Basic Pharmacology I

What does pharmacokinetics study?

Effect of the body with the drug

What does pharmacodynamics study?

Effect of a drug on the body

What does ADME stand for? And what Discipline does it fall under?

Absorption, Distribution, Metabolism, Elimination/Excretion

Pharmacokinetics

What is Absorption?

How the drug gets into the body. More specifically, how does the drug move from the site of administration into the body

What is Distribution?

Movement of the drug to the site of action.

This includes Q’s like, is it a local or systemic drug?

how does the systemic drug move into interstitial and intracellular fluids?

Does the drug sequester in fat?

Does it get through the placenta or the BBB?

How do hydrophobic drugs get eliminated through the urine?

First things first, they need to become hydrophilic.

phase 1 reactions: oxidation, reduction, hydrolytic reactions

• Cytochrome P450 enzyme system (found in the liver)

phase 2 reactions: conjugation

Can then pass through the kidney and enter urine

What happens to prodrugs after metabolism?

They become active drugs

Where are drugs eliminated

renal excretion via kidneys

biliary and fecal excretion via GI tract

other routes via saliva, tears, breast milk, sweat

What is pharmacodynamics?

study of the effect of a drug on the body

this also includes:

drug concentration and effect, time course, intensity/potency

What is Medicinal Chemistry?

Research and development of chemical compounds to use as drugs

What is sterochemistry?

spatial arrangements of atoms in molecules

• R and S enatiomers

  • D and L enatiomers

What is Pharmacogenomics?

The body’s response to a drug, based on an individual’s DNA

What is an example of Pharmacogenomics?

this includes genetic testing and interpretation of results.

VKORC1 gene polymorphism for warfarin sensitivity

What is Toxicology?

Study of the undesirable effects of chemicals and antidotes

What is Pharmacoepidemiology?

Study of the uses and effects of drugs, in the real world, on populations

What is Pharmacotherapeutics?

the art and science of the treatment of disease

What is the conventional definition of a drug?

a synthesized pharmaceutical molecule or compound intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease

If prescriptions and over the counter drugs are regulated by the FDA, who regulates vitamins, herbal/dietary supplements, and homeopathic products?

The Federal Trade Commission (FTC)

they notify FDA of safety info, but not efficacy

What is the formal drug classification system?

The United States Pharmacopeia

Broad category is Therapeutic Category → Pharmacologic Class → Formulary Key Drug Types

example

Cardiovascular agents → Diuretics → carbonic anhydrase inhibitors, loop diuretics, potassium-sparing diuretics, thiazide diuretics

What are 3 other classification systems besides the pharmacopeia?

1) mechanism of action: long-acting beta agonist, calcium channel blocker, etc.

2) chemical structure: vinca alkaloids, Benzodiazepines

3) Specific drug properties: anticholinergic, inducer/inhibitor of CYP450, etc.

Describe the regulatory classification systems

• prescription only vs. over-the-counter vs. dietary supplement

• brand vs. generic vs. biosimilar

• FDA-labeled indication and use vs. off-label indication/use

• controlled substance schedules

What are brand name drugs?

a drug marketed under proprietary, trademarked, patent-protected name

What can be patented in brand name drugs?

• the drug itself

• the way the drug is made

• way the drug is to be used

• method of drug delivery to the body/site of action

patent can last for 20 years

Example is EpiPen Autoinjector (epinephrine)

What are generic drugs?

drug marketed when it is no longer patent-protected

• the name is assigned by the US Adopted Names Council

  • becomes official name

• Must have the same active ingredient, dose, and formulation

• must prove bioequivalence, not necessarily safety and efficacy

What is Bioequivalence? What book contains the approved drugs with therapeutic equivalence?

two products that have no significant difference in the rate and extent to which the active pharmaceutical ingredient becomes available at the site(s) of drug action

the orange book. “A” is bioequiv. “B” is not bioequiv.

How is a branded generic drug different?

These drugs go through the Abbreviated New Drug Application (ANDA) process and then gets assigned a new brand name

has same process of generic drug and has to prove bioequivalence

what is an example of a branded generic drug?

