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Anti-inflammatory Agents
Inflammatory Response
Protects the body from injury and pathogens
Uses chemical mediators to produce the reaction that helps destroy pathogens and promote healing
Anti-inflammatory Agents
Block or alter the chemical reactions associated with the inflammatory response
Types of Anti-inflammatory Agents
Corticosteroids: used systemically to block the inflammatory and immune systems
Antihistamines: block the release of histamine in the initiation of the inflammatory response
Salicylates
Can block the inflammatory response
Have antipyretic (fever-blocking) properties
Have analgesic (pain-blocking) properties
NSAIDs
Provide strong anti-inflammatory and analgesic effects
Sold over the counter, which may lead to abuse
Common Salicylates
Aspirin (Bayer,etc.): treats inflammatory conditions
Balsalazide (Colazal): new drug that treats ulcerative colitis
Choline magnesium trisalicylate (Trilisate): treats mild pain and fevers as well as arthritis
Choline salicylate (Arthropan): treats mild pain and fevers as well as arthritis
Mesalamine (Pentasa, etc.): treats inflammation of the large intestine
Olsalazine (Dipentum): converted to mesalamine in the colon; has the same direct anti-inflammatory effects
Salsalate (Argesic, etc.): treats pain, fever, and inflammation
Sodium thiosalicylate (Rexolate): treats episodes of acute gout and muscular pain as well as rheumatic fever
Salicylates
Action/indication
Inhibit synthesis of prostaglandin; used to treat mild to moderate pain and fever
Pharmacokinetics
Absorbed from the stomach, peak in 5 to 30 min., metabolized in the liver, and excreted in the urine
Contraindications
Known allergy, bleeding abnormalities, and impaired renal function
Drug-to-drug interactions
Interact with other drugs by interfering with absorption
Salicylates—Adverse Effects
GI irritation
Nausea, dyspepsia, and heartburn
Clotting system
Blood loss and bleeding abnormalities
Eighth cranial nerve stimulation
Salicylism
Ringing in the ears
Acidosis
Nausea, vomiting, and diarrhea
Mental confusion and lassitude
Types of NSAIDs
Propionic acids
Acetic acids
Fenamates
Cyclooxygenase-2 inhibitors
NSAIDs Indications
Relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis
Relief of mild to moderate pain
Treatment of primary dysmenorrhea
Fever reduction
Contraindications to NSAIDs
Presence of allergy to any NSAID or salicylate
Cardiovascular dysfunction or hypertension
Peptic ulcer or known GI bleeding
Pregnancy and lactation
Caution with renal or hepatic dysfunction
Other Anti-inflammatory Agents
Acetaminophen (Tylenol)
Gold compounds
Antiarthritic drugs
Acetaminophen
Action/indications
Acts directly on the thermoregulatory cells of the hypothalamus
Mechanism of action related to analgesic effects is not certain
Used to treat pain and fever
Treatment of pain and fever associated with a variety of conditions, including influenza
Prophylaxis of children receiving diphtheria–pertussis–tetanus (DPT) immunizations
Relief of musculoskeletal pain associated with arthritis
Pharmacokinetics
Absorbed from the GI tract
Peaks in ½ to 2 hours
Metabolized in the liver
Excreted in the urine
T½ is about 2 hours
Contraindications
Known allergy
Use with caution in pregnancy and lactation
Adverse reactions
Headache, hemolytic anemia, renal dysfunction, skin rash, fever, and hepatotoxicity
Drug-to-drug interactions
Oral anticoagulants increase bleeding
Gold Compounds
Action
Absorbed by macrophages, which results in inhibition of phagocytosis
Indication
Tissue destruction is decreased
Pharmacokinetics
Absorption varies based on the site of administration
Widely distributed throughout the body
Contraindications
Known allergy
Diabetes, CHF, and renal or hepatic impairment
Adverse reactions
Stomatitis, glossitis, gingivitis, bone marrow depression, and dermatitis
Drug-to-drug interactions
Penicillamine, antimalarials, cytotoxic drugs, and immunosuppressive agents
Other Antiarthritis Drugs
Etanercept (Enbrel)
Leflunomide (Arava)
Penicillamine (Depen)
Hyaluronidase derivative (Synvisc)
Sodium hyaluronate (Hyalgan)
Anakinra (Kineret)
Use of Anti-inflammatory Agents Across the Lifespan
Use of Anti-inflammatory Agents Across the Lifespan
Prototype Salicylates
Prototype Salicylates
Prototype NSAIDs
Prototype NSAIDs
Prototype Acetaminophen
Prototype Acetaminophen
Prototype Gold Compound
Prototype Gold Compound
Nursing Considerations for Salicylates
Assessment (history and physical exam)
Nursing diagnosis
Implementation
Evaluation
Nursing Considerations for NSAIDs
Assessment (history and physical exam)
Nursing diagnosis
Implementation
Evaluation
Tags
