GP 11 - Pharmacokinetics 1 Flashcards
Define drug absorption and distribution
Absorption - transfer of a drug from its site of administration to the blood stream.
Distribution - the process by which a drug leaves the blood stream and enters the ECF and/or cells of the tissues
List the mechanisms of drug permeation.
- Aqueous diffusion (paracellular pathway)
- Lipid diffusion (transcellular pathway).
- Specifal Carriers.
- Endocytosis/Exocytosis (transcytosis)
List and briefly describe the enteral routes of drug administration. Comment on the absorption efficacy of each route
- Oral - drug is swallowed, most convenient but slowest absorption.
- Sublingual - drug dissolves under the tongue and enters the blood stream directly.
- Rectal - better absorption than oral but not as good as sublingual
List and briefly describe the parenteral routes of drug administration.
- Intravenously - complete absorption.
- Intramuscularly - administered into the muscle under the subcutaneous tissue.
- Subcutaneously - administered into the subcutaneous tissue.
- Intradermally - administered into the dermis.
- Oral Inhalation.
- Nasal Inhalation.
- Transdermal - applied to and absorbed across the skin.
- Topical - applied to the skin at its site of action.
What is the first-pass effect?
For drugs taken orally, a fraction of the drug is metabolized in the gut wall and liver before reaching systemic circulation. This also partially occurs for drugs taken rectally
What are the major factors that influence drug absorption?
- pH.
- Surface area available.
- Blood flow to the absorption site.
- Contact time at absorption site.
- P-glycoprotein
Which forms of weak acids and bases are ionized and non-inoized
HA → A- + H+
BH+ → B + H+
What is the henderson-hasselbach equation?
pH = pK + log [unprotonated]/[protonated]
What is the logarithm definition?
log10(x) = y
where 10y = x
When is the pH of a body compartment most important to pharmacokinetics? Explain why
During elimination of a drug via urine. The pH of the urine will determine if the drug is in its ionized or non-ionized form. If it’s in the non-ionized form, a significant portion of it will be reabsorbed across the renal tubules.
Where does the majority of drug absorption take place when a drug is taken orally? Why?
The small intestine because that is where the maximum surface area and blood flow is
What is P-glycoprotein also known as and why is it important to pharmacokinetics?
P-glycoprotein (MDR1) is a transporter protein that transports many different kinds of drugs out of cells, reducing drug absorption.
What is bioavailability?
The fraction of the administered dose of a drug that reaches systemic circulation
What variable is used to represent bioavailability? How is bioavailability determined?
- Plasma [drug] is plotted against time for a particular route of administration.
- Plasma [drug] is plotted against time for IV administration.
The area under the curve (AUC) of these graphs represents the extent of absorption, which is always 100% for IV administration. Therefore, the bioavailability (F) is then calculated by dividing the first AUC by the IV AUC and multiplying by 100 to get a percentage.
What are the major factors that influence bioavailaability?
- Drug Formulation.
- Chemical Instability.
- Food and Drug Interactions.
- First Pass Hepatic Metabolism.
- Drug Solubility.
- P-Glycoprotein
When are drugs considered to be pharmaceutically equivalent? When are they considered to be bioequivalent? Why is this distinction important?
If they contain the same active ingredient, are identical in concentration/dosage form, and are given by the same route of administration. Drugs are said to be bioequivalent when their concentration-time plots are superimposable. Only when two drug preparations are bioequivalent can they safely replace each other.
What factors are the major determinants of the amount of a drug that distributes into the tissues?
- Blood Flow
- Drug binding to plasma proteins
- Tissue binding
- Drug liposolubility
Which organs usually receive a drug first?
Liver, Kidney, Brain, and other well perfused organs
What are the primary plasma proteins drugs bind to? How does this affect distribution?
Acidic drugs bind to plasma albumin
Basic drugs bind to α1-acid glycoprotein
Plasma protein binding slows distribution
Where in the body does paracellular transport not occur? What does this mean for drug distribution?
The blood brain barrier (BBB)
It means that durgs must cross the BBB transcellularly which means they either have to be liposoluble or have a carrier that can transprot them across
