Central nervous system gastrointestinal drugs

Highly potent compounds advance to a battery of selectivity assays. Any clinical candidate must not only demonstrate effectiveness in the desired therapeutic area but lack side effects in other areas. A cardiovascular drug, for example, which patients may take for decades, should not show unwanted central nervous system, gastrointestinal, or respiratory activities. Comprehensive selectivity profiles in vitro and in vivo allow pharmacologists to compare and contrast potent compounds and thereby to choose among possible clinical candidates. Profiling reduces the number of candidates stiU further. 

Clinical signs and symptoms of toxicity are related to the overstimulation of muscarinic, nicotinic, and central nervous system receptors in the nervous system. Muscarinic receptors are those activated by the alkaloid drug muscarine. These receptors are under the control of the parasympathetic nervous system, and their hyperactivity results in respiratory and gastrointestinal dysfunction, incontinence, salivation, bradycardia, miosis, and sweating. Nicotinic receptors are those activated by nicotine. Hyperactivity of these receptors results in muscle fasciculations even greater stimulation results in blockade and muscle paralysis (Lefkowitz et al. 1996 Tafliri and Roberts 1987). Hyperactivity of central nervous system receptors results in the frank neurological signs of confusion, ataxia, dizziness, incoordination, and slurred speech, which are manifestations of acute intoxication. Muscarine and nicotine are not... 

Cartwright [124] reported that miconazole was slightly absorbed from epithelial and mucosal surface. The drug is well absorbed from the gastrointestinal tract, but caused nausea and vomiting in some patients. The drug may be given intravenously but was associated phlebitis. Up to 90% of the active compound was bound to plasma protein. Distribution into other body compartments was poor. Metabolism was primarily in the liver, and only metabolites were excreted in the urine. At therapeutic levels, they were relatively nontoxic both locally and systematically, but occasionally produced disturbances on the central nervous system. 

Principal side effects are gastrointestinal and central nervous system symptoms, including drowsiness, dizziness, and diarrhea. Zolpidem may increase the depressant effects of other sedative drugs, such as the an-tipsychotics, tricyclic antidepressants, and antihistamines. 

Abbreviations CNS, central nervous system COX, cyclooxygenase Gl, gastrointestinal NSAlDs, nonsteroidal anti-inflammatory drugs SIADH, syndrome of inappropriate antidiuretic hormone secretion. From Pick DM, Cooper IW, Wade WE, et al Updating the Beers criteria for potentially inappropriate medication use in older adults Results of a U.S. consensus panel of experts. Arch Intern Med 2003 163 2716. 

During prolonged administration, penicillin drugs may also cause central nervous system (CNS) problems (e.g., confusion, hallucinations), as well as certain blood disorders, such as hemolytic anemia and thrombocytopenia. Other relatively minor side effects of penicillin drugs include gastrointestinal problems such as nausea, vomiting, and diarrhea. 

Only the indications listed in the U.S. product labeling are included here. Many anticancer drugs are used for additional types of neoplastic disease. Gl = gastrointestinal CNS = central nervous system. ... 

Generally speaking, fentanyl acts on the central nervous system and the gastrointestinal tract. Because of this, most of the effects of the drug are physical. It also causes many of the same effects as heroin, including euphoria and drowsiness. However, some research shows that the effects of heroin are more euphoric, and fentanyl is more analgesic. 

Substance P is present in the central nervous system, where it is a neurotransmitter (see Chapter 21 Introduction to the Pharmacology of CNS Drugs), and in the gastrointestinal tract, where it may play a role as a transmitter in the enteric nervous system and as a local hormone (see Chapter 6 Introduction to Autonomic Pharmacology). 

Buspirone causes less psychomotor impairment than diazepam and does not affect driving skills. The drug does not potentiate the central nervous system depressant effects of conventional sedative-hypnotic drugs, ethanol, or tricyclic antidepressants, and elderly patients do not appear to be more sensitive to its actions. Tachycardia, palpitations, nervousness, gastrointestinal distress, and paresthesias may occur more frequently than with benzodiazepines. Buspirone also causes a dose-dependent pupillary constriction. Blood pressure may be elevated in patients receiving MAO inhibitors. A number of buspirone analogs have been developed (eg, ipsapirone, gepirone, tandospirone) and are under study. 

---