Bupivacaine is a widely used local anesthetic agent. Bupivacaine is often administered by spinal injection prior to total hip arthroplasty. It is also commonly injected into surgical wound sites to reduce pain for up to 20 hours after surgery. In comparison to other local anesthetics it has a long duration of action. It is also the most toxic to the heart when administered in large doses. Bupivacaine blocks the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. Bupivacaine binds to the intracellular portion of sodium channels and blocks sodium influx into nerve cells, which prevents depolarization. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers. The analgesic effects of bupivicaine are thought to potentially be due to its binding to the prostaglandin E2 receptors, subtype EP1 (PGE2EP1), which inhibits the production of prostaglandins, thereby reducing fever, inflammation, and hyperalgesia. Bupivacaine sometimes used in combination with epinephrine to prevent systemic absorption and extend the duration of action.

Bupivacaine is a widely used local anesthetic agent. Bupivacaine is often administered by spinal injection prior to total hip arthroplasty. It is also commonly injected into surgical wound sites to reduce pain for up to 20 hours after surgery. In comparison to other local anesthetics it has a long duration of action. It is also the most toxic to the heart when administered in large doses. Bupivacaine blocks the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. Bupivacaine binds to the intracellular portion of sodium channels and blocks sodium influx into nerve cells, which prevents depolarization. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers. The analgesic effects of bupivicaine are thought to potentially be due to its binding to the prostaglandin E2 receptors, subtype EP1 (PGE2EP1), which inhibits the production of prostaglandins, thereby reducing fever, inflammation, and hyperalgesia. Bupivacaine sometimes used in combination with epinephrine to prevent systemic absorption and extend the duration of action.

Alitretinoin, or 9-cis-retinoic acid, is a form of vitamin A. It is also used in medicine as an antineoplastic (anti-cancer) agent developed by Ligand Pharmaceuticals. Alitretinoin (9-cis-retinoic acid) is a naturally-occurring endogenous retinoid indicated for topical treatment of cutaneous lesions in patients with AIDS-related Kaposi's sarcoma. Alitretinoin inhibits the growth of Kaposi's sarcoma (KS) cells in vitro. Alitretinoin binds to and activates all known intracellular retinoid receptor subtypes (RARa, RARb, RARg, RXRa, RXRb and RXRg). Once activated these receptors function as transcription factors that regulate the expression of genes that control the process of cellular differentiation and proliferation in both normal and neoplastic cells. In the United States, topical alitretinoin (in the form of a gel; trade name Panretin) is indicated for the treatment of skin lesions in AIDS-related Kaposi's sarcoma.

Naloxone, sold under the brand name Narcan among others, is a medication used to block the effects of opioids, especially in overdose. Naloxone has an extremely high affinity for μ-opioid receptors in the central nervous system (CNS). Naloxone is a μ-opioid receptor (MOR) inverse agonist, and its rapid blockade of those receptors often produces rapid onset of withdrawal symptoms. Naloxone also has an antagonist action, though with a lower affinity, at κ- (KOR) and δ-opioid receptors (DOR). If administered in the absence of concomitant opioid use, no functional pharmacological activity occurs (except the inability for the body to combat pain naturally). In contrast to direct opiate agonists, which elicit opiate withdrawal symptoms when discontinued in opiate-tolerant people, no evidence indicates the development of tolerance or dependence on naloxone. The mechanism of action is not completely understood, but studies suggest it functions to produce withdrawal symptoms by competing for opiate receptor sites within the CNS (a competitive antagonist, not a direct agonist), thereby preventing the action of both endogenous and xenobiotic opiates on these receptors without directly producing any effects itself. When administered parenterally (e.g. intravenously or by injection), as is most common, naloxone has a rapid distribution throughout the body. The mean serum half-life has been shown to range from 30 to 81 minutes, shorter than the average half-life of some opiates, necessitating repeat dosing if opioid receptors must be stopped from triggering for an extended period. Naloxone is primarily metabolized by the liver. Its major metabolite is naloxone-3-glucuronide, which is excreted in the urine. Naloxone is useful both in acute opioid overdose and in reducing respiratory or mental depression due to opioids. Whether it is useful in those in cardiac arrest due to an opioid overdose is unclear. Naloxone is poorly absorbed when taken by mouth, so it is commonly combined with a number of oral opioid preparations, including buprenorphine and pentazocine, so that when taken orally, just the opioid has an effect, but if misused by injecting, the naloxone blocks the effect of the opioid. In a meta-analysis of people with shock, including septic, cardiogenic, hemorrhagic, or spinal shock, those who received naloxone had improved blood flow. Naloxone is also experimentally used in the treatment for congenital insensitivity to pain with anhidrosis, an extremely rare disorder (one in 125 million) that renders one unable to feel pain or differentiate temperatures. Naloxone can also be used as an antidote in overdose of clonidine, a medication that lowers blood pressure.

