synthetic opioids) with over 28,400 overdose deaths. synthetic opioids, predominantly<unk> .<unk> 's most common side effects, which affect more than 10% of people, include nausea, vomiting, constipation, dry mouth, somnolence, confusion, and asthenia (weakness). Less frequently, in 3-10% of people,<unk>  can cause abdominal pain, headache, fatigue, anorexia and weight loss, dizziness, nervousness, anxiety, depression, flu-like symptoms, dyspepsia (indigestion), shortness of breath, hypoventilation, apnoea, and urinary retention.<unk>  use has also been associated with aphasia. Despite being a more potent analgesic,<unk>  tends to induce less nausea, as well as less histamine-mediated itching, than morphine. The duration of action of<unk>  has sometimes been underestimated, leading to harm in a medical context. In 2006, the U.S. Food and Drug Administration (FDA) began investigating several respiratory deaths, but doctors in the United Kingdom were not warned of the risks with<unk>  until September 2008. The FDA reported in April 2012 that twelve young children had died and twelve more made seriously ill from separate accidental exposures to<unk>  skin patches.<unk>  has a therapeutic index of 270. Respiratory depression The most dangerous adverse effect of<unk>  is respiratory depression, that is, decreased sensitivity to carbon dioxide leading to reduced rate of breathing, which can cause anoxic brain injury or death. This risk is decreased when the airway is secured with an endotracheal tube (as during anesthesia). This risk is higher in specific groups, like those with obstructive sleep apnea. Other factors that increase the risk of respiratory depression are: * High<unk>  doses * Sleep * Older age * Simultaneous use of CNS depressants like benzodiazepines, barbiturates, alcohol, and inhaled anesthetics * Hyperventilation * Decreased CO2 levels in the serum * Respiratory acidosis * Decreased<unk>  clearance from the body * Decreased blood flow to the liver * Renal insufficiency Sustained release<unk>  preparations, such as patches, may also produce unexpected delayed respiratory depression. The precise reason for sudden respiratory depression is unclear, but there are several hypotheses: * Saturation of the body fat compartment in people with rapid and profound body fat loss (people with cancer, cardiac or infection-induced cachexia can lose 80% of their body fat). * Early carbon dioxide retention causing cutaneous vasodilation (releasing more<unk> , together with acidosis, which reduces protein binding of<unk> , releasing yet more<unk> . * Reduced sedation, losing a useful early warning sign of opioid toxicity and resulting in levels closer to respiratory-depressant levels. Another related complication of<unk>  overdoses includes the so-called wooden chest syndrome which quickly induces complete respiratory failure by paralyzing the thoracic muscles, explained in more detail in the Muscle rigidity section below. Heart and blood vessels *Bradycardia:<unk>  decreases the heart rate by increasing vagal nerve tone in the brainstem, which increases the parasympathetic drive. *Vasodilation: It also vasodilates arterial and venous blood vessels through a central mechanism, by primarily slowing down vasomotor centers in the brainstem. To a lesser extent, it does this by directly affecting blood vessels. This is much more profound in patients who have an already increased sympathetic drive, like patients who have high blood pressure or congestive heart failure. It does not affect the contractility of the heart when regular doses are administered. Muscle rigidity If high boluses of<unk>  are administered quickly, muscle rigidity of the vocal cords can make bag-mask ventilation very difficult. The exact mechanism of this effect is unknown, but it can be prevented and treated using neuromuscular blockers. Wooden chest syndrome A prominent idiosyncratic adverse effect of<unk>  also includes a sudden onset of rigidity of the abdominal muscles and the diaphragm which induces respiratory failure; this is seen with high doses and is known as wooden chest syndrome. The syndrome is believed to be the main cause of death as a result of<unk>  overdoses. Wooden chest syndrome is reversed by naloxone and is believed to be caused by a release of noradrenaline which activates α-adrenergic receptors and also possibly via an activation of cholinergic receptors. Wooden chest syndrome is unique to the most powerful opioids—which today comprise<unk>  and its analogs—while other less-powerful opioids like heroin produce mild rigidity of the respiratory muscles to a much lesser degree.
Fentanyl
Remifentanil
Ketamine
Alfentanil
Propofol
Etomidate
Sevoflurane
Methoxyflurane