-
KOW
octanl; water partitioning coefficent that tels you how lipid soluble a chemical is, the drug is added to water and octanol and is then measured to see how much is in the water or octanol phase
-
octanol
a surrogate for fat
-
Log KOW is 1
drug is water soluble
-
Log KOW is 10
the drug is lipid soluble
-
Most drugs have a KOW of?
log KOW of 1-4; most drugs are not lipid soluble because if it was lipid soluble then it would go to the fat which is distributed to the whole body
-
Ibuprofen with a pH 1 has a log KOW of? ph 7?
- pH 1 log KOW: 3-4
- pH 7 log KOW: <1
-
charge equates the
lipid solubility fo the drugs
-
Bioavailable drug
the amount of drugs that reaches blood stream; ex. propanolol ~20% Bioavailable dose of propanol
-
Passive diffusion
route that most drugs take; some drugs are so small they can diffuse through nuclear pores such as ethanol
-
Henderson-Hasselbalch equations
-
Benzoic acid
pH 1 then 99.9% of it is neutral/nonionized form so it will absorb easily in acidic environment (stomach)
-
Absorption in lungs (asthma)
does not take long because doesn't need to diffuse 100% of what is inhaled goes into the body
-
Absorption through the skin
most drugs can't penetrate into the blood by the skin
-
Factors affecting absorption
EDTA or co-solvents can increase absorption
-
3 factors limiting absorption
GI motility (are you eating? is your stomach active?), blood flow, and gastric emptying
-
GI motility example
you take a drug and then you eat something, the food will push the drug to the small intestine therefore the drug won't work
-
Surface area can also limit absorption because
the intestines contain many folds (everyone has different number of folds in the intestine)
-
Why do people have to sometimes take food siwth drugs?
to prevent ulcers
-
Volume of distribution (VOD)
measure of how widely distributed a drug is in the body. this measure tells us where the drug goes
-
VOD equation
dose/[] in plasma ; we usually don't want a drug to distribute all over the body
-
Drugs can be stored in:
plasma proteins (esp. albumin protein), liver and kidney, bone, fat and hydrophobic components
-
Drugs bound to albumin
increases the residence time in plasma
-
Drugs unbound to albumin
goes to the liver and tissues
-
Cmax depends on
absorption, distribution, metabolism, and excretion
-
Kidney
recieves 25% of CO and some drugs can be actively secreted into glomerulus into tubules
-
-
First-pass metabolism
when the drug goes from the large intestine back to the liver through the portal vein
-
Enterohepatic circulation
drug being reabsorbed in liver (ex. birth control drug); we are not able to control it but it is important to be aware of it
-
What is a good VOD?
the smaller the VOD the better. usually durgs are less than or equal to 3 are good. if the VOD value is closer to the value fo the plasma concentration the drug is more effective
-
Drugs that have a VOD less than or equal to 3
heparin and insulin
-
Drugs that have a VOD greater than 20
diazepam (valium) and ethanol (vod of 40-50)
-
Why does ethanol distribute so well?
it is so small so it has the ability to travel through pores
-
Distribution
blood flow and solubility
-
Most profused organs
brain, liver, kidneys, lungs and heart
-
Metabolism
generally happens int he liver but many other tissues are also metabolic
-
Liver metabolism
detoxification and bioactivation
-
The two stages of metabolism
Phase I and Phase II
-
Phase I of metabolism
oxidation, reduction, hydrolysis; most drugs go through this phase to make it more reactive
-
Phase II of metabolism
conjugation enzymes; phase II is to make drugs more water soluble to be eliminated easily
-
Phase I enzymes
alcohol dehydrogenase
-
Cytochrom P450
superfamily (there are subgroups such as CYP450 1 and CYP450 2) of heme containing proteins; contained in the endoplasmic reticulum
-
Induction causes enzymatic activity to increase or decrease?
increase
-
Scenario: if drug A induces CYP450 1 and drug B is metabolized by CYP450 1 then what effect will this cause?
if they are taken together drug B will be metabolized faster so the therapeutic affects of it are shorter
-
Inhibition causes enzymatic activity to increase or decrease?
decrease
-
Scenario: if drug A inhibits CYP450 1 and drug B is metabolized by CYP450 1 then what effect will this cause?
if they are taken together then drug B cannot be metabolized which increases half life of body
|
|
