Drug Therapy: Module 2A - Immune System

Module 2A: Drug Therapy - Immune System

• The agenda includes drug therapy for immune support and modification, drug therapy for infections and drug therapy for inflammation.
• Objectives include understanding vaccination, immunoglobulins, immunomodulators, describing medications utilized to treat bacterial, viral and fungal infections.
• Also included in the objectives are identifying the prototype, action, use, contraindications,adverse effects and nursing considerations of medications used to treat infections.
• Reading goals include NSAID action and use, acetaminophen as an analgesic, the differences of anti-arthritis agents, antigout agents and immune modulators.
• More reading goals include how vaccines and sera provide protection, anti-virals for URI and herpes, anti-fungal and classes of antibiotics.

Anti-Inflammatory Agents

• Anti-inflammatory agents block/alter the chemical reactions associated with the inflammatory response, which stops the signs and symptoms of inflammation.
• These agents relieve symptoms involved in the inflammatory process such as swelling, fever, aches and pains.

Salicylates

• Prototype is Aspirin (acetylsalicylic acid, ASA).
• Salicylates act as an anti-inflammatory, antipyretic and analgesic, and they also prevent platelet aggregation.
• Salicylates inhibit prostaglandin synthesis and treat mild to moderate pain, fever and inflammatory conditions.
• Salicylates are absorbed in the stomach, metabolized in the liver and excreted in urine.
• During pregnancy/lactation salicylates cross the placenta and enter breast milk, so do not use.
• Contraindications include known allergy, bleeding abnormalities, impaired renal function, chickenpox or influenza, and pregnancy or lactation.
• NSAIDs should also not be taken if allergic.
• Reye's syndrome is a contraindication in children.
• Adverse effects include nausea, vomiting, diarrhea, dyspepsia, heartburn, epigastric discomfort, blood loss, bleeding abnormalities, salicylism, dizziness, tinnitus, difficulty hearing and mental confusion.
• Drug-drug interactions include interactions with many other drugs.
• Nursing considerations include assessing for CNS/GI/bleeding effects, administering with food, monitor to avoid toxicity, providing supportive care and ensuring hydration.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

• NSAIDs have strong anti-inflammatory and analgesic effects.
• Choice depends on personal preference and patient's repsonse.
• May have good response to some but poor response to others.
• Has a black box warning for CV and GI risks.
• Includes propionic acids, acetic acids, fenamates, oxicam derivatives and COX-2 inhibitors.
• Acetaminophen (Tylenol) is not an NSAID.
• Prototypes include propionic acids, Advil (ibuprofen), Aleve (naproxen), Acetic Acids, Voltaren (diclofenac), Toradol (ketorolac), Fenamates, Meclofenamate (meclomen), Oxicam Derivative, Mobic (meloxicam), Cyclooxygenase-2 (COX-2) Inhibitor, and Celebrex (celecoxib).
• The actions and indications of NSAIDs involve the inhibition of prostaglandin synthesis and blocking COX-1 and COX-2 so inflammation is blocked before all signs and symptoms can develop.
• NSAIDs are rapidly absorbed in the GI tract, the peak effect occurs in 1-3 hours, metabolized in Liver, excreted in Urine.
• Not recommended in pregnancy and lactation, because it crosses the placenta and into breast milk.
• Contraindications include allergy, CV dysfunction, hypertension, peptic ulcer, known gastrointestinal bleeding, pregnancy, lactation.
• Caution should be taken with renal or hepatic dysfunction.
• There are multiple adverse effects. Nausea, dyspepsia, GI pain, constipation, diarrhea, flatulence, GI bleeding, headache, dizziness, somnolence, fatigue, bleeding, platelet inhibition, hypertension, bone marrow depression, rash, mouth, sores, anaphylaxis, and AKI also can occur.
• Interacts with loop dieuretics, decreasing dieuretic effect of the loop dieuretic. Beta-blockers, decreasing the anti-hypertensive effect.
• Risk of bleeding increased with alcohol, glucosorticoids, ginger, gingko bilboa, and ASA antiplatelet effects

Acetaminophen (Tylenol)

