Inamrinone (Amrinone) is a positive inotropic cardiotonic with vasodilator properties, phosphodiesterase inhibitory activity, and the ability to stimulate calcium ion influx into the cardiac cell. Inamrinone is a phosphodiesterase inhibitor (PDE3), resulting in increased cAMP and cGMP which leads to an increase in the calcium influx like that caused by beta-agonists resulting in increased inotropic effect. Inamrinone is used in the treatment of congestive heart failure.

Pimozide (Orap) is a diphenylbutylpiperidine that is effective as an antipsychotic agent and as an alternative to haloperidol for the suppression of vocal and motor tics in patients with Tourette syndrome. It is not intended as a treatment of first choice nor is it intended for the treatment of tics that are merely annoying or cosmetically troublesome. It should be reserved for use in Tourette’s Disorder patients whose development and/or daily life function is severely compromised by the presence of motor and phonic tics. Evidence supporting approval of pimozide for use in Tourette’s Disorder was obtained in two controlled clinical investigations, which enrolled patients between the ages of 8 and 53 years. Most subjects in the two trials were 12 or older. Pimozide is an orally active antipsychotic drug product, which shares with other antipsychotics the ability to blockade dopaminergic receptors on neurons in the central nervous system. Although its exact mode of action has not been established, the ability of pimozide to suppress motor and phonic tics in Tourette’s Disorder is thought to be a function of its dopaminergic blocking activity. However, receptor blockade is often accompanied by a series of secondary alterations in central dopamine metabolism and function which may contribute to both pimozide’s therapeutic and untoward effects. In addition, pimozide, in common with other antipsychotic drugs, has various effects on other central nervous system receptor systems which are not fully characterized.

Pentoxil (Pentoxifylline Extended-release Tablets, USP) is indicated for the treatment of patients with intermittent claudication based on chronic occlusive arterial disease of the limbs. Pentoxil can improve function and symptoms but is not intended to replace more definitive therapy, such as surgical bypass, or removal of arterial obstructions when treating peripheral vascular disease. Pentoxifylline and its metabolites improve the flow properties of blood by decreasing its viscosity. In patients with chronic peripheral arterial disease, this increases blood flow to the affected microcirculation and enhances tissue oxygenation. The precise mode of action of pentoxifylline and the sequence of events leading to clinical improvement are still to be defined. Pentoxifylline inhibits erythrocyte phosphodiesterase, resulting in an increase in erythrocyte cAMP activity. Subsequently, the erythrocyte membrane becomes more resistant to deformity. Along with erythrocyte activity, pentoxifylline also decreases blood viscosity by reducing plasma fibrinogen concentrations and increasing fibrinolytic activity. It is also a non-selective adenosine receptor antagonist. Pentoxifylline administration has been shown to produce dose-related hemorrheologic effects, lowering blood viscosity, and improving erythrocyte flexibility. Pentoxifylline has been shown to increase leukocyte deformability and to inhibit neutrophil adhesion and activation. Tissue oxygen levels have been shown to be significantly increased by therapeutic doses of pentoxifylline in patients with peripheral arterial disease. Clinical trials were conducted using either extended-release pentoxifylline tablets for up to 60 weeks or immediate-release pentoxifylline capsules for up to 24 weeks. Dosage ranges in the tablet studies were 400 mg bid to tid and in the capsule studies, 200-400 mg tid. The incidence of adverse reactions was higher in the capsule studies (where dose related increases were seen in digestive and nervous system side effects) than in the tablet studies. Studies with the capsule include domestic experience, whereas studies with the extended-release tablets were conducted outside the U.S.

Glyburide, a second-generation sulfonylurea antidiabetic agent, lowers blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. With chronic administration in Type II diabetic patients, the blood glucose lowering effect persists despite a gradual decline in the insulin secretory response to the drug. Extrapancreatic effects may be involved in the mechanism of action of oral sulfonyl-urea hypoglycemic drugs. The combination of glibenclamide and metformin may have a synergistic effect, since both agents act to improve glucose tolerance by different but complementary mechanisms. In addition to its blood glucose lowering actions, glyburide produces a mild diuresis by enhancement of renal free water clearance. Glyburide is twice as potent as the related second-generation agent glipizide. Sulfonylureas such as glyburide bind to ATP-sensitive potassium channels on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin. Glyburide is indicated as an adjunct to diet to lower the blood glucose in patients with NIDDM whose hyperglycemia cannot be satisfactorily controlled by diet alone. Glyburide is available as a generic, is manufactured by many pharmaceutical companies and is sold in doses of 1.25, 2.5 and 5 mg under many brand names including Gliben-J, Daonil, Diabeta, Euglucon, Gilemal, Glidanil, Glybovin, Glynase, Maninil, Micronase and Semi-Daonil. It is also available in a fixed-dose combination drug with metformin that is sold under various trade names, e.g. Bagomet Plus, Benimet, Glibomet, Gluconorm, Glucored, Glucovance, Metglib and many others.

