I'm having trouble with this in my mind...
I understand that if a drug with a pKa of say 7.4 were put into plasma with a pKa of 7.4, then 50% of the drug will be unionized and 50% will be ionized; the unionized form crosses membranes easier while the ionized doesn't (which is good or bad, depending on what action we want from the drug); the part I'm having trouble with is "at what pH is the drug more unionized vs ionized?"
alfentanil has a pKa of 6.5; does this mean that when injected into a body pH of 7.4 = more unionized which = faster onset?
for lower pKa drugs to be more unionized, do they need to be injected into closer to normal body pH's?
This is probably very simple, but I'm stuck and I don't have my G&G's with me today; can you guys please help...I can't see the forest from all the trees today!
[color=#660033][font=新]principle of lechaterlier
[font=新]( if the conditions of a system[font=新], originally in equilibrium, are changed, the new equilibrium shifts [font=新]in such a direction as to restore the original conditions).
[font=新]for a weak acid
[font=新]ah «[font=新] a[font=新]-[font=新] +h[font=新]+
[font=新]if [h[font=新]+[font=新]] increase[font=新](ph becomes lower) the reaction will be driven to the [font=新]left by mass action, and the proportion of drug in the nonionized form [font=新]will increase and, hence, the number of lipid soluble molecules. (acid in acid yields unionized, acid in base yields inonized)
[font=新]for a weak base, the dissociation equilibrium is
[font=新]bh [font=新]+ «[font=新] b +h[font=新]+
[font=新]if [h[font=新]+[font=新]] increases [font=新]the proportion of drug in the ionized form will [font=新]increase. (base in acid yields ionized, base in base yields unionized)
a[font=新]. for a [font=新]weak acid[font=新], when the ph is < the pk, the protonated form
[font=新](nonionized) predominates. when the ph is > the pk, the unprotonated [font=新](ionized) form predominates.
[font=新]b[font=新]. for a [font=新]weak base[font=新], when the ph is < the pk, the protonated form
[font=新](ionized) predominates. when the ph is > the pk, the unprotonated
[font=新](unionized) form predominates.
[font=新]c[font=新]. in the stomach (ph 2.0), weak acids are uncharged and will be [font=新]absorbed into the bloodstream, whereas weak base are charged and will [font=新]remain in the gi tract.
Last edit by mwbeah on Jan 29, '05