Sepsis, formerly known as septicemia or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is followed by suppression of the immune system. Common signs and symptoms include fever, increased heart rate, increased breathing rate, and confusion. There may also be symptoms related to a specific infection, such as a cough with pneumonia, or painful urination with a kidney infection. The very young, old, and people with a weakened immune system may have no symptoms of a specific infection, and the body temperature may be low or normal instead of having a fever. Severe sepsis causes poor organ function or blood flow. The presence of low blood pressure, high blood lactate, or low urine output may suggest poor blood flow. Septic shock is low blood pressure due to sepsis that does not improve after fluid replacement.
Septic shock is a potentially fatal medical condition that occurs when sepsis, which is organ injury or damage in response to infection, leads to dangerously low blood pressure and abnormalities in cellular metabolism. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defines septic shock as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by requiring a vasopressor to maintain a mean arterial pressure of 65 mm Hg or greater and having serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%.
Isoprenaline, or isoproterenol, is a medication used for the treatment of bradycardia, heart block, and rarely for asthma. It is a non-selective β adrenoceptor agonist that is the isopropylamine analog of epinephrine (adrenaline).
Dobutamine is a medication used in the treatment of cardiogenic shock and severe heart failure. It may also be used in certain types of cardiac stress tests. It is given by IV only, as an injection into a vein or intraosseous as a continuous infusion. The amount of medication needs to be adjusted to the desired effect. Onset of effects is generally seen within 2 minutes. It has a half-life of two minutes. This drug is generally only administered short term, although it may be used for longer periods to relieve symptoms of heart failure in patients awaiting heart transplantation.
Labetalol is a medication used to treat high blood pressure and in long term management of angina. This includes essential hypertension, hypertensive emergencies, and hypertension of pregnancy. In essential hypertension it is generally less preferred than a number of other blood pressure medications. It can be given by mouth or by injection into a vein.
Pramipexole, sold under the brand Mirapex among others, is medication used to treat Parkinson's disease (PD) and restless legs syndrome (RLS). In Parkinson's disease it may be used alone or together with levodopa. It is taken by mouth. Pramipexole is a dopamine agonist of the non-ergoline class.
The κ-opioid receptor or kappa opioid receptor, abbreviated KOR or KOP for its ligand ketazocine, is a G protein-coupled receptor that in humans is encoded by the OPRK1 gene. The KOR is coupled to the G protein Gi/G0 and is one of four related receptors that bind opioid-like compounds in the brain and are responsible for mediating the effects of these compounds. These effects include altering nociception, consciousness, motor control, and mood. Dysregulation of this receptor system has been implicated in alcohol and drug addiction.
Nalfurafine is an antipruritic that is marketed in Japan for the treatment of uremic pruritus in individuals with chronic kidney disease undergoing hemodialysis. It acts as a potent, selective, centrally-penetrant κ-opioid receptor (KOR) agonist, and is the first and currently the only selective KOR agonist to have been approved for clinical use. It has also been dubiously referred to as the "first non-narcotic opioid drug" in history.
Dopamine receptor D1, also known as DRD1. It is one of the two types of D1-like receptor family - receptors D1 and D5. It is a protein that in humans is encoded by the DRD1 gene.
Landiolol (INN) is an ultra short-acting, β1-superselective intravenous adrenergic antagonist, which decreases the heart rate effectively with less negative effect on blood pressure or myocardial contractility. In comparison to other beta blockers, landiolol has the shortest elimination half-life, ultra-rapid onset of effect, and predictable effectiveness with inactive metabolites. The pure S-enantiomer structure of landiolol is believed to develop less hypotensive side effects in comparison to other β-blockers. This has a positive impact on the treatment of patients when reduction of heart rate without decrease in arterial blood pressure is desired. Landiolol was developed by modifying the chemical structure of esmolol to produce a compound with a higher rate of cardioselectivity and a greater potency without increasing its duration of action. It is sold as landiolol hydrochloride. Based on its positive benefit risk profile, landiolol has been granted the marketing authorization and introduced to the European markets under the brand names Rapibloc, Raploc, Runrapiq, Landibloc mid 2016. Landiolol is available in Japan under the brand names Onoact (50 mg) and Corbeta.
