Stimulants with clonidine

T Blood pressure and stimulant Give clonidine or guanfacine 4- Dose or change to another medication Same as above but with baseline and... 

Another clinically important effect I would like to mention is the inhibition of salivary secretion by clonidine. Both the sympathetic nervous system and the parasympathetic nervous system are involved in the physiological regulation of salivation. HOEFKE (53) as well as RAND and coworkers (54) found that parasympathetic salivary secretion stimulated by electrical impulses on the chorda tympani and by carbachol could not be blocked by clonidine in anaesthetised animals. In our own experiments in rats with clonidine and the 2,6-diethyl derivative St 91 which does not penetrate to the CNS, secretion of saliva was blocked only after clonidine, (HOEFKE (55)) indicating a central mode of action. 

Injection of botulinum toxin A at the site of problematic tics is sometimes helpful. Treatment of any associated attention deficit disorder (eg, with clonidine patch, guanfacine, pemoline, methylphenidate, or dextroamphetamine) or obsessive-compulsive disorder (selective serotonin reuptake inhibitors or clomipramine) may be required. Bilateral thalamic stimulation is sometimes worthwhile in otherwise intractable cases. 

In 12 patients clonidine 50-100 micrograms/day relieved clozapine-induced sialorrhea, with good results in three and partial results in eight (178). Theoretically, the reduction in sialorrhea with clonidine could have been due to reduced plasma noradrenaline concentrations, resulting in less stimulation of unopposed p-adrenoceptors in the salivary glands. 

Postsynaptic a2-receptors are involved in suppression of pain perception, and their stimulation with the 02 agonist clonidine is used therapeutically. Some data even suggest that postsynaptic effects are also important in the blood pressure-reducing effects of 02 agonists. E.g., contrary to what one would expect from the textbook model (which ascribes the antihypertensive effect to presynaptic inhibition), the effect of clonidine persists after ablation of the presynaptic nerve terminals with 6-hydrox-ydopamine (see below). 

Dry mouth is common with clonidine, and investigation of the mechanism has come from an experimental study in which the direct effect of clonidine on salivary amylase excretion from rat parotid dispersed cells was measured in vitro (18). Clonidine stimulated calcium influx into the cells and inhibited postsynaptic alphai-adrenoceptor responses. 

Clinical data on BS-lOO-l l (2)(Sandoz) are now readily available. 2, 25 The compound is as effective an antihypertensive in man as clonidine but ten times less potent. Sedation and dry mouth appeared with the same frequency as with clonidine. The central a-stimulant action of guanabenz (3) in cats appears distinct from that of clonidine in that baroreceptor mechanisms are not involved in the hypotensive response.26 in the clinic, guanabenz (2it-48mg) produced modest blood pressure reduction with sedation as the major side-effect.27... 

III. Clinical presentation. Manifestations of intoxication result from generalized sympathetic depression and include pupillary constriction, lethargy, coma, apnea, bradycardia, hypotension, and hypothermia. Paradoxic hypertension, caused by stimulation of peripheral alpha-1 receptors, may occur with clonidine, oxymetazoline, and tetrahydrozoline (and possibly guanabenz) and is usually transient. The onset of symptoms is usually within 30-60 minutes, although peak effects may occur more than 6-12 hours after ingestion. Full recovery is usual within 24 hours. In an unusual massive overdose, a 28-year-old man who accidentally ingested 100 mg of clonidine powder had a three-phase intoxication over 4 days initial hypertension, followed by hypotension, and then a withdrawal reaction with hypertension. 

At present, no diugs exist that can selectively activate a2-receptor subtypes. Clonidine stimulates all three a2-subtypes with similar potency. Clonidine lowers blood pressure in patients with hypertension and it decreases sympathetic overactivity during opioid withdrawal. In intensive and postoperative care, clonidine is a potent sedative and analgesic and can prevent postoperative shivering. Clonidine and its derivative brimonidine lower... 

Cionidine. Clonidine dampens sympathetic activity originating at the locus coeruleus by stimulation of presynaptic a2-adrenergic receptors in the sympathetic chain (Covey and Classman 1991 Hughes 1994). It appears to have some efficacy for alcohol and opioid withdrawal and thus was evaluated for treatment of nicotine withdrawal as well (Covey and Classman 1991 Hughes 1994). Several clinical trials used oral or transdermal clonidine in doses of 0.1—0.4 mg/day for 2—6 weeks with or without behavior therapy. Three meta-analytic reviews reported that clonidine improved quit rates (Covey and Classman 1991 Courlay and Benowitz 1995 Law and Tang 1995). 

