Biological Response Modifier - an overview (2022)

A biological response modifier that inhibits viral replication in virus-infected cells, suppresses cell proliferation, increases phagocytic action of macrophages, and augments specific cytotoxicity of lymphocytes for target cells.

From: Mosby's Dental Drug Reference (Eleventh Edition), 2014

Leukopenia

Robert M. Kliegman MD, in Nelson Textbook of Pediatrics, 2020

Immune-Mediated Neutropenia

Immune-mediated neutropenia is usually associated with the presence of circulating antineutrophil antibodies, which may mediate neutrophil destruction by complement-mediated lysis or splenic phagocytosis of opsonized neutrophils, or by accelerated apoptosis of mature neutrophils or myeloid precursors.

Alloimmune neonatal neutropenia occurs after transplacental transfer of maternal alloantibodies directed against antigens on the infant's neutrophils, analogous to Rh-hemolytic disease. Prenatal sensitization induces maternal IgG antibodies to neutrophil antigens on fetal cells. The neutropenia is often severe and infants may present within the 1st 2 wk of life with skin or umbilical infections, fever, and pneumonia caused by the usual microbes that cause neonatal disease. By 7 wk of age, the neutrophil count usually returns to normal, reflecting the decay of maternal antibodies in the infant's circulation. Treatment consists of supportive care and appropriate antibiotics for clinical infections, plus granulocyte colony-stimulating factor (G-CSF) for severe infections without neutrophil recovery.

Mothers with autoimmune disease may give birth to infants who develop transient neutropenia, known asneonatal passive autoimmune neutropenia. The duration of the neutropenia depends on the time required for the infant to clear the maternally transferred circulating IgG antibody. It persists in most cases for a few weeks to a few months. Neonates almost always remain asymptomatic.

Autoimmune neutropenia (AIN) of infancy is a benign condition with an annual incidence of approximately 1 per 100,000 among children between infancy and 10 yr of age. Patients usually have severe neutropenia on presentation, with ANC <500/µL, but the total WBC count is generally within normal limits. Monocytosis or eosinophilia may occur but does not impact the low rate of infection. The median age of presentation is 8-11 mo, with a range of 2-54 mo. The diagnosis is often evident when a blood count incidentally reveals neutropenia in a child with a minor infection or when a routine complete blood count is obtained at the 12 mo well-child visit. Occasionally, children may present with more severe infections, including abscesses, pneumonia, or sepsis. The diagnosis may be supported by the presence of antineutrophil antibodies in serum; however, the test has frequent false-negative and false-positive results, so the absence of detectable antineutrophil antibodies does not exclude the diagnosis, and a positive result does not exclude other conditions. Therefore the diagnosis is best made clinically based on a benign course and, if obtained, a normal or hyperplastic myeloid maturation in the bone marrow. There is considerable overlap between AIN of infancy and “chronic benign neutropenia.”

Treatment is not generally necessary because the disease is only rarely associated with severe infection and usually remits spontaneously. Low-dose G-CSF may be useful for severe infections, to promote wound healing following surgery, or to avert emergency room visits or hospitalizations for febrile illnesses. Longitudinal studies of infants with AIN demonstrate median duration of disease ranging from 7-30 mo. Affected children generally have no evidence or risk of other autoimmune diseases.

Future Biological and Chemical Weapons

Robert G. Darling, Erin E. Noste, in Ciottone's Disaster Medicine (Second Edition), 2016

Biological Response Modifiers

BRMs direct the myriad complex interactions of the immune system. BRMs include erythropoietins, interferons, interleukins, colony-stimulating factors, granulocyte and macrophage colony-stimulating factors, stem cell growth factors, monoclonal antibodies, tumor necrosis factor inhibitors, and vaccines.28A growing understanding of the structure and function of BRMs is driving the discovery and creation of many novel compounds including synthetic analgesics, antioxidants, and antiviral and antibacterial substances. For example, BRMs are being used to treat debilitating rheumatoid arthritis by targeting cytokines that contribute to the disease process.29 By neutralizing or eliminating these targeted cytokines, BRMs may reduce symptoms and decrease inflammation. BRMs may also be used as anticarcinogens, with the following goals: (1) to stop, control, or suppress processes that permit cancer growth; (2) to make cancer cells more recognizable, and therefore more susceptible, to destruction by the immune system; (3) to boost the killing power of immune system cells, such as T cells, natural killer cells, and macrophages; (4) to alter growth patterns in cancer cells to promote behavior like that of healthy cells; (5) to block or reverse the processes that change a normal cell or a precancerous cell into a cancerous cell; (6) to enhance the ability of the body to repair or replace normal cells damaged or destroyed by other forms of cancer treatment, such as chemotherapy or radiation; and (7) to prevent cancer cells from spreading to other parts of the body.30,31

More of these promising new drugs are currently in development. It can be readily theorized that research to develop various BRMs can be subverted to a malicious end. That is, instead of using BRMs to suppress cancer growth or to decrease disease susceptibility, researchers could develop compounds to cause illness and death. Other drugs could be designed to alter certain metabolic processes or to alter brain chemistry to affect cognition or mood. The opportunity for mischief is limited only by the imagination of the person with ill intent.

