Drugs affecting the immune system

Chapters 43,44,45,46

NSAIDs


Large and chemically diverse group of drugs with the following properties:
   

Analgesic Anti-inflammatory Antipyretic Antirheumatic

NSAIDs: Indications
         

Analgesia (mild to moderate) Antigout effects Anti-inflammatory effects Antipyretic effects Relief of vascular headaches Platelet inhibition (ASA) Various bone, joint, and muscle pain Osteoarthritis Rheumatoid arthritis Dysmenorrhea

NSAIDs: Mechanism of Action



Analgesia treatment of headaches, mild to moderate pain, and inflammation Antipyretic: reduce fever
Inhibit prostaglandin E2 within the area of the brain that controls temperature

Salicylates also have antiplatelet activity



Inhibit platelet aggregation

Figure 43-1 Arachidonic acid pathway.

NSAIDS: Mechanism of action

Inflammation: response to tissue injury and infection Cardinal signs of inflammation Chemical Mediators
Prostaglandins
Vasodilation, relaxation of smooth muscles, increased capillary permeability & sensitization of nerve cells to pain

Cyclooxygenase (COX)
COX-1 & COX-2 Enzyme responsible for conversion of arachidonic acid into prostaglandins


-Leukotrienes

Chemical Categories of NSAIDs

Seven structurally related groups
1. 2.

Acetic acids Carboxylic acids (salicylates)

Acetylated and nonacetylated

3. 4. 5. 6. 7.

Propionic acids COX-2 inhibitors Fenamic acids Napthylalkanones (nonacidic) Oxicams

NSAIDs: Acetic Acid

   

diclofenac sodium, Voltaren Indomethacin, indocin Sulindac, Clinoril tolmetin

NSAIDs: Carboxylic Acids

Acetylated
 

acetylsalicytic acid diflunisal , Dolobid Ketorolac, Toradol sodium salicylate

Nonacetylated
 

NSAIDs: Propionic Acids

   

Flurbiprofen, Ansaid Ibuprofen, (Advil, Motrin) Ketoprofen(Orudis) Naproxen(Aleve, Anaprox, Naprosyn)

NSAIDs: Other Agents

COX-2 inhibitors
 

Celebrex Vioxx (removed in 2004)

NSAIDs: Other Agents (cont d)

Oxicams
 

Meloxicam, Mobic piroxicam mefenamic acid nabumetone

Fenamic acids


Nonacidic compounds


NSAIDs: Salicylates
salicylates (aspirin)


More potent effect on platelet aggregation and thermal regulatory centre in the brain  Analgesic  Antipyretic  Anti-inflammatory Antithrombotic effect: used in the treatment of MI and other thromboembolic disorders

NSAIDs: Antigout Agents



Gout: condition that results from inappropriate uric acid metabolism

 

Underexcretion of uric acid Overproduction of uric acid

Uric acid crystals are deposited in tissues and joints, resulting in pain

NSAIDs: Antigout Agents (cont d)

allopurinol


Used to reduce production of uric acid Reduces inflammatory response to the deposits of urate crystals Increase excretion of uric acid in the urine

colchicine


probenecid, sulfinpyrazone


NSAIDs: Side Effects

Gastrointestinal


Dyspepsia, heartburn, epigastric distress, nausea  GI bleeding*  Mucosal lesions* (erosions or ulcerations)
*misoprostol (Cytotec) can be used to reduce these dangerous effects

Renal
 

Reductions in creatinine clearance Acute tubular necrosis with renal failure

NSAIDs Salicylate Toxicity

 

Adults: tinnitus and hearing loss Children: hyperventilation and CNS effects Effects arise when serum levels exceed 300 mcg/mL Metabolic acidosis and respiratory alkalosis may be present

NSAIDs: Nursing Implications



Before beginning therapy, assess for conditions that may be contraindications to therapy, especially:
 

GI lesions or peptic ulcer disease Bleeding disorders

Assess also for conditions that require cautious use Perform laboratory studies as indicated (cardiac, renal, liver studies, CBC, platelet count)

Nursing Implications


Perform a medication history to assess for potential drug interactions. Several serious drug interactions exist
     

