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 groups1. Acetic acids2. Carboxylic acids (salicylates)

Acetylated and nonacetylated

3. Propionic acids4. COX-2 inhibitors5. Fenamic acids6. Napthylalkanones (nonacidic)7. Oxicams

NSAIDs: Acetic Acid diclofenac sodium, Voltaren Indomethacin, indocin Sulindac, Clinoril tolmetin

NSAIDs: Carboxylic Acids

Acetylated acetylsalicytic acid diflunisal , Dolobid

Nonacetylated Ketorolac, Toradol sodium salicylate

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

Fenamic acids mefenamic acid

Nonacidic compounds nabumetone

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

colchicine Reduces inflammatory response to the

deposits of urate crystals

probenecid, sulfinpyrazone Increase excretion of uric acid in the urine

NSAIDs: Side EffectsGastrointestinal 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

tacrolimus Used for the prevention of liver and

kidney transplant rejection

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 relapsing-remitting 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 full-blown 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

Artificially acquired passive immunity Acquired from an external source, such as

injection of antibodies or immunoglobulins

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:vaccinesAnitgens: foreign substancesAnitbodies: immunoglobulinsOnce 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

Severe effects Fever >38° C, encephalitis, convulsions,

anaphylactic reaction, dyspnea, others

Immunization schedule

Side Effects (cont’d) Minor reactions

Treated with acetaminophen and rest Serious or unusual reactions

Serum sickness Report serious or unusual reactions to

the Canadian Adverse Events Following Immunization Surveillance System

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

Cancer cells either: Grow and invade adjacent tissues Break away from original tumour

mass and travel by means of blood or lymphatic system to distant sites

Cancer (cont’d) Metastasis

Uncontrolled cell growth Neoplasm

Mass of new cells; tumour Tumour

Benign Malignant (cancer)

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