Pharmacology Facts from Previous Papers

·         Amantadine's mechanism of action involves inhibition of uncoating of the influenza A viral DNA. The primary target is the membrane M2 protein. The drug does not affect penetration and DNA-dependent RNA polymerase activity.

·         Cloramphenicol: Nitrobenzene group

·         8-aminoquinoline derivatives: Primaquine

·         4-quinoline derivatives: Chloro, Meflo, AmodiaQUINE

·         salicylamide derivative: Niclosamide

·         derivative of adamantine: Rimantadine

·         derivative of pyrophosphate: Foscarnet

·         derivative of chloroethylamine: Cyclophosphamide

·         derivative of ethylenimine: Thiotepa

·         derivative of alkylsulfonate: Busulfan

·         anticancer drug of plant origin: Vincristine

·          

·         Acyclovir not effective against CMV.

·         Antimicrobial drug causing myopathy – Daptomycin

·          

·         Drugs that cause osteoporosis are : ( GHALACTose)

1. glucocorticoids, GnRH antagonists

2. heparin

3. anticonvulsants, aluminium,

4. lithium

5. alcohol excess intake

6. cyclosporine, cytotoxic drugs

7. thyroxine excess

·         drugs causing gingival hyperplasia:

•phenytoin(dilantin)-antiepileptic

•cyclosporine-immunosuppresant

•calcium channel blockers especially nifedipine

·         drugs causing pseudotumor cerebri:

•tetracyclines,naldixic acid,nitrofurantoin

•indomethacin-NSAID

•oral contraceptive pills

•vitamin A

•isotretinon-retinoic acid derivative used for acne

•lithium-used in bipolar disorder

•danazol-antigonadotropic drug

·         drugs causing photosensitivity:

•tetracycline,fluroquinolones-antibiotics

•NSAIDs

•ACE(angiotensin converting enzyme)inhibitors-antihypertensives

•tricyclic antidepressants

•phenothiazines

•oral contraceptives.

·         Drugs that may produce disulfiramlike reactions with ethanol include the following:

•Mushrooms (eg, Coprinus atramentarius [inky cap], Clitocybe claviceps)

•Antibiotics

1.metronidazole,Tinidazole is chemically similar to metronidazole and so may cause the same reaction

2.sulfonamides(trimethoprim-sulfamethoxazole)

3.some cephalosporins( eg: cephamandole, cefoperazone, cefmenoxime, cefotetan, Moxalactam)- due to METHYLTETRAZOLETHIOL side chain.

4.nitrofurantoin,

5.chloramphenicol

6.furazolidine

7.Antimalarial Quinacrine

•Oral hypoglycemics (eg: chlorpropamide, tolbutamide)- these sulphonylureas compete with acetaldehyde for binding sites on ALDH.

•Pesticides (eg: carbamates, monosulfiram [Tetmosol])

•Chloral hydrate

•Antifungals (griseofulvin)

·         plants from which commonly used drugs are derived.

Claviceps purpurea                 Ergotamine
Erythroxylon coca                   Cocaine
Papavertum somniferum          Morphine, codeine, thebaine, papaverine etc.
Digitalis purpurea                    Lantana digoxin
Rauwolfia serpentina               Reserpine
Atropa belladonna                   Atropine
Hyocyamus niger                    Hyoscine

Source Element of Drugs

·         Pilocarpine is the chief alkaloid obtained from the leaflets of South American shrubs of the genus Pilocarpus.

·         Physostigmine, also called eserine, is an alkaloid obtained from the Calabar or ordeal bean, the dried, ripe seed of Physostigma venenosum, Balfour, a perennial plant found in tropical West Africa. The Calabar bean once was used by native tribes of West Africa as an "ordeal poison" in trials for witchcraft.

·         The most potent curare alkaloids are the toxiferines, obtained from Strychnos toxifera.

·         morphine is obtained from opium or extracted from poppy straw. Opium is obtained from the unripe seed capsules of the poppy plant, Papaver somniferum. The milky juice is dried and powdered to make powdered opium, which contains a number of alkaloids. Only a few¾morphine, codeine, and papaverine¾have clinical usefulness.

·         Senna is obtained from the dried leaflets on pods of Cassia acutifolia or Cassia angustifolia and contains the rhein dianthrone glycosides sennoside A and B.

·         Cascara sagrada ("sacred bark") is obtained from the bark of the buckthorn tree and contains the glycosides barbaloin and chrysaloin.

·         The two common preparations of pancreatic enzymes for replacement therapy are obtained from the pancreas of the hog (Sus scrofa Linne var. domesticus Gray).

·         6-aminopenicillanic acid could be obtained from cultures of P. chrysogenum

·         The rifamycins (rifampin, rifabutin, rifapentine) are a group of structurally similar, complex macrocyclic antibiotics produced by Amycolatopsis mediterranei

·         Recombinant interferon alfa-2b (IFN-alpha 2, INTRON A) is obtained from Escherichia coli by recombinant expression.

·         Chorionic gonadotropin which mimics the action of LH, is obtained from the urine of pregnant women.

·         Menotropins [men-oh-TROE-pin] (human menopausal gonadotropins, or hMG) are obtained from the urine of menopausal women and contain FSH and luteinizing hormone LH.

·         Urofollitropin is FSH obtained from menopausal women and is devoid of LH.

·         Sirolimus is a recently approved macrolide obtained from fermentations of a soil mold. The earlier name and one that is sometimes still used is rapamycin.

