Hypertension clonidine withdrawal

When clonidine is withdrawn abmpdy, patients may experience a rebound hypertensive phenomenon, whereia blood pressure rises rapidly to a level higher than the predmg level.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. 

Clonidine Beta-adrenoceptor blocking drugs Increased risk of clonidine withdrawal hypertension. 

Clonidine, methyldopa Activate K-2 adrenoceptors Reduce central sympathetic outflow reduce norepinephrine release from noradrenergic nerve endings Hypertension clonidine also used in withdrawal from abused drugs Oral t clonidine also patch Toxicity sedation t methyldopa hemolytic anemia... 

One method used for the control of hypertension is reduction of the impulses flowing from the CNS to the sympathetic nervous system which controls the tone of the cardiovascular system. The veratrum alkaloids do this at doses that are near the emetic dose, and reserpine acts both centrally and peripherally. The imidazoline clonidine (175) and some analogues in which the chlorine is replaced by fluorine or methyl groups decrease sympathetic outflow and cause vasomotor relaxation. However, they cause sedation, lack of saliva and renewed hypertension on withdrawal of the drug. 

The major therapeutic use of clonidine (Catapres, others) is in the treatment of hypertension. Clonidine also has apparent efficacy in the off-label treatment of a range of other disorders. Stimulation of ot2-receptors in the G1 tract may increase absorption of sodium chloride and fluid and inhibit secretion of bicarbonate. This may explain why clonidine has been found to be useful in reducing diarrhea in some diabetic patients with autonomic neuropathy. Clonidine also is useful in treating and preparing addicted subjects for withdrawal from narcotics, alcohol, and tobacco. It may help ameliorate some of the adverse sympathetic nervous activity associated with withdrawal from these agents, as well as decrease craving for the... 

Phentolamine (5 mg IV or IM, 1 to 2 hours before surgery) is indicated in prevention or control of hypertensive episodes that may occur in a patient with pheo-chromocytoma as a result of stress or manipulation during preoperative preparation and surgical excision and in prevention and treatment of dermal necrosis and sloughing following IV administration or extravasation of norepinephrine or dopamine. Phentolamine has been used to treat hypertensive crisis secondary to MAO inhibitors/sympathomimetic amine interactions and rebound hypertension on withdrawal of clonidine, propranolol, or other antihypertensives. It has also been used in combination with papaverine as an intracavern-ous injection for impotence. 

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... 

The answer is a. (Hardman, p 789. Katzung, pp 162—163.) Withdrawal of clonidine, particularly doses greater than 1 mg/d, is well known to cause such a syndrome (including severe hypertension, tachycardia, anxiety tremor, headache, abdominal pain, and sweating), even after one or two missed doses. 

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. 

For treatment of hypertensive rebound after withdrawal of clonidine, 0.2 mg is given initially, followed by 0.2 mg hourly until the DBP falls below 110 mm Hg or a total of 0.7 mg has been administered a single dose may be sufficient. 

Another pharmacological approach is to reduce the intensity of the symptoms with the o2 adrenergic antagonist clonidine, which is normally used to treat hypertension. Overactivity of the locus coeruleus is associated with opioid withdrawal signs such as tachycardia, nausea, vomiting, and sweating. 

Wilson, M.F., Haring, O., Lewin, A., Bedsole, G., Srepansky, W., Fillingim, J., Hall, D., Roginsky, M., McMahon, F.G., Jagger, P., and Strauss, M. (1986) Comparison of guanfacine versus clonidine for efficacy, safety and occurrence of withdrawal syndrom in step-2 treatment of mild to moderate essential hypertension. Am J Cardiol 57 43E-49E. 

Clonidine 0.003-0.01 bid or tid Tourette s syndrome ADHD Aggression/self-abuse Severe agitation Withdrawal syndromes Sedation (very frequent) Hypotension (rare) Dry mouth Confusion (with high dose) Depression Rebound hypertension Localized irritation with transdermal preparation... 

Similar to clonidine Higher risk for bradycardia and hypotension (dose dependent) and rebound hypertension Bronchospasm (contraindicated in asthmatics) Rebound hypertension on abrupt withdrawal Contraindicated in diabetics... 

Abrupt withdrawal of clonidine may result in rebound hypertension... 