There are two main treatments for the opiate withdrawal syndrome. One is replacement therapy with methadone or other X agonists that have a longer half-life than heroin or morphine, and produce mild stimulation rather than euphoria. They also produce cross-tolerance to heroin, lessening heroin s effect if patients relapse. Withdrawal is also treated with the 0C2 agonist clonidine, which inhibits LC neurons, thus counteracting autonomic effects of opiate withdrawal — such as nausea, vomiting, cramps, sweating, tachycardia and hypertension — that are due in part to loss of opiate inhibition of LC neurons. 

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. 

Noradrenaline is the neurotransmitter most closely associated with the peripheral and central stress response (Figure 9.5). There is experimental evidence to show that drugs such as yohimbine that block the noradrenergic autoreceptors (e.g. on cell bodies and nerve terminals) and thereby enhance noradrenaline release cause fear and anxiety in both man and animals. Conversely, drugs that stimulate these autoreceptors (as exemplified by clonidine) diminish the anxiety state because they reduce the release of noradrenaline. Benzodiazepines have been shown to inhibit the fear-motivated increase in the functional activity of noradrenaline in experimental animals, but it is now widely believed that the action of the benzodiazepines on the central noradrenergic system is only short term and may contribute to the sedative effects which most conventional benzodiazepines produce, at least initially. Nevertheless, altered noradrenergic... 

Clonidine is a selective o -adrenergic agonist. Clonidine has expressed hypotensive action, which is associated with a reduction of general peripheral vascular resistance, reduced frequency of cardiac beats, and a reduction of cardiac output. The mechanism of action of clonidine is caused by stimulation of o -adrenoreceptors of the inhibitory structures of the brain as well as a reduction of sympathetic impulses to the blood vessels and brain. 

Inattentiveness, impulsivity, hyperactivity 50% will continue to manifest the disorder into adulthood Stimulants (70% response for uncomplicated ADHD caution in patients with tic disorders) TCAs (70% response, first line for patients with comorbid MD or anxiety disorders, and for patients with ADHD + tics) requires serum levels and cardiovascular monitoring Bupropion Clonidine, guan-facine (first line for patients with ADHD + tics) MAOIs Combined pharmacotherapy for treatment-resistant cases... 

Gadow et al. (1995), however, found no increase in tics in a placebo-controlled trial of methylphenidate in children with ADHD and a tic disorder. Other trials of stimulants in such children have found little or no average increase in tic severity scores, but clinically significant increases of tics in a handful of subjects severe enough to prompt discontinuation of the stimulant (Castellanos et al., 1997 Law and Schachar, 1999) or to require addition of a medication to control their tic symptoms (Gadow et al., 1999). A multicenter, doubleblind, placebo-controlled, parallel group study of methylphenidate and clonidine, used alone or in combination in 136 children with ADHD and a comorbid... 

Antihistamines such as diphenhydramine, a mainstay of OTC sleep preparations, are also used widely by parents for their children at doses of 1 mg/kg. Most of the reports of the use of clonidine for sleep disorders are clinical and anecdotal case reports of use in children with ADFFD (Wilens et ah, 1994 Prince et ah, 1996). There are some safety concerns about using clonidine once a day at bedtime, especially in patients who take a daytime stimulant. Melatonin was studied using a double-blind, placebo-controlled, crossover design (Jan et ah, 1994) on a mixed group of 15 children with sleep disturbances, with some improvement reported. However, caution is warranted in using this agent because melatonin is unregulated, and there are concerns about the purity and safety of some commercially available preparations (Werry and Aman, 1999). 

As noted above, Zito and colleagues (2000) reported stimulant use in a Medicaid population of 12.3/1000 preschoolers, with rates of stimulants, antidepressants, and other medications such as clonidine increasing dramatically since 1991. Unfortunately, in the absence of efficacy data and details on the actual diagnoses of the children, as well as no documentation of the children s actual functioning or types of care received, this study... 

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