8/27 Chapter 1: Intro

pharmacokinetics

how the body deals with this drug in order to eliminate or remove the drug

pharmodynamics

how drug affects the living body → therapeutic side effects

medical pharmacology

medication that is prescribed for diseases and disorders

-environmental toxicology

pharmacotherapeutics

use of drugs in the treatment of diseases and disorders

receptors can be

proteins (usually), DNA, RNA, and lipids

agonist

binds to receptor through an attraction to form an effect

-low conc.=little effect, high conc.=high effect

competitive inhibitor/antagonist

competes with agonist to bind to same spot

-need increase a dose to have effect

allosteric activator

binds to different site, reach maximum effect

allosteric inhibitor

binds to different site, decreases max effort

agonist + allosteric activator

highest response per dose

agonist (graph)

second highest response per dose

agonist + allosteric inhibitor

needs more of dose to reach response

agonist + allosteric inhibitor

lowest response

binding affinity

how well a compounds are attracted to those different areas on a receptor

Kd

concentration for 50% saturation of the receptors and is inversely proportionate to the affinity of the drugs for the receptors

low concentration of Kd

high binding affinity → needs less of drug to bind to receptor

full agonist

prefers/stabilizes the active receptor state

receptor is pushed to active state → response increases → reaches max effect

Partial agonist

also favors receptor activation, but it doesn't activate the receptor as strongly as a full agonist → lower max effect

Antagonist

no preference for the active vs. inactive receptor state

-alone → no change in constitutive activity

inverse agonist

prefers/stabilizes the inactive receptor, pushes system to inactive state

pharmacology

study of substance that interact w/ living systems thru chemicals processes

two branches of pharmacology

medical pharmacology and environmental toxicology

medical pharmacology

science of substances used to prevent, diagnose, and treat diseases (includes toxic effects)

-pharmacokinetics and pharmacodynamics

environmental toxicology

effects of chemicals on all organism and their survival in groups and as species

translational research

taking discoveries from basic science/laboratory research and figuring out how to use them to improve patient care

pharmacologic profile

summary of how a drug behaves and what it does in the body

drug class, mechanism, effects, pharmacokinetics, ADRs

Whole animal studies

necessary to determine the effect of the drug on organ systems and disease models

-cardiovascular and renal function studies of new drugs

desired result of this screening procedure

lead compound

lead compound

leading candidate for a successful new drug

preclinical toxicity testing

testing a potential new drug for harmful or toxic effects before it is tested in humans

no-effect dose

maximum dose at which a specified toxic effect is not seen

minimum lethal dose

smallest dose that is observed to kill any experimental animal

median lethal dose (LD₅₀)

the dose that kills approximately 50% of the animals in a test group

limitations of preclinical testing

toxicity testing is time consuming

large amount of animals need to be obtained

sometimes toxic in animals but not humans

rare adr usually dont show in testing

crossover design

the same participants receive more than one treatment at different times (alternating periods)

placebo response

when a patient experiences a real change in symptoms after receiving an inactive treatment

single-blind design

clinical trial where one side does not know which treatment the participant is receiving

double-blind design

clinical trial where both the participants and the researchers interacting with/evaluating them do not know who is receiving the actual treatment versus the placebo/control

FDA

administrative body that oversees the drug evaluation process in the USA and grants approval for marketing of new drug products

Notice of Claimed Investigational Exemption for a New Drug (IND)

FDA application that allows a company/researcher to begin testing a new drug in humans

interdisciplinary institutional review board (IRB)

committee that reviews research involving human participants to make sure the study is ethical and protects the participants

Phase 1

are done to determine the probable limits of the safe clinical dosage range

-effects of the drug as a function of dosage are established in a small number (20–100) of healthy volunteers

Phase 2

drug is studied in patients with the target disease to determine its efficacy, has the highest rate of drug failures, and only 25% of innovative drugs move on to next phase

Phase 3

drug is evaluated in much larger numbers—usually thousands—of patients with the target disease to further establish and confirm safety and efficacy

New Drug Application (NDA)

formal application submitted to the FDA asking for permission to market and sell a new drug in the United States (new brand name drug)

Phase 4

monitoring the safety of the new drug under actual conditions of use in large numbers of patients, drug is approved to market a drug

abbreviated new drug application (ANDA)

application submitted to the FDA to get approval for a generic version of an already-approved brand-name drug

trademark

drug’s proprietary trade name and is usually registered

Adverse drug reactions are

fourth leading cause of death, higher than pulmonary disease, AIDS, accidents, and automobile deaths

Orphan drugs

medications developed to treat rare diseases or conditions that affect relatively small numbers of people

Why are they called “orphan” drugs?

If a disease affects only a small number of patients, pharmaceutical companies may have less financial incentive to develop a treatment because there are fewer potential customers

Orphan Drug Amendment of 1983

provides incentives for the development of drugs for treatment of a rare disease or condition defined as “any disease or condition