Pharmacokinetics Flashcards
What are the enteral drug administration methods?
Oral
Sub-lingual
Rectal
What are the parenteral drug administration methods?
Intravenous Inhalation Transdermal Subcutaneous Intramuscular
What are the different ways drugs can be absorbed in the gut?
Passive diffusion
Facilitated diffusion
Active transport
Endocytosis/Exocytosis
What types of molecules get transported passively by each transport type?
Passive diffusion: lipophilic molecules, non-ionised hydrophillic molecules
Facilitated diffusion: ionised molecules through SLC’s
What are the two types of SLC’s?
OAT: Organic Anionic Transporter
OCT: Organic Cationic Transporter
What types of molecules get transported actively by each transport type?
Active transport: molecules that resemble endogenous molecules for binding to specific carrier proteins
Endocytosis/Exocytosis: large molecules (requires Intracellular signalling)
What are some of the factors affecting absorption in the gut?
pH (pKa of drug ~ pH of target site as non-ionised form passes easiest)
Blood flow (High blood flow, keeps conc. gradient high)
Surface Area
Time to absorption surface, time at absorption surface (drug will start to be degraded)
Solubility of the drug
First-pass metabolism
Expression of P-glycoprotein
What is the P-glycoprotein?
Protein found on cell membranes that pump drugs out of the cells
Therefore in High expression, there is low drug absorption
What is first-pass metabolism?
The metabolism of a drug that occurs in the gut wall, hepatic portal vein and (mainly) liver, which lowers the bioavailability of a drug
What is the bioavailability of a drug and why do IV drugs have 100% bioavailability?
Percentage of a drug reaching circulation
IV drugs have no physical or metabolic barriers
What is oral bioavailability equal to?
Oral bioavailability (F) = total amount of drug (giving orally) reaching circulation / total IV drug given
What is bioequivalence?
Comparison of 2 drugs with:
Similar bioavailability
Similar time to reach peak Cp
How are drugs distributed from the blood to the target?
Bulk flow (arteries —> capillaries) Diffusion (capillaries —> interstitial fluid —> cells)
What are some of the barriers to diffusion?
Capillary permeability pH Blood flow Distribution of transporters Non-target binding
What is non-target binding?
When drugs bind to proteins outside their targets (plasma proteins or tissue proteins)
These proteins can act as reservoirs of a drug
What are some examples of plasma proteins that bind to drugs and what is their normal function?
Albumin (Globulins) - maintain oncotic pressure
What is: Ab Cp Vd and what is the equation that links them all?
Ab: Amount of a drug in the body
Cp: Plasma concentration of a drug
Vd: Volume of distribution of a drug
Ab = Cp * Vd
If a drug has increased penetration into tissues, how does the Ab, Vd, Cp change?
Ab: constant
Vd: increases
Cp: decreases
(Half life also increases)
If the Vd > 5 what does that say about the drug?
Vd > 5 means the drug is not just in the blood
Vd < 5 means the drug is most likely contained within the blood
What are the two stages of getting a drug into the body?
Absorption
Distribution
What are the two stages of getting a drug out of a body?
Metabolism
Excretion
In hepatic metabolism what are phase I enzymes and what are phase II enzymes?
Phase I: Cytochrome-P450
Phase II: Transferases
Describe Phase I metabolism
Oxidative reactions to increase the charge on molecules (cannot pass membrane)
Some sufficiently polarised molecules will leave via kidneys
Some drugs are only activated by CYP450
Describe phase II metabolism
Add charged species to molecules (increasing the ionic charge and molecular weight)
Molecules with a molecular weight < 300 leave in the urine via the kidneys
Molecules with a molecular weight > 300 become bile in the (liver then) gallbladder