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Neuroimmunology

Joseph Jankovic MD, in Bradley and Daroff's Neurology in Clinical Practice, 2022

Immune-Mediated Neuropathies

The immune-mediated neuropathies are a large and heterogeneous group of diseases. We shall focus on acute inflammatory demyelinating polyneuropathy (AIDP) and chronic inflammatory demyelinating polyneuropathy (CIDP), which may be defined by the time to peak disability; in the former, 4 weeks, and in the latter, 2 months. Although AIDP and CIDP share many characteristics, the question of whether one is a continuum of the other is still under debate. AIDP or Guillain-Barré syndrome (GBS) usually presents with symmetrical ascending weakness and may be associated with autonomic dysfunction and respiratory depression. Sensory systems may be involved and may present with paresthesias or numbness. Demyelination and axonal damage may be involved to varying degrees. If the patient’s symptoms continue to progress beyond 4 weeks, the illness is termedCIDP.

AIDP is the most common acute paralytic disease in the Western world, with a mean annual incidence of 1.8 per 100,000 persons. There is an increasing incidence with age. Mortality was generally due to respiratory failure and has now been significantly reduced with the introduction of positive-pressure ventilation. Epidemics have been found, most notably in northern China, where a high incidence has been associated withC. jejuni infections (McKhann, etal., 1993).

AIDP or GBS is characterized pathologically by an endoneurial lymphocytic, monocytic, and macrophage infiltrate. Several autoantibodies to myelin glycolipids have been identified; including GM1, GD1a, and GD1b. Antibody-mediated demyelination due to complement fixation has been identified in pathology specimens. In some cases, axonal damage is present and is believed to be a result of bystander damage. Activation of calcium-dependent processes within the nerve, including calpain activation, has been shown in animal models to augment axonal degeneration (O’Hanlon etal., 2003). GBS is primarily an antibody-mediated disease, as evidenced by the fact that many patients improve after treatment with plasmapheresis, and that serum from GBS patients causes demyelination after transfer into experimental animals and peripheral nerve cultures. The Miller-Fisher variant of GBS is characterized by ophthalmoplegia, ataxia, and areflexia and is associated with the presence of GQ1b antibodies in the serum.

The occurrence of AIDP has been linked to many infectious diseases, includingC. jejuni, herpesvirus,Mycoplasma pneumoniae, and many other bacterial and viral infections, as well as vaccinations. The incidence of infection has been reported to be 90% in the 30 days before occurrence of GBS.C. jejuni is one of the most commonly identifiable agents, and molecular mimicry and host susceptibility play a role in disease pathogenesis. Autoantibodies not present in controls have been identified in the sera of GBS patients associated withC. jejuni, including autoantibodies to the gangliosides GM1, GD1a, GD1b, and GQ1b (Sheikh, etal., 1998).

Thymosins

P. Samara, ... O.E. Tsitsilonis, in Vitamins and Hormones, 2016

(Video) Biologic response modifiers narrated

1 Introduction

Biologic response modifiers (BRMs) are endogenous (ie, naturally produced in the body) or exogenous (administered together with a drug) agents that modulate immunity. BRMs regulate, among others, the type, duration, and intensity of immune responses and are characterized by pleiotropy and redundancy. The thymic polypeptide prothymosin alpha (proTα) has been incorporated in the large family of BRMs, mainly because of its modulating effects on several properties of immune effectors. Its wide distribution in cells, tissues, and organs, its broad phylogenetic dissemination and the lack of a mechanism supporting its secretion, questioned the initial characterization of proTα as “thymic hormone.” Now, it is widely acknowledged that proTα possesses an essential intracellular role related to cell survival and growth, and at the same time, extracellularly it enhances the functionalities of diverse subpopulations of the immune system. Several novel functions, beyond immunomodulation, have also been ascribed to proTα.

Accumulated data suggest that its immunopotentiating activity could be therapeutically exploited in various clinical conditions associated with immunodeficiency, immunosenescence, cancer, and autoimmune diseases. Herein, we present the most prominent effects of the polypeptide, as reported by various research teams for over 30 years, propose a compiled scenario on its mode of action, and provide means, which eventually could lead to its incorporation in clinical trials as an immunostimulant/adjuvant.

