Neuropsychopharmacology Exam 1 Content

What is a drug?

An administered substance that alters physiological functioning.

Examples of what we consider a drug

vitamins, food, water, carbon monoxide

What do we call a drug?

Example: Tylenol

Tylenol = brand name

acetaminophen = generic name

What is a psychoactive drug?

A drug that affects mood, perception, thinking, and/or behavior by acting in the central nervous system.

How much of a drug is needed?

Depends on firstly weight.

Other considerations: disease history, age, biological sex, other drugs a person is taking, pregnancy status, desired effect, symptom severity, how long on the drug, prior history of similar drugs.

Is a pill a “dose?”

No

What is a dose?

The amount of drug relative to organism’s body weight.

Standard unit for doses

mg/kg

Standard unit for amount

mg

How to determine the dose of a drug?

dose response (DR) curve

What is a dose response (DR) curve?

The magnitude of dose effect by dose.

ED

effective dose

ED₅₀

50%

E_max

100%

The response/effect can be…

positive or negative

What is the therapeutic index (TI)?

separation between ED₅₀ and TD₅₀/LD₅₀

Why is the therapeutic index (TI) no longer used?

Because two drugs that have the same therapeutic index don’t always follow the same drug response curve.

Three names for certain safety index (CSI)

1. certain safety index (CSI)

2. certain safety factor

3. margin of safety

Formula for certain safety index (CSI)

x = TD₁/ED₉₉

x must be greater or equal to 2 CSI

What about other properties of drugs?

pharmacokinetics, pharmacodynamics, phramacogenetics

How do we define pharmacokinetics (PK)?

How drugs enter, move through, are affected by, and leave the body.

How do we define pharmacodynamics (PD)?

the study of how drugs molecularly produce their primary/desired effects in the body.

pharmacogenetics

How a person’s genetics affects responses to, and removal of, drugs. It can also affect pharmacokinetics (PK) and pharmacodynamics (PD).

ALDH

aldehyde dehydrogenase

ADH

alcohol dehydrogenase

EtOH

ethanol

Acetate

anion of acetic acid (vinegar)

ALDH2 genetic variation

single amino acid change (out of 517 amino acids) that results in decreased stability to break down acetaldehyde. This means that there is going to be a big buildup of acetaldehyde, which results in slower process for ALDH to break down acetaldehyde into acetate.

Extra Credit: What drug mimics the ALDH2 genetic variation

generic name: disulfiram

brand name: Antabuse

What are the components of pharmacokinetics?

1. absorption

2. distribution

3. metabolism or biotransformation

4. excretion

How can drugs enter the body?

Absorption

What is absorption?

how drugs pass from administration/entry site of blood

Example of how drugs can enter the body (not on exam)

intravenous (IV), intramuscular, oral (per os), inhalation, sublingual, transdermal, subcantaneous, mucos membrane absorption, topical, intrathecal (e.g., epidural)

Routes of administration (ROA)

Fastest to reach blood

1. intravenous (IV)

2. inhalation

3. intramuscular

4. ingestion (per os)

Slowest to reach blood

Define intravenous

administration of drug into bloodstream

Define inhalation

administration of drug directly into lungs

Define intramuscular

administration of drug directly into skeletal muscle

Define ingestion (per os)

administration of drug to reach the blood through the gastrointestional (GI) tract

Extra Credit: ROA of eyedrops

ocular

Extra Credit: ROA of ear drop

otic

Ok, the drug is in the blood - what happens next?

Distribution

What is distribution

how drug pass from the blood to other parts of body

What is bioavailability?

Drugs’ ability to reach site of action, so the percentage of the drug that can reach the site of action.

How easily do drugs reach the brain?

It’s actually pretty difficult due to the blood-brain barrier (BBB), and that’s a good thing!

What is the blood-brain barrier (BBB)?

cellular structure that regulates what molecules can reach the brain/CNS

Some ____, _____, and _____ compounds can bypass BBB for our purposes, drugs must have all 3 characteristics, or it will not cross alone.

1. small

2. uncharged

3. lipophilic

ionized

charged

non-ionized

uncharged

What is necessary for all other compounds that don’t have all 3 characteristics to cross BBB?

active transport, which requires energy

lipophilic

loves fat

lipo = fat

philic = liking/loving

lipophobic

fears fat

lipo = fat

phobic = fear/dislike

hydrophobic

fears water

hydro = water

phobic = fear/dislike

hydrophilic

loves water

hydro = water

philic = liking/loving

If a molecules is lipophilic, then it also must be…

hydrophobic

If a molecule is lipophobic, then it also must be…

hydrophilic

What determines how long drugs exist in the brain/body?

metabolism or biotransformation

What is metabolism (aka biotransformation)?

How drugs are transformed by enzymes (proteins) in the body. It usually but does not always make it easier to remove the drug.

What is a key metabolism consideration?

first pass metabolism

What is first pass metabolism?

• most influential for ingestion/per os ROA

• mostly occurs in the liver

• usually substantially decreases bioavailability

• all blood from GI tract must first go through the liver before reaching systematic circulation

When does drug metabolism (biotransformation) occur?

It can occur before AND/OR after distribution. This means that distribution can occur before AND/OR after metabolism (biotransformation).

So, AM/BDE or ADM/BE

prodrug

biotransformation is necessary to convert compound into active metabolite (“drug”).

active metabolite

• produces the desired effect(s)

• is not a prodrug

• can be conceptualized as a “drug,” however, it is not administered whereas the prodrug is administered

metabolite

produces effects, but they are not desired.

What is the pathway of pharmacokinetics that a typical drug undergoes?

What is the pathway of pharmacokinetics that a prodrug undergoes?