Withdrawal from hypertension caused

Manidipine is a dihydropyridine calcium channel blocker that can be given once a day for hypertension. In a comparison of manidipine 10 mg/day and amlodipine 5 mg/day in a multicenter, randomized, double-blind study in 530 patients with mild-to-moderate hypertension, the two drugs had comparable antihypertensive effects, but manidipine was associated with a significantly lower incidence of ankle edema (1). Nevertheless, adverse events caused withdrawal from treatment in a similar number of patients, 23 with manidipine and 26 with amlodipine. 

P Blockers may be of some value in the treatment of patients undergoing withdrawal from alcohol or those with akathisia. Propranolol and nadolol are efficacious in the primary prevention of variceal bleeding in patients with portal hypertension caused by hepatic cirrhosis. 

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. 

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. 

Potentiation of the antihypertensive effect of clonidine by ACE inhibitors can be clinically useful. However, limited evidence suggests that the effects of captopril may be delayed when patients are switched from clonidine. Note that sudden withdrawal of clonidine may cause rebound hypertension. 

Observational studies STRIDE-2X is the 1-year open extension study of the 18 week STRIDE-2 (Sitaxsentan To Relieve ImpaireD Exercise) investigation that followed patients taking sitaxsentan or bosentan for pulmonary artery hypertension [87 ]. As well as efficacy measures, the researchers included time to withdrawal because of adverse events and time to rises in hepatic aminotransferases in the outcome measures. For the analysis population, the risk of raised aminotransferases to more than 3 times the upper limit of normal at 1 year was 6% with sitaxsentan 100 mg/day and 14% with bosentan. The cumulative risk of withdrawal at 1 year with raised aminotransferases was 3% with sitaxsentan 100 mg/day and 9% with bosentan. Other adverse events were peripheral edema, nasopharyngitis, dyspnea, and cough, consistent with previous trials in pulmonary artery hypertension. The overall withdrawal rates at 1 year were 15% with sitaxsentan 100 mg/ day and 30% with bosentan. Sitaxsentan therefore seems to have similar efficacy to bosentan and from this evidence may have the advantage of causing fewer hepatic adverse events in longer-term treatment (but see below). 

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