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Hepatitis C

Mark Feldman MD, in Sleisenger and Fordtran's Gastrointestinal and Liver Disease, 2021

Immune-Mediated Mechanisms

HCV infection elicits an immune response in the host that involves both an initial innate response and a subsequent adaptive response. The innate response is the first line of defense against the virus and includes several arms such as natural killer (NK) cell activation and cellular antiviral mechanisms triggered by pathogen-associated molecular patterns recognized by the cell (seeChapter 2). These processes can lead to apoptosis of infected cells within the first few hours of infection. NK cells, as the effector cells of the innate immune system, also produce TNF-β and IFN-α, cytokines that are critical for dendritic cell maturation and subsequent induction of adaptive immunity. NK cells can also attack virus-infected cells directly, as do other immune cells by different effector molecules.108 Subsequently, however, the virus initiates a number of mechanisms that undermine the ability of the host to control the infection.

Virus-related disruption of the innate, and later adaptive, immune response occurs at several levels. NK cell function is slowed possibly because NK cell-mediated cytotoxicity and production of cytokines are interrupted when the HCV E2 protein binds its cellular receptor CD81.109 Expression of TNF-related apoptosis-inducing ligand on NK cells correlates with disease activity in both acute110 and chronic111 hepatitis C, thereby suggesting that NK cells have a direct role in the immunopathogenesis of hepatitis C. Pathogen-associated molecular patterns activate several cellular processes, including the JAK-STAT (Janus kinase‒signal transducer and activator of transcription) proteins pathway and Toll-like receptor-3, activation of both of which ultimately results in production of cellular IFNs, IFN-stimulated genes (ISGs), and IFN-regulated factors that convey antiviral properties to the cell. NS3/4 protease degrades TRIF, an essential intermediate in this pathway, and cleaves IFN promoter stimulator-1, an intermediate in the signaling cascade, to block activation of IFN when retinoic inducible gene-1 binds viral intermediates.112 In addition, HCV core protein promotes STAT-1 degradation, inhibits STAT-1 phosphorylation, promotes suppressor of cytokine signaling induction (an inhibitor of JAK-STAT signaling), and impairs ISG factor-3 (ISGF3), a heterotrimer of STAT-1, STAT-2, and IFN-β promoter stimulator (IRF-9) from binding to the promoter regions of IFN-stimulated response elements, thereby inhibiting transcription of IFN response genes. Even when IFN response genes are activated, NS5A and E2 both can disrupt protein kinase R function to suppress translation, thereby allowing viral replication to continue.112 In addition, NS5A inhibits 2′-5′-oligoadenylate synthetase, which is expressed in response to HCV infection and leads to HCV RNA degradation. Taken together, HCV is able to disrupt the innate immune response at several levels, and these strategies appear to be pivotal in establishing the chronicity of infection.

Immune System Toxicology

J.L. Bussiere, in Comprehensive Toxicology, 2010

Biological response modifiers (BRMs) are natural proteins that alter immune responses and that have been developed as both immunosuppressive and immunostimulating drugs. These may include natural products such as β-glucans or biotherapeutics such as monoclonal antibodies. Immunotoxicity testing of these immune modulators is not currently regulated by International Conference on Harmonization (ICH) guidelines and many of the standard immunotoxicity tests are used for understanding the pharmacology of the molecule. Since many biotherapeutics are only cross-reactive in nonhuman primates (NHPs), the standard immunotoxicity tests may need to be adapted (since rodents are the standard species used for immunotoxicity testing of small-molecule therapeutics). Unanticipated effects on the immune system may or may not be related to the mechanism of action, but would then be considered as immunotoxicity. Immunogenicity must also be assessed, which is the immune response to the drug. All of these factors make immunotoxicity testing of BRMs a challenge to toxicologists working in this field.

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Future Biologic and Chemical Weapons*

James M. Madsen, Robert G. Darling, in Disaster Medicine, 2006

Biologic Response Modifiers

BRMs direct the myriad complex interactions of the immune system. BRMs include erythropoietins, interferons, interleukins, colony-stimulating factors, granulocyte and macrophage colony-stimulating factors, stem-cell growth factors, monoclonal antibodies, tumor-necrosis-factor inhibitors, and vaccines.24

