Blood pressure clonidine effects

Recent experiments carried out by BOLME and coworkers (39) now raise the question of whether the receptors involved in reducing blood pressure are epinephrine receptors or noradrenaline receptors. These workers found that in rats small doses of yohimbine and piper-oxan blocked the blood pressure lowering effect of clonidine, but did not influence the clonidine-induced increase in flexor reflex activity. This effect on the reflex mechanism is possibly mediated by noradrenaline receptors which can be blocked only by higher doses of a-adrenolytic agents. HtfKFELT et al. (40) consider that epinephrine terminals possibly innervate noradrenaline cell bodies at the locus coeruleus. 

Einally, clonidine should only be used by patients who can be counted on to take their medication reliably. Clonidine is first and foremost a medication used to treat high blood pressure. Clonidine lowers blood pressure and can slow the pulse rate. However, when clonidine is suddenly stopped, dramatic rebound effects can occur, including a rapid rise in blood pressure that can be dangerous. Patients who suddenly stop taking clonidine or who routinely forget to take their clonidine run the risk of severe side effects. These risks must be discussed with the patient prior to initiating... 

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). 

The relationship between the measured effect and steady-state plasma concentration sometimes yields bell-shaped (e.g., nortriptyline) or U-shaped (e.g., clo-nidine) curves. Several unusual concentration-effect curves, including the U-shaped curve describing the blood pressure lowering effect of clonidine, have been explained by Paalzow and associates as being a result of multiple receptor responses. The drug then acts on several different receptors that can have opposite effects and that are triggered at different concentrations. 

The manufacturers of moxonidine advise avoiding tricyclic antidepressants, because of the lack of clinical experience of combined use. Presumably, this is because moxonidine is related to clonidine, and tricyclies may antagonise the blood pressure-lowering effects of clonidine, see Clonidine -t Tricyclic and related antidepressants , p.884. Tricyclics can also cause postural hypotension and sedation, both of which could potentially be additive with the effects of moxonidine. If the combination is used, it would be prudent to carefully monitor blood pressure and sedation. 

When clonidine is withdrawn abmpdy, patients may experience a rebound hypertensive phenomenon, whereia blood pressure rises rapidly to a level higher than the predmg level. These patients may experience symptoms of headache, tachycardia, agitation, and nervousness. If rebound hypertension occurs, resumption of clonidine therapy or adrninistration of phentolamine reduces the blood pressure. For clonidine withdrawal, the dose should be reduced gradually over a two-week period. The principal side effects are sedation, dry mouth, drowsiaess, di22iQess, and fatigue. 

Guanfacine. Guanfaciae, used ia patients having mild to moderate hypertension, can lower blood pressure 50/25 mm Hg (systoHc/diastoHc) ia hypertensive patients. Side effects such as sedation, dry mouth, and asthenia are less as compared to those of guanaben2 and clonidine. Guanfaciae reduces blood cholesterol and triglyceride and does not cause glucose iatolerance. 

Clonidine, delivered transdermally or orally, is an effective smoking-cessation treatment. It is given for 3 to 10 weeks and should not be discontinued abruptly. Abrupt discontinuation may cause nervousness, agitation, headache, tremor, and rapid rise in blood pressure. 

The most common clonidine side effects are dry mouth, dizziness, sedation, and constipation. Blood pressure should be monitored. 

Figure 8. Cardiovascular effects of clonidine (St 155) in an anaesthetized dog. Upper curve, blood pressure, heart frequency. Lower curve, nictitating membrane. At the whole dots carotid sinus occlusion reflex was elicited (11).

Figure 14. Effects of a group of clonidine derivatives on blood pressure in spinal rats and on heart rate in vagotomized rats. The distribution coefficient was measured with 0.1 m Sorensen phosphate buffer at a pH of 7.4.

Figure 27. Comparison of the relationship between antihypertensive and sympathomimetic activity and sedation and inhibition of gastric secretion of clonidine and two derivatives (St 600 and St 608). The antihypertensive activity was tested in genetic hypertensive rats. The sympathomimetic activity was measured as blood pressure increase in spinal rats. The sleep effect in chicks was tested according to the method in Reference 50, and the gastric secretion in rats was measured according to the method in Reference 57.

Because of their reflex cardiac effect, vasodilators, if used alone in the treatment of hypertension, have not been a successful therapeutic tool. However, the reflex tachycardia and increase in cardiac output can be effectively blocked by the therapeutic association with a sympathetic blocker guanethidine, reserpine, methyldopa, or clonidine. More specifically, blockade of the cardiac beta-adrenergic receptors will also prevent the cardiac response to hydralazine. Thus, the therapeutic combination of hydralazine and propranolol can be successfully employed for effective blood pressure reduction(11). 

The most common side effects of clonidine are constipation, dizziness, drowsiness, dryness of mouth, and unusual tiredness or weakness. However, there are more severe side effects that clinicians and patients should be aware of, such as allergic reaction, decreased heart rate, or unusually elevated or decreased blood pressure, as well as contraindications and drug interactions that should be evaluated prior to prescription. 

Clonidine (Catapres). Clonidine is largely used to treat high blood pressure. Although we don t fully understand how clonidine acts, it appears to reduce norepinephrine activity by stimulating a norepinephrine receptor known as the alpha-2 receptor. When clonidine binds to alpha-2 receptors on norepinephrine neurons, so-called autoreceptors, the cells are tricked into believing that there is already sufficient norepinephrine released and thus decrease any additional release of norepinephrine. As one might anticipate, clonidine is somewhat effective at reducing the hyperactivity and impulsivity of ADHD. It does not, however, provide nearly as much benefit for the inattention of ADHD. 

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. 

Because it has not been used extensively to treat ADHD, not as much is known about its safety in children. It appears to cause less sedation than clonidine and fewer untoward effects on blood pressure as well. Because of its similarity to clonidine, the same precautions should be taken when prescribing guanfacine. EKGs should be performed periodically, and blood pressure and pulse should be checked at each office visit. 

Unlabeled route of administration - Sublingual clonidine, using a dosage of 0.2 to 0.4 mg/day, may be effective in hypertensive patients unable to take oral medication. The onset occurs within 30 to 60 minutes and blood pressure appears to be maintained on a twice daily regimen. 

The decrease in blood pressure produced by clonidine correlates better with a decreased cardiac output than with a reduction in peripheral vascular resistance. The reduction in cardiac output is the result of both a decreased heart rate and reduced stroke work the latter effect is probably caused by a diminished venous return. 

Geriatric Considerations - Summary The alphaj-adrenergic agonist effect of tizani-dine lowers blood pressure in a manner similar to clonidine but is less potent. Older adults are at risk of hypotension and when discontinued, this drug should be tapered to avoid hypertensive rebound. 

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