Factors affecting drug absorption AND How these affect absorption

R S B L P

ü  Rate of dissolution 

o   Faster it dissolves the faster it is absorbed

o   Liquids tend to be absorbed faster than the solid form

o   Suspensions - Preparations of solid drug suspended in some liq will go into solution much faster

ü  SA:  larger the SA, faster it is absorbed (ie micro villi)

ü  Blood flow:   Increased blood flow, increases abs b/c it determines rate it is delivered to a tissue

ü  Lipid solubility

o   Lipid-soluble drugs are more quickly absorbed b/c they can readily cross the membranes that separate them from the blood

ü  pH of environment

o   absorption is enhanced when the difference between the pH plasma & the pH SOA is so the drug molecules will have a greater tendency to be ionized in the plasma

§   Will be pass into cells at SOA, but not be able to pass into cells in plasma.

o   Acids -> ionize in alkaline media, looses H à (-) | Bases -> ionize in acidic media, gains H è (+)

ü  Drug is dependent upon the chemical properties of the drug

Polar vs nonpolar; ionized vs non-ionized & relationship to mvmt across cell 

ü  Ionized – polar (electrically charged) – do NOT diffuse easily across lipid membranes

ü  Non-ionized – nonpolar – are soluble in lipids and are easily absorbed across lipid membranes

Effect of pH on drug movement across cell membranes

Drugs molecules accumulate on the side of a cell membrane that favors ionization b/c it cannot pass through cell; (ion trapping) acidic side of a membrane do not allow alkaline drugs b/c they are ionized and visa versa --- ie basic drug not absorbed in acidic stomach

Clinical use of manipulation of pH to affect pharmacokinetic processes

Some meds can alter the environment of the kidneys to prevent absorption or increase absorption. 

Factors influencing distribution

"Think Plasma Protien"

ü  Plasma Protein binding

o   Non specific

o   Bound vs free drug (binding is reversible & alters amt of free drug to be distributed)

o   Displacement (by drug that have a higher affinity)/ relative binding

Clinical implications of protein binding

ü  Pt w/ hypoalbuminemia – experience more response from a drug

ü  Must be conscious of relative binding affinity of a drug. Primary drug can be displaced by a secondary drug with higher affinity, increasing amt of primary drug in the blood

5 consequences of drug metabolism 

(PETIT)

1.     Accelerated drug excretion (we change the drugs lipid solubility à polarity – so when drug gets to kidney it can’t be reabsorbed across the membrane and must get excreted out) 

2.     Drug Inactivation – active drugs may transform into inactive form

3.     Increased Therapeutic Action – drug transforms into more effective form (codine à Morphine)

4.     Activation of Prodrugs – inactive drug metabolized into active drug (may protect from 1^st  pass)

5.     Toxicity Variations – drug metabolized into inactive TOXIC form

Role of lipid solubility (& water solubility) in metabolism and excretion

ü  Increase in water solubility, decrease in lipid solubility, more easily excreted in urine

Enzyme induction

Increase metabolic enzyme production \ greater metabolism of other drugs &/or themselves

o   Drug tolerance: (form of enzyme induction) it can be produced by enzyme induction - decreased response to a particular drug dose

Drug excretion in the kidney 

Glomerular Filtration (1)

ü  Filtration moves unbound drugs from blood to urine

ü  Protein-bound drugs are not filtered and stay in the blood

ü  Lipid soluble drugs move back into the blood.

ü  Polar and ionized drugs remain in the urine

ü  ionization depends upon the pH - change in pH of the urine will affect drug excretion

o   Ie.. ASA in acidic urine is non-ionized & reabsorbed; to rid ASA give NaHC0₃

o   Ie… Cranberry juice make urine acidic, and would help us excrete basic drug

Drug excretion in the kidney 

Active Tubular Secretion (3)

ü  There are active transport systems in the kidney tubule that pump drugs from the blood to the tubular urine. 2 sets of pumps (1 for organic acids & 1 for organic bases)

ü  Tubule cells also contain P-glycoprotien, which can pump a variety of drug into urine

o   Ie: probenecid jams up pumps that would excrete penecillin ® it competes with penicillin\ may be administered  together to ­ blood penicillin levels 

 Essential Info on a MAR

ü  Dates

ü  Med Info (pt name, dose, route, frequency)

ü  Initials

ü  Special instructions