A growing understanding of the structure and function of BRMs is driving the discovery and creation of many novel compounds including synthetic analgesics, antioxidants, and antiviral and antibacterial substances. For example, BRMs are being used to treat debilitating rheumatoid arthritis by targeting cytokines that contribute to the disease process.25 By neutralizing or eliminating these targeted cytokines, BRMs may reduce symptoms and decrease inflammation. BRMs may also be used as anticarcinogens, with the following goals: (1) to stop, control, or suppress processes that permit cancer growth, (2) to make cancer cells more recognizable, and therefore more susceptible, to destruction by the immune system, (3) to boost the killing power of immune system cells, such as T cells, natural killer cells, and macrophages, (4) to alter growth patterns in cancer cells to promote behavior like that of healthy cells, (5) to block or reverse the processes that change a normal cell or a precancerous cell into a cancerous cell, (6) to enhance the ability of the body to repair or replace normal cells damaged or destroyed by other forms of cancer treatment, such as chemotherapy or radiation, and (7) to prevent cancer cells from spreading to other parts of the body.26,27

More of these promising new drugs are currently in development. It can be readily theorized that research to develop various BRMs can be subverted to a malicious end. That is, instead of using BRMs to suppress cancer growth or to decrease disease susceptibility, researchers could develop compounds to cause illness and death. Other drugs could be designed to alter certain metabolic processes or to alter brain chemistry to affect cognition or mood. The opportunity for mischief is limited only by the imagination of the person with ill intent.

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(Video) Biological response modifiers - Medical Meaning

Immunity, inflammatory disorders, immunosuppressive and anti-inflammatory agents

ProfessorCrispian Scully CBE, MD, PhD, MDS, MRCS, FDSRCS, FDSRCPS, FFDRCSI, FDSRCSE, FRCPath, FMedSci, FHEA, FUCL, FBS, DSc, DChD, DMed (HC), Dr (hc), in Scully's Medical Problems in Dentistry (Seventh Edition), 2014

Biologics (Biological Response Modifiers)

(Appendix 19.3; see also Chapter 35.)

Biologics are produced mainly by recombinant DNA technology and are usually:

substances almost identical to key signalling proteins

monoclonal antibodies (mAbs)

receptor constructs, or fusion proteins.

Biological response modifiers (BRMs) block the inflammatory and immune responses, acting on immunocytes directly or via cytokines, inhibiting cellular activation and inflammatory gene transcription by various means.

Some are antibodies, soluble receptors or natural antagonists; others are small molecules that specifically inhibit intracellular, cell–cell and cell–matrix interactions intrinsic to inflammatory and immune processes. Examples are shown in Appendices 19.3 and 19.4.

Biologic therapies aim to modulate lymphocytes or cytokines. They include:

TNFα inhibitors

lymphocyte modulators

interleukin inhibitors.

TNFα inhibitors (etanercept, adalimumab, infliximab, golimumab, certolizumab, natalizumab) bind and⁄or neutralize soluble (both circulating and within tissue) and membrane-bound TNFα, so blocking its effects upon target inflammatory cells.

T-cell modulators act on specific CD antigens. Alefacept targets CD2+on memory T and NK cells. B-cell modulators, such as rituximab, act by targeting CD20, selectively depleting circulating B cells. An anti-CD28 is also available (abatacept).

Interleukin inhibitors include an IL-1 antagonist (anakinra) and an IL-6 antagonist (tocilizumab).

Labelled indications for use of BRMs include rheumatoid arthritis, ankylosing spondylitis, psoriasis, Crohn disease, ulcerative colitis and malignancies such as non-Hodgkin lymphoma. Off-label applications include pemphigus, recurrent aphthous stomatitis and Behçet disease, mucous membrane pemphigoid, lichen planus, orofacial granulomatosis and Sjögren syndrome.

One of the advantages of BRMs is that they act specifically to neutralize targeted immune components so there should, in theory, be relatively few adverse effects. They are administered by injection or infusion, and the most common adverse effect is a mild skin reaction at the injection site. All are injected preparations, with schedules varying with the condition being treated. Infliximab and rituximab must be given as periodic intravenous infusions; etanercept and adalimumab are given as regular subcutaneous injections; and alefacept is given as weekly intramuscular injections. Some patients develop headaches during infusion, and there may be an increased susceptibility to infection – a serious risk to patients already prone to infection (e.g. diabetics) or who have an active infection such as tuberculosis or hepatitis B virus (Tables 19.7 and 19.8). Immunomodulatory mAbs have an inherent risk for adverse immune-mediated drug reactions in humans, such as infusion reactions, cytokine storms, immunosuppression and autoimmunity. Other long-term effects are not yet clear (see also Chs 29 and 35). At least 30 therapeutic mAbs are marketed in a variety of indications, and have already had profound impacts on fields such as oncology, rheumatology, neurology, cardiology and gastroenterology. However, biologics can have a high cost and significant adverse effects, and the efficacy of murine human mAbs can be limited by development of human antichimeric antibodies.