·         Erythromycin: Streptomyces erythreus

·         Bacitracin: a polypeptide obtained from a strain (Tracy strain) of Bacillus subtilis

Withdrawn Drugs

·         Phenformin: lactic acidosis

·         Troglitazone: hepatotoxicity.

·         Terfenadine: CYP3A4 inhibition caused ventricular tachycardia.

·         fenfluramine and dexfenfluramine: cardiac toxicity.

·         Zimelidine (1^st SSRI) was withdrawn due to an association with febrile illness and Guillain-Barre ascending paralysis.

·         Nomifensine is a structurally distinct antidepressant that inhibits the transport of both norepinephrine and dopamine; it was withdrawn from clinical use in 1996 owing to risk of hemolytic anemia and intravascular hemolysis.

·         Rofecoxib: GI bleed

·         Bromfenac(NSAAID) - its association with severe, irreversible liver injury

·         Milrinone :increase in sudden cardiac death

·         Phenolphthalein, once among the most popular components of laxatives, has been withdrawn from the market in the United States because of potential carcinogenicity. Oxyphenisatin, another older drug, was withdrawn due to hepatotoxicity.

·         alosetron was withdrawn from the U.S. market because of an unusually high incidence of ischemic colitis

·         The CYP2D6 polymorphism has led to the withdrawal of several clinically used drugs (e.g., debrisoquine and perhexiline) and the cautious use of others that are known CYP2D6 substrates (e.g., encainide and flecainide  [antiarrhythmics], desipramine and nortriptyline  [antidepressants], and codeine).

Cross Reactivity

·         Because halofantrine displays erratic bioavailability, potentially lethal cardiotoxicity, and extensive cross-resistance with mefloquine, its use generally is not recommended.

·         Resistance to melarsoprol is likely to involve transport defects, although the situation is complicated by evidence for multiple transport mechanisms of the drug. The best-characterized transporter is an unusual adenine-adenosine transporter termed the P2 transporter that has activity on melarsoprol as well as pentamidine and berenil. Cross-resistance between these compounds is observed frequently.

·         Because of the similar structures of the penicillins and cephalosporins, patients who are allergic to one class of agents may manifest cross-reactivity to a member of the other class. Immunological studies have demonstrated cross-reactivity in as many as 20% of patients who are allergic to penicillin, but clinical studies indicate a much lower frequency (about 1%) of such reactions. There are no skin tests that can reliably predict whether a patient will manifest an allergic reaction to the cephalosporins.

·         Resistance to gentamicin indicates cross-resistance to tobramycin, amikacin, kanamycin, and netilmicin because the inactivating enzyme is bifunctional and can modify all these aminoglycosides

·         Tetracycline resistance due to a ribosomal protection mechanism (tetM) produces cross-resistance to doxycycline and minocycline because the target site protected is the same for all tetracyclines.

·         Because the mechanisms producing resistance to erythromycin affect all macrolides, cross-resistance among them is complete. Macrolide-resistant strains of S. aureus are potentially cross-resistant to clindamycin and streptogramin B (quinupristin).

·         Cross-resistance between rifampin and rifabutin is common in M. tuberculosis,

·         Some foscarnet-resistant CMV isolates show cross-resistance to cidofovir.

·         Lamivudine resistance confers cross-resistance to related agents such as emtricitabine and clevudine and is often associated with an additional non-YMDD mutation that confers cross-resistance to famciclovir.

·         The reverse transcriptase insertion mutations at codon 69 produce cross-resistance to all current nucleoside analogs, including didanosine

·         The K65R substitution is associated with cross-resistance to didanosine, abacavir, and tenofovir, as well as the cytosine analogs lamivudine and emtricitabine.

·         Cross-resistance extends to all FDA-approved NNRTIs with the most common mutations. Therefore, any patient who fails treatment with one NNRTI because of a specific resistance mutation should be considered to have failed the entire class.

·         For the treatment of suspected but unconfirmed acute adrenal insufficiency, 4 mg of dexamethasone sodium phosphate can be substituted for hydrocortisone, since dexamethasone does not cross-react in the cortisol assay and will not interfere with the measurement of cortisol (either basally or in response to the cosyntropin stimulation test).

·          

CROSS RECTIVITY NOT SEEN IN

·         Artemisinin are not cross-resistant with other drugs; indeed, sensitivity to the artemisinins may be increased paradoxically in chloroquine-resistant parasites. When used alone, the artemisinins are associated with a high level of parasite recrudescence; the reason for this is not clear but may be related to their rapid metabolism or perhaps to a post-antibiotic-like effect on the parasite. They have gametocytocidal activity but do not affect either primary or latent liver stages.

·         Acquired resistance to sulfonamide usually does not involve cross-resistance to antimicrobial agents of other classes.

·         Aztreonam has been used successfully for the therapy of a variety of infections. One of its notable features is little allergic cross-reactivity with b-lactam antibiotics, with the possible exception of ceftazidine (Perez Pimiento et al., 1998), with which it has considerable structural similarity. Aztreonam is therefore quite useful for treating gram-negative infections that normally would be treated with a b-lactam antibiotic were it not for the history of a prior allergic reaction.

