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

How does anorexia/bulimia impact drug absorption?

delayed gastric emptying and decreased total body fat

how does surgery impact drug absorption

bowel resection or gastric bypass

how does liver disease impact absorption?

the first-pass effect can occur

how does GERD impact drug absorption?

treatments increase gastric pH- which may impact absorption of iron and vitamin B12 among other drugs and nutrients

Ionized drugs are _____philic, nonionized drugs are _____philic

hydro; lipo

what allows ionized (hydrophilic) drugs to diffuse across membranes?

ion trapping and pH gradients

What are some practical barriers to absorption?

pt’s abilities

such as vomiting, ability to swallow, dexterity issues, hand-eye coordination, or even fear of needles

How do you instruct your patient to swallow a pill?

relax, keep eyes forward, drink water, place pill in middle of mouth and take several drinks

what is biopharmaceutics?

the branch of pharmacology concerned with the preparation, use, and sale of drugs

includes administration, absorption, and distribution

what is administration?

the effect of dosage forms on absorption and distribution

what is the enteral route of administration?

medications that are administered to the gastrointestinal tract

(oral, rectal, NG, PEG, or sublingual)

what forms can an enteral drug take?

tablet/capsule

lozenge (troche)

liquid (Tincture, Elixir, Suspension)

powder

chewable (gummy)

rectal formulations (cream, suppository, enema)

How to give SQ Injection

1. take out of fridge and inspect it

2. look at date

3. prep skin and clean it

4. pinch the skin to find target zone

5. go in at 45-90 degrees

6. push plunger down

7. dispose in sharps container

what factors influence drug distribution?

body fat percentage (if they are lipophilic drugs for example)

ability to cross various membranes (BBB, placenta, breastmilk)

protein binding → some drugs are highly protein bound and this delays distribution in blood and at target site

what are some examples of types of tablets and their distribution?

immediate release (IR)

sustained release (SR)

Extended release (ER)

long acting (LA)

Extended release (XR)

Orally disintegrating tablets (ODT)

Sublingual tablets (SL)

Film coated - dissolves in stomach

enteric coated - dissolves in small intestine

osmotic release (some immediate some delayed)

what is special about DiffCORE?

oral tablet that has a controlled and immediate release

T/F plasma volume affects distribution

T

adults have more plasma volume and have higher doses than children

what are the ages and stages of pediatrics?

preterm newborn

newborn 0-28 days

infant 28 days-12 months

toddler 12months to 23 months

preschool 2-5 years

school aged 6-11 years

adolescent 12-18 years

which pediatric age range has increased gastric emptying time?

birth to 6 months

which pediatric group has reduced gastric enzymes, bile acids, and pancreatic enzymes?

neonates

which pediatric age group has greater % of body water?

neonates 80% water

decreased protein binding also in infants

what are some changes in geriatric patients that causes differences in absorption?

slowed gastric emptying (delayed absorption)

increased gastric pH (stomach more basic)

fat increase and water decreases

albumin decreases

how does obesity affect distribution and absorption?

increased gastric pH, concern with transdermal or subcutaneous formulations (too much fat to get through)

increased volume of distribution

reduction of CYP3A4 in intestinal wall and liver

How does pregnancy alter drug absorption?

plasma volume increased by 30-50%

increased body fat

decreased albumin

gastric emptying time decreased (metabolism drops)

most drugs are not studied in pregnancy

what concerns should we have when it comes to drugs crossing into the placenta and breastmilk?

many drugs are safe, but some options are for a patient to pump the milk and dump it so the infant doesn’t drink it

specifically small molecular weight drugs and lipophilic drugs and low protein binding and high oral bioavailability

basic drugs are more likely to cross into placenta

what are the tablets/capsules you definitely should not cut, crush, or chew?

extended-release formulations

enteric-coated drugs

what are some parenteral routes of administration?

these are medications that bypass the gastrointestinal tract

• IV

  • subcutaneous (ex is pegfilgrstim, adalimumab)

  • intramuscular

  • intradermal (monkeypox vaccine)

  • pulmonary

  • intrathecal

  • topical

what is an example of a intradermal injection?

monkeypox vaccine

what is an example of a subcutaneous injection/injection device?

pegfilgrastim

adalimumab

what is an example of an autoinjector?

dulaglutide

tirzepatide

This is a phase of clinical trial that involves testing against a placebo in a large multi-center randomized trial

phase III

This is a phase of clinical trial that involves treating a healthy population with a drug to assess dose and toxicity

phase I

this is a phase of clinical trial that involves gathering safety data after a drug is submitted to the FDA

phase IV

T/F an investigational New Drug Application (IND) is filed after a drug has completed Phase III clinical trials

false

What are some examples of Intravenous injections/injection devices?

infusion

push

Y-site

This is a type of trial design to prove that a new treatment is essentially equivalent to comparison treatment

non-inferiority trial

what is an open label trial?

not blinded

often continues after non-inferiority trial

case-control study

study on patients who were exposed to an event vs patients were not exposed to an event

what are types of intrathecal injection?

infusion or injection

this is a term when a patient assigned to receive a placebo experiences side effects associated with active drug

nocebo

drugs that have serious side effects may be required by the FDA to have what additional research?

risk evaluation and mitigation strategy

What is the DEA registration Certificate/Number?

it is a registration that allows you to dispense, administer, or prescribe controlled substances in Schedule II-V.

Must complete 8 hrs of training

What is your DEA number?

an example is MK1234563

first 2 letters are registrant and last name initial

M=midlevel, K=Kliewer

define prescription

intended to be dispensed to or for an ultimate user/patient

define order

intended for immediate administration to the ultimate user/patient

Who can issue controlled substance prescriptions?

either

1) practitioners authorized to prescribe controlled substances and registered with the DEA

OR

an agent or employee of a hospital acting in the normal course of business or employment under the registration of the hospital or other insititution

what is required for prescriptions in WA state for non-controlled substances?

Patient’s full name

practitioner’s full name

Drug name

Strength 

Quantity

Directions for use

Number of refills

Date issued

Signature 

what does “dispense as written” mean

it means the drug must be in the name the practitioner says - brand name for example

what is required for prescriptions in WA state for controlled substances?

Patient’s full name and address

practitioner’s full name, address, and DEA number

Drug name

Strength 

dosage form

Quantity

Directions for use

Number of refills

Date issued

Signature 

why is indications of use on a prescription a good practice?

not required by law, but required in certain states, may be required by the electronic health record or system, and may be required by insurance

look at the dangerous abbreviations

QD instead of daily

QOD instead of every other day

MS, or MSO4 instead of morphine

.5 mg instead of leading 0 (should be 0.5mg)

5.0mg instead of 5mg (don’t use trailing 0)

how long are most schedule drugs valid for in WA? which has no refills and which has up to 5?

6 months

no refills for Schedule II

up to 5 refills for Schedule III, IV, and V

how long are non-schedule drugs valid for in WA?

12 months

what is required before prescribing a Schedule II Opioid?

you must determine that a non-opioid therapy is not appropriate with documented reasoning. 

you need to query the WA state prescription drug monitoring program 

what is the MAX prescription timeline for Schedule II opioids?

7 day supply (some cases with justification can extend to 14 days for postoperative patients)

what is Subacute Pain?

it begins 6 weeks after the acute nonoperative or perioperative pain began.