Biologics suppress the immune system and carry an increased risk of infections, which, in rare cases, can be serious. These agents undoubtedly can have serious potential adverse effects but they are generally considered safe. People with tuberculosis, heart failure or multiple sclerosis should not take biologics because they can bring on these conditions or make them worse. In rare cases, some people taking TNF inhibitors have developed certain cancers such as lymphoma. Natalimumab increases the risk of a rare, potentially fatal brain infection – progressive multifocal leukoencephalopathy (PML). Common side-effects from biologic use include headache, ’flu-like symptoms, nausea, rash, injection site pain and infusion reactions.

Use of biologics does require precautionary considerations, including screening for coexisting medical conditions. Before prescribing biologics, it is crucial to check for potential problems, such as active liver infection or tuberculosis. Monitoring includes include laboratory tests and possibly regular checks for cancer (Box 19.3).

Screening for, and use in, comorbid conditions are described below.

Viral infections

In patients with hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infection receiving biologics, viral reactivation may occur, with specific cautions and caveats related to use. Recommendations are that screening for risk factors for HBV, HCV and HIV should be carried out before commencing therapy with either TNFα inhibitors or rituximab. If previous viral infection is diagnosed, a full risk⁄benefit assessment should be undertaken before any proposed use, and HBV immunization should be considered in prospective patients considered at risk. However, most authorities advocate significant caution in patients with HBV or HCV and HIV infection, and use of any agents in active disease is generally contraindicated. If used, where relevant, HBV serology titres, serum aminotransaminases and HCV-RNA should be monitored. While anti-TNF therapy has been given in HIV infection, only those with controlled disease and whose immune competence is not especially low (e.g. CD4 count over 200 and HIV viral load below 60 000 mm3) should be considered eligible. Therapy must be given in combination with antiretroviral therapy (ART), and viral load and CD4 count should be monitored during biological therapy. Although rituximab can be used in HIV infection, limited data are available for its use in autoimmune conditions with coexistent HIV infection, and there are no clear recommendations for such use. As such, use of any agents is generally contraindicated. Alefacept is specifically contraindicated in HIV infection, as it reduces CD4 count.

Bacterial infections

Reactivation of mycobacterial infections with anti-TNF therapy is well recognized, and indeed, this can present with orofacial manifestations. It is crucial, therefore, that all patients in whom these agents may potentially be used should be screened for mycobacterial infections, especially tuberculosis, with consideration of prophylactic anti-tuberculosis therapy if there is evidence of latent disease and definitive anti-tuberculosis treatment in active disease. In contrast, there is no evidence of an increased frequency of tuberculosis with rituximab. It has been suggested that serious infections with rituximab may be more likely in patients being treated for mucocutaneous disease. Consequently, biological therapy should not be started in the presence of significant infection and clinical vigilance for such events is advocated; treatment should be stopped if serious infection develops. In clinical practice, any potential source of infection should be treated prior to initiation of anti-TNF therapies. An increased risk of surgical site perioperative infection has also been reported with anti-TNFα therapy; the general guidance is that, where possible, biological treatment should be stopped prior to surgery and reintroduced following satisfactory postoperative healing. When rituximab is used in the organ transplant setting, numerous reports exist of postsurgical infection; some studies identifying at least a trend towards increased risk, although some report that the incidence may be no greater than that for other transplant regimens. However, with such insufficient data available, it remains true that a potential impact on wound healing and infectious complications exists with rituximab, and similar cautions as for TNFα blockers should be applied. Concerns have been raised regarding reports of infective endocarditis in patients receiving biological therapies. Although some of these have included infection with atypical organisms, others have been caused by oral commensals such as Streptococcus intermedius.

Other effects

TNFα inhibitors may also be associated with an increased risk of malignancy. They should not be given in patients with multiple sclerosis and must used with caution in patients with a history of other demyelinating diseases, such as optic neuritis and Guillain–Barré syndrome. Cardiac failure is aggravated during TNFα blockade.

TNFα inhibitors use in pregnancy may cause fetal adverse effects, in particular those of the VACTERL spectrum – a syndrome usually seen in embryos and fetuses, characterized by abnormalities of vertebrae, anus, cardiovascular tree, trachea, oesophagus, renal system and limb-buds, and associated with the administration of sex hormones during early pregnancy. Rituximab treatment during pregnancy is specifically contraindicated and should be avoided in lactating women. A variety of adverse effects has been reported with administration of TNFα blockers, involving approximately 20% of patients, and ranging from minor reactions at injection sites to hypersensitivity reactions and anaphylaxis. Mucocutaneous drug eruptions may be seen in patients receiving biological therapies.