·         Linezolid inhibits protein synthesis by binding to the P site of the 50S ribosomal subunit and preventing formation of the larger ribosomal-fMet-tRNA complex that initiates protein synthesis. As mentioned above, there is no cross-resistance with other drug classes. Resistance in enterococci and staphylococci is due to point mutations of the 23S Rrna

·         Daptomycin binds to bacterial membranes resulting in depolarization, loss of membrane potential, and cell death. It has concentration-dependent bactericidal activity. Due to its unique mechanism of action, cross-resistance with other antibiotic classes seems not occur, and there are no known resistance mechanisms.

·         Mupirocin inhibits bacterial protein synthesis by reversible binding and inhibition of isoleucyl transfer-RNA synthetase. There is no cross-resistance with other classes of antibiotics.

·         cross-resistance between isoniazid and other agents used to treat tuberculosis (except ethionamide, which is structurally related to isoniazid) does not occur.

·         There is no cross-resistance between cycloserine and other tuberculostatic agents.

Safest Drugs

·         Fenofibrate, which is least likely to interfere with statin metabolism, appears to be the safest fibrate to use with statins.

·         Doxycycline at recommended doses does not accumulate significantly in patients with renal failure and thus is one of the safest of the tetracyclines for use in patients with renal impairment. The drug is excreted in the feces.

·         Because of its short half-life, TOLBUTAMIDE is the safest sulfonylurea for elderly diabetics.

·         The safest laxatives for chronic use include the bulk formers and stool softeners.

·         Nitrous oxide is safest of inhalational anaesthetics.

New Drug & New Uses

·         Anagrelide, a phosphodiesterase inhibitor, can reduce the platelet count and, if tolerated, is preferable to hydroxyurea because it lacks marrow toxicity. Rx of PRV & ET.

·         Lubiprostone, a chloride channel activator: for constipation

·         Abiraterone: Androgen Inhibitor for Prostate Cancer

·         Actemra: IL-6 mAb, Biological Therapy for  RA

·         Afamelanotide: synthetic alpha MSH, photoprotective drug for Rx of Light related skin d/o.

·         Afinitor: mTOR modulator, Rx of RCC

·         Almorexant: transient & reversible blocker of OREXIN receptor, Rx of Sleep d/o and Insomnia

·         roflumilast, cilomilast, and tofimilast: PDE 4 inhibitor, for COPD

·         Ceftaroline fosamil, the prodrug of ceftaroline, and ceftobiprole medocaril, the prodrug of ceftobiprole: beta-Lactam antibiotics with activity against methicillin-resistant staphylococci

(5^th generation cephalosporin ??)

·         Celvapan: H1N1 pandemic vaccine

·         Cervarix: Ca cervix vaccine

·         Cetilistat: restrics pancreatic lipases, Rx of Obesity

·         Dalvabancin: 2^nd gen glycopeptides, for serious GP infections

·         Darapladib: Lp-PLA2 inhibitor, for prevention of Atherosclerosis

·         Denosumab, an antibody to RANKL that suppresses bone resorption by interfering with RANKL/RANK induction of osteoclast differentiation and function, postmenopausal osteoporosis

·         Dimebon: for AD & HD

·         Fampridine: 4-aminipyridine, for Rx of MS-CNS

·         Fingolimod: S1P Receptor Modulator,Rx of MS-CNS

·         Fidaxomicin: Narrow Spectrum for Cl.difficile diarrhea

·         Gaboxadol: direct acting GABA-A agonist, Rx of Insomnia

·         Galinda: dual PPAR-alpha & PPAR-gamma agonist, for Rx of DM & Metabolic Syndrome

·         Vildagliptin, Sitagliptin: DPP 4 inhibitor, newer OHA

·         HCT 3012- CINOD: COX Inhibitor NO Donator, for nociceptive pain

·         Iloperidone: Atypical Antipsychotic for Schizophrenia

·         Although not a taxane, ixabepilone is a novel microtubule inhibitor that was recently approved for metastatic breast cancer in combination with the oral fluoropyrimidine capecitabine or as monotherapy. It is a semisynthetic analog of epothilone B, and is active in the M phase of the cell cycle. This agent binds directly to beta-tubulin subunits on microtubules, leading to inhibition of normal microtubule dynamics.

·         Kalbitor: Rx of HAE

·         Licofelone: COX+LOX inhibitor, DMAOAD

·         Pregabalin: new gabapentinoid, for neuropathic pain, epilepsy, anxiety,

·         M6G: new morphine derivative for pain relief

·         Motavizumab: RSV prevention

·         Dronedarone: arrhythmias

·         Nexavar: oral anticancer for liver and kidney cancer

·         ORAL-LYN: oral insulin

·         Peramivir: neuraminidase inhibitor for influenza

·         Phenserine: AChE inh for AD

·         Methyl Thioninium Chloride ( REMBER): for AD

·         SATIVEX: investigational Cannabis based Rx for Pain & MS

·         Tesofensine: AntiObesity -5HT, NE,Da reuptake inh

·         Lapatinib: dual Tyrosine Kinase inhibitor for solid tumors

·         Ustekimumab: Plaque Psoriasis

·          

·         Dabigatran: oral direct thrombin inhibitor

·         Prasugrel: antiplatelet

·         Aliskiren: Renin inhibitor for HTN

·          

·          

·         Eflornithine cream (Vaniqa) treatment for unwanted facial hair in women.

·         Alfimeprase: recombinant direct-acting fibrinolytic.

·         Daptomycin: parenteral drug for treating infections due to drug-resistant gram-positive pathogens.

