DRUGS THAT ENHANCE IMMUNE SYSTEM FUNCTION ADJUVANTS Adjuvants non-specifically augment the immune response when mixed with antigen or injected into the same site. This is achieved in the following ways: • release of the antigen is slowed and exposure to it is prolonged; • various immune cells are attracted to the site of injection and the interaction between such cells is important in antibody formation. There are a number of such substances, usually given as mixtures andoften containing lipids, extracts of inactivated tubercle bacilli and various mineral salts. IMMUNOSTIMULANTS Immunostimulants non-specifically enhance immune responses, examples include bacille Calmette-Guérin (BCG) or killed Corynebacterium parvum. INTERLEUKIN-2 (IL-2) Interleukin-2 is effective treatment for metastatic melanoma and renal cell carcinoma (Chapter 48). VACCINES IMMUNOLOGY AND GENERAL USE Vaccines stimulate an immune response. They may consist of: • an attenuated form of the infectious agent, such as the live vaccines used to prevent rubella, measles or polio, or BCG to prevent tuberculosis; • inactivated preparations of virus (e.g. influenza virus) or bacteria (e.g. typhoid vaccine); • detoxified exotoxins (‘toxoids’), e.g. tetanus vaccine. Live vaccine immunization is generally achieved with a single dose, but three doses are required for oral polio (to cover different strains). Live vaccine replicates while in the body and produces protracted immunity, albeit not as long as that acquired after natural infection. When two live vaccines are required (and are not in a combined preparation) they may be given at different sites simultaneously or at an interval of at least three weeks. Inactivated vaccines usually require sequential doses of vaccine to produce an adequate antibody response. Booster injections are required at intervals. The duration of immunity acquired with the use of inactivated vaccines ranges from months to years. The vaccination programmes recommended by the Department of Health (DH) in the UK are IMMUNOGLOBULINS AS THERAPY 407 described in detail in a memorandum entitled ‘Immunization against infectious disease’, available to doctors from the Department of Health. The British National Formulary summarizes the recommended schedule of vaccinations. Contraindications Postpone vaccination if the patient is suffering from acute illness. Ensure that the patient is not sensitive to antibiotics used in the preparation of the vaccine (e.g. neomycin and polymyxin). Egg sensitivity excludes the administration of several vaccines (e.g. influenza). Live vaccines should not be given to pregnant women, nor should they be given to patients who are immunosuppressed. Live vaccines should be postponed until at least three months after stopping glucocorticosteroids and six months after chemotherapy. Live vaccines should not be administered to HIV-1-positive individuals. Key points Vaccine therapy • Vaccines generally stimulate the production of protective antibodies or activated T cells. • Vaccines consist of: – attenuated infectious agents – antiviral vaccines (e.g. mumps, rubella, etc.). – inactivated viral/bacterial preparations (e.g. influenza virus or typhoid vaccine). – extracts of detoxified toxins (e.g. tetanus toxin). • Live vaccines produce protracted immunity and some (e.g. measles and mumps vaccines) have a low risk of causing a mild form of the disease. • Different countries have different vaccination schedules based on the prevalence of the disease in the population and the level of herd (‘population’) immunity. IMMUNOGLOBULINS AS THERAPY Immunoglobulin injection gives immediate passive protection for four to six weeks. Recombinant technology will yield antibodies of consistent quality in the future, but it is a challenge to replicate the diversity present in polyclonal human normal immunoglobulin. Currently, there are two types of immunoglobulin, namely normal and specific. HUMAN NORMAL IMMUNOGLOBULIN Human normal immunoglobulin (HNIG) is prepared from pooled donations of human plasma. It contains antibodies to measles, mumps, varicella, hepatitis A and other viruses. Uses HNIG is used to protect susceptible subjects from infection with hepatitis A and measles and, to a lesser extent, to protect the fetus against rubella in pregnancy when termination is not an option. Special formulations for intravenous administration are available for replacement therapy in agammaglobulinaemia,
408 CLINICAL IMMUNOPHARMACOLOGY hypogammaglobulinaemia and IgG subclass deficiency (e.g. Bruton’s agammaglobulinaemia, Wiskott–Aldrich syndrome), idiopathic thrombocytopenic purpura and for prophylaxis of infection in bone marrow transplant patients. Adverse effects The most common adverse effects occur during the first infusion and are dependent on the antigenic load (dose) given. They include the following: • fever, chills and rarely anaphylaxis – most commonly seen with the first dose, and reduced by slow administration and premedication with antihistamines and glucocorticosteroids; • increased plasma viscosity – caution is needed in patients with ischaemic heart disease; • aseptic meningitis (high dose). Contraindications Normal immunoglobulin is contraindicated in patients with known class-specific antibody to IgA. Interactions Live virus