Pentamidine (formulated as a salt, pentamidine diisethionate or dimesilate) is an antimicrobial medication given for prevention and treatment of pneumocystis pneumonia (PCP) caused by Pneumocystis jirovecii (formerly known as Pneumocystis carinii), a severe interstitial type of pneumonia often seen in patients with HIV infection. The drug is also the mainstay of treatment for stage I infection with Trypanosoma bruceigambiense (West African trypanosomiasis). Pentamidine is also used as a prophylactic against PCP in patients receiving chemotherapy and in some patients who have undergone organ transplantation, as they also have a depressed immune system as a direct side-effect of the drugs used. The mortality of untreated PCP is very high. Additionally, pentamidine has good clinical activity in treating leishmaniasis, and yeast infections caused by the organism Candida albicans. Pentamidine is also used as a prophylactic antibiotic for children undergoing treatment for leukemia. Studies suggest that the pentamidine isethionate interferes with microbial nuclear metabolism by inhibition of DNA, RNA, phospholipid and protein synthesis. However, the mode of action is not fully understood.

Ceftriaxone is a broad-spectrum cephalosporin antibiotic with a very long half-life. Ceftriaxone is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Ceftriaxone has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria. It is approved for the treatment of lower respiratory tract infections, acute bacterial otitis media, skin infections, urinary tract infections, pelvic inflammatory disease, bacterial septicemia, bone and joint infections, intraabdominal infection, meningitis, and surgical prophylaxis. Common adverse reactions include erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, pseudomembranous enterocolitis, hemolytic anemia, hypersensitivity reaction, kernicterus, renal failure, and lung injury. Vancomycin, amsacrine, aminoglycosides, and fluconazole are incompatible with Ceftriaxone in admixtures. Precipitation of Ceftriaxone-calcium can occur when Ceftriaxone for Injection is mixed with calcium-containing solutions in the same intravenous administration line.

Amdinocillin is a novel, semisynthetic penicillin effective against many gram-negative bacteria. The antibacterial activity of amdinocillin is derived from its ability to bind specifically and avidly to Penicillin Binding Protein-2 (PBP 2). Amdinocillin is active alone against many gram-negative organisms. Pseudomonas and non-fermenting gram-negative bacteria, however, are usually resistant. Amdinocillin, in combination with many beta-lactams, exhibits marked synergy against many enterobacteriaceae. No such synergy can be demonstrated for gram-positive organisms or pseudomonas species. Amdinocillin is not beta-lactamase stable. Organisms which produce high levels of plasma-mediated beta-lactamase are resistant to the drug. Used in the treatment of urinary tract infections caused by some strains of E. coli and klebsiella and enterobacter species. Used mainly against Gram negative organisms. Amdinocillin is not available in the United States.

Glipizide, a second-generation sulfonylurea, is used with diet to lower blood glucose in patients with diabetes mellitus type II. The primary mode of action of glipizide in experimental animals appears to be the stimulation of insulin secretion from the beta cells of pancreatic islet tissue and is thus dependent on functioning beta cells in the pancreatic islets. In humans glipizide appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. In man, stimulation of insulin secretion by glipizide in response to a meal is undoubtedly of major importance. Fasting insulin levels are not elevated even on long-term glipizide administration, but the postprandial insulin response continues to be enhanced after at least 6 months of treatment. Some patients fail to respond initially, or gradually lose their responsiveness to sulfonylurea drugs, including glipizide. Sulfonylureas likely bind to ATP-sensitive potassium-channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin. Glipizide is used as an adjunct to diet for the control of hyperglycemia and its associated symptomatology in patients with non-insulin-dependent diabetes mellitus (NIDDM; type II), formerly known as maturity-onset diabetes, after an adequate trial of dietary therapy has proved unsatisfactory. Glipizide is marketed by Pfizer under the brand name Glucotrol in the USA, where Pfizer sells Glucotrol in doses of 5 and 10 milligrams and Glucotrol XL (an extended release form of glipizide) in doses of 2.5, 5, and 10 milligrams. Other companies also market glipizide, most commonly extended release tablets of 5 and 10 milligrams.

Sufentanil is a synthetic opioid analgesic. Sufentanil interacts predominately with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, sufentanil exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. Sufentanil may increase the patient's tolerance for pain and decrease the perception of suffering, although the presence of the pain itself may still be recognized. In addition to analgesia, alterations in mood, euphoria and dysphoria, and drowsiness commonly occur. Sufentanil depresses the respiratory centers, depresses the cough reflex, and constricts the pupils. Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. Binding of the opiate stimulates the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline is inhibited. Opioids also inhibit the release of vasopressin, somatostatin, insulin and glucagon. Sufentanil's analgesic activity is, most likely, due to its conversion to morphine. Opioids open calcium-dependent inwardly rectifying potassium channels (OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability. Sufentanil is used as an analgesic adjunct in anesthesia and as a primary anesthetic drug in procedures requiring assisted ventilation and in the relief of pain.

Clavulanic acid is produced by the fermentation of Streptomyces clavuligerus. It is a β-lactam structurally related to the penicillins and possesses the ability to inactivate a wide variety of β-lactamases by blocking the active sites of these enzymes. Clavulanic acid is particularly active against the clinically important plasmid-mediated β-lactamases frequently responsible for transferred drug resistance to penicillins and cephalosporins. Clavulanic acid is used in conjunction with amoxicillin for the treatment of bronchitis and urinary tract, skin, and soft tissue infections caused by beta-lactamase producing organisms. Clavulanic acid competitively and irreversibly inhibits a wide variety of beta-lactamases, commonly found in microorganisms resistant to penicillins and cephalosporins. Binding and irreversibly inhibiting the beta-lactamase results in a restauration of the antimicrobial activity of beta-lactam antibiotics against lactamase-secreting-resistant bacteria. By inactivating beta-lactamase (the bacterial resistance protein), the accompanying penicillin/cephalosporin drugs may be made more potent as well.