Alcohol Heparin Phenytoin Oral anticoagulants Steroids Sulfonamides

Nursing Implications (cont d)



Salicylates are NOT to be given to children under age 12 because of the risk of Reye s syndrome Because these agents generally cause GI distress, they are often better tolerated if taken with food, milk, or an antacid to avoid irritation Explain to clients that therapeutic effects may not be seen for 3 to 4 weeks

Nursing Implications (cont d)



Educate clients about the various side effects of NSAIDs, and to notify their physician if these effects become severe or if bleeding or GI pain occurs Clients should watch closely for the occurrence of any unusual bleeding, such as in the stool Enteric-coated tablets should not be crushed or chewed

Nursing Implications (cont d)



Monitor for therapeutic effects, which vary according to the condition being treated  Decrease in swelling, pain, stiffness, and tenderness of a joint or muscle area

Case Study: NSAIDS



   

Mrs Jones is 78 years old and has been discharged from hospital following an open reduction internal fixation of her Right tib/fibula. She has a remote history of GI bleed in her 60 s Her orthopedic surgeon prescribes: Cytotec, ASA 81 mg Celebrex

Your discharge instructions will be:



ASA: Celebrex: Cytotec:

Client teaching about NSAIDS:

   

Take with food/milk Check stools for blood Report stomach pain Report to other health care providers (ie dentist)

Immune System


Defends the body against invading pathogens, foreign antigens, and its own cells that become cancerous Can also sometimes attack itself, causing autoimmune diseases or immune-mediated diseases Participates in analphylaxis & tissue/organ rejection

Immunosuppressants


Agents that decrease or prevent an immune response, thus suppressing the immune system Used to prevent or treat rejection of transplanted organs

Immunosuppressants (cont d)


All suppress certain T-lymphocyte cells lines, preventing their involvement in the immune response Result: a pharmacologically immunocompromised state Mechanisms of action vary according to agent

Immunosuppressants (cont d)
    

Corticosteroids azathioprine muromonab-CD3 daclizumab sirolimus

    

cyclophosphamide cyclosporine tacrolimus basiliximab glatiramer acetate

Immunosuppressants (cont d)
 

Indications vary from agent to agent Primarily indicated for the prevention of organ rejection Some also used for immunological diseases such as rheumatoid arthritis and multiple sclerosis

Immunosuppressants (cont d)


azathioprine


Used as an adjunct medication to prevent rejection of kidney transplants Also used in the treatment of rheumatoid arthritis

Immunosuppressants (cont d)


cyclosporine


Primary agent used in the prevention of kidney, liver, heart, and bone marrow transplant rejection May be used for other autoimmune disorders Used for the prevention of liver and kidney transplant rejection

tacrolimus


Immunosuppressants (cont d)


glatiramer acetate


The only immunosuppressant agent used for the treatment of multiple sclerosis (MS) Used to reduce the frequency of MS relapses (exacerbations) in relapsingremitting multiple sclerosis (RRMS)

Immunosuppressants (cont d)


Side effects vary according to agents, and may be devastating **All immunosuppressed clients have a heightened susceptibility to opportunistic infections**

Nursing Implications


Thorough assessment should be performed before administering these agents

   

Renal, liver, and cardiovascular function Respiratory assessment Baseline vital signs Baseline laboratory studies, including hemoglobin, hematocrit, WBC, and platelet counts

Nursing Implications (cont d)



Assess for contraindications, drug allergies Monitor WBC counts throughout therapy; if the count drops below 3.0 x 109/L the drug should be discontinued, but only after contacting the physician

Nursing Implications (cont d)

 

Oral immunosuppressants should be taken with food to minimize GI upset Oral forms are used when possible to decrease the risk of infection that may occur with parenteral injections Oral antifungal agents are usually given with these agents to treat oral candidiasis that may occur Observe the oral cavity often for white patches on the tongue, mucous membranes, and oral pharynx

Nursing Implications (cont d)



Follow guidelines for parenteral administration carefully Clients need to be told that lifelong therapy with immunosuppressants is indicated with organ transplantation

