A drug is any substance that, when absorbed into the body of a living organism, alters normal bodily function.
Routes of Drug Administration:
1. Enteral route:
Oral
Sublingual
Rectal
2. Parenteral :
Intravascular (I.V)
Intramuscular (I.M)
Subcutaneous (S.C)
3. Other:
Inhalation
Intranasal
Intrathecal (injection into the spinal canal )
intradermal
Topical
Most drugs gain entry to cells by passive diffusion with 1st order kinetics
The passive flux of molecules down a concentration gradient is given by Fick’s Law:
Flux(molecules per unit time)=
(C1-C2)x area x permeability coefficient
thickness
Where:
C1 is the higher concentration, C2 is the lower concentration
area is the area across which diffusion is occurring,
permeability coefficient is a measure of mobility of the drug molecules in the medium of the diffusion path, and thickness is thickness of diffusion path.
Ionization
Many drugs are weak acids or weak bases and can exist in either non ionized or ionized forms in an equilibrium depending on the p H of the environment and their p Ka (the p H at which the molecule is 50 % ionized and 50% nonionized ).
Only the non ionized (uncharged) form of a drug crosses biomembranes.
· Ionized = water soluble
· Non ionized=lipid soluble
· acidic media: p H < p Ka
· basic media p H >p Ka
Weak acid =
R.COOH ßà R.COO- + H+
(cross membranes)
Weak base =
R.NH3+ ßà R.NH2 + H+
(protonated weak base) (cross membranes)
Weak acids:
· Aspirin
· Salicylic acid
· Ibuprofen
· Phenobarbital
· Acetazolamide
Weak bases :
· Atropine
· Cocaine
· Codeine
· Morphine
Only nonionized forms of drug undergo active secretion and active or passive reabsorption
Change of urinary pH:
· Acidification of urine à increases ionization of weak bases àincreases renal elimination.
· Alkalization of urineàincreases the ionization of weak acids àincreases renal elimination.
TO CHANGE URINARY pH
· Acidify :NH4Cl, vitamin C, Cranberry juice
· Alkalinize: NaHCO3
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