Daptomycin is bactericidal, and synergy has been demonstrated with gentamicin against staphylococci and enterococci. Daptomycin is currently approved only for complicated skin and skin structure infections. Daptomycin achieves suboptimal levels in the lungs and should not be used for pulmonary infections.

·         Eprodisate is the first targeted inhibitor for diseases of protein misfolding and deposition to become available to patients. This drug is well tolerated and appears to markedly delay progression of AA renal disease.

·         diflunisal, that stabilize TTR in a nonpathogenic tetrameric conformation. For Amyloidosis.

·         Simvastatin has a moderate protective effect against chronic rejection: it suppresses T-cell function.

·         Daclizumub, basiliximab- IL-2 receptor blockers that prevent clonal expansion of T cells

·         Dronabinol is a useful prophylactic agent in patients receiving cancer chemotherapy when other antiemetic medications are not effective. It also can stimulate appetite and has been used in patients with acquired immunodeficiency syndrome (AIDS) and anorexia.

·         FTY720, an S1P receptor prodrug, is the first agent in a new class of small molecules, sphingosine 1-phosphate receptor (S1P-R) agonists, which reduce recirculation of lymphocytes from the lymphatic system to the blood and peripheral tissues, including inflammatory lesions and organ grafts.

FTY720 may have an important role in combination immunosuppression therapy in the prevention of acute rejection. FTY720 is not effective as monotherapy; it has demonstrated efficacy in clinical trials with cyclosporine and prednisone or in combination with the mTOR inhibitor everolimus and steroids. In Phase II trials with cyclosporine, FTY720 at daily doses of 2.5 and 5 mg showed comparable efficacy in the prevention of acute rejection in de novo renal transplant patients when compared to immunosuppression with cyclosporine, mycophenolate mofetil, and prednisone. FTY720 now is in Phase III trials.

·         Rituximab: Anti CD 20 / Anti B cell MAb. Human study underway for treatment of ANCA+ vasculitis.

·         Infliximab: Humanized Mouse Chimeric Anti TNFa (Rheumatoid Arthritis, Crohn’s)

·         Adalimumab: Fully humanized Anti TNFa (Rheumatoid Arthritis)

·         Etanercept: Recombinant TNF-receptor-Ig fusion protein Inhibit TNF-a (RA, JRA, Psoriasis).

·         Anakinra: Recombinant IL-1 receptor antagonist (IL-1Ra) : rheumatoid arthritis

·         OKT3: Anti-CD3 and T cell murine monoclonal antibody: Inhibit T cell function; induce T cell lymphopenia: treatment of cardiac and renal allograft rejection.

·         hOKT3 gamma-1: Humanized anti-CD3 monoclonal antibody: Eliminates auto-reactive T cells: Human study underway in Type I diabetes, psoriasis.

·         Daclizumab: Humanized anti-CD25 (IL-2R) monoclonal antibody, for graft versus host disease and UC (trial).

·         Omalizumab: Humanized anti-IgE monoclonal antibody, Human study underway for allergy (Hay fever, allergic rhinitis).

·         Exenatide: For the adjunctive treatment of Type 2 diabetes mellitus

·         Mecasermin: For the treatment of growth failure due to Primary IGFD

·         Pramlintide: Amylin Analogue, For the treatment of type I and type II diabetes

·         Tipranavir: For the adjunctive treatment of HIV-1 infections

·         Entecavir: For the treatment of chronic hepatitis B infections with evidence of active viral replication

·         Ibandronate: For the treatment and prevention of osteoporosis

·         Galsulfase: For the treatment of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome)

·         Laronidase: For the treatment of Mucopolysaccharidosis I (MPS I) in subjects aged 5 to 65

·         Agalsidase beta: For the treatment of Fabry disease in adult patients

·         Ramelteon: For the treatment of sleep-onset insomnia

·         Natalizumab: For the treatment of relapsing forms of multiple sclerosis

·         Nelarabine: For the treatment of T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma

·         Bevacizumab: For the treatment of metastatic carcinoma of the colon or rectum

·         Cetuximab: For the treatment of EGFR-expressing, metastatic colorectal cancer, palliation in HNSCC

·         Azacitidine: For the treatment of several myelodysplastic syndrome subtypes including refractory and chronic myelomonocytic leukemias

·         Telithromycin: For the treatment of infections caused by bronchitis, bacterial sinusitis and Community-acquired pneumonia

·         Rifaximin: For the treatment of Travelers' diarrhea caused by noninvasive strains of Escherichia coli

·         Fosrenol, lanthanum carbonate; For the treatment of hyperphosphatemia related to kidney dysfunction

·         Trospium chloride: For the treatment of overactive bladder with symptoms of urge urinary incontinence

·         Cinacalcet: For the treatment of secondary hyperparathyroidism and hypercalcemia in parathyroid carcinoma patients

·         Solifenacin succinate: For the treatment of overactive bladder with symptoms of urge urinary incontinence

·         Eszopiclone: For the treatment of insomnia and sleep maintenance

·         clofarabine: For the treatment of acute lymphoblastic leukemia in pediatric patients

·         Erlotinib, OSI 774: For the treatment of advanced refractory metastatic non-small cell lung cancer

·         Pegaptanib: For the treatment of wet age-related macular degeneration

·         Duloxetine: For the treatment of major depressive disorder

·         Rosuvastatin calcium: For the treatment of primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia

·         Vardenafil: For the treatment of erectile dysfunction related to sexual activity in men