Nursing Implications (cont d)



Clients taking immunosuppressants should be encouraged to take measures to reduce the risk of infection
 

Avoiding crowds Avoiding people with colds or other infections

Clients should be told to report any fever, sore throat, chills, joint pain, fatigue, or other signs of a severe infection immediately

Immunity


Immune response
 

Antigens Antibodies

 

Active immunization Passive immunization

Table 45-1 Active versus passive immunity

Immunizing Biologicals


Biological antimicrobial agents

     

Also called biologicals Antitoxins Serum Toxoids Vaccines Used to prevent, treat, or cure infectious diseases

Toxoids
   

Antigenic (foreign) preparations or bacterial exotoxins Detoxified with chemicals or heat Cannot revert back to a toxic form Stimulate one s immune system to produce a specific antibody The production of these antibodies protect against future exposures to the antigen Ex. Tetanus

Vaccines


Suspensions of live, attenuated (weakened) or killed (inactivated) micro-organisms The weakened form prevents the person from contracting the disease

Vaccines (cont d)


Also stimulate the production of antigens against a specific antibody Vaccinations with live bacteria or virus provide lifelong immunity Vaccinations with killed bacteria or virus provide partial immunity, and booster shots are needed periodically

Active Immunization


The body is exposed to a relatively harmless form of an antigen The immune system is stimulated, and remembers this antigen if subsequent exposures occur The immunizations do not cause a fullblown infection

Examples of Active Immunizing Agents

 

 

 

BCG vaccine (tuberculosis) Diphtheria,tetanus, and pertussis toxoids, several forms Cholera vaccine Haemophilus influenzae type b conjugate vaccine Hepatitis A and B virus vaccines Measles, mumps, and rubella virus vaccine, live several forms Poliovirus vaccine, several forms

Examples of Active Immunizing Agents (cont d)

    

Rabies virus vaccine Smallpox virus vaccine Tetanus toxoid Varicella virus vaccine (chicken pox) Yellow fever virus vaccine

Indications


Active immunization


Prevents infection caused by bacterial toxins or viruses Provides long-lasting or permanent immunity Herd immunity

Passive Immunization


 

Serum or concentrated immune globulins from humans or animals are injected into a person The substances needed to fight off invading micro-organisms are given directly to a person The immune system is bypassed Short-lived compared with active immunization, but works faster

Passive Immunization (cont d)



Naturally acquired passive immunity

 

From mother to fetus through the placenta From mother to infant through breast milk Acquired from an external source, such as injection of antibodies or immunoglobulins

Artificially acquired passive immunity



Examples of Passive Immunizing Agents

       

Antivenins Diphtheria antitoxin Hepatitis B immune globulin Immune globulin, various forms Rabies immune globulin (human) Rh0(D) immune globulin (RhoGAM) Tetanus immune globulin Varicella zoster immune globulin (chicken pox/shingles)

Indications (cont d)


Passive immunization
 

Antitoxins, antivenins, immune globulins Minimizes effects of poisoning by the venoms of spiders and certain snakes Provides quick immunity before a person s own immune system has a chance to make antibodies (such as in cases of exposure to hepatitis B or rabies viruses)

Indications (cont d)


National Advisory Committee on Immunization recommendations for adult and pediatric immunizations (Canada)


Provide specific dosages and intervals for immunizations

Mechanism of action:vaccines
Anitgens: foreign substances Anitbodies: immunoglobulins Once the vaccine is administered the body produces immunoglobulins: IgG, IgA, IgE, IgD, IgM to attack and kill the foreign invader Anitbody titre: the amount of immunoglobulin in the body that must be present to protect the body against the pathogen Booster shot: given when antibody titre reveals low levels

Side Effects


Range from mild and transient to very serious or life threatening Minor effects


Fever, minor rash, soreness at injection site, itching Fever >38 C, encephalitis, convulsions, anaphylactic reaction, dyspnea, others

Severe effects


Immunization schedule

Side Effects (cont d)



Minor reactions


Treated with acetaminophen and rest Serum sickness Report serious or unusual reactions to the Canadian Adverse Events Following Immunization Surveillance System

