Drugs for Immune System Modulation Prepared By I Gede Purnawinadi, S.Kep., M.Kes.

Preview The body is under continuous attack from a host of foreign invaders that include viruses, bacteria, fungi, and even single- celled animals. Our extensive body defenses are capable of mounting a rapid and effective response against many of these pathogens. Immunomodulator is a general term referring to any drug or therapy that affects body defenses.

Innate (Nonspecific) Body Defenses and the Immune Response The first line of protection from pathogens consists of the innate (nonspecific) body defenses, which serve as general barriers to microbes or environmental hazards. The innate defenses are unable to distinguish one type of threat from another; the response or protection is the same regardless of the pathogen. The innate defenses, also called nonspecific defenses, include physical barriers, such as the epithelial lining of the skin, and the respiratory and gastrointestinal mucous membranes, which are potential entry points for pathogens. Other innate defenses are phagocytes, natural killer (NK) cells, the complement system, fever, and interferons. From a pharmacologic perspective, one of the most important of the innate defenses is inflammation.

Humoral Immune Response and Antibodies The humoral immune response is initiated when an antigen encounters a type of lymphocyte known as a B cell. Circulating through the body are antibodies, also known as immunoglobulins (Ig), which physically interact with the antigens to neutralize or mark them for destruction by other cells of the immune response. After the antigen challenge, memory B cells are formed that will remember the specific antigen–antibody interaction. Should the body be exposed to the same antigen in the future, the body will be able to manufacture even higher levels of antibodies in a shorter period, approximately 2 to 3 days.

IMMUNIZATION AGENTS Vaccines are biologic agents used to stimulate the immune system. Vaccinations are one of the most important medical interventions for the prevention of serious infectious disease. Vaccination, or immunization, is the process of introducing foreign proteins or inactive cells (vaccines) into the body to trigger immune activation before the patient is exposed to the real pathogen. As a result of the vaccination, memory B cells are formed. When later exposed to the actual infectious organism, these cells will react by rapidly producing large quantities of antibodies that will help to neutralize or destroy the pathogen.

IMMUNOSUPPRESSANTS Drugs used to inhibit the immune response are called immunosuppressants. They are used for patients receiving transplanted tissues or organs and to treat severe inflammatory disorders. Immunosuppressants are drugs given to dampen the immune response. One or more immunosuppressants are administered at the time of transplantation and are continued for several months following surgery. In some cases, they are continued indefinitely at low doses. Transplantation would be impossible without the use of effective immunosuppressant drugs.

INFLAMMATION Inflammation is a nonspecific defense system of the body. Through the process of inflammation, a large number of potentially damaging chemicals and microorganisms may be neutralized. Inflammation is a body defense mechanism that occurs in response to many different stimuli, including physical injury, exposure to toxic chemicals, extreme heat, invading microorganisms, or death of cells. Inflammation may be classified as acute or chronic. Acute inflammation has an immediate onset and 8 to 10 days are normally needed for the symptoms to resolve and for repair to begin. If the body cannot contain or neutralize the damaging agent, inflammation may continue for long periods and become chronic.

General Strategies for Treating Inflammation When treating inflammation, the following general principles apply: Inflammation is not a disease, but a symptom of an underlying disorder. Whenever possible, the cause of the inflammation should be identified and treated. Inflammation is a natural process for ridding the body of antigens, and it is usually self-limiting. For mild symptoms, nonpharmacologic treatments such as ice packs and rest should be used whenever applicable. Topical drugs should be used when applicable because they cause few adverse effects. Inflammation of the skin and mucous membranes of the mouth, nose, rectum, and vagina are best treated with topical drugs.

NONSTEROIDAL ANTI-INFLAMMATORY DRUGS NSAIDs such as aspirin and ibuprofen have analgesic, antipyretic, and anti-inflammatory properties. They are widely prescribed for mild to moderate inflammation. NSAIDs act by inhibiting the synthesis of prostaglandins. Prostaglandins are lipids found in all tissues that have potent physiological effects, in addition to promoting inflammation, depending on the tissue in which they are found. NSAIDs block inflammation by inhibiting cyclooxygenase (COX), the key enzyme in the biosynthesis of prostaglandins.

FEVER Like inflammation, fever is a natural defense mechanism for neutralizing foreign organisms. Many species of bacteria are killed by high fever. Often, the health care provider must determine whether the fever needs to be dealt with aggressively or allowed to run its course. Drugs used to treat fever are called antipyretics. The goal of antipyretic therapy is to lower body temperature while treating the underlying cause of the fever, usually an infection.

Pathogenicity and Virulence The human body has adapted quite well to living in a world teeming with microorganisms (microbes). Present in the air, water, food, and soil, microbes are an essential component of life on the planet. Microbes that are capable of causing disease are called pathogens. Human pathogens include viruses, bacteria, fungi, unicellular organisms (protozoans), and multicellular animals (fleas, mites, and worms). Some pathogens are extremely infectious and life threatening to humans, whereas others simply cause annoying symptoms or none at all. The ability of an organism to cause infection, or pathogenicity, depends on an organism’s ability to evade or overcome body defenses.

Anti-Infective Drugs Anti-infective is a general term that applies to any drug that is effective against pathogens. In its broadest sense, an anti-infective drug may be used to treat bacterial, fungal, viral, or parasitic infections. The most frequent term used to describe an anti-infective drug is antibiotic. Technically, antibiotic refers to a natural substance produced by bacteria that can kill other bacteria. In clinical practice, however, the terms antibacterial, anti-infective, antimicrobial, and antibiotic are often used interchangeably.

Actions of Anti-Infective Drugs The primary goal of antimicrobial therapy is to assist the body’s defenses in eliminating a pathogen. Medications that accomplish this goal by killing bacteria are called bacteriocidal. Some drugs do not kill the bacteria but instead slow their growth, allowing the body’s natural defenses to eliminate the microorganisms. These growth-slowing drugs are called bacteriostatic.

Nursing Consideration Acquired resistance occurs when a pathogen acquires a gene for bacterial resistance, either through mutation or from another microbe. Resistance results in loss of antibiotic effectiveness and is worsened by the overprescribing of these agents. Careful selection of the correct antibiotics through the use of culture and sensitivity testing, is essential for effective pharmacotherapy and to limit adverse effects.