Monitoring during biological therapy

Monitor the following every 3–6 months:

Cardiac function

Neurological status

Full blood count

Liver function tests

In patients taking alefacept, CD4+T-cell count every 2 weeks.

Screen for tuberculosis annually.

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(Video) Biological response modifier which activate their immune system and help in destroying the tumor is

I

In Mosby's Dental Drug Reference (Eleventh Edition), 2014

Drug Class:

Biologic response modifier

Mechanism of Action

A biological response modifier that inhibits viral replication in virus-infected cells, suppresses cell proliferation, increases phagocytic action of macrophages, and augments specific cytotoxicity of lymphocytes for target cells.

Therapeutic Effect: Inhibits viral growth in condylomata acuminatum.

Uses

Intralesional treatment of refractory or recurring external condylomata acuminata in patients 18yr or older

PharmacoKinetics

Plasma levels below detectable limits.

Indications and Dosages

▸ Condyloma Acuminatum
Intralesional
Adults, Children 18yr and older.

0.05ml (250,000 international units) per wart twice a wk up to 8wk. Maximum dose/treatment session: 0.5ml (2.5 million international units). Do not repeat for 3mo after initial 8wk course unless warts enlarge or new warts appear.

Side Effects/Adverse Reactions

Frequent

Flu-like symptoms

Occasional

Dizziness, pruritus, dry skin, dermatitis, altered taste

Rare

Confusion, leg cramps, back pain, gingivitis, flushing, tremor, nervousness, eye pain

Precautions and Contraindications

Previous history of anaphylactic reaction to egg protein, mouse immunoglobulin, or neomycin

Caution:

CV disease, unstable angina, uncontrolled CHF, severe pulmonary disease, diabetes mellitus with ketoacidosis, coagulation disorders, severe myelosuppression, seizure disorders, risk of transmitting blood-borne infectious disease, lactation, use in children younger than 18yr has not been established

Drug Interactions of Concern to Dentistry

Serious Reactions

!

Hypersensitivity reaction occurs rarely.

!

Severe flu-like symptoms may occur at higher doses.

Dental Considerations

General:

Determine why the patient is taking the drug.

Following injection, advise patient to take acetaminophen (if there are no contraindications for its use) in pm to ease flu-like symptoms.

Advise patient if dental drugs prescribed have a potential for photosensitivity.

Consider semisupine chair position for patient comfort if GI side effects occur.

Consultations:

Medical consultation may be required to assess disease control.

Teach Patient/Family to:

Update medical/drug records if physician makes any changes in evaluation or drug regimens.

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A

In Mosby's Dental Drug Reference (Eleventh Edition), 2014

Drug Class:

Antineoplastic

Mechanism of Action

A biological response modifier that acts like human recombinant interleukin-2, promoting proliferation, differentiation, and recruitment of T and B cells, lymphokine-activated and natural cells, and thymocytes.

Therapeutic Effect: Enhances cytolytic activity in lymphocytes.

Uses

Treatment of metastatic renal cell cancer

(Video) Biologic Response Modifiers

Pharmacokinetics

Primarily distributed into plasma, lymphocytes, lungs, liver, kidney, and spleen. Metabolized to amino acids in the cells lining the kidneys. Half-life: 85min.

Indications and Dosages

▸ Metastatic Melanoma, Metastatic Renal Cell Carcinoma
IV
Adults 18yr and older.

600,000 units/kg q8h for 14 doses; followed by 9 days of rest, then another 14 doses for a total of 28 doses per course. Course may be repeated after rest period of at least 7wk from date of hospital discharge.

Side Effects/Adverse Reactions

Side effects are generally self-limiting and reversible within 2–3 days after discontinuing therapy.

Frequent

Fever, chills, nausea, vomiting, hypotension, diarrhea, oliguria or anuria, mental status changes, irritability, confusion, depression, sinus tachycardia, pain (abdominal, chest, back), fatigue, dyspnea, pruritus

Occasional

Edema, erythema, rash, stomatitis, anorexia, weight gain, infection (UTI, injection site, catheter tip), dizziness

Rare

Dry skin, sensory disorders (vision, speech, taste), dermatitis, headache, arthralgia, myalgia, weight loss, hematuria, conjunctivitis, proteinuria

Precautions and Contraindications

Abnormal pulmonary function or thallium stress test results, bowel ischemia or perforation, coma or toxic psychosis lasting longer than 48hr, GI bleeding requiring surgery, intubation lasting more than 72hr, organ allografts, pericardial tamponade, renal dysfunction requiring dialysis for longer than 72hr, repetitive or difficult-to-control seizures; retreatment in those who experience any of the following toxicities: angina, MI, recurrent chest pain with EKG changes, sustained ventricular tachycardia, uncontrolled or unresponsive cardiac rhythm disturbances

Drug Interactions of Concern to Dentistry

Possible reduction in antitumor efficacy: glucocorticoids

Serious Reactions

!