acute gout , analgesic effects , aspirin bayer , balsalazide , chemical mediators , choline magnesium trisalicylate , colazal , dipentum , drug to drug interactions , gi irritation , impaired renal function , inflammatory agents , large intestine , mild pain , pentasa , response types , rheumatic fever , salicylates aspirin , salsalate , trilisate
Introduction to the Immune Response and Inflammation
Body’s Defenses
Barrier defenses
Cellular defenses
Inflammatory response
Immune response
Barrier Defenses
Skin
Protects the internal tissues and organs of the body
Mucous membrane
Lines the areas of the body that are exposed to external influences but do not have skin protection
Gastric acid
Secreted by the stomach in response to many stimuli
Major histocompatibility complex
Distinguishes between self-cells and foreign cells
Types of Cellular Defenses
Mononuclear phagocyte system (MPS)
Composed of:
Thymus gland
Lymphatic tissue
Leukocytes
Lymphocytes
Numerous chemical mediators
Types of White Blood Cells—Leukocytes—Produced by the Body
Types of White Blood Cells Leukocytes Produced by the Body
Types of Leukocytes
Types of Leukocytes
The Inflammatory Response Hageman Factor (Factor XII)
A chemical in the plasma activated by cell injury
Responsible for activating three systems in the body
The kinin system
The clotting cascade: starts blood clotting
The plasminogen system: starts the dissolution of blood clots
The Role of Bradykinin
Causes local vasodilation
Stimulates nerve endings to cause pain
Causes the release of arachidonic acid
This release of arachidonic acid causes the release of autocoids
Types of Autocoids Released
Prostaglandins
Some augment the inflammatory reaction and some block it
Leukotrienes
Some can cause vasodilation and increased capillary permeability and some can block the reactions
Thromboxanes
Cause local vasoconstriction and facilitate platelet aggregation and blood coagulation
Clinical Presentation
Calor (heat)
Caused by increased blood flow
Tumor (swelling)
Caused by fluid that leaks into the tissues
Rubor (redness)
Caused by the increase in blood flow due to vasodilation
Dolor (pain)
Caused by the activation of pain fibers
Inflammatory Response
Inflammatory Response
Immune Response
Specific invasions stimulate specific responses through the immune system
Lymphocytes produced in the bone marrow can develop into T lymphocytes or B lymphocytes
Other identified lymphocytes include natural killer cells and lymphokine-activated killer cells
These cells are aggressive against neoplastic or cancer cells and promote rapid cellular death
Types of T Cells
Effector or cytotoxic T cells
Helper T cells
Suppressor T cells
Function of T Cells
Effector or cytotoxic T cells
Found throughout the body
Aggressive against non-self cells
Can directly destroy foreign cells or mark cell so other cells can destroy them
Helper T cells
Stimulate the activity of B cells and effector T cells
Suppressor T cells
Monitor the chemical activity in the body
Act to suppress B-cell and T-cell activity when the foreign antigen is under control
Cell-Mediated Response
Cell-Mediated Response
The Role of the B Cell
Programmed to identify specific proteins or antigens
Involved in humoral immunity
Produces antibodies or immunoglobulins
Humoral Immune Response
Humoral Immune Response
Response to the Varicella Virus
Response to the Varicella Virus
Other Mediators in the Immune Response
•nterferons
Prevent viral replication and suppress malignant cell replication and tumor growth
Interleukins
Chemicals secreted by active leukocytes to influence other leukocytes
Tumor necrosis factor (TNF)
Chemical released by macrophages; inhibits tumor growth and can cause tumor regression
Conditions That Cause Problems Involving the Immune System
Neoplasm
Viral invasion
Autoimmune disease
Transplant rejection
Theories of Autoimmune Disease
Result of response to a cell that was invaded by a virus, leading to antibody production to similar cells
In a state of immunosuppression, the suppressor T cells do not suppress autoantibody production
There is a genetic predisposition to develop autoantibodies
Tags
autocoids , blood coagulation , bradykinin , capillary permeability , cellular defenses , chemical mediators , clinical presentation , clotting cascade , immune response , inflammatory reaction , inflammatory response , internal tissues , major histocompatibility complex , mononuclear phagocyte system , nerve endings , organs of the body , types of white blood cells , vasoconstriction , vasodilation , white blood cells
Anti-infective Agents
Drug Therapy Across the Lifespan
Drug Therapy Across the Lifespan
Development of Anti-infective Therapy
1920s