Alitretinoin, or 9-cis-retinoic acid, is a form of vitamin A. It is also used in medicine as an antineoplastic (anti-cancer) agent developed by Ligand Pharmaceuticals. Alitretinoin (9-cis-retinoic acid) is a naturally-occurring endogenous retinoid indicated for topical treatment of cutaneous lesions in patients with AIDS-related Kaposi's sarcoma. Alitretinoin inhibits the growth of Kaposi's sarcoma (KS) cells in vitro. Alitretinoin binds to and activates all known intracellular retinoid receptor subtypes (RARa, RARb, RARg, RXRa, RXRb and RXRg). Once activated these receptors function as transcription factors that regulate the expression of genes that control the process of cellular differentiation and proliferation in both normal and neoplastic cells. In the United States, topical alitretinoin (in the form of a gel; trade name Panretin) is indicated for the treatment of skin lesions in AIDS-related Kaposi's sarcoma.

Alitretinoin, or 9-cis-retinoic acid, is a form of vitamin A. It is also used in medicine as an antineoplastic (anti-cancer) agent developed by Ligand Pharmaceuticals. Alitretinoin (9-cis-retinoic acid) is a naturally-occurring endogenous retinoid indicated for topical treatment of cutaneous lesions in patients with AIDS-related Kaposi's sarcoma. Alitretinoin inhibits the growth of Kaposi's sarcoma (KS) cells in vitro. Alitretinoin binds to and activates all known intracellular retinoid receptor subtypes (RARa, RARb, RARg, RXRa, RXRb and RXRg). Once activated these receptors function as transcription factors that regulate the expression of genes that control the process of cellular differentiation and proliferation in both normal and neoplastic cells. In the United States, topical alitretinoin (in the form of a gel; trade name Panretin) is indicated for the treatment of skin lesions in AIDS-related Kaposi's sarcoma.

Alitretinoin, or 9-cis-retinoic acid, is a form of vitamin A. It is also used in medicine as an antineoplastic (anti-cancer) agent developed by Ligand Pharmaceuticals. Alitretinoin (9-cis-retinoic acid) is a naturally-occurring endogenous retinoid indicated for topical treatment of cutaneous lesions in patients with AIDS-related Kaposi's sarcoma. Alitretinoin inhibits the growth of Kaposi's sarcoma (KS) cells in vitro. Alitretinoin binds to and activates all known intracellular retinoid receptor subtypes (RARa, RARb, RARg, RXRa, RXRb and RXRg). Once activated these receptors function as transcription factors that regulate the expression of genes that control the process of cellular differentiation and proliferation in both normal and neoplastic cells. In the United States, topical alitretinoin (in the form of a gel; trade name Panretin) is indicated for the treatment of skin lesions in AIDS-related Kaposi's sarcoma.

Naloxone, sold under the brand name Narcan among others, is a medication used to block the effects of opioids, especially in overdose. Naloxone has an extremely high affinity for μ-opioid receptors in the central nervous system (CNS). Naloxone is a μ-opioid receptor (MOR) inverse agonist, and its rapid blockade of those receptors often produces rapid onset of withdrawal symptoms. Naloxone also has an antagonist action, though with a lower affinity, at κ- (KOR) and δ-opioid receptors (DOR). If administered in the absence of concomitant opioid use, no functional pharmacological activity occurs (except the inability for the body to combat pain naturally). In contrast to direct opiate agonists, which elicit opiate withdrawal symptoms when discontinued in opiate-tolerant people, no evidence indicates the development of tolerance or dependence on naloxone. The mechanism of action is not completely understood, but studies suggest it functions to produce withdrawal symptoms by competing for opiate receptor sites within the CNS (a competitive antagonist, not a direct agonist), thereby preventing the action of both endogenous and xenobiotic opiates on these receptors without directly producing any effects itself. When administered parenterally (e.g. intravenously or by injection), as is most common, naloxone has a rapid distribution throughout the body. The mean serum half-life has been shown to range from 30 to 81 minutes, shorter than the average half-life of some opiates, necessitating repeat dosing if opioid receptors must be stopped from triggering for an extended period. Naloxone is primarily metabolized by the liver. Its major metabolite is naloxone-3-glucuronide, which is excreted in the urine. Naloxone is useful both in acute opioid overdose and in reducing respiratory or mental depression due to opioids. Whether it is useful in those in cardiac arrest due to an opioid overdose is unclear. Naloxone is poorly absorbed when taken by mouth, so it is commonly combined with a number of oral opioid preparations, including buprenorphine and pentazocine, so that when taken orally, just the opioid has an effect, but if misused by injecting, the naloxone blocks the effect of the opioid. In a meta-analysis of people with shock, including septic, cardiogenic, hemorrhagic, or spinal shock, those who received naloxone had improved blood flow. Naloxone is also experimentally used in the treatment for congenital insensitivity to pain with anhidrosis, an extremely rare disorder (one in 125 million) that renders one unable to feel pain or differentiate temperatures. Naloxone can also be used as an antidote in overdose of clonidine, a medication that lowers blood pressure.