• Used to treat moderate to mild pain and fever and a frequent drug for managing pain and fever in children.
• Available OTC and found in many combination products, labels should be checked to avoid accidental overdose.
• Extremely toxic at high doses, causes severe liver toxicity that leads to death.
• The maximum daily dose is 4 grams/day, less if combined with alcohol or hepatic injury.
• Acts directly on thermoregulatory cells in the hypothalamus causing sweating and vasodilation, releasing heat and lowering fever, analgesic effect not identified.
• Absorbed from the GI tract, peaks in 0.5-2 hours, extensively metabolized in liver, excreted in urine.
• Available IV for adults and children if PO not possible and crosses placenta and enters breast milk.
• Contraindications include allergy, caution in pregnancy and lactation, hepatic dysfunction, chronic alcoholism, renal impairment.
• Should not ingest alcohol while taking.
• The adverse effects are headache, hemolytic anemia, renal dysfunction, skin rash, fever, hepatotoxicity (potentially fatal).
• The antidote is acetylcysteine (Mucomyst)
• Increases bleeding risk with oral anticoagulants, toxicity with chronic ethanol ingestion, and hepatotoxicity with seizure medications.
• Asses for contraindications and allergy, baseline status, and monitor for adverse effects.
• Does not reduce inflammmation, should check all OTC's incase they contain Tylenol

Anti-arthritis Agents - Gold Compound (Chrysotherapy)

• Prototype Ridaura (auranofin)
• Contraindications: Pregnancy and breastfeeding - barrier contraceptives should be used. Allergy. Severe diabetes, CHF, sever debilitation, renal/hepatic impairment, HTN, blood dyscrasias, recent radiation, hx toxic levels of heavy metals. Can be a very toxic substance.
• Action and Indications: Gold inhibits phagocytosis – tissue destruction is decreased.
• Used for rheumatic inflammatory conditions that do not respond to conventional therapy.
• Does not repair damage, may prevent further damage, most effective in early disease.
• Adverse Effects: stomatitis, glossitis, gingivitis, pharyngitis, laryngitis, colitis, diarrhea, GI inflammation, gold bronchitis, interstitial pneumonitis, bone marrow depression, vaginitis, nephrotic syndrome, dermatitis, pruritis, allergic reactions (including anaphylaxis), renal toxicity causing proteinuria.
• Pharmacokinetics: Absorbed at varying rates depending on route. Widely distributed throughout body, concentrate in HPA system, adrenal, and renal cortices. Excreted in urine and feces. Crosses placenta, enters breastmilk.
• There is no combining with penicillamine, anti malarial agents, cytotoxic drugs, and immunosuppressive agents.

Anti-Arthritis Agents - Tissue Necrosis Factor (TNF) Blockers

• First class agents in progressive arthritis.
• Acts to decrease local effects of TNF, slow the inflammatory response and associated joint damage and used to treat many types of arthritis.
• Prototype: Humira (adalimumab)
• Must be given SQ, except for infliximab, which is administered IV with slow onset, takes 48-72 hours to peak and is excreted in the tissues with half life in 115 hours – 2 weeks.
• Cannot be used with acute infection, cancer, sepsis, TB, hepatitis, myelosuppression, or demyelinating disorders.
• Blocks the immune/inflammatory response and should use caution with renal/hepatic disorders, HF, and latex allergies.
• There is a boxed warning for serious to fatal infections and development of lymphomas and cancers.
• Screen and monitor patients accordingly and demyelinating disorders have occurred such as MS, MI, HF, and HTN and irritation at injection site.
• Using other immune suppressant drugs increases risk of serious infection and cancer.
• NO live vaccines.
• Used for rheumatoid arthritis.

Other Disease-Modifying Antirheumatic Drugs (DMARDs):

• Used when patients do not respond to other drug therapy
• They directly decrease pain in joints affected by arthritis
• Some antineoplastic drugs can modify the disease process in rheumatoid arthritis
• See text for drug specifics

Antigout/Hyperuricemia Agents

• Gout disorders are often characterized by elevated uric acid and urate crystal deposits in kidneys and joints = pain
• Prototype: Lopurin or Zyloprim (both are allopurinol)
• Action/Indication: lowers blood uric acid levels
• Pharmacokinetics: absorbed orally, peak serum in ~1.5 hours, half life 1-2 hours, excreted renally/via feces
• Contraindications: Discontinue if rash or allergic reaction, hypersensitivity, renal insufficiency/receiving thiazide meds, may have an increase in gouty attacks, can be administered with colchicine prophylactically
• Adverse effects: first few months of treatment may increase hypersensitivity reactions, hepatic and renal dysfunction, N/V, transient increase in gout attacks
• Drug-Drug Interactions: Slows metabolism of warfarin = increased risk of bleeding

Immune Modulators

• Immune stimulants work by boosting the immune system when exhausted fighting prolonged invasion, or needing help fighting specific pathogens or cancer cells.
• Immune suppressants work by suppressing the immune system in cases of organ transplantation, autoimmune disorders, and some cancers.

