Pharmacokinetics Principles 2 (absorption and distribution) Flashcards
list the 4 steps of pharmacokinetics?
1- absorption.
2- distribution.
3- metabolism.
4- excretions.
the transfer of a drug from the site of administration to the blood stream
absorption of drugs.
absorption depends on 2 factors, what are they?
1- drug’s chemical characteristics.
2- route of drug administration.
what is the most importants site of absorption for orally administered drugs?
small intestine.
bioavailability for I.V delivery is ___%
100%
for absorption to happen drugs need to cross _______
biological membranes.
list the 4 mechanisms of absorption
1- passive diffusion.
2- facilitated diffusion.
3- active transport.
4- endocytosis and exocytosis.
in passive diffusion drugs move ____ (along, against) the concentration gradient?
along.
from higher conc. to lower conc.
which mechanisms of absorption don’t need energy?
passive diffusion and facilitated diffusion.
which mechanism of absorption is not saturable?
passive diffusion.
in facilitated diffusion carrier proteins undergo which type of change to transport drugs?
conformational change.
in facilitated diffusion, drugs move ____ (along, against) conc. gradient.
along the conc gradient, higher to lower.
which mechanisms of absorption are saturable?
facilitated diffusion and active transport.
facilitated diffusion is inhibited by drugs that ______ for the carrier.
compete.
in active transport, drugs move ____ (along, against) conc. gradient.
against.
lower to higher.
which mechanism of absorption is selective?
active transport.
active transport can be competitively ____ by other co-transported substances?
inhibited.
engulfment of the drug by the cell membrane and transport in the cell in a drug-filled vesicle.
endocytosis
endocytosis and exocytosis are used for the transport of drugs of ____ size across membranes
large.
_______ is absorbed by endocytosis from the GIT?
vitamin B12.
_________ are stored in vesicles and released by exocytosis?
neurotransmitters.
list the 5 factors affecting absorption?
1- pH.
2- blood flow to the absorption site.
3- total surface area available for absorption.
4- contact time at the absorption surface.
5- expression of P-glycoprotein.
ionized forms of drugs are _____ (lipid, water) soluble.
water
unionized forms of drugs are _____ (lipid. water) soluble.
lipid
__________ (ionized, unionized) form is better absorbed?
unionized.
A drug crosses biological membrane readily if it is ______
uncharged.
weak acids are unionized at _____ pH.
acidic
weak bases are unionized at ____ pH.
basic.
the pH at which the drug is 50% ionized
pKa of a drug.
the _____ pKa of a drug the more acidic it is
lower.
give an example of an acidic drug that gets largely unionized at gastric pH
aspirin
where are basic drugs absorbed from?
the intestine.
greater the blood flow to the absorption site the ____ is the absorption
more
shock ____ absorption from subcutaneous route.
decreases.
greater the surface area. ____ is the absorption
more
more is the contact time, _____ is the absorption
more
in areas of high expression.P-glycoprotein ______ drug absorption.
reduces.
P-glycoprotein is associated with what?
associated with multidrug resistance.
where is P-glycoprotein expressed?
liver, kidneys, placenta, intestines, and brain capillaries.
fraction of administered drug that reaches the systemic circulation in unchanged form
bioavailability
bioavailability is important for calculating drug doses for which administration route?
non-intravenous.
bioavailability of i.v given drug is ___%?
100%
list the 4 factors affecting bioavailability?
1- first- pass hepatic metabolism.
2- solubility of drug.
3- chemical instability.
4- nature of drug formulation.
bioavailability of penicillin and insulin when given orally is ___?
0%
how does first pass metabolism affect bioavailability?
the amount of drug that reach the systemic circulation in unchanged form is decreased.
90% of _____ (which drug?) is cleared during a single passage through the liver, which is why it is given through the ______ route.
nitroglycerine,
sublingual route.
for a drug to be absorbed it must be ___ in aqueous solutions.
soluble
drugs which are poorly soluble have ___ bioavailability.
low
list the 4 factors that influence the ease of dissolution?
1- particle size.
2- salt form.
3- enteric coatings.
4- presence of excipients.
2 related drug preparations are bioequivalent if the show _____________ and ____________________
complete bioavailability, and similar times to achieve peak blood concentration.
the process by which a drug reversibly leaves the blood stream and the extracellular fluid and tissues
drug distribution
list the 4 factors that affect drug distribution
1- differences in regional blood flow.
2- binding of drugs to plasma proteins and tissue proteins.
3- presence of tissue-specific transporters.
4- lipid solubility.
what is the most common protein drugs bind to?
albumin
redistribution happens only in ___ ____ soluble drugs.
highly lipid soluble drugs.
give an example of a drug that undergoes redistribution
thiopentone sod.
an anaesthetic.
the BBB limits the entry of _____ soluble drugs into the CNS.
non-lipid soluble drugs.
inflammation of the meninges _____ permeability of the BBB
increases.
acidic drugs bind to _____ (which protein?) and basic drugs bind to ______ (which protein?)
acidic = plasma protein.
basic = alpha 1 acid glycoprotein.
highly protein-bound drugs are ___ acting.
long
plasma protein binding is a ______ (reversible, irreversible) process
reversible.
irreversible binding of drugs can result in ____.
toxicity.
give an example of an irreversible binding of a drug that results in toxicity
the irreversible binding of paracetamol metabolites to the hepatocytes.
most drugs bind to which protein?
albumin
what is the most abundant plasma protein
albumin
what is the major source of drug and prolongs its action or cause local drug toxicity?
tissue reservoir
give an example of a drug that concentrates in tissues and can give drug toxicity?
tetracyclins
give an example of a drug that concentrates in tissues and can give drug toxicity?
tetracyclines
the volume that would accommodate all the drug in the body if the concentration throughout was the same as in plasma
apparent volume of distribution (Vd)
list the 3 compartments that take up the drug once it enters the body?
1- plasma compartment.
2- extracellular fluid.
3- total body water.
list the 6 factors that Vd depends on?
1- lipid solubility.
2- plasma protein binding.
3- tissue sequestration.
4- pKa of the drug.
5- age, sex, obesity, pregnancy.
6- diseases like CHF, uremia, cirrhosis.
drugs with ___ (high,low) of distribution are not easily removed by dialysis in case of poisoning
high
Vd is expressed by?
Vd= dose administered I.V / plasma concertation.
if a drug has a large Vd, most of the drug is in the _____ space and is unavailable to the ____ organs.
extraplasmic space.
excretory,
what does an extremely high Vd indicate?
that the drug is sequestered in some tissues.