Brand name: Ortho Micronor

Generic name: norethindrone

Branded generic name: Camila, Errin

What are authorized generic drugs?

identical to the brand name drug - exactly the same

marketed by the brand company or another with permission

no ANDA needed or proof of bioequivalence necessary

Example of an authorized generic drug

Viagra permitted UpJohn to produce Viagra (sildenafil) in 2017

note: the generic drug may have different inactive ingredients than the brand name, but it brings a generic to market faster

What are biologic drugs?

vaccines, immunomodulators, monoclonal antibodies, and growth factors

What are FDA-Approved Biosimilar Drugs?

the biologic has been compared to an FDA-approved biologic reference drug and is similar in:

• purity

• molecular structure

• bioactivity

and has no clinically meaningful difference in how it works in the body, or immunogenictiy assessments.

What book contains biosimilar drugs?

purple

what is a biosimilar drug example for Lantus? what is the generic name? what are the biosimilars? Why is Basaglar not biosimilar?

generic name: insulin glargine

biosimilars: insulin glargine-yfgn (Semglee) and insulin glargine-aglr (Rezvoglar)

Basaglar is also an insulin glargine but, not biosimilar and has a different manufacturing process

Does biosimilar mean a drug is interchangeable?

NO

Humira has 9 biosimilars, 5 of which are interchangeable

In what ways might a drug be considered off-labeled use?

If you prescribe a drug for an indication other than what the FDA approved it for

this could be a different therapeutic use, diff. dosing, diff. intended population, or with a different formulation

Prazosin (Minipress)

FDA labeled use and Off-label use

FDA: hypertension

Off-label: nightmares associated with PTSD

Amitriptyline (Elavil)

FDA labeled use and Off-label use

FDA: depression

Off-label: insomnia, chronic pain, diabetic peripheral neuropathy

Gabapentin (Neurontin)

FDA labeled use and Off-label use

FDA: adjunctive therapy for partial seizures ages 3+, postherpetic neuralgia in adults

Off-label: hot flashes, diabetic peripheral neuropathy, anxiety, restless leg syndrome

What is the criteria for controlled substance schedules?

• relative abuse potential

• likelihood of causing dependence when abused

• if there is an acceptable medical use for medication in the US

Schedule I Controlled Substances

Not accepted for medical use, high potential for abuse, lack of safety data

examples

Flunitrazepam (Rohypnol)

Narcotics like Heroin and Fentanyl (and their derivatives)

Hallucinogens: LSD, Peyote, PCP (angel dust), and Methamphetamine derivatives like Ecstasy/MDMA

Marijuana/cannabis (federally. but some states legalized it.)

Schedule II Controlled Substances

Currently accepted medical use with severe restrictions, high potential for abuse, can lead to severe psychological or physical dependence

Examples:

Opioids like morphine, oxycodone, hydrocodone, hydromorphone, codeine, fentanyl

Stimulants like cocaine, amphetamine salts, lisdexamfetamine, methylphenidate

Depressants like: Pentobarbital, secobarbital, or amobarbital

Schedule III Controlled Substances

currently accepted medical use, some potential for abuse, may lead to high psychological or moderate to low physical dependence

examples:

Opioids like buprenorphine, acetaminophen/codeine #3

anabolic steroids like testosterone and its esters, or methyltestosterone

depressants like butalbital (fiorinal) or ketamine

cannabinoids like dronabinol and maybe marijuana in the future

Schedule IV controlled substances

currently accepted medical use, low potential for abuse, may lead to limited psychological or physical dependence

examples:

opioids like butorphanol, tramadol

stimulants like armodafinil, modafinil, phentermine

depressants like benzodiazepines, zolpidem, zaleplon, lacosamide, phenobarbital

Schedule V controlled substances

currently accepted medical use, low potential of abuse, limited psychological or physical dependence

examples:

Antitussive (200mg and less) of codeine per 100ml/100g

Antidiarrheal

Pregabalin