Pharmacokinetics - Drug Movementkd

What determines parmacokinetics?

Absorption

Distribution

Metabolism

Elimination

What is pharmacokinetics?

What animal does to the drug

What is absorption?

From site of administration into the vasculature

• Oral, SC, IM, TD, inhalation, rectal

What does absorption exclude?

IV (already in vasculature

What is distribution?

Within the body

• Plasma protein binding, tissue barriers, intracellular, blood flow, lipophilictiy, transporters

What is metabolism?

A chemical change of the drug in the body

• Hepatic (phase 1, phase 2, intestine, spleen, lungs, plasma

What is elimination?

Renal elimination, biliary secretion, exhalation

What is pharmacodynamics?

Effects the drug elicits

What is required for a drug to work?

Enough concentration at the correct receptor/target for a period of time

What are the factors affecting drug delivery to a specific tissue?

Plasma protein binding

Anatomic barriers

Dug lipophilicity

Blood floow

Drug transporters

Drug ionization

How would plasma protein binding affect drug delivery?

If a drug is stuck on a plasma protein it may not enter tissue

What are some anatomic barriers affecting drug delivery?

Blood-brain barrier, blood-prostate barrier, blood-ocular barrier, blood-bronchus barrier

Why does blood flow affect drug delivery?

Blood flow to tissue mass ratio determines how well a drug enters

What has a low blood flow : tissue mass?

Adipose tissue, bone

What has an intermediate blood flow : tissue mass?

Muscle, skin, GI tract

What has a high blood flow : tissue mass?

Lungs, brain, heart, kidneys, liver, endocrine organs

What affect does drug ionization have on a drug?

A charged drug does not diffuse through lipid membranes well

What are drug transporters?

Things that move drugs across tissue barriers

What happens to cefovecin when it enters the vasculature?

99% binds to plasma proteins with high affinity

When it gets to arterial capillary bed only 1% can enter the tissue fluid

What happens to morphine after giving IV?

30% binds to plasma proteins

At arterial capillary beds, most of drug flows into tissue fluid with plasma water by lipid diffusion

At venous capillary beds, drug in tissue is reabsorbed into the vasculature and some will stay in the tissue

What is a fenestrated capillary?

Holes in a capillary allow for plasma water and aqueous drugs to pass through

Why does Cefovecin not enter some tissues with anatomic barriers?

There is a low lipophilicity so it cannot bass through intracellular fluid, blood-brain barrier, blood-prostate barrier, blood-ocular barrier, blood-bronchus barrier

Why is morphine able to enter most tissues?

Low protein binding

High lipophilicity

Lack of drug efflux

Can enter blood brain barrier, blood-prostate barrier etc

What is drug efflux?

Drug gets pumped out of tissues

DOoes does the blood-brain barrier work with drug efflux?

There are active transporters that pump drugs from the CNS back into the vasculature

What is a transporter?

Can be active or facilitated transport that can potentially move some drugs across cell membrane if the drug is a substrate for the transporter

T/F transporter/drug affinity is specific?

True

T/F transporters can move drugs either into the ell or out of the cell

T

T/F transporters may have limited anatomic locations, may be organ specific or may not be located throughout the body

True

What is facilitated diffusion?

No energy used

Protein carrier provides pathway for substrate to cross membrane

How does facilitated diffusion differ from diffusion?

It is saturable and specific

What are two examples of facilitated diffusion?

Ion channels

Glucose channels

What is active transport?

Energy is expended, it is saturable and specific

What transport can go with or against concentration gradient?

Active transport

T/F genetic mutations can inactivate or up-regulate transporters?

True

What is an example of an active transporter?

p-glycoprotein (MDR)

Describe the relationship between morphine and transporters?

Morphine is very lipophilic so it is not transported really