vaccinations may be rendered less effective. SPECIFIC IMMUNOGLOBULINS These antibodies are prepared by pooling the plasma of selected donors with high levels of the specific antibody required. The following are currently available and effective: rabies immunoglobulin, tetanus immunoglobulin (human origin-HTIG), varicella zoster immunoglobulin (VZIG) (limited supply); anti-CMV immunoglobulin (on a named patient basis). ANTI-D (RHO) IMMUNOGLOBULIN This immunoglobulin is used to prevent a rhesus-negative mother from forming antibodies to fetal rhesus-positive cells that enter the maternal circulation during childbirth or abortion. An intramuscular injection is given to rhesus-negative mothers up to 72 hours after the birth/abortion. This prevents a subsequent child from developing haemolytic disease of the newborn. Case history A 35-year-old woman had a cadaveric renal transplant for polycystic kidneys two years previously and was stable on her immunosuppressive regimen of ciclosporin, 300 mg twice a day, and mycophenolate mofetil, 1 g twice a day. Her usual trough ciclosporin concentrations were 200–250 μg/L and her hepatic and liver function was normal. She went on holiday to southern California for ten days, where she was well, but drank plenty of fluids (but no alcohol) as she was warned about the dangers of dehydration. By the end of her visit, she noted some nausea and a mild tremor. Following a long return flight, she went to her local hospital and sustained a brief spontaneously remitting epileptic fit in the outpatient department where she was having her blood ciclosporin concentration checked. The fit lasted about one minute and she was taken to the Accident and Emergency Department. Examination revealed no abnormalities apart from slight tremor which she said she had noted for the last 48 hours. Her ciclosporin concentration was 650 μg/L. All other medical biochemistry tests were normal. She was not taking any other prescribed medications or over-the-counter drugs. Questions What caused this patient’s seizures? How can you explain the markedly elevated trough ciclosporin concentration? Answer In this patient, the development of an acute epileptic seizure in the context of a very high ciclosporin trough concentration indicates ciclosporin toxicity; epilepsy is a well-recognized toxic effect of high ciclosporin concentrations. The difficult issue in the case is why she developed high ciclosporin blood concentrations (in the face of normal renal and hepatic function) when she was adamant that there had been no alteration in the daily dose of ciclosporin she was taking, nor had she started any other drugs (prescribed or over-the-counter agents). Further questioning defined that she was drinking about 1 L/day of grapefruit juice – a taste she had acquired while on holiday in California. Grapefruit juice contains psoralens and flavonoids which inhibit CYP3A (gastrointestinal and hepatic) and flavonoids which inhibit P-gp in the gut wall, increasing the bioavailability of ciclosporin by 19–60%, the combined effect leading to higher concentrations without a change in dose. The patient had her ciclosporin dosing stopped until the concentration was �300 μg/L. She had no further fits, her nausea and tremor subsided, and she was then restarted on her normal dose with clear instructions not to drink grapefruit juice. Examples of other drugs whose oral bioavailability is increased in humans with co-ingestion of grapefruit juice include midazolam, oestrogens, atorvastatin (and most statins except pravastatin), testosterone, felodipine, nifedipine (but not diltiazem), some anti-HIV protease inhibitors, other calcinerin inhibitors. Patients who are taking these agents or other drugs metabolized by CYP3A/P-gp should be warned not to ingest even single cupfuls of grapefruit juice, as this may precipitate toxic drug concentrations. FURTHER READING Golightly LK, Greos LS. Second-generation antihistamines: actions and efficacy in the management of allergic disorders. Drugs 2005; 65: 341–84. Lindenfeld J, Miller GG, Shakar SF et al. Drug therapy in the heart transplant recipient: part II: immunosuppressive drugs. Circulation 2004; 110: 3858–65. Lipsky JJ. Drug profile. Mycophenolate mofetil. Lancet 1996; 348: 1357–9. Plaut M, Valentine MD. Clinical practice. Allergic rhinitis. New England Journal of Medicine 2005; 353: 1934–44. Simons ERF, Simons KJ. Drug therapy:the pharmacology and use of H1-receptor antagonist drugs. New England Journal of Medicine 1994; 330: 1663–70. Waldman TA. Immunotherapy: past, present and future. Nature Medicine 2003; 9: 269–77.
Soliman s Auricular Therapy Textbook: New Localizations and Evidence Based Therapeutic Approaches was created ( M.D. Nader Soliman )
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Soliman s Auricular Therapy Textbook This textbook is considered the finest ever written in the field of auricular therapy. The auricular acupuncture microsystem is one of the most widely used special acupuncture techniques. This textbook is dedicated to teaching the sound foundations of this unique approach as introduced by its founder Dr. Paul Nogier of France. The scientific bases of the acupuncture microsystem with its three dime... Full description
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