drug exam two

What does ADME stand for in drug discovery?

Absorption, Distribution, Metabolism, Excretion

What is the role of absorption in pharmacokinetics?

It refers to how the drug gets into the bloodstream.

What does distribution refer to in pharmacokinetics?

It describes how the drug moves from the bloodstream to the rest of the body.

How is metabolism defined in the context of drug discovery?

It is the process by which the drug is chemically transformed in the body.

What does excretion mean in pharmacokinetics?

It refers to how the drug is eliminated from the body.

What impact does formulation have on pharmacokinetics?

Formulation can dramatically affect drug exposure.

What is the significance of the pharmacokinetic profile of a drug?

It encompasses the overall behavior of the drug in the body, including absorption, distribution, metabolism, and excretion.

What is PEG in the context of drug formulation?

PEG stands for polyethylene glycol, which is used in drug formulation.

What is Cmax in pharmacokinetics?

Cmax is the maximum concentration of a drug in the bloodstream.

What does AUC0-t represent?

AUC0-t is the area under the concentration-time curve from time zero to time t, indicating drug exposure over time.

What does t1/2 signify in pharmacokinetics?

t1/2 is the half-life of a drug, indicating the time it takes for the drug's concentration to reduce by half.

What does Cl represent in pharmacokinetics?

Cl stands for clearance, which is the volume of plasma from which the drug is completely removed per unit time.

What is the significance of the route of administration in pharmacokinetics?

The route of administration affects the absorption and overall pharmacokinetic profile of the drug.

What is the difference between IV and PO administration?

IV (intravenous) administration delivers the drug directly into the bloodstream, while PO (oral) administration involves taking the drug by mouth.

What is the impact of species on pharmacokinetics?

Different species can exhibit varying pharmacokinetic profiles due to biological differences.

What is PEG in drug formulation?

Polyethylene glycol, used as a solvent or excipient.

Name three solvents used in drug formulation.

DMSO, NMP, DMA.

What role do surfactants play in drug formulation?

Surfactants like Cremophor help stabilize emulsions.

What is an excipient?

An usually inert substance that forms a vehicle for a drug.

Why are excipients important in drug formulation?

They often differ between generic and non-generic drugs.

What forms can drugs take in formulation?

Pills, capsules, gel caps, and time release caps.

How does drug morphology affect pharmacokinetics?

Morphology impacts dissolution rates and absorption.

What factors influence drug morphology?

Particle size, crystallinity, and salt selection.

What is the significance of salt selection in drug formulation?

It affects solubility, particle size, and hygroscopicity.

What is the bioavailability (%F) of Acetaminophen?

88%.

What is the clearance (CL) of Ibuprofen?

0.75 mL/min*kg.

What is the half-life (t1/2) of Morphine?

1.9 hours.

What is the protein binding percentage of Paclitaxel?

98%.

What does ADMET stand for?

Absorption, Distribution, Metabolism, Excretion, and Toxicity.

What is a common predictor of cardiotoxicity in drugs?

Interactions with CYP3A4, as seen with Terfenadine.

What is the effect of co-administering Terfenadine with ketoconazole?

It can lead to severe cardiac arrhythmia.

What does the term 'first pass metabolism' refer to?

The metabolism of a drug before it reaches systemic circulation.

What is the volume of distribution (Vss) of Zolpidem?

0.54 L/kg.

How does particle size affect drug dissolution rates?

Smaller particles generally dissolve faster.

What is the protein binding percentage of Nicotine?

4.9%.

What is the significance of pharmacokinetic (PK) profiles?

They help determine the efficacy and safety of drugs.

What is the clearance (CL) of Methadone?

1.4 mL/min*kg.

What is the half-life (t1/2) of Zolpidem?

2.2 hours.

What does the term 'hygroscopicity' refer to in drug formulation?

The ability of a substance to absorb moisture from the air.

What is the bioavailability (%F) of Paclitaxel?

0%.

What is the half-life (t1/2) of Ibuprofen?

2.0 hours.

What is the volume of distribution (Vss) of Acetaminophen?

0.95 L/kg.

What is the role of hERG in drug discovery?

hERG is a human gene that encodes a potassium ion channel, and its activity is tested for cardiotoxicity in drug discovery.

When was hERG identified?

hERG was identified in 1994.

What drug was identified as a potent hERG inhibitor in 1996?

Terfenadine (Seldane).

What recommendation did the FDA make regarding terfenadine?

In 1997, the FDA recommended terfenadine be removed from the market.

What does ADME/Tox stand for?

Absorption, Distribution, Metabolism, Excretion, and Toxicity.

What is a 'hit' in drug discovery?

A 'hit' is a compound that demonstrates activity in an assay that meets a threshold set by the investigator.

What are the four main sources of 'hits' in drug discovery?

Screening, modification of standards, literature/patent mining, and docking.

What does the term 'screening' refer to in drug discovery?

Screening refers to the process of testing various compounds to identify potential drug candidates.

What is the NIH's role in drug screening?

The NIH has a Molecular Libraries Program to help screen compounds against assays.