·         Alefacept: For moderate to severe chronic plaque psoriasis

·         Pegvisomant: Injectable formulation for the treatment of acromegaly (GHRH Ant)

·         Palonosetron: For the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy

·         Aprepitant: For the treatment of nausea and vomiting associated with chemotherapy (substance P ant)

·         Bexxar; For the treatment of patients with CD20 positive, follicular, non-Hodgkin's lymphoma following chemotherapy relapse

·         Atazanavir sulfate: For the treatment of HIV-1 infection in combination with other antiretroviral agents

·         Zemaira (alpha1-proteinase inhibitor: For the treatment of alpha1-proteinase inhibitor deficiency (Alpha-1) and emphysema

·         Enfuvirtide: For the treatment of HIV-1 infection in combination with other antiretroviral agents

Fusion inhibitor

·         Fosamprenavir calcium: For the treatment of HIV infection in adults in combination with other antiretroviral agents

·         Intravenous caffeine (500 mg as the benzoate salt administered over 4 hours) also has been advocated for the treatment of post-dural puncture headache. If two epidural blood patches are ineffective in relieving the headache, the diagnosis of post-dural puncture headache should be reconsidered.

·         Ipratropium is FDA approved for the treatment of perennial and common cold-associated rhinorrhea.

·         Trospium is a quaternary amine approved recently for use in the United States for treatment of overactive bladder.

·         Solifenacin is newly approved for overactive bladder.

·         Pyridostigmine has recently been approved by the FDA for prophylaxis against soman, an organophosphate that rapidly ages following inhibition of cholinesterases.

·         dexmedetomidine (a2 adrenergic agonist) for short-term sedation of critically ill adults.

·         Articaine is a recently introduced amino amide, approved in the United States for dental and periodontal procedures.

·         Zaleplon and zolpidem are effective in relieving sleep-onset insomnia. Both drugs have been approved by the FDA for use for up to 7 to 10 days at a time.

·         Meprobamate is a bis-carbamate ester, antianxiety.

·         Newer norepinephrine selective reuptake inhibitor atomoxetine is approved for ADHD.

·         Clozapine is the first drug to be FDA approved for an antisuicide indication.

·         Divalproex, the sodium salt of valproic acid, is FDA approved for mania and is extensively used off-label for long-term prophylactic treatment of bipolar disorder patients. In addition, lamotrigine is the first agent given FDA approval for long-term prophylactic treatment in bipolar disorder without an indication for acute mania; it is particularly effective against bipolar depression with minimal risk of inducing mania.

·         long-term effectiveness of olanzapine in bipolar I disorder

·         Felbamate is a dicarbamate for partial seizures. (aplastic anemia)

·         Apomorphine: as a "rescue therapy" for the acute intermittent treatment of "off" episodes in patients with a fluctuating response to dopaminergic therapy.

·         The only currently approved therapy for ALS, riluzole.

·         Naltrexone is approved by the FDA for treatment of alcoholism.

·         Acamprosate is a competitive inhibitor of the N-methyl-D-aspartate (NMDA)-type glutamate receptor for alcoholism.

·         COCAINE ADDICTION: topiramate, Baclofen, modafinil

·         Topical (ophthalmic) ketorolac is FDA approved for the treatment of seasonal allergic conjunctivitis and postoperative ocular inflammation after cataract extraction.

·         Omalizumab is the first "biological drug" approved for the treatment of asthma. Omalizumab is a recombinant humanized monoclonal antibody targeted against IgE. IgE bound to omalizumab cannot bind to IgE receptors on mast cells and basophils, thereby preventing the allergic reaction at a very early step in the process

·         Nedocromil generally is more effective than cromolyn in animal models and human beings. Nedocromil is approved for use in asthmatic patients 12 years of age and older; cromolyn is approved for all ages.

·         Nimodipine has been approved for use in patients with neurological deficits secondary to cerebral vasospasm after the rupture of a congenital intracranial aneurysm.

·         Nesiritide (NATRECOR), a recombinant form of human brain natriuretic peptide (BNP), has been approved by the FDA for treatment of dyspnea due to congestive heart failure.

·         Ezetimibe is the first compound approved for lowering total and LDL-C levels that inhibits cholesterol absorption by enterocytes in the small intestine. (The putative transport protein is NPC1L1)

·         Tegaserod is a partial 5-HT4 agonist constipation-dominant irritable bowel syndrome.

·         Alosetron is a much more potent antagonist of the 5-HT3 receptor than ondansetron, for diarrhea-predominant irritable bowel syndrome.

·         Inhibitor of apicoplast (a specialized organelle of algal origin, appears to be important for lipid and heme biosynthesis) DoxP isoprenoid biosynthesis, fosmidomycin, developed as an antibacterial drug, has shown efficacy in combination with clindamycin against P. falciparum malaria

·         nitazoxanide, represents the first drug developed and approved specifically for protozoal infections, cryptosporidiosis and giardiasis, is also active against E. histolytica.

·         Caspofungin: Susceptible fungi include Candida species and Aspergillus species.

·         Docosanol is a long-chain saturated alcohol that has been approved by the FDA as a 10% over-the-counter cream for the treatment of recurrent orolabial herpes. Docosanol inhibits the in vitro replication of many lipid-enveloped viruses, including HSV, at millimolar concentrations.

·         Fomivirsen, antisense therapy for viral infections, CMV.

