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1
Permeation Solubility (lipid X water)
Concentration (generally down the
gradient free uniozed drugs
contributes to the gradient)
Suerface area and vascularity
2
Ionization For weak acids and bases:
ionized = water soluable (Renal
Cleared)
Nonionized = lipid soluable (Crosses
membrane)
3
,Draw the drug biodisposition chart
4
Draw the degree of ionization
clearence Vs pH deviation from pKa
5
Clinical Correlate - Lactulose and Lactulose --gut bacteria--> Lactid
Hepatic Encephalopathy Acid; this acidify the fecal masses
and estimulate the process of:
ammonia --> ammonium
most of nitrogen is concentrated in
fecal bacteria
, reduced urea production = reduced
entry of ammonia in portal blood
colonic ammonia - ureolysis +
metabolism of the intracolon
contents
6
How does ionization increase renal only free unbound forms of the drug
clearence of the drug? can be secreted
Nonionnized can suffer active
secretion and active/passive
reabsorption -> not secreted
Ionized are "trapped" in the filtrate ->
secreted
Acidifiation of urine -> increase
ionization of weak bases -> increase
in renal secretion
Alcalinization of urine -> increase
ionization of weak acids -> increase in
renal secretion
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