Term
| what are the MS drugs which work by decreasing the number/severity of attacks as well as the number of brain lesions? what is the MOA? |
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Definition
| avonex (IFN beta-1a), betaseron (IFN beta-1b), copaxone (glatiramer acetate), gilenya (fingolimod), novantrone (mitoxantrone), and rebif (IFN beta-1a). MOA for all: suppression of immune system activity |
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Term
| what is relapsing-remitting MS? |
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Definition
| relapsing-remitting MS is characterized by unpredictable acute attacks (exacerbations) with worsening of symptoms followed by full, partial, or no recovery of some function. these attacks appear to evolve over several days to weeks. recovery from an attack takes weeks sometimes months. the disease does not worsen in the periods between the attacks. this pattern usually occurs early in the course of MS in most people. |
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Term
| what is primary progressive MS? |
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Definition
| primary progressive MS is characterized by a gradual but steady progression of disability, without any obvious relapses and remissions. this form of disease occurs in just 15% of all people with MS, but it is the most common type of MS in people who develop the disease after the age of 40. |
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Term
| are there disease-modifying therapies proven effective for primary progressive MS? |
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Definition
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Term
| what is secondary progressive MS? |
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Definition
| secondary progressive MS initially begins with a relapsing-remitting course, but later evolves into progressive disease. the progressive part of the disease may begin shortly after the onset of MS, or it may occur years or decades later. |
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Term
| are there disease-modifying therapies proven effective for secondary progressive MS? |
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Definition
| betaseron (IFN beta-1b) and novantrone (mitoxantrone) |
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Term
| what is a true exacerbation (relapse) of MS caused by? |
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Definition
| an area of inflammation in the nerves of the brain and spinal cord system followed by demyelination. this change results in the formation of a plaque on the nerve which then causes impulses to be slowed, distorted, or halted, producing the symptoms of MS. this usually lasts usually lasts from several days to several weeks, although they may extend into months. often tx: corticosteroids. |
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Term
| what is a pseudoexacerbation of MS? |
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Definition
| an increase in symptoms that is unrelated to the underlying MS, but is caused by factors such as fever, infection, or hot weather that can temporarily aggravate MS. some pts report a worsening of their symptoms during or after periods of intense stress. |
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Term
| what are the major theories for MS etiology? |
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Definition
| immunologic (abnormal immune response directed against the CNS), environmental (people who are born in an area of the world with a high risk of MS and move to an area with a lower risk, acquire the risk of their new home, if the move occurs prior to adolescence), viral (some viruses are known causes of demyelination and inflammation, it is possible that a virus is the triggering factor in MS), and genetic (while MS is not hereditary, having a first-degree relative such as a parent or sibling with MS increases an individual's risk of developing the disease several-fold above the risk for the general population). |
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Term
| what form of MS was IFN beta-1b developed for? |
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Definition
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Term
| what form of MS was glatiramer acetate developed for? |
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Definition
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Term
| what form of MS was IFN beta-1a (avonex) developed for? |
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Definition
| relapsing forms or a single clinical episode if the MRI features are consistent w/MS |
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Term
| what form of MS was mitoxantrone developed for? |
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Definition
| worsening relapsing-remitting, progressive-relapsing, or secondary-progressive (not primary progressive MA) |
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Term
| what form of MS was IFN-beta 1a (rebif) developed for? |
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Definition
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Term
| what form of MS was natalizumab developed for? |
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Definition
| relapsing. was pulled off market, not back on, but w/limitations due to association w/progressive multifocal leukocencephalopathy |
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Term
| what form of MS was fingolimod developed for? |
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Definition
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Term
| what is the MOA for glatiramer acetate (copaxone)? |
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Definition
