CNS-stimulants

AH three of these materials are apparentiy central nervous system (CNS) stimulants. It is beheved that for most individuals caffeine causes greater stimulation than does theophylline. Theobromine apparentiy causes the least stimulation. There is some evidence that caffeine acts on the cortex and reduces drowsiness and fatigue, although habituation can reduce these effects. 

Compounds that have agonistic properties at glutamate or aspartate receptors are also CNS stimulants, readily cause convulsions, and presumably could also be employed as analeptics. Three separate excitatory amino acid receptor subtypes have been characterized pharmacologically, based on the relative potency of synthetic agonists. These three receptors are named for their respective prototypical agonists A/-methyl-D-aspartate [6384-92-5]... 

The mechanism by which the methylxanthines produce CNS stimulation is not clearly estabUshed. These agents may function, ia part, to limit chloride channel activation ia a manner similar to that of pentylenetetra2ol (7) or hicuculline (8). Another possibiUty is a specific antagonism of the inhibitory neurotransmitter adenosiae [58-61-7] (19) (19). 

Pemoline [2152-34-3] (24), stmcturally dissimilar to amphetamine or methylphenidate, appears to share the CNS-stimulating properties. As a consequence, pemoline is employed in the treatment of ADHD and of narcolepsy. There are several other compounds that are stmcturally related to amphetamines, although not as potent and, presumably, without as much abuse potential. These compounds also have anorexic effects and are used to treat obesity. Some of the compounds available are phentermine [122-09-8] fenfluramine [458-24-2] and an agent that is available over-the-counter, phenylpropanolamine [1483815-4] (26). 

Normally, dietary tyramine is broken down in the gastrointestinal tract by MAO and is not absorbed. In the presence of MAOI, however, all of its potent sympathomimetic actions are seen. Other side effects of MAOI include excessive CNS stimulation, orthostatic hypotension, weight gain, and in rare cases hepatotoxicity. Because the monoamine oxidase inhibitors exhibit greater toxicity, yet no greater therapeutic response than other, newer agents, clinical use has been markedly curtailed. The primary use for MAOIs is in the treatment of atypical depressions, eg, those associated with increased appetite, phobic anxiety, hypersomnolence, and fatigues, but not melancholia (2). 

Other Drugs. Agents not considered to be CNS stimulants yet employed for the treatment of certain types of depression includes lithium carbonate for the treatment of bipolar disorder. In most patients, lithium is the sole agent used to control manic behavior and is very effective (see... 

Compounds available in the United States are Hsted in Table 1. Whereas they vary in degree, all of them share similar HabiUties of cardiovascular side effects, the potential for central nervous system (CNS) stimulation, the development of tolerance, and abuse potential. AH, with the exception of ma2indol, are derivatives of phenethylamine. The introduction of an oxygen atom on the -carbon of the side chain tends to reduce CNS stimulant properties without decreasing the anorectic activity. Following the Federal Controlled Dmg Act of 1970, dmgs were classified into one of five schedules according to medical utiUty and abuse potential. 

The Class I agents have many similar side effects and toxicities. The anticholinergic side effects include dry mouth, constipation, and urinary hesitancy and retention. Common gastrointestinal (GI) side effects include nausea, vomiting, diarrhea, and anorexia. Cardiovascular adverse effects are hypotension, tachycardia, arrhythmias, and myocardial depression, especially in patients with congestive heart failure. Common central nervous system (CNS) side effects are headache, dizziness, mental confusion, hallucinations, CNS stimulation, paraesthesias, and convulsions. 

A somewhat more complex application of this notion is represented by the CNS stimulant fencamfine (83). Diels-Alder addition of cyclopentadiene and nitrostyrene affords the norbomene derivative, 80. Catalytic hydrogenation reduces both the remaining double bond and the nitro group (81). ° Condensation with acetaldehyde gives the corresponding imine (82) a second reduction step completes the synthesis of fencamfine (83). ... 

A thiazole derivative that incorporates a fragment of the amphetamine molecule shows some CNS stimulant activity more specifically, the compound antagonizes the depression caused by overdoses of barbiturates and narcotics. Reaction of benzalde-hyde with sodium cyanide and benzenesulfonyl chloride gives the toluenesulfony1 ester of the cyanohydrin (141). Reaction of this with thiourea leads directly to aminophenazole (143) It is probable the reaction proceeds by displacement of the tosylate by the thiourea sulfur to give 142 addition of the amino group to the nitrile followed by tautomerization affords the observed product. ... 

Acylation of norephedrine (56) with the acid chloride from benzoylglycolic acid leads to the amide (57), Reduction with lithium aluminum hydride serves both to reduce the amide to the amine and to remove the protecting group by reduction (58), Cyclization by means of sulfuric acid (probably via the benzylic carbonium ion) affords phenmetrazine (59), In a related process, alkylation of ephedrine itself (60) with ethylene oxide gives the diol, 61, (The secondary nature of the amine in 60 eliminates the complication of dialkylation and thus the need to go through the amide.) Cyclization as above affords phendimetra-zine (62), - Both these agents show activity related to the parent acyclic molecule that is, the agents are CNS stimulants... 

