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pharm
1/8/98 1-2
Robinson

Pharmacokinetics
							
over the 
next two days we'll get a view of the useful parts of pharmacokinetics. 
we'll find out that things are pretty simplified so we don't have to get 
into the awful mathematics of this. what will happen is that today, he'll 
create a table on the board, that is the essence of the information we 
need. something new this year - he'll create another handout that will be 
useful, and then tomorrow, he will create a third table that covers all 
the math we're going to need for this. so he'll do that as we move along, 
to reinforce basic principles. before then, he has to explain why this is 
important. what we're going to find is that drugs have an effect, and 
that effects are characterized by dose/response relationships. in 
summary, looking at a log curve, with dose on x axis and effect on y axis 
you get an s curve type of thing and you get therapeutic effects in one 
dose range, and toxic effects in another dose range. in general, you give 
drugs repeatedly over time, so you get a yo yoing curve when you graph 
with y=concentration and x=time, that hopefully stays within the 
therapeutic range of the drug and doesn't go into the toxic or 
subtherapeutic ranges.

dose/response relationships don't vary to as 
great an extent in different spp as do the pharmacokinetic principles.  
species variation is usually related to 
pharmacokinetic differences and 
not to pharmacodynamic differences. 

[note: handout contains all slides, 
and contains more info than we really need.]

example:

in cats, they do 
not metabolize aspirin anywhere near the rate that humans do. this slowed 
metabolism requires us to carefully consider the dosing regimen.

see 
diagram p 1 of handout - shows terms that will be used - bioavailability, 
distribution, clearance, pharmacokinetics, pharmacodynamics. all these 
factors are needed. say you give an anxiolytic - it must be absorbed, 
distributed into CNS, must have a certain bioavailability, then must be 
metabolized or cleared. ultimately, the concentration of drug at site of 
action is directly proportional to concentration at site of action, and 
it causes desirable and undesirable effects.


					______Species 
Variations______

Cats: have very slow metabolism of aspirin and similar 
drugs	
Ruminants: have rumens with acid pH (more alkaline than plasma) 
and long 				   retention time. Can trap weakly basic drugs in rumen.

Horse: hindgut fermenter - depends on colonic bacteria to digest some 
things
	   can't give something that kills colonic bacteria!



					
__Routes of Administration of Drugs__

PARENTERAL				ENTERAL	 			OTHER			


IV						PO					inhalation
IM						PRectum				intramedullary				
IP						
sublingual			transdermal
SQ											intrathecal (into CSF)
											
nasal

what makes a route of administration good or bad? 

ease of use, 
absorption rate (fast, slow, consistent, inconsistant), client 
compliance. 
						
PARENTERAL	absorbance			advantages			disadvantages				
	

IV 			instant			irritants ok to use.	irreversible, difficult
							
rapidly reach thera-
							peutic dose.

IM			variable								painful		
			
slow- oil
			rapid- aqueous

IP			variable/slow

SQ			slow			can 
manipulate rate		can cause tissue necrosis
							of absorption by 
changing
							formula, coinjecting
							a vasoconstrictor

ENTERAL		
absorbance			advantages			disadvantages	

oral		rel. slow			easy/painless		
may irritate GI tract
								cheap				gets digested in stomach
													
can be irregular - affected
													by presence of food, pH

rectal		
rel. slow								irregular		

sublingual	rapid				avoids first pass	
								
effect, easy			

OTHER		absorbence			advantages			disadvantages

inhaled		
rapid
nasal		rapid
transderm	slow/sustained		easy, painless
intrathecal	
rapid

Absorbance:

diffusion - drugs may be absorbed by diffusion. the 
rate of absorption is not saturable because it is not enzyme mediated or 
carrier mediated. 

a saturable process implies that some protein or 
carrier moves the drug across the membrane. This concept also affects 
distribution and excretion, because many drugs are excreted through 
kidneys, and often this is a carrier mediated process where drug or 
metabolite is transported across the membrane by a protein. 

properties 
of passive diffusion/absorption:
not saturable
depends on lipid 
solubility
depends on size of molecule and pH

Now, the lecture is over 
but we're going to reinforce the Henderson/Hasselbach equation before we 
leave.  he doesn't care if we know the equation or not. We should, 
however, consider how pH can affect absorption and refer back to species 
variation. 

Ok. So.

R-COO-


R-NH3+

most drugs we give will have an 
amino group or a carboxyl group. These drugs can be concentrated on 
different sides of a membrane, or be better absorbed, based on pH. The 
acid is more likely to be better absorbed in the acidic stomach, where it 
will be uncharged. It has a better chance of being absorbed in the 
stomach (assuming it will dissolve in the stomach) because it will accept 
a proton from stomach acid and become uncharged. 

The base is more 
likely to be absorbed in the intestine where environment is basic, 
because it will donate a proton and become uncharged.


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