if a clinical trial passes the third phase?
application is sen for review if it can be marketed for sale (can take several years)
what are randomized control trials?
trial in which participants are randomly assigned to a treatment group
what are single and double blind procedure? what is their use?
single blind: patient does not know which treatment group they are in; Double blind: neither patient or researcher knows which group patient is in. Eliminates subconscious bias and placebo
what are some examples of drugs that may be exceptions to the clinical trial rules?
drugs for life-threatening illnesses such as cancer, HIV etc
what is a DIN?
drug identification # that is assigned to all products approved by Health Canada
what is the purpose of a DIN?
allows tracking of adverse reactions, recalls etc
T?F a drug product sold in Canada without a DIN is not in accordance with Canadian Law
true
what is an NPN and what region is it specific to?
natural product number; Canada
what are the 3 components in the application process to manufacture and sell a generic version of a known drug?
- must show quality manufacturing
- the active ingredient must be present in listed amount
- other components of formulation may differ from the original
what is the chemical name of a drug?
the IUPAC name of the compound
what is the Generic name of a drug? Example?
the universal name of a drug; EX: ibuprofen and acetaminophen
what is the brand name of a drug?
name chosen by the manufacturer, usually different across the world
materia-medica
the science of drug preparation and medical use of drugs
until the implementation of ___, it was impossible to accurately evaluate therapeutic claims
controlled clinical trial
___ is the biological substrate of drug action
drug receptor
what are orphan receptors?
no ligand has been discovered for them so their function can only be guessed at
osmotic agents are drugs that ___
interact almost exclusively with water
chemical antagonist drugs are drugs that __
interact directly with other drugs
drugs made in the body
hormones
chemical not made in the human body are called __
xenobiotics
what are toxins? Example?
poisons of biologic origin; arsenic
to interact with a receptor, a drug must have the correct __. ___. ___, and ___
size, shape charge, atomic composition
provide three qualities of a useful drug
- is able to be transported in the body
- can be inactivated/ecreted from the body
- react at a reasonable rate to have the effects last for a desired duration
drugs should usually be at least ___-MW units inside
100
what is a potential con of large drugs?
need to be able to move through the body
a drug greater than ___ MW units in size needs to be administered directly to action site
1000
a drug can bind to a receptor through what sort of bonds?
covalent, H bonds, electrostatics
covalent bonds are reversible or irreversible under biological conditions?
irreversible
which drugs are more selective? those that bind strongly or those that bind weakly?
those that bind weakly
more than __ % of drugs are chiral
50
t/f when stereochemistry is involved, typically there is one isomer which is more potent as a drug than the other
true
enzymes are ___ , therefore one enantiomer of a drug is more susceptible to drug metabolizing enzymes
stereoselective
t/f the effector may be part of the receptor, a separate molecule, responsible for final change in function
true
allosteric drugs are those which __
bind to the same receptor as the agonist, but do not prevent binding of agonist
t/f allosteric drugs can enhance or inhibit action the agonist
true
role of competitive inhibitor
mimic agonist
what is constitutive activity?
when a receptor can exist in both active and inactive forms and can sometimes become activated without against
role of full agonists
cause activation of almost all receptors
role of partial agonists
can’t illicit as great a response, no mater the concentration
partial agonists are said to be drugs with low ___
intrinsic activity
what is neutral antagonism?
an antagonist at the receptor site blocks the agonists
inert binding site
non-regulatory molecule, binding to it will result in no change in biological function
prodrug
precursor to the active form of the drug
permeation can proceed through what 3 methods?
- passive diffsuion
- vehicles to transport
- end/exocytosis
most new drugs are developed through what 4 processes?
- identification of new drug target
- rational drug design, based on biological mechanisms and receptor structure
- screening for biological activity of a large # products and banks
- chemical modification of pre-existing drugs (me-too_
molecular drug screenings involve __
screening for receptor binding activity
cellular drug screening involves __
determining if the drug will act as an agonist, antagonist, partial inverse etc
whole animal drug screening involves __
screening the effect on organ systems and disease models
the desired result of drug screening is a __ compound
lead
t/f some chemicals can be deemed completely safe
false
what is the “no effect dose”?
the max dose at which a specified toxic effect is not seen
what is the minimum lethal dose?
the smallest dose observed to kill an experimental animal
Median lethal dose (LD50)
dose expected to kill 50 % of experimental animals (can be extrapolated to human dosing)
some conditions can wax and wane in severity, when developing a trial to administer a drug to treat these diseases what sort of method should be used to reduce confounding variables?
cross over technique ( alternating periods of administration)
what is the fourth phase of a clinical trial?
monitoring for safety