| glatiramer acetate is a synthetic protein which resembles proteins that are naturally part of myelin. this drug seems to block T cells by acting as a myelin decoy. unlike the IFN drugs however, glatiramer acetate has not been shown to reduce or delay disability, but it does *reduce the frequency of attacks. |
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Term
| how is glatiramer acetate administered? |
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Definition
| subcu 1x/day. generally needs to be refrigerated. injection site reactions are common. the pap test may be affected by glatiramer acetate. |
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Term
| has glatiramer acetate been studied in pregnant/breastfeeding women? |
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Definition
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Term
| what ADRs are associated w/glatiramer acetate? |
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Definition
| injection site rxn (swelling, development of a hardened lump, redness, tenderness, increased warmth of the skin, itching at injection site and/or flushing or chest tightness with heart palpitations, anxiety, and difficulty breathing), runny nose, tremor, unusual tiredness/weakness, wt gain. |
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Term
| what is the MOA for mitoxantrone (novantrone)? |
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Definition
| mitoxantrone is an immune system suppressing drug - suppresses activity of T cells, B cells, and macrophages (also used to treat some cancers). mitoxantrone reduces neurologic disability and/or the frequency of clinical relapses in patients with secondary progressive, progressive relapsing, or worsening relapsing-remitting MS. it can be given to anyone who is experiencing a worsening of disease and has been shown to delay delay the time to first treated relapse and time to disability progression. |
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Term
| what characterizes administration of mitoxantrone? |
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Definition
| evaluation of cardiac output is necessary before tx and mitoxantrone should only be used in pts w/normal cardiac function. periodic cardiac monitoring is required throughout the tx period and the lifetime cumulative dose is 140 mg/m2 (~8-12 doses over 2-3 yrs) b/c of possible cardiotoxicity. CBCs and LFTs must also be performed (mitoxantrone can increase infection risk by decreasing WBCs) |
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Term
| what precautions exist for mitoxantrone tx? |
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Definition
| live vaccines should only be administered w/medical approval (no polio). physician should be contacted if the pt believes an infection is occurring or if they are experiencing fever, chills, cough, hoarseness, lower back/side pain, of dysuria. the physician needs to know if the pt has had exposure to amphotericin B, antithyroid, azathioprine, chloramphenicol, colchicine, flucytosine, ganciclovir, plicamycin, probenecid, sulfinpyrazone, and zidovudine. if the pt has been been treated w/radiation or cancer meds. if the pt has had chicken pox, gout, heart disease, herpes zoster, kidney stones, or liver disease. *urine or eyes may turn bluish. **birth defects are possible if the man or woman is receiving it at the time of conception - also *may cause permanent sterility. mitoxantrone is secreted in breast milk. a higher incidence of leukemia has been reported in CA pts, previously on chemo, also treated w/mitoxantrone. |
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Term
| what possible ADRs are associated w/mitoxantrone? |
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Definition
| those which may disappear: nausea, alopecia, menstrual disorders. those which need to be reported immediately: fever or chills, lower back or side pain; painful or difficult urination; swelling of feet and lower legs; black, tarry stools, cough or shortness of breath; sores in mouth and on lips, stomach pain. |
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Term
| what is the MOA for the IFN beta drugs (avonex: IFN beta-1a, betaseron: IFN beta-1b, rebif: IFN beta-1a)? |
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Definition
| these resemble the interferons (cytokines) that the body naturally produces during a response by the immune system which mediate antiviral, antiproliferative and immunomodulatory activities in response to viral infection (neutralize viruses) and other biological inducers (foreign nucleic acids). IFN-beta exerts its biological effects by binding to specific receptors on the surface of human cells. this binding initiates a complex cascade of intracellular events that leads to the expression of numerous interferon-induced gene products and markers, including 2', 5'-oligoadenylate synthetase, ß2-microglobulin and neopterin. these products have been measured in the serum and cellular fractions of blood. |
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Term
| what characterizes IFN-beta 1b (betaseron)? |
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Definition
| IFN-beta 1b is made from recombinant DNA in e. coli. effect: *fewer exacerbations, a *longer time between exacerbations, and *less severity when they occur. *lesion area was also not increased (MRI proven). |
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Term
| what is proper IFN-beta 1b (betaseron) administration? |
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Definition
| subcu every other day. no refrigeration necessary. since flu-like symptoms are a common side effect associated with at least the initial weeks of taking betaseron, it is recommended that the medication be taken at bedtime (along w/NSAIDs). injection site rxns: common. |
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Term
| what precautions are associated w/IFN-beta 1b (betaseron)? |
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Definition
