Re: How do drugs taken intranasally get into the bloodstream & affect the body?

First, this answer would also apply to any other mucosal surface such as 
the mouth, e.g. nitroglycerin for angina is taken by placing the tablet 
under the tongue.

Mucosal surfaces are a) relatively large and b) have a fairly large blood 
flow.  This provides a large surface area from which to absorb a drug and 
subsequently, access to the blood for rapid distribution throughout the 
body.  So the problem is not distribution, but how does a drug get through 
the mucosal layer and the blood vessel into the bloodstream?  The answer 
is exactly the same as for a drug in the small intestine. (Orally 
administered drugs are primarily absorbed in the small intestine, not in 
the stomach.)  Absorption of a drug depends in general on a) passive, non-
ionic diffusion of the drug through the membrane (>95% of all drugs) and 
b) specific transport of a drug by a transport system, usually because the 
drug is an analog of some normal compound in the organism.

What is passive, non-ionic diffusion?  Drugs are chemicals obviously and 
as such that have groups on them that can be ionized or are polar/non-
polar. (Think of polar as a partial charge separation between two atoms.  
In a compound with a carbonyl group, the oxygen is partially charged 
negatively since it attracts the electrons, which the carbon is partially 
postively charged because the electrons have been attracted to the oxygen.)

If a compound is charged, it generally CANNOT pass through a membrane.  
The membrane is a hydrophobic barrier (water phobia or dislike of water, 
e.g., grease).  Charged compounds cannot pass through it or become 
dissolved in it.  As an example, if you mix a salt (sodium chloride) 
solution with olive oil, not only do the oil and water not mix, but if you 
measured the content of sodium or chloride ions in the olive oil, you 
would find only a very, very ,very small amount, for practical purposes 
zero, since the charged ions are not soluble in a hydrophobic 
environment.  Charged compounds like salt are far happier in a hydrophilic 
(water liking).  

So, if a drug is NOT charged, some part of it will be able to dissolve in 
the mucosal membrane and get into the blood.  Since as soon as it is in 
the blood, it is swept away throughout the body, the concentration 
gradient of the drug is still high at the mucosal membrane and very low at 
the blood vessel membrane.  This means the the drug will continue to 
diffuse from a region of high concentration to low concentration and will 
this eventually be absorbed.

What about a charged compound?  Well, that depends on the pH of the 
environment (usually about pH 6-7).  pH is the proton concentration.  Thus 
at pH 7, the proton concentration is 10-7 M or 0.1 micromolar.  A charged 
compound in aqueous solution is in equilibirum with the proton in the 
solution.  Some portion of the compound will be uncharged.  If the pKa 
(affinity of proton for the compound) of the compound for proton is 7 and 
the pH is 7, then 50% is charged and 50% is uncharged.  The 50% that is 
uncharged is then able to cross the mucosal membrane and eventually get to 
the blood.  Exactly the same thing applies even if the pKa is, for example 
3. In that case, at pH 7, almost all the compound will have proton bound.  
If the compound is a weak organic base, then most of it will be charged.  
BUT, there is a small part (10-fold for each log difference in pH and pKa, 
so 4 logs (pH of 7 and pKa of 3) would mean a 10e4 or 10,000-fold 
difference.  That very small portion of the drug that is uncharged could 
pass through the mucosal membrane and get into the blood.  Since there is 
now, at the microscopic level, no uncharged compound left in solution 
outside the mucosa, by the Law of Mass Action, some of the charged 
compound will very rapidly (essentially instantaneously) lose a proton and 
become uncharged, reestablishing the equilibrium.  Then the process starts 
over again.

In summary, uncharged compounds can pass through a hydrophobic barrier 
like the membrane by passive diffusion (passive,"non-ionic" diffusion 
since we are talking about an uncharged compound in a hydrophobic 
environment.  Only uncharged compounds can do so.