Intro Stuff: Basic Concepts & Drug Decision-Making

According to the FDA definition, what is a drug?

articles intended for use in diagnosis, cure, mitigation, treatment, or prevention of disease in man or other animals

What is the first step to making good decisions regarding choosing a drug and regimen?

Identify alteration(s) in the patient

Identify the alterations in this case: Fern, a 6yo beagle dog, presents with a history of neck pain and fever. After physical exam and preliminary blood work, your presumptive diagnosis is non-infectious meningitis.

fever, inflammation (pain), meningitis

*What are 5 components of a systematic approach for choosing a drug and regimen?

1) identify alteration in the patient

2) define a therapeutic goal for the patient

3) Consider available alternatives (including not treating)

4) Choose and dispense/prescribe

5) Follow-up/monitor outcomes

When "consider[ing] available alternatives/options" as part of your systematic approach to choosing a drug and regimen, what 6 things should be considered?

1) the likelihood of desired effect (and estimate of its magnitude)

2) Likelihood of adverse effect (and estimate of its magnitude)

3) Legal/regulatory issues

4) Client desires and expectations

5) Ability to get into the animal

6) Cost

Choosing a drug always starts with knowing why you're considering a drug: ______________ IN THE PATIENT

ALTERATION

What is a big 'ol tenant of clinical pharmacology covered in the first lecture? --> ______________ (of drug) matters.

Concentration

*What is one big ol piece of information we can gather from a time vs. concentration in plasma graph of a certain drug?

The rate of absorption

Can we make inferences about effectiveness in these time vs. drug concentration graphs?

NERP

Complete this principle of pharmacology: drugs must be present at the site of _________

action

Complete this principle of pharmacology: in most cases, drug concentration in ________ or _______ is proportional to drug concentration at the "site of action"

blood, plasma

What is the difference between the drug molecule and the drug product or preparation?

drug molecule is the thing that interacts in the animal/infectious agent and has its therapeutic effect and the drug product is how we administer that drug molecule

What does API stand for?

active pharmaceutical ingredient

What are the three most common routes of drug delivery in veterinary medicine?

1) oral

2) injectable

3) topical

Understand that not all pharmaceutical formulations/dosage forms are the same.

There, now ya understand. This can be helpful to understand when choosing a drug

What are the four processes of drug movement - or what the body does to the drug?

Absorption

Distribution

Metabolism

Excretion

*What is drug absorption?

the process of drug going from the site of administration into the systemic circulation

What is drug distribution?

the process of drug moving from systemic circulation, not being eliminated, to target tissue/action site

The movement of drug from the site of administration to the interior of a cell (where many drugs act) requires traversing several ____________.

membranes

What are two ways/processes in which a drug can leave systemic circulation? i.e. what is the fate of drugs that leave systemic circulation?

elimination or distribution

What are the two ways in which a drug can leave the body?

by being metabolized or excreted as the "parent" drug

Phase I and II reactions are two types of ways in which drugs are metabolized in the ________

liver

Chemical reactions such as oxidation and reduction that introduce functional groups to drugs are known as phase ____ reactions. What group of enzymes help with these types of reactions?

I (one)

CYP450

Conjugation reactions that add compounds to drugs or Phase I metabolites of drugs to make more water soluble or polar are known as phase ____ reactions.

II (two)

Complete this principle of pharmacology: one drug can interfere with the ___________ of another

metabolism

What is the most common route of excretion for metabolites and for parent drug?

via the kidney in urine

*Complete this principle of pharmacology: some drugs work by __________ or __________ normal physiological activity.

mimicking, blocking

*Complete this principle of pharmacology: one common way drugs work is referred to as "__________" and "___________"

agonist, antagonist

*What is a drug that functions as an agonist?

a drug that binds to a receptor and stimulates an effect

*What is a drug that functions as an antagonist?

A drug that binds to a receptor, and no effect is stimulated. Drug may also block other ligands from binding.