| IFN-beta 1b (betaseron) should not be used during pregnancy/women trying to become pregnant (OCPs necessary). pts w/severe depressive disorders need to be monitored. |
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Term
| what are possible ADRs are associated w/IFN-beta 1b (betaseron)? |
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Definition
| flu-like symptoms, injection site rxns, depression (including suicide attempts), and hepatoxicity. |
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Term
| what may reduce the efficacy of IFN-beta 1b (betaseron)? |
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Definition
| pts may develop neutralizing Ab against it after ~18 mos |
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Term
| how long can the benefits of IFN-beta 1b (betaseron) tx last (while on tx)? |
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Definition
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Term
| what characterizes IFN beta-1a (avonex)? |
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Definition
| produced by recombinant DNA technology from mammalian cells (chinese Hamster ovary cells), this was the first drug to demonstrate in clinical trials the ability to slow the progression of MS in addition to reducing the frequency of neurologic attacks. effects: reduced risk of disability progression, fewer exacerbations, reduction in number and size of active lesions in the brain (MRI proven). |
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Term
| how is IFN beta-1a (avonex) administered? |
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Definition
| 1x/wk IM (may have better side effect profile b/c injection # is lower). since flu-like symptoms are a common side effect associated with at least the initial weeks of taking betaseron, it is recommended that the medication be taken at bedtime (along w/NSAIDs). |
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Term
| what precautions are associated w/IFN beta-1a (avonex)? |
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Definition
| IFN beta-1a (avonex) should not be used during pregnancy/women trying to become pregnant (OCPs necessary). there is no increase in depression associated w/IFN beta-1a (avonex) - but remain possible. possible problems in pts w/hx of: seizure disorder, cardiac disease, including angina, congestive heart failure, or arrhythmia |
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Term
| what side effects are associated w/IFN beta-1a (avonex)? |
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Definition
| flu-like symptoms, depression, hepatoxicity |
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Term
| what differentiates IFN-beta 1a (avonex) from IFN-beta 1a (rebif)? |
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Definition
| IFN-beta rebif: a lower relapse rate, prolonged time to first relapse, a higher proportion of relapse-free patients, a lower number of active lesions on MRI, and delay in progression of disability. the effects of IFN-beta 1a are more pronounced at higher dosages. *injected subcu 3x/wk. can affect liver function (precautions in pts with any type of liver disease, thyroid problems, blood problems). some pts taking IFN-beta 1a (rebif) have experienced severe allergic reactions leading to difficulty breathing and loss of consciousness. |
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Term
| what characterizes natalizumab? MOA? ADRs? |
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Definition
| this recombinant humanized IgG4-kappa monoclonal antibody is produced in murine myeloma cells. in MS, lesions are believed to occur when activated inflammatory cells (T cells) cross the BBB, the process of which, natalizumab interferes with (blockage of molecular interaction between T cell integrin and VCAM-1 on vascular endothelial cells or CS-1/osteopontin on parenchymal brain cells). this can cause a reduction in leukocyte migration into the brain parenchyma and reduction of plaque formation as detected by MRI. natalizumab hwever, may lead to ***progressive multifocal leukoencephalopathy (PML).*** |
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Term
| what is the MOA for fingolimod (gilenya)? |
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Definition
| fingolimod is biotransformed by sphingosine kinase to the active metabolite, fingolimod-phosphate, which is a *sphingosine 1-phosphate receptor modulator - binds with high affinity to sphingosine 1-phosphate receptors 1, 3, 4, and 5 and *blocks ability of lymphocytes to exit lymph nodes, reducing lymphocytes in peripheral blood. the mechanism by which fingolimod exerts therapeutic effects in MS may involve reduction of lymphocyte migration into the CNS. |
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Term
| how is fingolimod metabolized? implication? |
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Definition
| primarily via human CYP4F2 with minor contribution of CYP2D6, 2E1, **3A4, and 4F12. inhibitors or inducers of these isozymes might alter exposure of fingolimod or fingolimod-phosphate |
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Term
| what warnings/precautions are associated w/fingolimod? |
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Definition
| a decrease in heart rate and/or atrioventricular conduction after first dose (observe pts for signs of bradycardia for 6 hrs after 1st dose). infection risk may be increased (do CBC before initiating tx). IgM and IgG titers will be decreased. macular edema may occur. PFTs may decrease. |
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Term
| what drugs may interact w/fingolomid? |
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Definition
| class Ia/III antiarrhythmic drugs, beta blockers, Ca++ channel blockers = increased bradycardia risk. ketoconazole. avoid live attenuated vaccines. |
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