Indeed, one suggested use for lofexidine is to ease withdrawal symptoms of methadone dependence. Its use is approved in the United States for up to 14 days. Other clinical uses
The possibility of using lofexidine to treat alcohol withdrawal symptoms has been investigated, and has not yet been shown to be an effective treatment. It is also used in treatment of cases with postmenopausal hot flashes. Special populations
Lofexidines safety in pregnancy or in the setting of breastfeeding are unknown. Caution is warranted if chronic kidney impairment is present. Adverse effects
Adverse effects that have occurred after taking lofexidine include the following:
Slow heart rate
Dizziness
Sleepiness
Mouth dryness
Low blood pressure
QT prolongationIn addition, people may experience a sudden jump in blood pressure after stopping lofexidine. Overdose
The LD50 of lofexidine is above 77 mg/kg in animals. Studies of high-dose, single administrations of lofexidine proved tolerable for animals, but repeat administration induced symptoms consistent with toxicity. In studies on mice, rats, and dogs, these included ataxia, somnolence, and tremors. It is expected that an overdose of lofexidine would result in symptoms akin to its pharmacological side effects in humans, such as bradycardia and hypotension. Interactions
Many drug-drug interactions with lofexidine are possible. QT prolongation
Lofexidine prolongs the QT interval, which can result in a severe interaction (torsade de pointes) when combined with other drugs that also prolong the QT interval. Patient-specific characteristics that increase the risk for a clinically significant drug-drug interaction include:
increasing age
female sex
cardiac disease
electrolyte disturbances (low blood potassium)As a result, there are many QT-prolonging drugs that may interact with lofexidine.
Esmolol, sold under the brand name Brevibloc, is a cardio selective beta1 receptor blocker with rapid onset, a very short duration of action, and no significant intrinsic sympathomimetic or membrane stabilising activity at therapeutic dosages. It is a class II antiarrhythmic. Esmolol decreases the force and rate of heart contractions by blocking beta-adrenergic receptors of the sympathetic nervous system, which are found in the heart and other organs of the body. Esmolol prevents the action of two naturally occurring substances: epinephrine and norepinephrine.It was patented in 1980 and approved for medical use in 1987. Medical uses
To terminate supraventricular tachycardia,
Episodic atrial fibrillation or flutter,
Arrhythmia during anaesthesia,
To reduce HR and BP during and after cardiac surgery, and
In early treatment of myocardial infarction. Esmolol is also used in blunting the hemodynamic response to laryngoscopy and intubation. Dosing
A loading dose of 0.5 mg/kg is given followed
by 0.05–0.2 mg/kg/min infusion. Metabolism
Esmolol is considered a soft drug, one that is rapidly metabolized to an inactive form. Esmolol is rapidly metabolized by hydrolysis of the ester linkage, chiefly by the esterases in the cytosol of red blood cells and not by plasma cholinesterases or red cell membrane acetylcholinesterase. Total body clearance in man was found to be about 20 L/kg/hr, which is greater than cardiac output; thus the metabolism of esmolol is not limited by the rate of blood flow to metabolizing tissues such as the liver or affected by hepatic or renal blood flow. Esmolols short duration of action is based on the ester-methyl side chain which allows for quick hydrolysis.