·         Ifosfamide is approved for use in combination for germ cell testicular cancer and is widely used to treat pediatric and adult sarcomas.

·         only FDA-approved indication for pemetrexed is for second-line therapy in mesothelioma; it also is used, however, for refractory non-small cell lung cancer.

·         Capecitabine is approved for metastatic breast cancer.

·         Irinotecan and topotecan, currently the only camptothecin analogs approved for clinical use, have established activity in colorectal, ovarian, and small cell lung cancer

·         Valrubicin for intravesical therapy of bacille Calmette-Guerin-refractory urinary bladder carcinoma in situ.

·         mitoxantrone, has been approved for use in AML.

·         ALEMTUZUMAB- is a humanized mAb that has been approved for use in chronic lymphocytic leukemia. The antibody targets CD52.

·         Efalizumab is a humanized IgG1 mAb targeting the CD11a chain of LFA-1 (lymphocyte function associated antigen). For Pretransplant therapy & Psoriasis.

·         Interferon alfa-2b: hairy cell leukemia, malignant melanoma, follicular lymphoma, and AIDS-related Kaposi's sarcoma. It also is indicated for infectious diseases, chronic hepatitis B, and condylomata acuminate.

·         Interferon beta-1a: antiviral and immunomodulatory properties. They are FDA approved for the treatment of relapsing and relapsing-remitting multiple sclerosis (Brain) to reduce the frequency of clinical exacerbations.

·         Interferon gamma-1b: It is indicated to reduce the frequency and severity of serious infections associated with chronic granulomatous disease.

·         Recombinant human interleukin-11 oprelvekin for use in patients undergoing chemotherapy for nonmyeloid malignancies that displayed severe thrombocytopenia

·         Three preparations of iron are FDA-approved for parenteral therapy, sodium ferric gluconate complex in sucrose (FERRLECIT), iron sucrose (SACCHARATE), and iron dextran (INFED, DEXFERRUM). Unlike iron dextran, which requires processing by macrophages that may require several weeks, approximately 80% of sodium ferric gluconate is delivered to transferrin with 24 hours. Sodium ferric gluconate also has a much lower risk of inducing serious anaphylactic reactions than iron dextran

·         The FDA also has approved GH therapy for AIDS-associated wasting and for malabsorption associated with the short bowel syndrome.

·         Pegvisomant (SOMAVERT) is a GH antagonist that is FDA approved for the treatment of acromegaly. Pegvisomant binds to the GH receptor but does not activate Jak-Stat signaling or stimulate IGF-1 secretion

·         Clomiphene is approved for the treatment of infertility in anovulatory women, and fulvestran is used for the treatment of breast cancer in women with disease progression after tamoxifen.

·         An extended-release form of the GnRH antagonist abarelix (PLENAXIS) is approved for treating prostate cancer

·         calcium-sensing receptor agonist cinacalcet to suppress PTH secretion.

·         Systemic vinblastine (VELBAN, others) is approved for use in Kaposi's sarcoma and advanced cutaneous T-cell lymphoma. Intralesional vinblastine also is used to treat Kaposi's sarcoma

·         Alefacept (AMEVIVE) was the first immunobiological agent approved for the treatment of moderate-to-severe psoriasis in patients who are candidates for systemic therapy. Alefacept consists of a recombinant fully human fusion protein composed of the binding site of the leukocyte function-associated antigen 3 (LFA-3) protein and a human IgG1 Fc domain.

·         Efalizumab (RAPTIVA) is a humanized monoclonal antibody against the CD11a molecule of LFA-1 for the treatment of moderate-to-severe psoriasis in patients who are candidates for systemic therapy.

·         Capsaicin is FDA approved for the treatment of postherpetic neuralgia and painful diabetic neuropathy, although its efficacy in relieving pain is debatable.

·         Verteporfin (VISUDYNE) is approved for photodynamic therapy of the exudative form of age-related macular degeneration with predominantly classic choroidal neovascular membranes. Verteporfin also is used in the treatment of predominantly classic choroidal neovascularization caused by conditions such as pathological myopia and presumed ocular histoplasmosis syndrome.

·         Tranilast [N-(3¢4¢-demethoxycinnamoyl)-anthranilic acid] is an investigational drug used for the prevention of restenosis in patients that have undergone transluminal coronary revascularization (intracoronary stents). Tranilast therapy in patients with Gilbert's syndrome has been shown to lead to hyperbilirubinemia as well as potential hepatic complications resulting from elevated levels of tranilast.

·         Fedotozine, an investigational opioid that appears to be a peripherally active, selective k-receptor antagonist, produces marginal improvement in symptoms in patients with irritable bowel syndrome and functional dyspepsia.

·         Enfuvirtide is the only available HIV entry inhibitor.

·         mifepristone also for: induction of labor after fetal death; the induction of labor at the end of the third trimester; treatment of endometriosis, leiomyomas, breast cancer, and meningiomas; and as a postcoital or luteal-phase contraceptive.

·         Pregabalin recently became the first medication to be approved by the Food and Drug Administration for the treatment of fibromyalgia.

·         Bapineuzumab is a humanized monoclonal antibody that acts on the nervous system and has potential therapeutic value for the treatment of Alzheimer's disease and possibly glaucoma.

