Alvimopan (LY246736, ADL 8-2698, trade name Entereg) is a potent, peripherally selective mu-opioid receptor antagonist. Alvimopan was developed by Adolor Corporation (now Cubist Pharmaceuticals) and GlaxoSmithKline for the treatment of postoperative ileus. Postoperative ileus is the impairment of gastrointestinal motility after intra-abdominal surgery or other non-abdominal surgeries. This may potentially delay gastrointestinal recovery and hospital discharge until its resolution. Morphine and other mu-opioid receptor agonists are universally used for the treatment of acute postsurgical pain; however, they are known to have an inhibitory effect on gastrointestinal motility and may prolong the duration of postoperative ileus. Following oral administration, alvimopan antagonizes the peripheral effects of opioids on gastrointestinal motility and secretion by competitively binding to gastrointestinal tract mu-opioid receptors.

Difluprednate is a corticosteroid used as an anti-inflammatory steroidal drug used primarily in ocular surgery. It is thought to act by the induction of phospholipase A2 inhibitory proteins (lipocortins). It is postulated that these proteins control the biosynthesis of potent mediators of infammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2. It is marketed by Alcon under the tradename Durezol.

Ambrisentan (alternative Names: BSF 208075; GSK 1325760; GSK1325760A; Letairis) is an endothelin receptor antagonist that is selective for the endothelin type-A (ETA) receptor. The chemical name of ambrisentan is (+)-(2S)-2-[(4,6-dimethylpyrimidin-2-yl)oxy]-3-methoxy-3,3-diphenylpropanoic acid. Ambrisentan is indicated for the treatment of pulmonary arterial hypertension. It is approved in Europe, Canada and the United States for use as a single agent to improve exercise ability and delay clinical worsening. In addition, it is approved in the United States for use in combination with tadalafil to reduce the risks of disease progression, hospitalization and to improve exercise ability. As an endothelin receptor antagonist, ambrisentan prevents endogenous endothelin peptide from constricting the muscles in blood vessels, allowing them to relax and permit a reduction in blood pressure. Endothelin-1 (ET-1) is a potent autocrine and paracrine peptide. Two receptor subtypes, ETA and ETB, mediate the effects of ET-1 in the vascular smooth muscle and endothelium. The primary actions of ETA are vasoconstriction and cell proliferation, while the predominant actions of ETB are vasodilation, antiproliferation, and ET-1 clearance. In patients with PAH, plasma ET-1 concentrations are increased as much as 10-fold and correlate with increased mean right atrial pressure and disease severity. ET-1 and ET-1 mRNA concentrations are increased as much as 9-fold in the lung tissue of patients with PAH, primarily in the endothelium of pulmonary arteries. These findings suggest that ET-1 may play a critical role in the pathogenesis and progression of PAH. Ambrisentan is a high-affinity (Ki=0.011 nM) ETA receptor antagonist with a high selectivity for the ETA versus ETB receptor (>4000-fold). The clinical impact of high selectivity for ETA is not known.

Fluticasone furoate is a synthetic trifluorinated corticosteroid with potent anti-inflammatory activity. Fluticasone furoate is a anti-allergic agents that is FDA approved for the treatment of symptoms of seasonal and perennial allergic rhinitis, asthma and for reducing exacerbations in patients with chronic obstructive pulmonary disease. Fluticasone furoate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor. The clinical relevance of these findings is unknown. The most common adverse reactions (>1% incidence) included headache, epistaxis, pharyngolaryngeal pain, nasal ulceration, back pain, pyrexia, and cough. Coadministration of ritonavir is not recommended. Use caution with coadministration of other potent CYP3A4 inhibitors, such as ketoconazole.

Nebivolol is a competitive and highly selective beta-1 receptor antagonist with mild vasodilating properties, possibly due to an interaction with the L-arginine/nitric oxide pathway. In preclinical studies, nebivolol has been shown to induce endothelium-dependent arterial relaxation in a dose dependent manner, by stimulation of the release of endothelial nitric oxide. Nitric oxide acts to relax vascular smooth muscle cells and inhibits platelet aggregation and adhesion. Activation of β1-receptors by epinephrine increases the heart rate and the blood pressure, and the heart consumes more oxygen. Nebivolol blocks these receptors which reverses the effects of epinephrine, lowering the heart rate and blood pressure. In addition, beta blockers prevent the release of renin, which is a hormone produced by the kidneys which leads to constriction of blood vessels. At high enough concentrations, this drug may also bind beta 2 receptors. Marketed under the brand name BYSTOLIC, Nebivolol is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.

