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.

Activation of presynaptic α2 receptors results in feedback inhibition of the release of norepinephrine.

Inhibition of presynaptic α2 receptors will increase the release of norepinephrine.

Direct-acting cholinergic agonists have a direct action on the receptor for acetylcholine. Some drugs are specific for the muscarinic receptor; others are specific for the nicotinic receptor.

The indirect-acting cholinomimetics act by blocking the metabolism of acetylcholine by cholinesterases. These drugs effectively increase the concentration of acetylcholine at all cholinergic synapses.

Activation of nicotinic receptors results in muscle contraction (fasciculations and weakness).

BETHANECHOL is used in the treatment of urinary retention.

The side effects of these drugs are directly related to their interaction with muscarinic receptors.

Nicotine is a direct agonist at nicotinic receptors.

EDROPHONIUM is used in the diagnosis of myasthenia gravis.

NEOSTIGMINE, PYRIDOSTIGMINE, and ambenonium are used in the treatment of myasthenia gravis.