Introduction to Pharmacology - Key Concepts and Drug Development Stages

What is a drug?

-any substance that, when taken into a living organism, may modify one or more of its functions

What did the pure food and drug act of 1906 do?

-established the FDA

-req'd listing on the label the presence and amt of certain dangerous drugs

What did the Food, Drug and Cosmetic Act of 1938 do?

-new drugs had to have the approval of the FDA predicated on demonstrated safety

What did the Kefauver-Harris Amendment of 1962 do?

-spurred by thalidomide

-req'd drugs to actually show proof of efficacy and safety

What are key issues in drug development (lab)

-what causes the disease

-what is the target (usually a cell receptor)

-once target is ID'd does it play a role in the disease

-does the molecule interact with the target in the desired fashion?

Key issues in drug development (clinic)

-is the molecule-target interaction safe

-does the molecule-target interaction have the intended clinical effect

Current drug approval process

-manufacturer files an investigational new drug application which allows human testing

-after testing manufacturer files a new drug application with all the data testing

-this includes proposed labeling

-manufacturing process

-application reviewed by FDA panel of physicians and scientists (pharm, nurses, PhDs) to determine safety, efficacy and a quality manufacturing plan

Pre-clinical

-is it reasonably safe for initial use in humans

-is it sufficiently effective against the target disease in animals/assays

phase 1

-pharmacology/toxicology studies in healthy population

-goal: determine safety in humans and relationship of dose to effects

phase 2

-effectiveness in target disease population

-continued safety studies, and dose/effect relationships

phase 3

-continued assessment of effectiveness, duration of effect, effect of differing populations, varying dosages

-ongoing safety eval as population increases, drug-drug interactions

ongoing/phase 4

-phase 1-3 studies are generally brief with a limited pt population

-new safety information is discovered as we use drugs in larger populations

-after market surveillance

Prescription

-must be allocated by qualified professional

OTC

-relatively minor problems

-relatively safe drug profile

-increased availability

-less expensive

Manufacturer is allowed to market and hold a new tx proprietarily for up to ___________years after the NDA is approved

-20 yrs

When can generic meds be manufactured?

-20 yrs

Orphan drugs

-drug or biological product to prevent, dx, or tx a rare disease or condition

Orphan drug designation qualifies sponsors for incentives including

-tax credits for qualified clinical trials

-exemption from user fees

-potential 7 yrs of market exclusivity after approval

chemical

-may be proprietary or non-proprietary

generic

-always non-propriety

trade/brand name

-always proprietary

Important Rule for drug naming

-Whenever possible the USAN council will assign substances to existing stems or nomenclature schemes that describe the substance, its action, or its use

-stat (class, generic, brand name)

-lipid lowering agent

-atorvastatin

-lipitor

-prazole (class, generic, brand name)

-proton pump inhibitor

-lansoprazole

-prevacid

-lukast(class, generic, brand name)

-leukotriene receptor agonist

-montelukast

-singulair

oxetine (class, generic, brand name)

-SSRI

-fluoxetine

-prozac

sartan

-angiotensin II receptor antagonist

-valsartan

-diovan

oxacin

-fluoroquinolone antibiotics

-levofloxacin

-levaquin

vir

-antiviral compounds

-acyclovir

-zovirax

mab

-monoclonal antibodies

-bevacizumab

-avastin

afil

-phosphodiesterase 5 inhibitors

-sildenafil

-viagra

olol

-beta blocking agents

-metoprolol

-tenormin

pril

-angiotensin converting exnzyme inhibitors

-enalapril

-vasotec

Naming standard (prefixes)

-ar, es, lev and dex

-all represent stereoisomers of other compounds

Controlled substances schedule I

-highest abuse potential

-restricted to rsrch applications

-illicit street drugs

-for rsrch only

-need license from FDA to study

Controlled substances schedule II

-next highest abuse potential

-specific therapeutic purposes

-higher addiction potential

-ex: fentanyl

-prescribed drugs

Controlled substances schedule III

-specific therapeutic purposes

-lower addiction potential

-ex: methadone, narcan, naltrexone

Controlled substances schedule IV

-limited addiction potential

-OTC

Controlled substances schedule V

-not addictive

off label prescribing

-use of a drug to treat conditions other than those that the drug was originally approved to treat

-based on clinical judgement and evidence form additional rsrch

-DFA can't dictate how qualified clinicians prescribe meds if they have good reason to do so

Challenges to off label prescribing

-may not be recognized by insurance companies

-controversy whether off label use can be marketed

Emergency Use Authorization (EUA)

-declared by sec of the dept of HHS

-FDA may authorize unapproved med products or unapproved uses of approved med products to be used in emergency to dx, tx or prevent serious life-threatening diseases or conditions caused by chem, biological , radiological or nuclear threat agents

-incl when there aren't adequate, approved and avail alternatives

ex: COVID tests

Why do meds/drugs cost so much?

- ~5% of IND and New drug applications make it through approval process

-single agent approval is about $1billion

Where does the money go?

-synthesis of molecules

-animal studies

-human studies

-FDA

-failed drugs (A LOT GOES HERE)

-Time: 10-15 yrs to bring new drug to market