Serious or unusual reactions

 

Nursing Implications


Assess client s health history, medication history, allergies, pregnancy status Assess previous reactions and responses to immunizations Assess for contraindications, including immunosuppression

Nursing Implications (cont d)



Before giving any agent, recheck the specific protocols for administration and schedules for administration Follow manufacturer s guidelines for drug storage, administration, routes, and site of administration

Nursing Implications (cont d)



If discomfort occurs at the injection site, apply warm compresses and give acetaminophen Do not give acetylsalicylate acid to children Monitor for therapeutic responses and adverse reactions

Cancer
   

Cellular transformation Uncontrolled and rapid cellular growth Invasion into surrounding tissue Metastasis to other tissues or organs

Cancer (cont d)


Cancerous cells do not have:

 

Growth control mechanisms Positive physiological function Grow and invade adjacent tissues Break away from original tumour mass and travel by means of blood or lymphatic system to distant sites

Cancer cells either:

 

Cancer (cont d)


Metastasis


Uncontrolled cell growth Mass of new cells; tumour Benign Malignant (cancer)

Neoplasm


Tumour
 

Table 46-2 Tumour classification based on specific tissue of origin

Etiology of Cancer
      

Age- and sex-related differences Genetic factors Ethnic factors Oncogenic factors (viruses) Occupational and environmental carcinogens Radiation Immunological factors

Chemotherapy
  

Pharmacological treatment of cancer Antineoplastic agents Divided into two groups based on where in the cellular life cycle they work
 

Cell cycle nonspecific (CCNS) Cell cycle specific (CCS)

Chemotherapy (cont d)
 

Drugs have a narrow therapeutic index Combination of agents is usually more effective than single-agent therapy Nearly all agents cause side effects and adverse effects Dose-limiting side effects

Chemotherapy (cont d)


Harmful to all rapidly growing cells

 

Harmful cancer cells Healthy, normal human cells

  

Hair follicles GI cells Bone marrow cells

Chemotherapy: Contraindications


Few given the fatal outcome of cancer Low wbc Infectious process

Extravasation
Leaking of an antineoplastic drug into surrounding tissues during IV administration  Can result in permanent damage to nerves, tendons, muscles, loss of limbs  Skin grafting or amputations may be necessary Prevention is essential, Continuous monitoring of the IV site is essential


Extravasation (cont d)
 

If suspected, stop the IV infusion immediately but do not remove the IV tube If possible, aspirate remaining drug or blood from the tube Follow instructions for giving the appropriate antidote (if one exists) through the existing IV tube, then remove the catheter Some antidotes are not given through the IV catheter

Extravasation (cont d)


Cover area with sterile, occlusive dressing Apply warm or cold compresses, depending on the extravasated agent Elevate the limb

Nursing Implications


Assess baseline blood counts before giving any antineoplastic agents Follow specific administration guidelines for each antineoplastic agent Remember that all rapidly dividing cells (both normal and cancer cells) are affected
  

Mucous membranes Hair follicles Bone marrow component

Nursing Implications (cont d)



Monitor for complications



GI mucous membranes: stomatitis, altered bowel function with high risk for poor appetite, nausea, vomiting, diarrhea, and inflammation and possible ulcerations of GI mucosa

Nursing Implications (cont d)



Monitor for complications



Hair follicles: loss of hair (alopecia) Bone marrow components: dangerously low (life-threatening) blood cell counts

Nursing Implications (cont d)



Implement measures to monitor for and prevent infection in clients with neutropenia Implement measures to monitor for and prevent bleeding in clients with thrombocytopenia and anemia Keep in mind that anemia may result in severe fatigue

Nursing Implications (cont d)



Monitor for stomatitis (oral inflammation and ulcerations) and implement measures to reduce the effects if it occurs Anticipate nausea and vomiting and implement measures to reduce these effects Women of childbearing age will need to use a nondrug form of contraception during therapy

Nursing Implications (cont d)



In addition to physical measures, keep in mind the need for emotional support during this time for both the client and family Monitor for therapeutic responses to antineoplastic therapies and the many possible side/adverse effects