Pharmacokinetics 1 Flashcards
Pharmacokinetics
What does the animal do to the Drug
Absorption
Distribution
Metabolism
Elimination
Absorption
From the site of administration into the vasculatrure
Exculdes IV injections
Oral, Subcutaneous, Intramuscular, Transdermal, Inhalation, Rectal
Distribution
Throughout the body
Plasma protein binding, tissue barriers, intracellular, blood flow, lipophilicity, transporters
Metabolism
SOme, but not all drugs are chemically changed
Hepatic (phase 1/2), non-hepatic
Elimination
Drug and Metabolites
Renal elimination, biliary secreations, exhalation
Pharmacodynamics
What the drug does to the animal
Effects the drug elicits
Factos that affect drug delivery to specific tissue:
Plasma Protein Binding
If a drug is stuck ona plasma protein, it may not enter into the tissue
Factors affecting drug delivery:
Anatomic Barriers
Extra barriers decreasing/restricting drug movement
Blood-Brain Barrier
Blood-Prostate Barrier
Blood-Occular Barrier
Blood-Bronchus Barrier
Factors affecting drug delivery:
Drug Lipophilicity
Can the drug diffuse across a lipid membrane?
Does it need to?
Factors affecting drug delivery:
Blood Flow
Actual blood flow:
- Tissue mass is more important thatn total blood flow
- Low:
- Adipose tissue, bone
- Poorly Perfuse
- Intermediate:
- Muscle, Skin, GI tract
- High:
- Lungs, Brain, Heart, Kidneys, Liver, Endocrine glands
- Well perfuce
Factors affecting drug delivery:
Drug Transporter
p-glycoprotein
Factors affecting drug delivery:
Drug Ionization
A charged drug does not diffuse through lipid membranes well.
Fenestrated Capillary
Aqueous pores are similar in regards to drug movement
Drug Movement:
Diffusion:
Lipid
Across biologic membranes
Drug Movement:
Diffusion:
Aqueous
Through pores, within body cavity
Drug Movement:
Diffusion
Not saturable, no competition, not specific
Always moves from a higher concentration to lower
Physiochemical properties of the drug affect movement
Protein binding
Lipophilicity
Molecular Weight
Ionization: pKa
Properties of the cell membranes / capillaries
Drug Lipophilicity and Transporters
- Transporter (active or facilitated) can potentially move soem drugs across cell membranes IF the drug is a Substrate for the transporter
- Transporter / Substrate affinity is specific
- Transporter can be in either direction depending on orientation of the transporter
- Amino acid transporters move hydrophilic gabapentin into the CNS
- P-glycoprotein transporter effluxes loperamide, an opioid, out of the CNS
- Morphine, an opioid, is not affected sustantially by transporters so lipophilic morphine does penetrate into the CNS can eleicit central effects
- Transporters may have limited anatomic locations - may be organ specific and may not be located throughout body
Carrier Mediated Drug Transporters:
Fcilitated Diffusion
No energy expended
Protein carrier provides pathway for substrate across membrane
Ion channels, Glucose Transporters
Moves from High concentration to Low Concentration
Saturable and Specific
Carrier Mediatied Drug Transporters:
Active Transport
Energy expended
Saturable and Specific
Can go with or against concentration gradient depending on orientation
Genetic Mutations can inactivate or up-regulate transporters
Impact of Blood Flow on Tissue Drug Exposure