Complete this principle of pharmacology: Efficacy describes how drugs work and can be characterized by ______

EC(50)

*What is EC(50)?

it is the concentration of drug required to reach half of Emax

Emax is the ____________ effect of the drug that you can get

maximal

*A more potent drug, would have a _________ lower/higher EC(50) compared to a drug with low potency.

lower

*What parameter is used in measuring drug potency?

EC(50)

*Is potency the same as efficacy?

NO!

*Which of the following uses of a compound would be considered "drugs" (select all that apply)

a) use of the prescription injectable antibiotic oxytetracycline for pneumonia in cattle according to the label on the bottle

b) use of aloe vera bought at Walmart for treating burns

c) use of injectable Vitamin B in a dog on TPN (total parenteral nutrition)

d) use of IV fluids to rehydrate a puppy with diarrhea

A, B, and D would be considered drugs

C would not because the Vitamin B is not being used to treat a disease (although I'm sure some would argue that pregnancy would count as a disease)

*Complete this Principle of Pharmacology: __________ index is the ratio of concentration needed for efficacy to the concentration that causes toxicity.

(LD50)/(ED50)

therapeutic

The extreme end of the efficacy would be ________

lethal

*What is LD(50)?

the dose of drug that will kill 50% of the animals it is given to.

*Therapeutic index is an indication of the likelihood of __________ effects at therapeutic doses.

adverse

Drug molecules move into, through, and out of the body in ____________ ways

predictable

Name agencies responsible for drug regulations at the state and federal level

USDA, FDA CVM, FDA CDER, EPA, FARAD

Board of Veterinarians

Board of Pharmacies

Apply information from drug labels and AMDUCA to determine the legality of a given drug use

idk, look at moodles

Complete this principle of pharmacology: Drugs are approved in a standardized manner, with certain studies performed to demonstrate ________ and ________, including human safety if appropriate

safety

efficacy

What are some differences/similarities between an FOI (Freedom of Information) summary and a drug label.

A lot of times they will contain the same information and the FOI will contain additional information (like the studies performed) that proves the safety and efficacy of the drug

Complete this principle of pharmacology: Not all _________ drug use is illegel.

extralabel

*Compounding is considered _________ use, some is legal and others not.

extralabel

*list to memorize over time (not for first exam necessarily)- the specific drugs that are prohibited from extrlabel use as listed in 21 CFR 530.41 (mostly food animal) should be familiar with throughout the semester

- Chloramphenicol

- Clenbuterol

- Diethylstilbestrol

- Dimetridazole

- Ipronidazole

- Other nitromidazoles

- Furazolidone

- Nitrofurazone

- Sulfonamide drugs in lactating diary cattle

- Fluoroquinolones

- Glycopeptides

- Phenylbutazone in female dairy cattle 20 months of age or older

- Cephalosporins

*A drug used as on the label is _________ use

legal

*A drug used extralabel for therapeutic purposes, by or on the order of a licensed veterinarian, with a VCPR, and that does not cause a residue above a tolerance or that is a threat to public health; extralabel use also requires specific labeling of the drug and record-keeping and may require disclosure to clientis is considered __________ use of a drug

legal

*Use of a drug compounded from bulk in a companion animal is considered _________ use of a drug.

Illegal, but of low regulatory priority

*Use of a feed additive extralabel in a minor species (see CPG 615.115) is considered _________ use of a drug.

Illegal, but of low regulatory priority

*Extralabel use of a USDA approved drug is considered ___________ use of a drug

Unclear legality

*Extralabel uses listed in 21 CFR 530.41 are considered __________ uses of a drug.

illegal

*Extralabel use in or on animal feed (whether OTC or VFD) is considered ___________ use of a drug

illegal

*Extralabel use for production or non-therapeutic uses is considered ___________ use of a drug

illegal

*Use of a drug without an approval, e.g., drug approved in another country, CBD products, is considered ___________ use of a drug.

illegal

*Extralabel use of an EPA-approved drug is considered __________ use of a drug

illegal

*Use of a drug compounded from bulk in a food animal is considered ____________ use of a drug.

illegal

*Some uses of controlled substances (improper documentation or prescriptions, e.g.) are considered ___________ uses of a drug.

illegal

*What is extralabel use of a drug?

according to Sarah's dictionary: using a drug for any other purpose that is not mentioned as its indicated use on the drug label (and what it has been approved for by the FDA)

What is a prescription?

according to google: an instruction written by a medical practitioner that authorizes a patient to be provided a medicine or treatment.

