Pharmacokinetics - Absorption Flashcards
State different means of absorption from GI tract:
a. Passive Diffusion; b. Facilitated diffusion;
c. Active Transport; d. Endocytosis & Exocytosis
Definition of Absorption?
Transfer of drug from site of administration to blood stream.
What is the driving force for Passive Diffusion?
The concentration gradient across a membrane separating 2 body compartments.
Passive Diffusion means that the drug moves from _____ to ______.
A region of higher concentration to a region of lower concentration.
Give properties of Passive Diffusion:
- Does not involve a carrier.
- Is not saturable.
- Shows low structural specificity.
Which absorption mechanism allows access to a vast majority of drugs, to the body?
Passive Diffusion
Water soluble drugs penetrate the cell membrane through:
Aqueous Channel or Pores
Lipid-soluble drugs readily move across most biologic membranes due to:
Their solubility in the membrane lipid bilayers
Absorption through which, agents can enter the cell through specialized transmembrane carrier proteins that facilitate the passage of large molecules.
Facilitated Diffusion
Give Properties of Facilitated diffusion
- Carrier protein is involved which goes through conformational changes.
- It moves the drug from an area of higher to lower concentration.
- Can be saturated (via drugs that compete for the protein)
- Does not require energy.
Energy-dependent active transport in Active Transport, is driven by:
Hydrolysis of adenosine triphosphate
What is Active Transport?
A few drugs that closely resemble the structure of naturally occurring metabolites are actively transported across cell membranes using these specific carrier proteins.
Moved from an area of lower to higher concentration via Hydrolysis of ATP to ADP.
Is Active Transport Saturable?
Yes. Active transport systems are selective and may be competitively inhibited by other cotransported substances.
What is Endocytosis?
Transportation of an exceptionally large drug molecule through cell membrane.
How is drug molecule transported in endocytosis?
By engulfing of the large molecule via cell membrane and pinching of the drug filled vesicle.
What is the reverse process of endocytosis?
Exocytosis.
what is exocytosis used for?
For excretion of large molecules.
Give example of Endocytosis.
Vit B12 is transported across the gut wall via endocytosis
Give example of exocytosis.
Certain neurotransmitters (for example, norepinephrine) are stored in intracellular membrane-bound vesicles in the nerve terminal and are released by exocytosis
What are the factors influencing drug absorption?
- pH
- Blood flow to the absorption site
- Surface area
- Contact time with the absorption surface.
- Expression of p-glycoprotein.
A drug passes through the membrane more readily if it is:
Uncharged
_____ is the measure of strength of a compound with a proton.
pKa
Th lower the pKa, the more ____ the drug is, The higher the pKa, the more ______ the drug is.
Acidic ; Basic
For a weak acidic drug, which form can pass through the membrane. HA or A-
HA
For a weak basic drug which from can pass through the membrane. HB or B
B
Highly lipid-soluble drugs rapidly cross membranes and often enter tissues at a rate determined by:
Blood flow
Absorption is favored more from
a. Stomach
b. Intestine
b. Intestine
due to more blood flow and larger surface area
The surface area of intestine is _____ times more than the stomach.
1000 times
Severely reduces blood flow to cutaneous tissues, thereby minimizing the absorption from SC administration
Shock
In diarrhea, the absorption of drug is not well because:
The drug moves too quickly through GI tract, giving less time of contact.
The presence of ____ in the stomach both dilutes the drug and slows gastric emptying.
Food
A drug taken with a meal is generally absorbed:
a. more rapidly
b. more slowly
b. more slowly
Anything that delays the transport of the drug from the stomach to the intestine delays the:
Rate of absorption of the drug
_________ is a multidrug transmembrane transporter protein responsible for transporting various molecules, including drugs, across cell membranes
P- glycoprotein
Function of p-glycoprotein in Liver?
Transporting drug into bile for elimination.
Function of p-glycoprotein in Kidney?
Pumping drug into urine for excretion.
Function of p-glycoprotein in Placenta?
transporting drugs back into maternal blood,
thereby reducing fetal exposure to drugs
Function of p-glycoprotein in Intestine?
Transporting drugs into the intestinal lumen and
reducing drug absorption into the blood
Function of p-glycoprotein in brain?
Pumping drugs back into blood, limiting
drug access to the brain.
In areas of high expression, P-glycoprotein _____drug
absorption.
a. Increases
b. Decreases
b. Decreases
In addition to transporting many drugs out of cells, p-glycoprotein is also associated with _______
multidrug resistance
Bioavailability is:
The fraction of administered drug that reaches the systemic circulation
If 100 mg of a drug are administered
orally, and 70 mg of this drug are absorbed unchanged, the bioavailability is:
0.7 or 70%
Determining bioavailability is important for
calculating drug dosages for _____ routes of administration.
non-intravenous
Factors affecting bioavailability of a drug?
- Route of administration
- First pass hepatic metabolism
- Chemical Properties of the drug (chemical instability)
- Physical properties of the drug (solubility)
- Nature of drug formulation
Bioavailability is determined by:
Comparing plasma levels of a drug after a particular route of administration vs plasma drug levels after IV administration.
The ratio of the area calculated for oral administration compared with the area calculated for IV injection if doses are equivalent
Bioavailability
Equation for bioavailability =
AUC Oral
————– x 100
AUC Injected
After oral administration, The drug absorbed from GI tract, enters in portal circulation instead of Systemic circulation. This is called:
The first pass effect
Give an example of a drug with low oral bioavailability due to first pass.
NITROGLYCERINE
(more than 90% is cleared during a single passage through Liver.
So it is instead administered Sublingually)
Very hydrophilic drugs are poorly absorbed because:
Inability to cross the lipid-rich cell
membranes
Extremely hydrophobic drugs are poorly absorbed because:
they are totally insoluble in aqueous body fluids, therefore cannot gain access to the cell surface
For a drug to be readily absorbed, it must be:
Largely hydrophobic, yet have some solubility in aqueous solutions.
i.e weak acid or weak base
_____ is unstable in the pH of the gastric contents.
Penicillin G
______are destroyed in the GI tract by degradative enzymes
Insulin
Two related drug preparations are__________ if they show comparable bioavailability and similar times to achieve peak blood concentrations.
Bioequivalent
Two similar drug products are ________ if they are pharmaceutically equivalent with similar clinical and safety profiles
therapeutically equivalent
Clinical effectiveness often depends on a. The maximum serum drug concentrations b. The time required (after administration) to reach peak concentration c. Both
Both
Two drugs that are bioequivalent may not be ________
therapeutically equivalent
Excipients such as binders and dispersing
agents can influence the ease of ________
Dissolution
