Lecture 34 & 35 Flashcards
Pharmacokinetics are the ____steps of the drugs, from absorption
Pharmacokinetics are the first steps of the drugs, from absorption
ADME stands for:
Absorption
Distribution
Metabolism
Excretion
Oral - __ _____- portal vein - _____
This is problem as the ____may inactivate the majority of the drug
Oral - GI tract - portal vein - liver
This is problem as the liver may inactivate the majority of the drug = hepatic first pass
Injections can be:
injections can be
venous
muscular
arterial (uncommon)
Crossing the epithelium, what are the ways in which this can happen?
Through aqueous channels (size and charge limitation)
Across cell membrane (lipid soluble)
via Transporters
Diffusion
The fastest method of cell absorption is?
Lipid soluble diffusion
true or False:
The uncharged species of a drug are much more likely to be lipid soluble than a charged species
True
Aspirin is a weak acid - can change to a ______species in the blood - pH trapped
Aspirin is a weak acid - can change to a charged species in the blood this
Endothelial cell in capillary is continuous except for little _____
Endothelial cell in capillary is continuous except for little vesicles
Fenestrated capillaries are leaky, the leak
whatever is in the blood,
in both directions
Where do you get Fenestrated capillaries
Kidneys, intestines and Liver
Brain capillaries have
tight junctions
What are the two ways drugs can enter the brain then?
Be lipid soluble or use a transporter, like those used to transport Glucose (GLUT 3?)
Fat has a ____blood flow
low
With a single capillary (from a drug distribution perspective), the rate of delivery will be depend on __________ and _____
High flow - delivery only dependent on ___________in the blood
Low flow - dependent on _____
With a single capillary (from a drug distribution perspective), the rate of delivery will be depend on concentration and flow
High flow - delivery only dependent on concentration in the blood
Low flow - dependent on both
Thiopental is ___-___ dependant
Thiopental is blood-flow dependant
high blood flow in blood - goes in readily.
then leaves after a period of time and disperses around the body (particularly in the fat - high affinity for lipids)
Protein binding affects drug distribution and __________
Protein binding affects drug distribution and clearance
Tends to have a longer half-life in the blood
Thyroxine - ___% protein bound in the plasma
99.96%
Aspirin is readily absorbed into the ______ ____ circulation
Higher conc. in the ______ blood than in systemic circulation so, _____dose is effective in the portal blood
– then acts to acetylate COX in platelets.
Aspirin is readily absorbed into the hepactic portal circulation
Higher conc. in the potrtal blood than in systemic circulation so, low dose is effective in the portal blood
– then acts to acetylate COX in platelets.
Hepatic metabolism:
_______drugs
________drugs (prodrugs)
Makes drugs more easily excreted by the _______
Hepatic metabolism:
Inactivates drugs
Activates drugs (prodrugs)
Makes drugs more easily excreted by the kidneys
2 Types of reactions in liver, phase 1 and 2:
Phase 1 - modification of _______ ____
Phase 2 - attachment of ______derivative 3 (enhances water solubility)
2 Types of reactions, phase 1 and 2
Phase 1 - modification of functional group
phase 2 - attachment of sugar derivative 3 (enhances water solubility)
Secretion is the ______pumping of solutes into the _______
Secretion is the active pumping of solutes into the filtrate:
organic cation transporters
organic anion transporters.
Secretion can also occur in the ______, where drugs are pumped into the _____- then reabsorbed.
Secretion can also occur in the liver, where drugs are pumped into the bile - then reabsorbed.
Lipid soluble drugs tend to be eliminated inefficiently in the _____, because they come back out of _____in into the blood.
Why the liver is also important - to make _____soluble.
Lipid soluble drugs tend to be eliminated inefficiently in the kidney because they come back out of urine in into the blood.
Why the liver is also important - to make water soluble.
Bioavailabilty is the fraction of the drug reaching ______circulation that is administered.
Bioavailabilty is the fraction of the drug r4eaching systemic circulation that is administered.
What are some things that can affect bioavailability?
intestinal transit time
stomach emptying time (acid secretion can be inhibited to help)
for destruction:
hepatic disease
competition between drugs and enzymes
enzyme inhibitors
Volume of distribution is:
amount of drug in body / plasma drug concentration
the volume which would have to hold the amount of drug in the body for it to be at a concentration equal to the plasma drug concentration
V (d) is influenced by:
Protein distribution
Access to body compartments
Lipid solubility
