Intro to Pharmacology Flashcards
pharmacology
the study of substances that alter bodily functions when introduced into an organism
drug
any substance that alters body function when introduced into a living organism;
has some effect on a specific target molecule (receptor)
factors that influence the effect of a drug
size, electrical charge, shape, and atomic composition of the drug molecule
pharmacodynamics
the actions of a drug on the body;
effects at the receptor and the results
pharmacokinetics
the actions of the body on a drug;
absorption, distribution, metabolism, and excretion;
how the drug moves into and out of the body
agonist
binds to and activates a receptor;
full agonist or partial agonist
antagonist
prevents other molecules from binding to a receptor; prevents receptor from being activated; either reversible or irreversible
the intended site of drug action must be ___ by the drug (administration/absorption)
reachable
a drug may reach its intended target as an ____ or it might require conversion prior to it being ____ (metabolism)
active molecule;
active (prodrug)
most often a drug is administered into one body compartment and must ____ (distribution)
move to the intended site of action
a drug must be ___ after it has an effect (metabolism, elimination)
eliminated
drugs have 3 names
- chemical name
- generic name
- brand name (proprietary, trade)
chemical name
- complex
- little concern to medical professionals
generic name
- internationally recognized
- drugs only have one generic name
- often indicates class or mechanism of action
brand name (proprietary, trade)
- patented exclusive property of manufacturer
- often shorter and easier to remember
- one drug may have many trade names
patent on a new drug lasts ___
20 years
exclusive right to sell a drug can be much shorter than patent length:
- certain conditions must be met
- exists to ___
encourage competition
trade name lasts for at least ___
50 years
time from patenting to marketing takes ___
8-10 years
steps of drug development:
- _____
- study of ____
- leads to increased _____
- study of ____
- first in animals then in humans
- ____
- ____ studies
discovery; biological interactions; efficacy, potency, and selectivity; safety; marketing; post-marketing
most drugs originate in ___ but are developed in ___
research institutions (university, etc.); pharmaceutical companies
only ____ marketed drugs return their R&D investments
2 in 10
global market for pharmaceuticals in 2015 was over ___
$950 billion
____% of health care expense in the US is on prescription drugs
10-12
most new drugs are developed through these approaches:
- identification of a new ____
- design of a new molecule based on understanding of ____
- screening for ____ of natural products
- chemical modification of a ____
drug target;
receptor structure;
biological activity;
known active molecule
once identified, the process moves to ____
translational research (preclinical and clinical testing)
the type and number of initial screening tests depends on the _____
pharmacologic and therapeutic goal; anti-infectives tested against many different infectious organisms, etc.
the molecule is also tested for a broad array of other actions:
- helps determine the ____
- determines ___
MOA;
selectivity
pharmacologic profile is studied: defines the _____ of the molecule
pharmacokinetics and pharmacodynamics
animal studies help determine the ____ and disease models; ____ studies are usually first
effect on organ systems;
cardiovascular and renal
modifications to the compound may result from screening:
- poor ____
- interactions with ____
- potential for ____
- potential ____
bioavailability;
liver enzymes;
abuse;
drug interactions
the result of all screening procedures is a ___
“lead compound”
lead compound:
- leading ____ for a successful new drug
- if it is a new compound a ___ will be filed
- a previously known chemical entity discovered to have a new therapeutic use can receive a ___
candidate;
patent application;
“use patent”
toxicity testing
seek to define the limiting toxicities and the therapeutic index; how toxic is this compound?
usually go through the following toxicity tests
- acute toxicity
- subacute toxicity
- chronic toxicity
- effect on reproductive performance
- carcinogenic potential
- mutagenic potential
acute toxicity test
determines the no-effect dose and the maximum tolerated dose
subacute toxicity test
determines the biochemical and physiologic effects of long-term dose (weeks to months)
chronic toxicity test
used when drug is expected to be needed in humans for prolonged periods of time
preclinical testing goal
to determine potential human toxicities and to design tests to further define the toxic mechanism; also predicts the most relevant toxicities to monitor in clinical trials
limitations of preclinical testing
- time-consuming and expensive (can take up to 6 years)
- large numbers of animals needed to obtain valid data (computer modeling and cell cultures are increasingly being used)
- animal to human toxicity data not always predictive
- rare adverse effects are not likely to be identified
human testing:
- very ___ guidelines
- overseen by the ___
- “safe” can mean different things to patient, physician, and society- no drug can be completely absent of ___
strict;
FDA;
risk
confounding factors in clinical trials
- variable nature of most diseases
- presence of other diseases or risk factors
- subject and observer bias - placebo effect
Notice of Claimed Investigational Exemption for a New Drug (IND):
- filed w/ FDA
- includes:
- composition and source of the drug
- chemical and manufacturing information
- all data from animal studies
- proposed plans for clinical trials
- names and credentials of all physicians who will conduct the trials
- compilation of the key data relevant to study of the drug in humans
clinical trials: Phase 1
- effects of the drug as a function of dosage
- small number (20-100) of healthy volunteers
- determine the probable limits of the safe clinical dosing range
- can use individuals with the disease IF the drug is expected to have significant toxicity (ex: cancer or AIDS therapy)
- absorption, half-life, and metabolism are also often studied in this phase
*small number of healthy volunteers; what is the effective dose?
clinical trials: Phase 2
- the drug is studied in patients with the target disease to determine efficacy
- also helps determine doses to be used in follow-up trials
- 100-200 subjects used
- have the highest rate of drug failures
- only 25% of new drugs get past phase 2
*small number of patients with the target disease; does this drug work?; highest rate of drug failures
clinical trials: Phase 3
- drug is evaluated in larger numbers of patients with the target disease (usually thousands of patients)
- establish and confirm safety and efficacy
- designed to minimize errors caused by placebo effects and disease variations
- usually performed in settings similar to what is anticipated for the ultimate use of the drug (hospitals, clinics, etc.)
- if results meet expectations, application is made for permission to market the new drug
*large number of patients with the target disease; is this drug safe and does it work?
clinical trials: marketing approval
- requires submission of a New Drug Application (NDA)
- full reports of all preclinical and clinical data
- can take months to years to gain approval
- if urgent need for the drug is perceived, the process of FDA review can be accelerated
- once approval has been granted, phase 4 studies begin
clinical trials: Phase 4
- monitor the safety of the new drug under actual conditions of use in large numbers of patients
- requires reporting by all physicians using the medications
- some adverse effects may become apparent only after chronic dosing
- no fixed duration (as long as the drug is in use)
lifetime of a patent is ____; often includes the ____; average effective patent life for major pharmaceuticals is around ___
20 years;
approval time (5 years or more);
11 years
when the patent expires any company can produce the drug without paying license fees to the original patent owner
- file an abbreviated new drug application (ANDA)
- demonstrate required equivalence
- market the drug as a generic product
- occasionally paid by patent owner NOT to introduce a generic version
___% of prescriptions in the US are for generics
67
conflicts of interest:
-manufacturers often “paid” physicians to ___
use their medications in preference to older drugs
conflicts of interest:
-sponsored small and poorly designed clinical studies after marketing approval
publish favorable results but often hold back unfavorable resutls
conflicts of interest:
-sponsored CE events for physicians and staff
attractive vacation sites
conflicts of interest:
-distribute ___
samples of new drugs
pharmacogenomics
genetic makeup and the individual response to specific drugs
full agonist
light is either on or off
partial agonist
light has a dimmer- on but not all the way
biological drugs
drugs created by antibodies; MAB= monoclonal antibodies