Bapineuzumab is an antibody to the beta-amyloid (Aβ) plaques that are believed to underlie Alzheimer's disease neuropathology. In previous clinical trials for vaccination against human beta amyloid, called AN-1792, patients with Alzheimer's disease using active immunization had positive outcomes with removal of plaques and quality of life increases, but 6% of subjects developed aseptic meningitis and the trial was stopped.

·         Epratuzumab is a humanized monoclonal antibody. Potential uses may be found in oncology and in treatment of inflammatory autoimmune disorders, such as SLE

·         Monoclonal anti–IL-5 antibody therapy (e.g., mepolizumab at monthly intravenous doses of 750 mg) for hypereosinophilia has a number of unique advantages related to the specificity of IL-5 for the eosinophil lineage.

·         3F8 is a murine, IgG3[1] monoclonal antibody which binds to GD2.It has been used in the detection and treatment of neuroblastoma.

·         Yttrium Y 90 ibritumomab tiuxetan, also known as IDEC-Y2B8 monoclonal antibody, is a combination of the radioisotope yttrium-90 and a monoclonal antibody. Once attached to a cell, it can either kill it or deliver radioactive cancer-killing substances to it without harming normal cells.

·         Olcegepant is the first potent and selective non-peptide antagonist of the calcitonin gene-related peptide 1 (CGRP1) receptor, a key modulator in neurogenic inflammatory pain. Under development by Boehringer Ingelheim GmbH, olcegepant is an intravenously formulated treatment for acute attacks of migraine. In preclinical studies, olcegepant attenuated arterial dilation induced by CGRP or electrical stimulation. In a phase II clinical trial, olcegepant reduced the severity of headache in 60% of migraine sufferers and met secondary endpoints including headache-free rate and rate of sustained response. Only mild-to-moderate transient adverse events were observed, with no adverse cardiovascular symptoms reported. The compound appears to be an effective anti-migraine medication that is well tolerated and does not display the vasoconstrictive effect that precludes the use of triptans and dihydroergotamine in certain patients. For a successful marketing of olcegepant, larger clinical trials and the development of an effective oral formulation will be necessary

·         Bexarotene (Targretin) is an oral antineoplastic agent indicated by the FDA for cutaneous T cell lymphoma.It has been used off-label for lung cancer,breast cancer, and Kaposi's sarcoma.

·         Silodosin: Treatment for: Benign Prostatic Hyperplasia, Silodosin is an alpha(1)- adrenoreceptor antagonist for the treatment of the signs and symptoms associated with benign prostatic hyperplasia (BPH), or enlarged prostate.

·         Clevidipine butyrate (Injectable Emulsion): Treatment for: Hypertension, Clevidipine butyrate is an intravenous, ultrashort-acting calcium channel blocker under development for the treatment of severely elevated blood pressure in the hospital setting when oral therapy is not feasible or desirable.

·         Romiplostim: Treatment for: Idiopathic (Immune) Thrombocytopenic Purpura, romiplostim is a thrombopoietin mimetic peptibody for the treatment of thrombocytopenia in adult patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP)

·         Difluprednate: Treatment for:Postoperative ocular inflammation and pain, Difluprednate is a corticosteroid, a derivative of prednisolone obtained by fluorination at the 6- and 9-positions, followed by esterification of the 17 and 21-hydroxyl groups with butyric acid and acetic acid, respectively (see figure). Accordingly, difluprednate is sometimes abbreviated DFBA, for difluoroprednisolone butyrate acetate

·         Gadoxetate disodium: Treatment for: Diagnostic, gadoxetate disodium is a gadolinium-based contrast agent for intravenous use in T1-weighted magnetic resonance imaging (MRI) of the liver to detect and characterize lesions in adults with known or suspected focal liver disease.

·         Tetrabenazine: Treatment for: Huntington’s chorea, tetrabenazine is a selective and reversible centrally-acting dopamine depleting drug indicated for the treatment of chorea associated with Huntington's disease.

·         Alvimopan: Treatment for: Postoperative Ileus, alvimopan is a peripherally-acting mu opioid receptor antagonist used to help patients regain gastrointestinal (GI) function earlier following bowel resection surgery.

·         Methylnaltrexone bromide (Subcutaneous Injection): Treatment for: Constipation, Methylnaltrexone bromide is peripherally acting mu-opioid receptor antagonist indicated to treat opioid-induced constipation.

·         Etravirine: Treatment for HIV Infection, Etravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) which in combination with other antiretroviral agents is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adult patients.

·         Sapropterin dihydrochloride: Treatment for Phenylketonuria, sapropterin dihydrochloride is the synthetic form of 6R-BH4 (tetrahydrobiopterin), a naturally occurring enzyme cofactor that works in conjunction with phenylalanine hydroxylase to metabolize phenylalanine (Phe). It is indicated for the treatment of phenylketonuria, an inherited metabolic disease caused by a deficiency of the enzyme phenylalanine hydroxylase.

·         Rotateq (rotavirus vaccine, live oral pentavalent) : RotaTeq is a live, orally administered pentavalent vaccine specifically indicated for the prevention of rotavirus gastroenteritis in infants and children caused by the rotavirus serotypes G1, G2, G3, and G4 in infants between the ages of 6 to 32 weeks.  Supplied as a pale yellow clear suspension for oral delivery,it is designed to elicit immune response against a broad spectrum of Rotavirus strains. The vaccine is composed of 5 strains of live reassorted rotavirus. The vaccine is designed to target the viral serotypes which are most common and most frequently associated with severe gastroenteritis.

