pharmacology II Flashcards
what is a drug?
any substance that brings about a change in biologic functions through its chemical actions
what is a medicine
a subset of drugs used for selective, therapeutic effects
what is a xenobiotic
chemicals not synthesized in the body
absorption if affected by what four things
route of administration
blood flow
drug characteristics
cell membrane characteristics(diffusion or active transport)
what are some drug characterisitcs
lipid or water soluble size of molecule formulation concentration acidity
passive transfer methods
filtration
water soluble molecules small enough to pass through membrane channels
passive transfer methods
simple diffusion
lipid-soluble drugs across lipoprotein membranes
***only non-ionized drugs are soluble in lipid
specialized transport methods
active transport
facilitate diffusion
what is bioavailability
the fraction of unchanged drug reaching the systemic circulation following administration by any route
what affects bioavailability?
dissolving of drug in the GI tract
destruction of drug by the liver
how much of a drug is bioavailable if delivered intravenously?
100%
what two things are important determinants for determining dose to be administered to a patient?
distribution and clearance
what is volume of distribution?
the measure of the apparent space in the body available to contain a drug
V=amount of drug in body/concentation
volume of plasma
3L
volume of extracellular space
14L
volume of total body water
42L
as the volume of distribution gets bigger the drug is more or less restricted?
more restricted because less of it is found through out the body thus a small concentation
drugs with very high volumes of distribution have much higher concentrations in extra vascular tissue than where?
in the vasculature compartment
drugs that are completely retained within the vasculature compartment would have a minimum possible volume of distribution equal to the blood component in which they are distributed. T/F
true
eg. 3.0L for a drug that is restricted to the plasma compartment
if the volume of distribution is much greater than 40-50L, the drug is probably being concentrated where?
in tissues outside the plasma and interstitial fluid
what is clearance
- the process of drug elimination form the body or from a single organ without identifying the individual processes involved
- clearance=rate of elimination/concentration of drug
- mL/min or L/hr
t1/2 is =?
0.693 Volume of distribution/clearance
how are drugs cleared?
urine (mostly)
feces(some)
lungs
salivary glands, sweat and hair (small amount)
drug transporters
solute carrier (SLC) transporters ie OCTs and OATs ATP binding cassestte (ABC) transport ie p-glycoproteins
what do p-glycoprotiens do?
transports drug molecule from cells back into the intestinal lumen for excretion
half life
time it take to eliminate 50% of drug
after 4.5 half-lives, how much remains assuming 1st order kinetics?
95%
t1/2-0.693 Vd/Cl
zero order
a constant amount of drug is eliminated per unit time. The process that takes place at a constant rate INDEPENDENT of drug concentration involved in process
eg 100%->80%->60%->40%
first order
the process that is DIRECTLY proportional to the drug concentration involved in process
eg. 100%->90%->81%->72%->64% or 5->2.5->1.25
metabolism of drugs does what?
inactivates
makes it more hydrophilic
makes it less toxic
phase II can come before phase I
what is phase I
oxidation, reduction and hydrolysis
phase I metabolites that are hydrophilic are excreted all others go to phase II
what is phase II
Includes glucuronidation and glutathione conjugation thus making drug more hydrophilic
cytochrome p450
heme containing enzyme primarily found in liver hepatocytes and small intestine enterocytes
-key for drug oxidation, biotransformation, and detox
substrate
a drug that is the target of a particular enzyme
inducer
increases the activity of a particular p450 enzyme and thus increases metabolism and clearance of a drug
inhibitor
inhibits the activity of a particular p450 enzyme and thus decreases metabolism and clearance of a drug
-grapefruit juice
types of conjugation of phase II
there are 7
glucuronidation acetylation glutathione glycine sulfation methylation water conjugation
factors that affect hepatic drug metabolism
microsomal enzyme inhibition of CYP450
microsomal enzyme induction
plasma binding protein(if bound won’t enter liver)
liver disease
microsomes
purified liver endoplasmic reticulum
rough microsomes contain ribosome
smooth microsomes contain mixed function oxidases
smooth microsomes
NADPH-cyp450-oxidoreductase
Cyp450