Clonidine [KLOE ni deen] is an a2 agonist that is used in essential hypertension to lower blood pressure because of its action in the CNS (see p. 189). It can be used to minimize the symptoms that accompany withdrawal from opiates or benzodiazepines. Clonidine acts centrally to produce inhibition of sympathetic vasomotor centers. Recently, an endogenous substance, agmantine, which appears to be the natural ligand at clonidine binding sites, has been identified. 

Clonidine, an antihypertensive drug, also has been used in the treatment of mania. Sudden withdrawal can produce a rebound hypertensive crisis. Consistent with the brain-disabling principles, it can produce a variety of psychiatric symptoms, including sedation, vivid dreams or nightmares, insomnia, restlessness, anxiety, and depression. More rarely, it can cause hallucinations. Unfortunately, this drug is too commonly used as a so-called mood stabilizer in children. When mistakenly prescribed with stimulants, it causes an elevated risk of cardiac arrhythmia and cardiac arrest in children. 

CENTRALLY ACTING ANTI HYPERTENSIVES BETA-BLOCKERS Risk of withdrawal t BP (rebound t BP) with clonidine and possibly moxonidine Withdrawal of clonidine, and possibly moxonidine, is associated with t circulating catecholamines beta-blockers, especially non-cardioselective ones, will allow the catecholamines to exert an unopposed alpha action (vasoconstriction) Do not withdraw clonidine or moxonidine while a patient is taking beta-blockers. Withdraw beta-blockers several days before slowly withdrawing clonidine and moxonidine... 

May be useful in decreasing the hypertension, tachycardia, and tremulousness associated with alcohol withdrawal, but not the seizures or delirium tremens In complicated alcohol withdrawal Clonidine may Improve social relationships, affectual responses, and sensory responses In autistic disorder Clonidine may reduce the Incidence of menopausal flushing Growth hormone response to clonidine may be reduced during menses Clonidine stimulates growth hormone secretion (no chronic effects have been observed)... 

Clonidine reduces blood pressure with little postural or exercise related drop. Its most serious handicap is that abrupt or even gradual withdrawal causes rebound hypertension. This is characterised by plasma catecholamine concentrations as high as those seen in hypertensive attacks of phaeochro-mocytoma. The onset may be rapid (a few hours) or delayed for as long as 2 days it subsides over 2-3 days. The treatment is either to reinstitute clonidine, i.m. if necessary, or to treat as for a phaeochro-mocytoma. Clonidine should never be used with a p-adrenoceptor blocker which exacerbates withdrawal hypertension (see phaeochromocytoma). Common... 

The hypertensive crisis that can follow the withdrawal of clonidine can be accentuated by beta-blockers. It has also been reported that when beta-blockers are used in conjunction with drugs that cause arterial vasoconstriction they can have an additional effect on peripheral perfusion, which can be hazardous. Thus, combining beta-blockers with ergot alkaloids, as has been recommended for migraine, can cause severe peripheral ischemia and even tissue necrosis (408). 

Transdermal clonidine (clonidine TTS) has been used with some success for the treatment of mild hypertension. Systemic adverse effects are similar to those seen after oral administration, but are less frequent and milder. They include dry mouth, drowsiness, headache, sexual disturbance, cold extremities, obstipation, and fatigue (31-33). These adverse effects rarely necessitate withdrawal of clonidine TTS. 

A withdrawal syndrome with rebound hypertension has been reported with methyldopa (12). Although it is similar to that associated with clonidine, it is less well defined, less severe, and less freqnent. 

Unlike clonidine, moxonidine does not appear to cause sedation or to impair psychomotor performance or cognitive function. However, possible potentiation of the effect of benzodiazepines can ocenr. There is no evidence of a withdrawal syndrome or rebonnd hypertension associated with sudden withdrawal. 

Clonidine (Catapres) is an alpha-2 adrenergic agonist, which thereby functions as a presynaptic irdiibitor of norepinephrine release. It is usually used to treat hypertension (like the beta blockers) but has been used to treat amciety disorders with some success. It is also used to treat opiate withdrawal. A typical starting dose is 0.1 mg two to three times daily (see figure 16-C). It is also available as a transdermal patch. 

---