Naloxone, sold under the brand name Narcan among others, is a medication used to block the effects of opioids, especially in overdose. Naloxone has an extremely high affinity for μ-opioid receptors in the central nervous system (CNS). Naloxone is a μ-opioid receptor (MOR) inverse agonist, and its rapid blockade of those receptors often produces rapid onset of withdrawal symptoms. Naloxone also has an antagonist action, though with a lower affinity, at κ- (KOR) and δ-opioid receptors (DOR). If administered in the absence of concomitant opioid use, no functional pharmacological activity occurs (except the inability for the body to combat pain naturally). In contrast to direct opiate agonists, which elicit opiate withdrawal symptoms when discontinued in opiate-tolerant people, no evidence indicates the development of tolerance or dependence on naloxone. The mechanism of action is not completely understood, but studies suggest it functions to produce withdrawal symptoms by competing for opiate receptor sites within the CNS (a competitive antagonist, not a direct agonist), thereby preventing the action of both endogenous and xenobiotic opiates on these receptors without directly producing any effects itself. When administered parenterally (e.g. intravenously or by injection), as is most common, naloxone has a rapid distribution throughout the body. The mean serum half-life has been shown to range from 30 to 81 minutes, shorter than the average half-life of some opiates, necessitating repeat dosing if opioid receptors must be stopped from triggering for an extended period. Naloxone is primarily metabolized by the liver. Its major metabolite is naloxone-3-glucuronide, which is excreted in the urine. Naloxone is useful both in acute opioid overdose and in reducing respiratory or mental depression due to opioids. Whether it is useful in those in cardiac arrest due to an opioid overdose is unclear. Naloxone is poorly absorbed when taken by mouth, so it is commonly combined with a number of oral opioid preparations, including buprenorphine and pentazocine, so that when taken orally, just the opioid has an effect, but if misused by injecting, the naloxone blocks the effect of the opioid. In a meta-analysis of people with shock, including septic, cardiogenic, hemorrhagic, or spinal shock, those who received naloxone had improved blood flow. Naloxone is also experimentally used in the treatment for congenital insensitivity to pain with anhidrosis, an extremely rare disorder (one in 125 million) that renders one unable to feel pain or differentiate temperatures. Naloxone can also be used as an antidote in overdose of clonidine, a medication that lowers blood pressure.

Megestrol acetate is a progestational hormone used most commonly as the acetate ester. As the acetate, it is more potent than progesterone both as a progestagen and as an ovulation inhibitor. It has also been used in the palliative treatment of breast cancer. MEGACE Oral Suspension is indicated for the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS). The precise mechanism by which megestrol acetate produces effects in anorexia and cachexia is unknown at the present time. But its progestin antitumour activity may involve suppression of luteinizing hormone by inhibition of pituitary function. Studies also suggest that the megestrol's weight gain effect is related to its appetite-stimulant or metabolic effects rather than its glucocorticoid-like effects or the production of edema. It has also been suggested that megestrol may alter metabolic pathyways via interferences with the production or action of mediators such as cachectin, a hormone that inhibits adipocyte lipogenic enzymes. The major route of drug elimination in humans is urine. When radiolabeled megestrol acetate was administered to humans in doses of 4 to 90 mg, the urinary excretion within 10 days ranged from 56.5% to 78.4% (mean 66.4%) and fecal excretion ranged from 7.7% to 30.3% (mean 19.8%). The total recovered radioactivity varied between 83.1% and 94.7% (mean 86.2%). Megestrol acetate metabolites which were identified in urine constituted 5% to 8% of the dose administered. Respiratory excretion as labeled carbon dioxide and fat storage may have accounted for at least part of the radioactivity not found in urine and feces. Plasma steady-state pharmacokinetics of megestrol acetate were evaluated in 10 adult, cachectic male patients with acquired immunodeficiency syndrome (AIDS) and an involuntary weight loss greater than 10% of baseline. Patients received single oral doses of 800 mg/day of MEGACE Oral Suspension for 21 days. Plasma concentration data obtained on day 21 were evaluated for up to 48 hours past the last dose.