Sitagliptin (MK-0431), chemically (2R)-4-Oxo-4-[3- (trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin- 7(8H)-yl]-1-(2,4,5-trifl uorophenyl)butan-2-amine has a very high selectivity towards DPP-4, with an IC(50) of 18 nM. There is no affinity towards other DDP enzymes (DPP- 8 and DPP-9). It has been approved for the treatment of type 2 diabetes in the USA and Europe and is registered by the name Januvia (Merck Pharmaceuticals, Whitehouse Station, NJ, USA). In healthy volunteers and in patients with type 2 diabetes of different ethnic background, the tolerability of different doses given once or twice daily is good. The drug works to competitively inhibit a protein/enzyme, dipeptidyl peptidase 4 (DPP-4), that results in an increased amount of active incretins (GLP-1 and GIP), reduced amount of release of glucagon (diminishes its release) and increased release of insulin. Sitagliptin is an incretin enhancer and the first marketed medication belonging to the gliptin class. In fact, no published literature exists regarding incidence or severity of hypoglycemia when sitagliptin is used off-label in combined with insulin therapy. However, is recommended to use methods to avoid hypoglycemia when using this off-label combination. Approximately 79% of sitagliptin is excreted unchanged in the urine with metabolism being a minor pathway of elimination. Elimination of sitagliptin occurs primarily via renal excretion and involves active tubular secretion. Sitagliptin is a substrate for human organic anion transporter-3 (hOAT-3), which may be involved in the renal elimination of sitagliptin

Lubiprostone is a medication used in the management of idiopathic chronic constipation. It is a bicyclic fatty acid (prostaglandin E1 derivative) which acts by specifically activating ClC-2 chloride channels on the apical aspect of gastrointestinal epithelial cells, producing a chloride-rich fluid secretion. These secretions soften the stool, increase motility, and promote spontaneous bowel movements (SBM). Lubiprostone acts by specifically activating ClC-2 chloride channels, which is a normal constituent of the apical membrane of the human intestine, in a protein kinase A action independent fashion. Activation of ClC-2 chloride channels causes an efflux of chloride ions into the lumen, which in turn leads to an efflux of sodium ions through a paracellular pathway to maintain isoelectric neutrality. As a result, water follows sodium into the lumen in order to maintain isotonic equilibrium, thereby increasing intestinal fluid secretion. By increasing intestinal fluid secretion, lubiprostone increases motility in the intestine, thereby increasing the passage of stool and alleviating symptoms associated with chronic idiopathic constipation. Activation of ClC-2 chloride channels may also stimulate the recovery of muscosal barrier function by restoring tight junction protein complexes in the intestine. Patch clamp cell studies in human cell lines have indicated that the majority of the beneficial biological activity of lubiprostone and its metabolites is observed only on the apical (luminal) portion of the gastrointestinal epithelium. Lubiprostone is marketed under the trade name Amitiza among others.

Ciclesonide is a glucocorticoid receptor agonist indicated for the treatment of allergic rhinitis (Omnaris nasal spray) and asthma (Alvesco). It was also developed by Byk Gulden for chronic obstructive pulmonary disease (COPD), but no development had been reported for this indication since 1999. Ciclesonide is a pro-drug and rapidly metabolized to C21-desisobutyryl-ciclesonide which is more potent toward GR receptor than the parent drug.

Posaconazole is a triazole antifungal drug that is used to treat invasive infections by Candida species and Aspergillus species in severely immunocompromised patients. It marketed in the United States, the European Union, and in other countries by Schering-Plough under the trade name Noxafil. Noxafil is used for prophylaxis of invasive Aspergillus and Candida infections in patients, 13 years of age and older, who are at high risk of developing these infections due to being severely immunocompromised as a result of procedures such as hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD), or due to hematologic malignancies with prolonged neutropenia from chemotherapy. Also for the treatment of oropharyngeal candidiasis, including oropharyngeal candidiasis refractory to itraconazole and/or fluconazole. Posaconazole blocks the synthesis of ergosterol, a key component of the fungal cell membrane, through the inhibition of cytochrome P-450 dependent enzyme lanosterol 14α-demethylase responsible for the conversion of lanosterol to ergosterol in the fungal cell membrane. This results in an accumulation of methylated sterol precursors and a depletion of ergosterol within the cell membrane thus weakening the structure and function of the fungal cell membrane. This may be responsible for the antifungal activity of posaconazole. It is absorbed within three to five hours and predominately eliminated through the liver, and has a half-life of about 35 hours. Oral administration of posaconazole taken with a high-fat meal exceeds 90% bioavailability and increases the concentration by four times compared to fasting state.

Darifenacin is a selective muscarinic receptor M3 antagonist which was approved by FDA for the treatment of overactive bladder.