But when someone attempts to misuse the medication via either injection or inhalation, the naloxone is intended to act as an antagonist and either reduce the opioids euphoric effects or even precipitate withdrawal in those dependent on opioids. This helps reduce the potential for deviating from the prescribers intended use relative to buprenorphine, though it does not eradicate it. One reason that naloxone might have limited efficacy as an abuse deterrent is that buprenorphine binds more tightly to the mu-opioid receptor than naloxone. Pharmacokinetics
There are small differences in the pharmacokinetics between different sublingual buprenorphine/­naloxone products. These differences may require changes in dose when a person switches from one product to another. The buprenorphine/­naloxone sublingual film (e.g. trade name Suboxone) achieves higher buprenorphine maximum plasma concentrations (Cmax) and area under the curve (AUC, a measure of total drug exposure) than the original buprenorphine/­naloxone sublingual tablets at equal doses. For example, at a buprenorphine/­naloxone dose of 8 mg/2 mg, the buprenorphine Cmax after a single dose of the original tablet formulation is around 3 ng/mL whereas that of the 8 mg/2 mg film formulation is around 3.55 ng/mL. The Zubsolv trade name sublingual tablets have higher buprenorphine bioavailability than the original sublingual tablets, while the Bunavail trade name buccal films have the highest bioavailability. For example, a single dose of Bunavail 4.2 mg/0.7 mg achieves a Cmax around 3.41 ng/mL. Buprenorphine
Buprenorphine is metabolized by the liver, primarily via the cytochrome P450 (CYP) isozyme CYP3A4, into norbuprenorphine.
Major valves of the heart become stiffened and reduce the efficiency of the hearts pumping action. This may not cause symptoms at rest but with exertion, the heart is unable to keep up with increased demands leading to syncope. Aortic stenosis presents with repeated episodes of syncope. Rarely, cardiac tumors such as atrial myxomas can also lead to syncope. Structural cardiopulmonary disease
Diseases involving the shape and strength of the heart can be a cause of reduced blood flow to the brain, which increases risk for syncope. The most common cause in this category is fainting associated with an acute myocardial infarction or ischemic event. The faint in this case is primarily caused by an abnormal nervous system reaction similar to the reflex faints. Women are significantly more likely to experience syncope as a presenting symptom of a myocardial infarction. In general, faints caused by structural disease of the heart or blood vessels are particularly important to recognize, as they are warning of potentially life-threatening conditions.Among other conditions prone to trigger syncope (by either hemodynamic compromise or by a neural reflex mechanism, or both), some of the most important are hypertrophic cardiomyopathy, acute aortic dissection, pericardial tamponade, pulmonary embolism, aortic stenosis, and pulmonary hypertension. Other cardiac causes
Sick sinus syndrome, a sinus node dysfunction, causing alternating bradycardia and tachycardia. Often there is a long pause (asystole) between heartbeats.Adams-Stokes syndrome is a cardiac syncope that occurs with seizures caused by complete or incomplete heart block.