For a weak base, when the pH is less than the pK, the ionized form (protonated) predominates. When the pH is greater than the pK, the unprotonated (nonionized) form predominates.

In the stomach (pH 2.0), weak acids are uncharged and will be absorbed into the blood- stream, whereas weak bases are charged and will remain in the GI tract.

Bioavailability is the amount of drug that is absorbed after administration by route X compared with the amount of drug that is absorbed after intravenous (IV) administra- tion. X is any route of drug administration other than IV.

Clearance is a term that indicates the rate at which a drug is cleared from the body. It is defined as the volume of plasma from which all drug is removed in a given time. Thus, the units for clearance are given in volume per unit time.

Total body clearance is the sum of the clearances from the various organs involved in drug metabolism and elimination.

Volume of distribution (VD) is a calculation of the apparent volume in which a drug is dissolved.

Most drugs disappear from plasma by processes that are concentration-dependent, which results in first-order kinetics. With first-order elimination, a constant percentage of the drug is lost per unit time. An elimination rate constant can be described.

The half-life (t1/2) is the period of time required for the concentration of a drug to decrease by one half.

Clearance of a drug is different from the elimination rate.

Drugs that saturate routes of elimination disappear from plasma in a non–concentration dependent manner, which is zero-order kinetics.

Repeated dosing is associated with peak and trough plasma concentrations.

Important points of Drug Metabolism and Renal Elimination

-Liver Metabolism
-Renal Metabolism

Phase I reactions frequently involve the P-450 system. Phase II reactions are conjugations, mostly with glucuronide.

Renal elimination of drugs involves three physiological processes: glomerular filtration, proximal tubular secretion, and distal tubular reabsorption.

Important Note

When the pH is higher than the pK, the unprotonated forms (A− and B) predominate. When the pH is less than the pK, the protonated forms (HA and BH+) predominate.

Receptors for norepinephrine are divided into α and β receptors. These receptors are further subdivided, into α1 and α2, and β1, β2, and β3, respectively.

Contraction of the radial muscle (sympathetic innervation) causes dilation, or mydriasis (expected sympathetic response), while contraction of the circular muscle (parasympathetic innervation) causes constriction or miosis (expected parasympathetic response).

The heart is the main site for β1 receptors.

If a drug is specific for β1 receptors, its main effect will be on the heart. β1 Receptors are also involved in the release of renin from the kidney.

Activation of β2 receptors relaxes smooth muscle.

Activation of α receptors causes contraction or constriction, mostly vasoconstriction.