Anemia, thrombocytopenia, and leukopenia occur commonly.

!

GI bleeding and pulmonary edema occur occasionally.

!

Capillary leak syndrome results in hypotension (systolic pressure less than 90mm Hg or a 20-mm Hg drop from baseline systolic pressure), extravasation of plasma proteins and fluid into extravascular space, and loss of vascular tone. It may result in cardiac arrhythmias, angina, MI, and respiratory insufficiency.

!

Other rare reactions include fatal malignant hyperthermia, cardiac arrest, CVA, pulmonary emboli, bowel perforation, gangrene, and severe depression leading to suicide.

Dental Considerations

General:

Monitor vital signs at every appointment because of cardiovascular side effects.

If additional analgesia is required for dental pain, consider alternative analgesics (NSAIDs) in patients taking narcotics for acute or chronic pain.

Examine for oral manifestation of opportunistic infection.

Avoid products that affect platelet function, such as aspirin and NSAIDs.

Chlorhexidine mouth rinse prior to and during chemotherapy may reduce severity of mucositis.

Patient on chronic drug therapy may rarely present with symptoms of blood dyscrasias, which can include infection, bleeding, and poor healing. If dyscrasia is present, caution patient to prevent oral tissue trauma when using oral hygiene aids.

Palliative medication may be required for management of oral side effects.

Short appointments and a stress-reduction protocol may be required for anxious patients.

Provide emergency dental care only during drug use.

Patients may be at risk of bleeding; check for oral signs.

Oral infections should be eliminated and/or treated aggressively.

Consultations:

Medical consultation should include routine blood counts including platelet counts and bleeding time.

Consult physician; prophylactic or therapeutic antiinfectives may be indicated if surgery or periodontal treatment is required.

Medical consultation may be required to assess immunologic status during cancer chemotherapy and determine safety risk, if any, posed by the required dental treatment.

Medical consultation may be required to assess disease control and patient's ability to tolerate stress.

Teach Patient/Family to:

See dentist immediately if secondary oral infection occurs.

Be aware of oral side effects.

Encourage effective oral hygiene to prevent soft tissue inflammation.

Report oral lesions, soreness, or bleeding to dentist.

Prevent trauma when using oral hygiene aids.

Update health and medication history if physician makes any changes in evaluation or drug regimens; include OTC, herbal, and nonherbal remedies in the update.

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(Video) The Role of Biological Response Modifier (BRM) as an Immunostimulant - Prof. Iris

https://www.sciencedirect.com/science/article/pii/B9780323169165000018

  The immune system recognizes and protects the body from foreign invaders, such as bacteria or viruses; it also destroys damaged, diseased, or abnormal cells, including cancer cells. When the…

Indirect therapies stimulate the body’s immune system and do not directly target cancer cells.. With the exception of monoclonal antibodies, BRMs are a complex set of proteins produced by the immune system ( Fig.. Type I interferons include IFN-alfa (leukocyte IFN) and IFN beta (fibroblast and epithelial cell IFN).. 34.2 Cells of the Immune System.. A: IV: Induction: 20 million units/m 2 for 5 consecutive d/wk for 4 wk. For MS. Pregnancy category: C ∗ ; PB: UK; t½: 8 min-4.3 hA, Adult; AIDS, acquired immunodeficiency syndrome; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; C, child; CBC, complete blood count; d, day; h, hour; IM, intramuscular; IV, intravenous; LDH, lactate dehydrogenase; maint, maintenance; min, minute; mo, month; MS, multiple sclerosis; NHL, non-Hodgkin lymphoma; PB, protein binding; q, every; subcut, subcutaneous; t½, half-life; UK, unknown; wk, week; y, year; >, greater than; <, less than.. Mean serum concentrations after IM and subcutaneous administration were similar.. Antineoplastic effects may result from IFN’s ability to induce a host response to the tumor (e.g., immunomodulatory effects), cause a cytostatic effect on tumor cells, and slow the rate of cell proliferation by enhancing or inhibiting the synthesis of specific proteins, modifying cell-surface antigen expression, and/or modulating the immune system.. The effect of IFN on the CYP450 system might increase enzyme degradation or inhibit CYP450 system.