Immune Stimulants - Interferons (IFNs)

• Naturally released by H cells invaded by viruses, uses recombinant DNA tech, large class of proteins known as Cytokines
• Prototype: Intron-A (interferon alfa-2b)
• Act to prevent virus particles inside the cells.
• Inhibit tumor growth and replication, stimulate cytotoxic T-cells, improve inflammatory response
• Generally well SC or IM Most have rapid onset, broken down in liver or kidneys, excreted. through Kidneys.
• Peak 3-8 hours, half life of 3-8 hours
• Contraindicated: Known Allergies, many teratogenic in animals
• Use barrier contraceptives, Adverse Effects: Relate to immune or inflammation reaction. Headache, Dizziness, Bone marrow depression, depression, liver impairment
• Concurrent use with the opposing leads to theophylline toxicity
• Used for Multiple Sclerosis and used with chemo and rad to treat cancers

Immune Stimulants: Interleukins

• Synthetic compounds which communicate between lymphocytes to stimulate cellular immunity, inhibit tumor growth & increase platelets
• Prototype: aldesleukin (Proleukin)
• Therapeutic Actions & Indications: activates cellular immunity & inhibits tumor growth by increasing lymphocytes, natural killer cells, cytokine activity and circulating platelets.
• Pharmacokinetics: rapidly absorbed after injection
• Give IV, 13min peak, 85min half-life, cleared with the kidneys
• Contraindications: known allergies to drug or E.coli, should not be used while pregnant, use barrier protection
• Adverse Effects: sever drowsiness, respiratory difficulties (capillary leak syndrome), CNS changes that progress to coma, and cardiac arrhythmias
• Drug-Drug Interactions: May make cardio and neurotoxic adverse effects, increase risk for hypersensitivity if used with antineoplastics
• Use: kidney and skin cancer.

Immune Stimulants: Colony Stimulating Factors

• Increases the production of WBC’s (White Blood Cells) to reduce the incidence in bone marrow suppression, decrease neutropenia and used in various blood related cancers.
• Prototype: filgrastim (Neupogen)
• Pharmacokinetics: IV or SC Injection, peaks in 2hours IV 8hours SC
• Half life of 220 minutes, the duration is 4 days
• Contraindications: known allergy to drugs or E.coli, Potential effects are unknown during pregnancy.
• Adverse Effects: includes fatigue, headache, alopecia, generalized pain along with splenomegaly
• Interactions: caution with lithium or corticosteroids.
• Nursing considerations: Monitor WBC counts

Immune Suppressants - Immune Modulators

• Actions and indications: blocks cytokines involved in the inflammatory response and activation of lymphocytes for a decrease in immune response.
• Pharmacokinetics: dependent on the drug, see text
• Contradictions: Pregnancy can cause fetal harm use barrier contraception to prove the patient isn't pregnant throughout therapy.

Immune Suppressants: T and B Cell Suppressors

• Decrease production of B Cells, inhibit T cells, change the releases of interleukin and T cell
• Inhibits suppressor and helper T cells
• Prototype- cyclosporine (Neoral).
• Well absorbed and reaches peak in 1-2 hours. Metabolized in liver and excreted in bile
• Contraindicated for those that allergic/pregnant caution with liver/renal impairment, increased infections risks
• Drug-Drug Interactions: toxicity increased w/ nephrotoxic/hepatotoxic drugs.
• Adverse Effects: increase neoplasm development
• Use: Crohn's, Eczema, an organ rejection.

Immune Suppressants: Interleukin Receptor antagonist

• Anakinra is only available, the prototype is Kineret
• Action and indications: antagonizes the interleukin one receptor that reduces rheumatoid arthritis
• Pharmacokinetics: 3-7 hours peak metabolized in tissue and excreted in urine, 4-6 hour 1/2 life
• Contraindications: allergy to e-Coli, caution in pregnancy and lactation and renal impairment increase risk of infection
• Drug to drug: Enbrel and Abatacept
• Adverse effects- headache, nausea, infection
• Uses: cryopyrin & rheumatoid arthritis

Immune Suppressants: Monoclonal Abs

• Designed to attract to a target, treat cancers, specific types of arthritis and MS as well.
• Prototype, bevacizumab (avastin) - injection (IM,IV), SC depending on the drug or Rapidly Broken
• Fluid overload can be exacerbated and you must used caution if previous history of fever
• Contraindications: pregnancy, murine products, known allergy and Previous MAB use
• Drug to Drug: Reduce dose if on another agent
• Adverse Effect: cytokine Syndrome with increased infection risk, along with sever fluid retention and pulmonary Edema.
• Nursing considerations- indenting and adverse event management
• Use: Covid a and Breast Cancer.