What are some examples of assay types used in drug discovery?

Electrophysiology/patch clamp and Langendorff heart model.

What is the importance of a standard in an assay?

A standard is required to show that the assay works effectively.

What are 'me-too' drugs?

Drugs that are modifications of existing drugs, often seen as improvements in exposure, half-life, metabolism, or side effects.

What are some concerns associated with 'me-too' drugs?

Concerns include the cost of development and intellectual property issues.

What is the significance of cardiotoxicity in drug development?

Cardiotoxicity is a critical factor that can lead to the rejection of a drug candidate during development.

What is the function of CYP isoforms in drug metabolism?

CYP isoforms are enzymes that metabolize drugs, with known substrates for each isoform.

Which CYP isoform is phenacetin associated with?

CYP 1A2, which is inhibited by furafylline.

Which CYP isoform is tolbutamide associated with?

CYP 2C9, which is inhibited by sulfaphenazole.

Which CYP isoform is dextromethorphan associated with?

CYP 2D6, which is inhibited by quinidine.

Which CYP isoform is midazolam associated with?

CYP 3A4, which is inhibited by ketoconazole.

What is the role of biochemical and cellular assays in drug discovery?

They are used to evaluate the pharmacological properties and safety of drug candidates.

What is the purpose of literature/patent mining in drug discovery?

To identify potential drug candidates or modifications of existing drugs through research and patents.

What is the importance of automation in drug screening?

Automation allows for running millions of assays in a short time frame, increasing efficiency.

What is a common limitation in high-throughput screening?

Reagents can be costly and may have availability issues.

What is the significance of the Langendorff heart model?

It is used to study the effects of drugs on heart function in a controlled environment.

What is the role of electrophysiology in drug discovery?

It helps in assessing the electrical activity of cells and the effects of drugs on ion channels.

What is the purpose of hit generation in lead discovery?

To identify compounds that show potential activity for further development into drug candidates.

What is a patent?

A legal right to exclude others from practicing a novel invention.

What are the three main types of patent claims in drug discovery?

Composition of matter, method of use, and article of manufacture.

What is a Composition of Matter claim?

Requested when something has been created that has never been created before.

What does a Method of Use claim cover?

Any matter if a use for that matter has been discovered.

What is an Article of Manufacture claim?

Requested for any matter if a method for manufacturing that matter has been discovered.

What is a patent claim?

A specific statement of a discovery that defines what the inventors claim to have discovered.

What is the difference between a patent and a patent application?

A patent grants exclusive rights, while a patent application is a request for those rights and is published but not guaranteed.

Which organization publishes patent applications?

The World Intellectual Property Organization (WIPO).

What are the two types of patent applications?

Regular (nonprovisional) and provisional.

What is the duration of a regular patent application?

Expires 20 years after the filing date.

What is the purpose of a provisional patent application?

Establishes an invention date and does not require an examination.

What must happen to a provisional application after one year?

It must be converted into a nonprovisional application or a new provisional application can be filed.

What does the USPTO require for an invention to be patentable?

It must be useful, novel, and nonobvious, among other requirements.

What does 'usefulness' mean in patent law?

The invention must have a specific, practical use.

What is 'novelty' in the context of patent applications?

The claims must not have been previously published or claimed in another patent application.

What is 'nonobviousness'?

The invention must not be obvious to a person having ordinary skill in the relevant art.

What is the significance of the Leahy-Smith America Invents Act?

It changed the U.S. patent system from 'first to invent' to 'first to file'.

What is required from inventors regarding prior art?

All relevant prior art must be disclosed to the patent office.

What is the burden of proof in patent applications?

Inventors must prove they actually invented what they claim.

What does the term 'enablement' refer to in patent law?

The requirement that the patent application provides sufficient detail for someone skilled in the art to replicate the invention.

What is meant by 'best mode' in patent applications?

The inventor must disclose the best method known for carrying out the invention.

What happens if a patent application is not converted to a nonprovisional application?

The provisional application will expire after one year.

What is the role of the patent examiner?

To investigate claims in a patent application and determine if they constitute a new invention.

What does 'prior art' refer to?

Any evidence that the invention was known or used by others before the applicant's filing date.

What is the significance of a claim being 'obvious'?

If an invention is obvious, it cannot be patented, even if it has not been previously disclosed.

What does it mean for a claim to be 'generic'?

A claim that describes a broad category of compounds without specifying a particular compound.

What is the consequence of not having a claimed use for a compound?

A generic structure does not automatically convey a claim to any compound that falls within its description.

How long does a regular patent last?

20 years after the filing date.

What significant change did the Leahy-Smith America Invents Act introduce?

Changed the prioritization of inventions from 'first to invent' to 'first to file'.

What are the six basic requirements for patentability?

Usefulness, novelty, nonobviousness, written description, enablement, and best mode.

What does nonobviousness mean in patent law?

A patent may not be obtained if the differences between the invention and prior art would have been obvious to a person skilled in the art.

What are some characteristics that can indicate nonobviousness?

Improved pharmacokinetics (PK), such as absorption, metabolism, efflux, and activity against a different target.