Effects of stimulants

Isoproterenol. Isoproterenol hydrochloride is an nonselective P-adrenoceptor agonist that is chemically related to NE. It mimics the effects of stimulation of the sympathetic innervation to the heart which are mediated by NE. It increases heart rate by increasing automaticity of the SA and AV nodes by increasing the rate of phase 4 diastoHc depolarization. It is used in the treatment of acute heart block and supraventricular bradyarrhythmias, although use of atropine is safer for bradyarrhythmias foUowing MI (86). 

The thiazolidinediones have also been reported to act as inhibitors of the respiratory chain at high concentrations, and this appears to account for their ability to activate AMGPK in cultured cells. However, the primary target of the thiazolidinediones appears to be the peroxisome proliferator-activated receptor-y ( PPAR-y), a member of the nuclear receptor superfamily expressed in adipocytes. One of the major effects of stimulation of PPAR-y in adipocytes is the release ofthe... 

The rewarding effects of stimulants are mediated thtough the mesocotti-colimbic dopamine neutons of the ventral tegmental atea and theit tatget... 

Stimulants induce both tolerance and sensitization to their behavioral effects. Tolerance develops to the anorectic and euphoric effects of stimulants (Schuster 1981) however, chronic intermittent use of low doses of stimulants delays the development of tolerance. With the doses commonly used in clinical practice, patients treated for narcolepsy or for depressive or apathetic states find that the stimulant properties usually persist without development of tolerance however, the persistence of antidepressant effects remains a matter of controversy. Sensitization has been linked to the development of amphetamine-induced psychosis (Yui et al. 1999). Sensitization to the induction of psychosis is suggested because psychosis is induced by progressively lower doses and shorter periods of consumption of amphetamine following repeated use over time (Sato 1986). Sensitization for amphetamine-induced psychosis may persist despite long periods of abstinence. 

On the other hand, the length of the fracture is shorter, because the acid reacts with the formation and therefore is spent. If traces of fluoride are in the hydrochloric acid, then insoluble calcium fluoride is precipitated out. Therefore plugging by the precipitate can jeopardize the desired effect of stimulation. 

Conners, C.K. Psychological effects of stimulant drugs in children with minimal brain dysfunction. Pediatrics 49 702-708, 1972. 

Adverse effects of stimulants can be generalized to the whole class (Table 39-3). Most of these side effects can be... 

The effect of stimulation of cardiac adrenoceptors is even more leisurely because several more steps follow activation of the Gs protein by the p-adrenoceptor. For example, to increase the force of cardiac contraction, we have (1) activation of adenylate cyclase by Gas-GTP, (2) formation of cAMP, (3) activation of protein kinase A by the cAMP, then (4) phosphorylation of the calcium channel protein by the kinase. As a result, it takes about 5 to 6 sec from the time the receptors are... 

Fleckenstein, A. E., Gibb, J. W. and Hanson, G. R. Differential effects of stimulants on monoaminergic transporters pharmacological consequences and implications for neurotoxicity. Eur. J. Pharmacol. 406 1-13,2000. 

The most common side effect of clonidine is drowsiness. This can begin with the very hrst dose and usually goes away after a few weeks. Clonidine s sedating effects can actually be useful when it s taken at bedtime. Insomnia is a common problem for patients with ADHD either as a side effect of stimulants or as a consequence of rebound hyperactivity at night when the daytime dose of stimulant has worn off. Clonidine can help the ADHD patient with insomnia to go to sleep. Other side effects of clonidine include low blood pressure, dizziness, depression, dry mouth, nausea, and slowed heart rate. One important point to remember is that not only does clonidine not cause tics, it can, in fact, relieve tics when they appear in patients with ADHD. 

Jensen P. Longer term effects of stimulant treatments for attention-deficit/hyperactivity disorder. J Attention Disord 2002 6(Supplement 1) S17-S30. 

Less frequent side effects of stimulants include euphoria, nervousness, irritability, headache, involuntary movements (tics), increased heart rate, and psychosis. If psychosis or tics develop, the patient s doctor should be notified immediately, and the medication should be stopped. Other side effects should also be reported and may necessitate a medication change. 

Take a Medication Holiday. Some side effects are not a problem on a daily basis nonetheless, they can be qnite distnrbing. The best examples are sexual side effects of some antidepressants or the possible effects of stimulants upon the growth of children with ADHD. One approach has been to skip taking the medication for a brief period of time. For example, those with antidepressant-induced sexual dysfunction have sometimes circnmvented this problem by skipping a single day s dose when they plan to have sex. In a similar fashion, parents concerned with the effects of stimulants on their child s growth may have their child skip doses on the week-... 

Hukovi CS, Stankovi CD, Brankov K. 1969. Effect of trinitrotoluene (TNT) and nitrobenzene on the effect of stimulation of cholinergic nerves of the bladder. Arh Hig Rada Toksikol 20 267-273. 

In the mammalian CNS powerful inhibitory systems function continually to slow the number of action potentials generated. The effects of stimulating an excitatory pathway can appear to be exaggerated if normal inhibitory influences to that region are diminished. Correspondingly, an inhibitory pathway will appear exaggerated if part of the excitatory influence to that system has been removed. 

Can antidepressants such as tricyclics or buproprion augment the effect of stimulants on nondepressed children with ADHD Randomized controlled trials have yet to address this question. Nonetheless, such combinations are common in clinical practice. One case report showed leukopenia in a child treated with a combination of MPH and tricyclics for 4 months, although the doses were not specified (Burke et ah, 1995). Another case report indicated that obsessive-compulsive symptoms developed secondary to the combination of MPH and tricyclics (Pataki et ah, 1993). On a cautionary note, MPH has been found to interact with guanethidine to produce paradoxical hypotension. Patients on monoamine oxidose (MAO) inhibitors are likely to develop hypertensive crises if given a stimulant. 

The effects of stimulant medication generally cease upon discontinuation of the treatment. One double-blind study, however, did not find this to be necessarily true for DEX (Gillberg et ah, 1997). Many patients favor a period off the medication, a drug holiday, to deal with the partial suppression of weight gain, worries about long-term effects, or to assess the need for staying on medication. This type of trial is best done when the child is not scheduled for important school tests or social activities (e.g., summer camp). 

Pliszka, S.R. (2000) Comparing the effects of stimulant and nonstimulant agents on catecholamine function implications for theories of attention deficit hyperactivity disorder (ADHD). In Solanto, M. and Castellanos, X., eds. The Neuropharmacology of Psychostimulant Drugs Implications for AD/HD, 1st ed. New York Oxford University Press, pp. 141-160. 

Schmidt, K., Solanto, M.V., and Sanchez, M. (1984) The effect of stimulant medication of academic performance, in the context of multimodal treatment, in attention deficit disorders with hyperactivity. / Clin Psychopharm 4 100—103. 

Swanson, J. (1993) Effect of stimulant medication on hyperactive children a review of reviews. Exceptional Child 60 154-162. 

Castellanos, F.X., Giedd, J.N., Elia, J., Marsh, W.L., Ritchie, G.F., Hamburger, S.D., and Rapoport, J.L. (1997) Controlled stimulant treatment of ADHD and comorbid Tourette s syndrome effects of stimulant and dose. / Am Acad Child Adolesc Psychiatry 36 589-96. 

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