Robinul

ROBINUL Info

Glycopyrrolate Info [] fda site __Katsung__ (pg153) Glycopyrrolate (generic, Robinul) Oral: 1, 2 mg tablets Parenteral: 0.2 mg/mL for injection (pg167) __Stoeling & Hiller__ 10 Anticholinergic drugs competitively antagonize the effects (parasympathetic) of the neurotransmitter acetylcholine at cholinergic postganglionic sites designated as muscarinic receptors (Stoelting RK, Hillier SC. Anticholinergic drugs. In: //Pharmacology and Physiology in Anesthetic Practice,// 4th ed. Philadelphia. Lippincott Williams & Wilkins, 2006:266-275). Muscarinic cholinergic receptors are present in the heart, salivary glands, and smooth muscles of the gastrointestinal and genitourinary tract. Acetylcholine is also the neurotransmitter at postganglionic nicotinic cholinergic receptors (nAChRs) located at the neuromuscular junction (NMJ) and autonomic ganglia. In contrast to the effects at muscarinic receptors, usual doses of anticholinergic drugs exert little or no effect at nAChRs. As such, anticholinergic drugs may be considered to be selectively antimuscarinic. Naturally occurring anticholinergic drugs (atropine and scopolamine) are esters formed by the combination of tropic or mandelic acid and an organic base (tropine or scopine). Like acetylcholine, anticholinergic drugs contain a cationic portion that can fit into the muscarinic cholinergic receptor. Anticholinergic drugs combine reversibly with muscarinic cholinergic receptors and thus prevent access of the neurotransmitter acetylcholine to these sites. As competitive antagonists, the effect of anticholinergic drugs can be overcome by increasing the concentration of acetylcholine in the area of the muscarinic receptors. Five distinct muscarinic receptor subtypes, with recognized tissue distributions, are designated M1-M5 (Table 10-1). Muscarinic cholinergic receptors are examples of G protein-coupled receptors that also depend on second-messenger coupling. Muscarinic cholinergic receptors that control salivary and bronchial secretions (M3 receptors) areinhibited by lower doses of anticholinergic drugs than are necessary to inhibit receptors that regulate acetylcholine effects on the heart and eyes (M2 receptors). Even larger doses of anticholinergic drugs are needed to inhibit gastric secretion of hydrogen ions (M1 receptors). As a result, a dose of anticholinergic drug that inhibits the gastric secretion of hydrogen ions invariably affects salivary secretions, heart rate, ocular accommodation, and micturition. Examples of differences in anticholinergic potency between drugs are the greater antisialagogue and ocular effects of scopolamine compared with atropine (Table 10-2). Atropine, scopolamine, and glycopyrrolate do not discriminate among M1, M2, and M3 receptors; instead, they act as highly selective competitive antagonists of acetylcholine at all muscarinic receptors. The paradoxical slowing of heart rate that may follow the administration of anticholinergic drugs most likely reflects a blockade of presynaptic inhibitory M1 receptors on vagus nerve endings that usually provide negative feedback on further acetylcholine release. Intravenous or intramuscular administration is used most often for the delivery of anticholinergic drugs. Atropine and scopolamine are lipid-soluble tertiary amines that easily penetrate the blood-brain barrier, whereas glycopyrrolate is a poorly lipid soluble quaternary ammonium compound with minimal ability to cross the blood-brain barrier and produce CNS effects. (pg 200 CH10)
 * Anticholinergic Drugs **
 * STRUCTURE-ACTIVITY RELATIONSHIPS **
 * MECHANISM OF ACTION **
 * PHARMACOKINETICS **