Xanthines such as caffeine (1)> theophylline (aminophylline) (2), and theobromine (3) are a class of alkaloids that occur in numerous plants. The CNS stimulant activity of aqueous infusions containing these compounds has been recognized since antiquity. This has, of course, led to widespread consumption of such well-known beverages as coffee (Coffea arabica), tea (Thea sinesis), mate, and cola beverages (in part Cola acuminata). The annual consumption of caffeine in the United States alone has been estimated to be in excess of a billion kilos. The pure compounds have found some use in the clinic as CNS stimulants. In addition, caffeine is widely used in conjunction with aspirin in various headache remedies. 

Substitution of somewhat more complex side chains on the imidazole nitrogen of the purines leads to CNS stimulant drugs that have also been used as vasodilators and antispasmodic agents. Thus, alkylation of theophyline (2) with ethyl bromoacetate followed by saponification of the product gives acephylline (9). Alkylation with l-bromo-2-chloroethane gives the 2-chloroethyl derivative (10). Reaction of that intermediate with amphetamine yields fenethylline (11). ... 

CNS (Central Nervous System). The brain and the spinal cord. CNS stimulant. A drug that counteracts fatigue and somnolence. 

Therapeutic Function CNS stimulant Chemical Name 5-hydroxytryptophan Common Name —... 

Restlessness, apprehension, anxiety, fear, CNS stimulation, cardiac arrhythmias, sweating, pallor, flushing, nausea... 

The CNS stimulants include the analeptics, drugs tiiat stimulate the respiratory center of the CNS the amphetamines, drugs witii a high abuse potential because of dieir ability to produce euphoria and wakefulness and the anorexiants, drugs used to suppress die appetite... 

Caffeine is a mild to potent CNS stimulant, with the degree of its stimulating effect dependent on the dose administered. Caffeine stimulates the CNS at all levels, including the cerebral cortex, die medulla, and the spinal cord. Caffeine has mild analeptic (respiratory stimulating) activity. Other actions include cardiac stimulation (which may produce tachycardia), dilatation of coronary and peripheral blood vessels, constriction of cerebral blood vessels, and skeletal muscle stimulation. Caffeine also has mild diuretic activity. 

The CNS stimulants have limited use in medicine. Examples of CNS stimulants are given in the Summary Drug Table Central Nervous System Stimulants. 

The adverse reactions associated with the administration of doxapram include excessive CNS stimulation, symptoms of which may include headache, dizziness, apprehension, disorientation, and hyperactivity. Other adverse reactions include nausea, vomiting, cough,... 

One of the chief adverse reactions associated with the amphetamines and anorexiants is overstimulation of the CNS, which may result in a variety of adverse reactions, including insomnia, tachycardia, nervousness, headache, anorexia, dizziness, and excitement. In some instances, die intensity of diese reactions is dose dependent, but some individuals may experience an intense degree of diese symptoms even widi low doses. Odier individuals experience few symptoms of CNS stimulation. 

The CNS stimulants are contraindicated in patients with known hypersensitivity or severe hypertension, in newborns, and in patients with epilepsy or convulsive... 

Assessment of the patient receiving a CNS stimulant depends on the drug, the patient, and the reason for administration. 

ANALEPTICS. When a CNS stimulant is prescribed for respiratory depression, initial patient assessments will include the blood pressure, pulse, and respiratory rate. It is important to note the depth of the respirations and any pattern to the respiratory rate, such as shallow respirations or alternating deep and shallow respirations. The nurse reviews recent laboratory tests (if any), such as arterial blood gas studies. Before administering the drug, the nurse ensures that the patient has a patent airway. Oxygen is usually administered before, during, and after drug administration. 

The expected outcomes for the patient depend on the reason for administration of a CNS stimulant but may include an optimal response to therapy, management of adverse drug reactions, and an understanding of the drug regimen. 

When a CNS stimulant such as dextroamphetamine is administered to treat a child with ADD, the drug regimen will be periodically interrupted to determine if the child still exhibits the symptoms of ADD. 

Q Risk for Injury related to adverse drug effects (CNS stimulation, drug dependency, other [speafy])... 

When use of the CNS stimulants causes insomnia, the nurse administers the drug early in the day (when possible) to diminish sleep disturbances. The patient is encouraged not to nap during the day. Other stimulants, such as coffee, tea, or cola drinks, are avoided. In some patients, nervousness, restlessness, and palpitations may occur. The vital signs are checked every 6 to 8 hours or more often if tachycardia, hypertension, or palpitations occur. Many times these adverse reactions will diminish with continued use as tolerance develops. If tolerance develops, the dosage is not increased. 

Older adults are especially sensitive to the effects of the CNS stimulants and may exhibit excessive anxiety, nervousness insomnia, and mental confusion. Cardiovascular disorders common in the older adult, maybe worsened by the CNS stimulants Careful monitoring is important because the presence of these reactions may result in the need to discontinue use of the drug. 

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