PMCY 2020 EXAM 2 REVIEW

Pharmacokinetics

what the body does to the drug

Pharmacodynamics

what the drug does to the body

ADME

absorption, distribution, metabolism, excretion

Absorption

The process by which drug molecules gain access to the bloodstream

Distribution

The process by which drugs and their metabolites are moved through out the body

Metabolism

The process by which drugs are chemically changed by the body

Excretion

The process by which drugs and their metabolites are removed from the body

Pharmacokinetics usually occurs during what phase

Pre-clinical testing and phase 1

A drug can fail if it eliminates ___ in the body

quickly

Beyond 24 hours causes a patient to

forget to take the drug

Most people remember to take their medicine

Monday through Friday; taking the weekends off

Dose

Amount of drug administered (molar, mmol, mg)

Dosing interval

Amount of time between drug dose administration

Cmax

The peak plasma concentration

What makes pharmacokinetics useful for us?

There is a direct linear relationship between drug concentration and response, which tells us the that it is predictable

Tmax

The time to reach Cmax (hr)

Volume of distribution

The apparent volume in which a drug is distributed

Concentration

The amount of a drug in a given volume of plasma (mg/L)

Elimination half time (T 1/2)

Time required for the concentration of a drug to decrease by half (hr)

It is important to know where the drug is going in the body because it

Shows us how to monitor the organs for toxicity

Clearance (CL)

The volume of plasma cleared of a drug per unit of time (L/h)

Bioavailability (F)

The fraction of the dose available to the body (usually expressed as a %)

What fluids/tissues can we sample?

Blood, plasma, urine, saliva

Taking ____ levels became an easier form of being tested over blood samples on astronauts

saliva

Why do we look at plasma levels over blood levels?

Blood is a hard fluid to clean up for analysis

You can use plasma concentrations to predict

what is happening in the tissues

As the plasma concentrations decline,

the tissue concentrations will also decline

Most common route of administration

Oral

Absorption phase is when the concentration is

rising

Cmax is where the rate of absorption is ___ to elimination

equal

If you double the dose, the area under the curve will

double

Area under the curve is usually used to calculate the

bioavailability

Rich data

Data around the peak

After 4-5 half lives, you've eliminated about ___% of the drug

90%

Half lives can help us identify

How much of the drug needs to be administered

What is the least common route of administration for absorption?

Intravenously

Who has trouble taking tablets?

Children and elderly

If a drug is an extended release, you cannot

Crush it into smaller pieces so that it'll be easier to take

A drug has to be scored for it to be

Crushed into smaller pieces

Where can you look to see if a drug can be crushed?

Package insert

Does the route of exposure alter the absorption of a drug?

Yes

Why would you use acetaminophen by IV?

It is a way to manage pain without being reliant on opioids

It's better to stay ahead of pain so that

you don't have to chase the pain

What group would use acetaminophen rectally?

Babies and children that run fevers which cause them to vomit

What is the drawback of giving acetaminophen or any drug by a different route?

They will produce different concentration time profiles

What factors influence the release and absorption kinetics of a drug following oral administration of a solid dosage form

Release characteristics of dosage form, physical chemical properties, dissolution of the drug, physiology of GI tract, disease states, drug interactions

Extended release yields a ___ blood level

constant

Dissolution of a drug is useful because a

drug has to be in solution before it can be absorbed into the body

Physical chemical properties of a drug are useful because of the

ionization state, molecular weight, lipophilicity

Molecular weight cutoff is

500 from the GI tract

What kind of diseases can alter absorption in the GI tract?

Crohn's disease, ulcerative colitis, congestive heart failure, diabetes

Most absorption of orally administered drugs takes place in

the small intestine

Once absorbed from the small intestine, drugs will be taken to the

liver

Active transport requires

energy

Influx transporters

Move drugs into the systematic circulation

Efflux transporter

Transporting drugs back to the GI tract/small intestine

Primary sites for first pass metabolism

GI tract and liver

Goal of drug metabolism

Increase molecular weight of drug and make it more polar

Once the drug is metabolized, it is usually considered to be

Inactive

Bioavailability

The amount of drug that reaches the blood

Bioavailability is primarily determined by

physical properties of the drug, formulation, food effects, gastric emptying, transporters, GI system health, enzyme induction, metabolism variation, disease state, route of exposure

Bioavailability of an IV given drug

100%

Bioavailability of a drug given any other route than IV is usually

less than 100%

Relative bioavailability is useful for

Making a generic drug and seeing how it compares to the brand name product

Apparent volume of distribution

relates the amount of drug in the body to the plasma concentration

The apparent volume of distribution is a good indicator of

the extent of a drug distribution into body fluids and tissues

Clearance

Volume of blood from which drug is completely removed from the plasma per unit of time

What factors influence clearance?

Age, disease, drug concentration, liver function, kidney function

The higher the clearance, the shorter the

T ½ (half-life)

Clearance is ____ to each drug

specific

CL=

0.693 x Vd/T 1/2

F=

AUC (oral) x Dose (IV)/ AUC (IV) x Dose (oral)

Volume and half-life are

directly proportional

Key determinants of drug clearance

Metabolism, renal, hepatobiliary, can have CL for each organ

For many drugs, the total body clearance is dependent on

renal and hepatic clearance

Clearance can be a __ or ___ order process

first or zero

Half life

time necessary to eliminate 50% of the drug in the body

One compartment model

Simplest model, first order kinetics, reference compartment plasma, instantaneous distribution, kinetically homogenous unit rapid equilibrium

What types of drugs follow one compartment model?

Drugs with small distribution, more hydrophilic

Drugs with high volume of distribution

Have concentration in tissue rather than in plasma, lipid soluble, distributed into cells

What are the considerations that must be taken into account during dosing?

Therapeutic index, therapeutic range, adverse drug reactions, PK parameters(elimination half life), formulations available, clinical factors, local or systemic effect

Therapeutic range is

where the majority of patients have an optimal response

Therapeutic index

Minimum toxic concentration/minimim therapeutic concentration

Examples of adverse drug reactions

Infused too quickly, GI distress, irritation to skin, bad taste in mouth

Examples of clinical factors regarding dosing

Inherent person to person variability, disease, age and weight, drug-drug interactions

Who is at most risk for drug-drug interactions

The elderly

What could cause variability between subjects?

Renal function, drug-drug interactions, gender, ethnicity

Pharmacogenetics is

The move towards personalized medicine based on genetic testing

3 questions to answer when dealing with dosing regimes?

How much, how long, and how often?

Local effect

eye drops, antibiotic ointment, ear drops

systemic effects

drug administered throughout the body by the bloodstream to internal organs

Very short half life

Less than 20 minutes

Short half life

20 minutes-3 hours

Intermediate half life

3-8 hours

Long half life

8-24 hours

Very long half life

Longer than 24 hours

Types of study designs for bioequivalence

Fasting study, food intervention study, a multiple dose

How long does it take to get to steady state?

4-5 half lives

The Three R's (for animal research)

Reduction, replacement, refinement

Reduction

Any strategy that will result in fewer animals being used in research