Biologic Response Modifiers are the substances that modulate the immune response by either increasing or decreasing the immunogenic effect. These are used in immunotherapy or biological therapy for enhancing the activity of immune system to fight infection and disease. These substances are naturally produced in small amounts in the body but some of them such as interleukins, monoclonal antibodies, interferons […]

Increasing prevalence of cancer and autoimmune diseases worldwide and upsurge in the success rates of immunotherapy treatment is going to increase the demand of Biologic Response Modifiers.. Biologic Response Modifiers Market is likely to proliferate in the future as per current trends of increase in the number of cancer patients and autoimmune disorder cases across the globe.. Some of the side effects such as increased risk of certain serious and opportunistic infections for patients receiving these Biologic Response Modifiers therapeutic agents, especially the risks of Tuberculosis and viral infections restraints their market to grow.. Biologic Response Modifiers Market: Overview. Market for Biologic Response Modifiers has increased since the last decade with dozens of drugs been approved by FDA and several research studies in this area.. Biologic Response Modifiers Market: Key Players. Market Segments Market Dynamics Market Size Current Trends/Issues/Challenges Competition & Companies involved Value Chain. The report provides in-depth analysis of parent market trends, macroeconomic indicators and governing factors along with market attractiveness as per segments.. Biologic Response Modifiers Market Segmentation. Detailed overview of parent market Changing market dynamics in the industry In-depth market segmentation Historical, current and projected market size in terms of volume and value Recent industry trends and developments Competitive landscape Strategies of key players and products offered Potential and niche segments, geographical regions exhibiting promising growth A neutral perspective on market performance Must-have information for market players to sustain and enhance their market footprint. About Future Market Insights (FMI) Future Market Insights (FMI) is a leading provider of market intelligence and consulting services, serving clients in over 150 countries.

Originally published as: Masihi, K.N., Schfer, H. Overview of Biologic Response Modifiers in Infectious Disease (2011) Infectious Disease Clinics of North America, 25 (4), pp. 723-731. DOI: 10.1016/j.idc.2011.07.002 This is an author manuscript. The definitive version is available at: http://www.sciencedirect.com/ Overview of Biological Response Modifiers in Infectious Disease K. Noel Masihi, Ph.D and Hubert Schfer, Ph.D Robert Koch Institute, Berlin, Germany The authors have nothing to disclose. Keywords: biological response modifiers, immunomodulators, cytokines, infections, Corresponding author for proof and reprints: Coauthor address: Hubert Schfer, Ph.D K. Noel Masihi, Ph.D Robert Koch Institute Robert Koch Institute Nordufer 20 Nordufer 20 D - 13353 Berlin D - 13353 Berlin Germany Germany (+49 30) 18754-2544 (+49 30) 18654-2602 schaeferh@rki.de masihik@rki.de 1 INTRODUCTION Infectious diseases continue to impact human morbidity and mortality. The massive explosions of tourism wit

Recombinant IFN- 2a is licensed for treatment of chronic active hepatitis B and for hepatitis C virus infections.. 10. family has expanded to 80 ligands including CXCL, CCL, XCL and CX3CL chemokines and chemokine receptors including CXCR, CCR, XCR and CX3CR Many erudite reviews on human immunodeficiency virus (HIV) /AIDS etiology and manifestation have been published, and these will not be dealt with here.. X4 HIV infection augments the expression of chemokines such as MIP-1 (macrophage inflammatory protein) and RANTES (regulated upon activation normal T cell expressed and secreted) [16].. Most existing HIV drugs work inside the body's immune cells, after the virus has infected and can cause anemia, diarrhea and nerve pain.. HIV induces -defensin-2 and 3 in human oral epithelial cells which exhibit strong anti-HIV activity due to the direct antiviral effect or competition for the chemokine receptors that HIV uses to enter the cell [32].. The expression of murine -defensin was enhanced in influenza-infected lungs, trachea and nasal mucosa [35] and treatment of cell cultures with human neutrophil peptides soon after infection - resulted in marked inhibition of influenza virus replication and viral protein synthesis [36].. Studies have shown that human alpha-defensins can inhibit BKV infection [37], inhibit adenovirus infection [38], and -defensins and human - defensin inhibited herpes simplex virus infection [39].

Videos

1. Biological response modifiers chapter 34
(Jordyn Hepler)
2. B Glucans As Natural Biological Response Modifiers Biochemistry Research Trends
(J. Abigail)
3. Biological response modifiers | Wikipedia audio article
(wikipedia tts)
4. Pharm Ch 47 Biologic Response modifying and antirheumatic drugs Keynote
(Ms Foreman's Class videos)
5. What Is The Definition Of BMRs biological response modifiers Medical Dictionary Free Online
(Medical Dictionary Online)
6. Biological Response
(Medical Biomaterials)

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