What does OTC stand for?

Over The Counter

(can attain without a prescription)

*What does VFD stand for? What is it?

VFD --> Veterinary Feed Directive.

According to FDA Website: A VFD is a written order issued by a licensed veterinarian in the course of the veterinarian's professional practice that authorizes the client (the owner or other animal caretaker) to obtain and use a VFD drug in or on animal feed. A VFD animal drug must have the following statement on the label:

''Caution: Federal law restricts medicated feed containing this veterinary feed directive (VFD) drug to use by or on the order of a licensed veterinarian.''

*What does VCPR stand for?

Veterinary Client Patient Relationship

*What is compounding?

According to the FDA: Drug compounding is often regarded as the process of combining, mixing, or altering ingredients to create a medication tailored to the needs of an individual patient. Compounding includes the combining of two or more drugs. Compounded drugs are not FDA-approved.

What is a controlled substance?

According to Wikipedia: A controlled substance is generally a drug or chemical whose manufacture, possession, or use is regulated by a government, such as illicitly used drugs or prescription medications that are designated by law.

What is a trade name?

According to Wikipedia: Many drugs are also known by a brand or trade name chosen by the pharmaceutical company making and selling that drug as a medicine. So, for example, the drug infliximab (generic name) is also known as Remicade (brand name).

What is a non-proprietary name?

According to NIH: Non-proprietary name is the name for the active ingredient in the medicine that is decided by an expert committee and is understood internationally (WHO, 2013a). Thus, paracetamol/acetaminophen is the non-proprietary name (generic name) while Crocin/Metacin/Meftal/Tylenol etc. are brand names.

*What is withdrawal time?

The time animal product must be withheld from the food supply after drug administration

Determined as the time it takes for 99% of the population of animals to deplete the drug given at a label dosage to less than the established tolerance, estimated with a 95% level of statistical confidence.

*What is tolerance as it pertains to drugs?

The maximum concentration of a drug (or its marker residue) that can legally remain in a specific edible tissue of a treated animal

What does USDA stand for?

United States Department of Agriculture

*What is FDA CVM?

It is the FDA's Center for Veterinary Medicine

FDA --> Federal Drug Administration

*What is FDA CDER?

FDA's Center for Drug Evaluation and Research

What is EPA?

Environmental Protection Agency

*What is FARAD?

From the Internet: Food Animal Residue Avoidance Databank (FARAD)

FARAD contributes estimated withdrawal times for species and indications for which the databank pharmacologists believe there is sufficient data available to make an acceptable recommendation.

*What does AMDUCA stand for? What it's relevance in dispensing drugs in vet med?

Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA)

veterinarians can use approved animal drugs in an extra-label manner, and they may prescribe approved human drugs for use in animals, under certain specified conditions

What is the bioavailability of a drug?

Percentage of drug that enters the bloodstream from the site of administration (may happen over time, not necessarily all at once)

*What is potency?

the amount of drug needed for a particular effect

*What is steady state?

When the amount of drug being taken in or administered is equal to the amount being eliminated. Steady state is assumed to be achieved at approximately 4-5 elimination half-lives. NOTE: arrival at steady state is not necessarily an indication of therapeutic effectiveness.

What is the first-pass effect?

When measurable metabolism of drug happens between the GI tract and the central circulation - first pass metabolism only happens to drug given orally

*What is metabolism or biotransformation?

Chemical reactions that change drug molecules; most common site of metabolism is hepatocytes

*What is elimination/excretion?

Movement of drug out of the body