·         Darifenacin works by blocking the M3 muscarinic acetylcholine receptor, which is primarily responsible for bladder muscle contractions. It thereby decreases the urgency to urinate. It should not be used in people with urinary retention.it is used in treatment of urge incontinence.

·         Fedotozine is more or less selective of kappa(1)-opioid receptors and particularly for the kappa(1a)-receptor subtype, where it acts as an agonist. Pharmacological studies have shown that fedotozine exerts a peripheral antinociceptive action, comparable with that of other kappa-agonists. Its main effects have been demonstrated at the level of the afferent nerve pathways originating from the gut. Fedotozine alters the processing of visceral sensations along these pathways and hence, the perception of gut stimuli at the brain level. It modifies reflexes induced in various pathological conditions, like experimental inflammation of the gut, chemically-induced peritonitis or post-operative ileus. Clinical trials undertaken in patients with functional digestive disorders, non-ulcer dyspepsia and irritable bowel syndrome, have shown that fedotozine relieves abdominal pain in these patients in 6-week treatments

·         Alosetron is a 5-HT3 antagonist used for the management of severe diarrhoea-predominant irritable bowel syndrome (IBS) . Alosetron was withdrawn from the market in 2000 owing to the occurrence of serious life-threatening gastrointestinal adverse effects, but was reintroduced in 2002 with availability and use restricted; it was the first drug ever returned to the U.S. market after withdrawal for safety concerns

·         Asoprisnil is an investigational selective progesterone receptor modulator tested for treatment of progesterone sensitive myomata.

·         Certolizumab pegol is a monoclonal antibody directed against tumor necrosis factor alpha. More precisely, it is a PEGylated Fab' fragment of a humanized TNF inhibitor monoclonal antibody. Used for crohn's disease and investigated for RA

·         Fesoterodine is an antimuscarinic drug to treat overactive bladder syndrome.most common side effect is dry mouth

·         Aviptadil, also known as vasoactive intestinal polypeptide (VIP), is a 28 amino acid neuropeptide that belongs to the glucagon-growth hormone-releasing factor secretion superfamily. It exerts potent anti-inflammatory and immunomodulatory effects. In addition, Aviptadil acts as a potent systemic vasodilator and bronchodilator, it inhibits the proliferation of vascular and bronchial smooth muscle cells and decreases platelet aggregation. These biological effects are mediated by specific VIP receptors. Uses:sarcoidosis

·         Rupatadine is a new selective histamine H1 receptor and platelet-activating factor (PAF) antagonist. Rupatadine is approved for the treatment of allergic rhinitis. It can also be used for allergic urticaria.

·         Mebeverine HCI is a musculotropic antispasmodic drug without atropic side-effects whose major therapeutic role is in the treatment of irritable bowel syndrome. It is also indicated for treatment of gastrointestinal spasm secondary to organic disorder

·         Sermorelin acetate is the acetate salt of an amidated synthetic 29- amino acid peptide (GRF 1-29 NH 2 ) that corresponds to the amino-terminal segment of the naturally occurring human growth hormone-releasing hormone (GHRH or GRF) consisting of 44 amino acid residue.

Sermorelin is approved for diagnostic evaluation of pituitary function and also for increasing growth in children. Off label usage may include acute or age-related growth hormone insufficiency

·         Lacosamide (INN, formerly known as erlosamide) is a medication developed by UCB for the adjunctive treatment of partial-onset seizures and diabetic neuropathic pain . Lacosamide acts by enhancing slow inactivation of voltage gated sodium channels.

·         Gardasil, a vaccine against four strains of human papillomavirus (HPV), may help prevent genital warts in boys and men.That's according to a new study presented this week in Nice, France, at the annual meeting of the European Research Organization on Genital Infection and Neoplasia (EUROGIN).

·         Otelixizumab,( TRX4) is a novel monoclonal antibody which is being developed for the treatment of type 1 diabetes and other autoimmune diseases.

·         Flavopiridol was the first relatively selective CDK inhibitor identified, with Ki or IC50s in the 40- to 400-nM range. Although flavopiridol was initially thought to prevent tumor cell proliferation by inhibition of cell cycle CDKs, it is now clear that regulation of cellular transcription elongation by the CDK7/cyclin H and CDK9/cyclin T1 complexes may be the critical target of flavopiridol. Phase II clinical trials of flavopiridol are in progress; responses have been reported in chronic lymphocytic leukemia after a dosing schedule was defined to optimize the pharmacokinetics of the drug.

·         bryostatin 1: PKC inhibitor, PKC is the target of tumor-promoting phorbol esters, and its activation can modulate cell proliferation, differentiation, and tumorigenesis.

·         Desmoteplase, which is more fibrin-specific than t-PA, is being investigated for the treatment of acute ischemic stroke. With a potential for enhanced safety, desmoteplase may extend the window for treatment beyond 3 h. An ongoing phase III clinical trial is exploring this possibility.

·         Alfimeprase is a metalloproteinase that degrades fibrin in a plasmin-independent fashion. Because of its unique mechanism of action, it was hoped that alfimeprase would provide more rapid degradation of thrombi. However, a phase III trial investigating the use of this agent in patients with peripheral arterial occlusion has been halted, at least temporarily. Therefore, the future of this drug is uncertain.

·         Three pharmaceutical preparations of surfactant are now available: calfactant, beractant, and poractant alfa. They are given to neonates with respiratory distress syndrome by direct intratracheal instillation.