Bradycardia antagonists

Clinical Trials. In Phase I studies, good documentation and additional investigations should be standard practice. Serious reactions are pretty unusual in these studies, which will detect only very common ADRs, in particular those that are pharmacologically mediated (e.g., bradycardia with beta adrenergic receptor antagonists). 

Pronounced bradycardia with a beta blocker pronounced hypotension with an angiotensin II receptor antagonist... 

Nalorphine has less of an analgesic effect than morphine however, it does not have much value as an independent analgesic. It is used as an antagonist to narcotic analgesics. It eliminates suppression of the respiratory center, bradycardia, and vomiting caused by opiate receptor agonists. 

NSAID and warfarin ACE inhibitors and K-sparing dinretic Verapamil and beta-adrenergic antagonists Nenromnscnlar (NM) blockers and aminoglycosides Alcohol and benzodiazpines Thioridazine and halofantrine Clozapine and co-trimoxazole Increased risk of bleeding Increased risk of hyperkalaemia Bradycardia and asystole Increased NM blockade Increased sedation Increased risk of QT interval prolongation Increased risk of bone marrow suppression... 

They have a low incidence of adverse reactions and the reactions that occur are generally mild. Rapid intravenous infusion of H2 antagonists may cause bradycardia. Cimetidine is more inclined to cross the blood-brain barrier and CNS effects such as somnolence and confusion have been described, especially in the elderly and in patients with impaired renal function. Cimetidine in high doses, as the only one of its class, has antiandrogenic effects which could be explained by an increase of prolactin secretion, binding to androgen receptors and inhibition the cytochrome P450 mediated hydroxylation of estradiol. 

The reflex nature of the bradycardia induced by parenterally administered norepinephrine can readily be demonstrated by administration of atropine, a choli-noreceptor antagonist. Atropine abolishes the compensatory vagal reflexes. Under conditions of vagal blockade, the direct cardiac stimulatory effects of norepinephrine are unmasked. There is marked tachycardia, an increase in stroke volume, and as a consequence, a marked increase in cardiac output (Fig. 10.4). 

Alpha-antagonists are generally contraindicated in obstructive valvular heart disease and hepatic failure. Ketanserin should not be given to patients with AV-conduction disturbances, bradycardia or syndromes with a prolonged QT interval. 

Isoprenaline occasionally has a place in the management of cardiac conditions in which bradycardia is a feature, e.g. low cardiac output associated with slow heart rate after extracorporeal circulation in patients with excessive p-blocking therapy. It may also be used in the treatment of overdose with (3-adrenoceptor antagonists and for refractory bradyarrhythmias prior to cardiac pacing. Isoprenaline is used in the treatment of bronchial asthma on account of its 32 effects. 

Considerable evidence indicates that the hypotensive effect of clonidine is exerted at a adrenoceptors in the medulla of the brain. In animals, the hypotensive effect of clonidine is prevented by central administration of a antagonists. Clonidine reduces sympathetic and increases parasympathetic tone, resulting in blood pressure lowering and bradycardia. The reduction in pressure is accompanied by a decrease in circulating catecholamine levels. These observations suggest that clonidine sensitizes brain stem vasomotor centers to inhibition by baroreflexes. 

H2 antagonists may rarely cause blood dyscrasias. Blockade of cardiac H2 receptors may cause bradycardia, but this is rarely of clinical significance. Rapid intravenous infusion may cause bradycardia and hypotension through blockade of cardiac H2 receptors therefore, intravenous injections should be given over 30 minutes. H2 antagonists rarely cause reversible abnormalities in liver chemistry. 

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