Paul Ehrlich worked on developing a synthetic chemical effective against infection-causing cells only
Scientists discovered penicillin in a mold sample
1935
The sulfonamides were introduced
Mechanisms of Action
Interfere with biosynthesis of the bacterial cell wall
Prevent the cells of the invading organism from using substances essential to their growth and development
Interfere with steps involved in protein synthesis
Interfere with DNA synthesis
Alter the permeability of the cell membrane to allow essential cellular components to leak out
Mechanism of Anti-infective Agents
Mechanism of Anti infective Agents
Anti-infective Activity
Anti-infectives vary in their effectiveness against invading organisms
Some are selective: they are effective only for a small number of organisms
Bactericidal: kill the cell
Bacteriostatic: prevent reproduction of the cell
Narrow Spectrum vs Broad Spectrum
Narrow spectrum of activity
Effective against only a few microorganisms with a very specific metabolic pathway or enzyme
Broad spectrum of activity
Useful in treating a wide variety of infections
Human Immune Response
Goal of anti-infective therapy is reduction of the population of the invading organism
Drugs that eliminate all traces of any invading pathogen might be toxic to the host as well
Immune response is a complex process involving chemical mediators, leukocytes, lymphocytes, antibodies, and locally released enzymes and chemicals
Problems With Treating Infections in Immunosuppressed Patients
Anti-infective drugs cannot totally eliminate the pathogen without causing severe toxicity in the host
These patients do not have the immune response in place to deal with even a few invading organisms
Resistance
Anti-infectives act on a specific enzyme system or biological process; many microorganisms that do not act on a specific system are not affected by the particular drug
This is considered natural or intrinsic resistance to that drug
Acquired Resistance
Microorganisms that were once sensitive to the particular drug have begun to develop acquired resistance
This results in serious clinical problems
Ways Resistance Develops
Producing an enzyme that deactivates the antimicrobial drug
Changing cellular permeability to prevent the drug from entering the cell
Altering transport systems to exclude the drug from active transport into the cell
Altering binding sites on the membranes or ribosomes, which then no longer accept the drug
Producing a chemical that acts as an antagonist to the drug
Preventing Resistance
Limit the use of antimicrobial agents to the treatment of specific pathogens sensitive to the drug being used
Make sure doses are high enough, and the duration of drug therapy long enough
Be cautious about the indiscriminate use of anti-infectives
Identification of the Pathogen
Identification of the infecting pathogen is done by culture
A culture of a tissue sample from the infected area is done
A swab of infected tissue is allowed to grow on an agar plate
Staining techniques and microscopic examination identify the bacterium
Stool can be examined for ova and parasites
Sensitivity of Pathogen
Shows which drugs are capable of controlling the particular microorganism
Important to be done for microorganisms that have known resistant strains
Along with a culture, identifies the pathogen and appropriate drug for treatment
Factors Affecting Prescribing Anti-infective Agents
Identification of the correct pathogen
Selection of the right drug
One that causes the least complications for that particular patient
One that is most effective against the pathogen involved
Combination Therapy
Use of a smaller dosage of each drug
Some drugs are synergistic
In infections caused by more than one organism, each pathogen may react to a different anti-infective agent
Sometimes, the combined effects of the different drugs delay the emergence of resistant strains
Adverse Reactions to Anti-infective Therapy
Kidney damage
Gastrointestinal (GI) tract toxicity
Neurotoxicity
Hypersensitivity reactions
Superinfections
Prophylaxis of Anti-infective Agents
People traveling to areas where malaria is endemic
Patients who are undergoing gastrointestinal or genitourinary surgery
Patients with known cardiac valve disease, valve replacements, and other conditions requiring invasive procedures
Tags
anti infective drugs , bacterial cell wall , biosynthesis , broad spectrum , cell membrane , cellular components , chemical mediators , dna synthesis , human immune response , immunosuppressed patients , lifespan , lymphocytes , metabolic pathway , narrow spectrum , pathogen , paul ehrlich , permeability , protein synthesis , sulfonamides , synthetic chemical