AL-34662 is an indazole derivative drug that is being developed for the treatment of glaucoma. It acts as a selective 5-HT2A receptor agonist, the same target as that of psychedelic drugs like psilocin, but unlike these drugs, AL-34662 was designed specifically as a peripherally selective drug, which does not cross the blood–brain barrier. This means that AL-34662 can exploit a useful side effect of the hallucinogenic 5-HT2A agonists, namely reduction in intra-ocular pressure and hence relief from the symptoms of glaucoma, but without causing the hallucinogenic effects that make centrally active 5-HT2A agonists unsuitable for clinical use. In animal studies, AL-34662 has been shown to be potent and effective in the treatment of symptoms of glaucoma, with minimal side effects.
Befiradol is an experimental drug being studied for the treatment of levodopa-induced dyskinesia. It is a potent and selective 5-HT1A receptor full agonist.
WAY-267464 is a potent, selective, non-peptide agonist for the oxytocin receptor, with negligible affinity for the vasopressin receptors. Contradictorily however, though originally described as selective for the oxytocin receptor and lacking affinity for the vasopressin receptors, it has since been reported to also act as a potent vasopressin V1A receptor antagonist. WAY-267464 has been shown to cross the blood-brain-barrier to a significantly greater extent than exogenously applied oxytocin, and in animal tests produces centrally-mediated oxytocinergic actions such as anxiolytic effects, but with no antidepressant effect evident. It was developed by a team at Ferring Pharmaceuticals.
Barusiban (INN) is a non-peptide drug which is among the most potent and selective oxytocin receptor antagonists known. It was trialed by Ferring Pharmaceuticals as a treatment of preterm labor but failed to demonstrate effectiveness and was not pursued any further.
Merotocin (INN) (developmental code name FE-202767), also known as carba-1-(4-FBzlGly7)dOT, is a peptidic agonist of the oxytocin receptor that was derived from oxytocin. It is under development by Ferring Pharmaceuticals for the treatment of preterm mothers with lactation failure requiring lactation support, and is in phase II clinical trials for this indication. Merotocin is potent (EC50 < 0.1 nM) and highly selective (>1000-fold over the related vasopressin receptors).
Dopamine, sold under the brandname Intropin among others, is a medication most commonly used in the treatment of very low blood pressure, a slow heart rate that is causing symptoms, and, if epinephrine is not available, cardiac arrest. In newborn babies it continues to be the preferred treatment for very low blood pressure. In children epinephrine or norepinephrine is generally preferred while in adults norepinephrine is generally preferred for very low blood pressure. It is given intravenously or intraosseously as a continuous infusion. Effects typically begin within five minutes. Doses are then increased to effect.
ERB-196, also known as WAY-202196, is a synthetic nonsteroidal estrogen that acts as a highly selective agonist of the ERβ. It possesses 78-fold selectivity for the ERβ over the ERα. The drug was under development by Wyeth for the treatment of inflammation and sepsis starting in 2004 but development was discontinued by 2011.
Vasopressin infusions are in use for septic shock patients not responding to fluid resuscitation or infusions of catecholamines to increase the blood pressure while sparing the use of catecholamines. These argipressins have much shorter elimination half-life than synthetic non-arginine vasopresines with much longer elimination half-life of many hours. Further, argipressins act on V1a, V1b, and V2 receptors which consequently lead to higher eGFR and lower vascular resistance in the lungs. A number of injectable arginine vasopressins are in clinical use in the United States and the European Union. Pitressin among others, is a medication most commonly used in the treatment of frequent urination, increased thirst, and dehydration such as that resulting from diabetes insipidus, which causes increased and diluted urine. It is used to treat abdominal distension following some surgeries, and in stomach roentgenography. Vasopressin is a hormone that affects the kidneys and reduces urine flow.
The β3 adrenergic receptor agonist or β3-adrenoceptor agonist, also known as β3-AR agonist, are a class of medicine that bind selectively to β3-adrenergic receptors.
Vasodilatory shock, vasogenic shock, or vasoplegic shock is a medical emergency belonging to shock along with cardiogenic shock, septic shock, allergen-induced shock and hypovolemic shock. When the blood vessels suddenly relax, it results in vasodilation. In vasodilatory shock, the blood vessels are too relaxed leading to extreme vasodilation and blood pressure drops and blood flow becomes very low. Without enough blood pressure, blood and oxygen won't be pushed to reach the body's organs. If vasodilatory shock lasts more than a few minutes, the lack of oxygen starts to damage the body's organs. Vasodilatory shock like other types of shock should be treated quickly, otherwise it can cause permanent organ damage or death as a result of multiple organ dysfunction.