Vaccines

• Artificial stimulating active immunity- exposing the body to less toxic proteins that deal with disease.
• vaccines made from inactivated microorganisms or live/weakened bateria/virues
• Toxoids: made bacteria toxins.
• Population specific vaccinations
• immune response w/o course of disease-
• Injection processed for bad allergy- expose people to be immune
• Best source is centers of disease control

Vaccines

• Actions and indications: Stimulate active immunity in high risk for developing a particular disease- long term
• Pharmacokinetics: Endogenous antibodies are similar to how the vaccine is developed
• Contraindications- immune deficiency, pregnant, known allergies/components
• Adverse effects: Stimulate/ Inflammatory , pain, swelling, fever, rash, chill- severe reaction/seizures.
• Interacts with Immunosupreseant drugs.
• Nursing consideration: educate patient, check expiration date, manufacturer

Immune Sera

• Can contain antibodies to toxins (anti toxin)/ bacteria/ antigenic factors
• Artificial Immunity- provide antibodies and specific antigen, immune sera is the best choice
• Early treatment for known treatment to known antigens and is very specified.

Immune Sera (Immune globulins)

• Action Indications: passive immunity for agent
• Pharmacokinetics: Available
• Contraindications: Past allergies to sera Effects: effect on system ( fever, rash, etc.) or allergic reaction , swelling or pain

Antibiotics

• Decrease invaders to immune response deals with pathogen
• broad: targets many, narrow: targets selected
• Kills bateria and stops repro

Antibiotics - Aminoglycosides

• Prototype: Garamycin (gentamicin) (-micin, -mycin, -cin suffixes)
• Have the potential to be toxic, have serious adverse effects, usually replaced in treatment.
• Action and Indications: gram - bacilli, binding to ribosomes
• Poorly absorbed by GI, but given through IM.
• Contraindications: Known allergy, Kidney disease(renal), hearing loss, parkison in new borns
• Pregnancy/ lactation: cross but excreted
• Drug to Drug: penicillin decrease
• Adverse Effect: toxicity nephro-/ Oto toxicity.
• Nursing: Kidney/Liver/Hearing

Antibiotics: Carbapenems

• Broad spectrum beta lactam- lots of combinations.
• Action: Inhibits cells = death- Gram neg and postive.
• Prototype: Invanz penem, -pim suffix
• Contraindications: Allergy to kidney- pregnancy
• Pharmacokinetics: IM, widely distributed with little kidney
• Drug/Drug: valpro levels will fall Side Effects abdominal- CNS ( seizures Nursing assessment: text in details

Antibiotics - Cephalosporins

• Like but penicillin Beta- lactam antibiotic and and multiple generations and increase activity in Positive and Neg
• Second gen
• Known Allergy - lower dose for renal impairment.
• Action and Indications: interferes with the cell
• Prototype: Ceclorf- cef
• Kidney- Monitor BUN - May have cross action with Penicillin

Fluroquinolones

• Prototype: Cipro
• Actinos: Bacteria, but DNA interfered = UT I

multiple black box Warning- Tendon Adverse Effect: kidney long QT

• Sun sensitivity
• Decreace w/ Iron can cause Tor de Pointes

Antibiotics - Penicillins

• Prototype: Amoxcil, cillin suffix
• Indications: Inhibit by building cell walls
• Pharmocokinestics: Rapidly absorded but empty stomach Contraindications: Allery + Renal with caution/ perform- and test
• Adverse Effect: Diahrrea and superinfection
• Amin inactivated

Antibiotics- Sulfonamides

• Prototype: Septa- blocks DNA= no cardioslis + inexpensive.
• Good Absorption and excreted through urine. Drug- Drug effects: high potassium and low blood sugar

Antibiotics- Tetracycline antibiotics

• Prototype: Tetracycline- Cyline
• Basteriatiic and inhibits.
• Poor adequately: affected other drugs + Calcium
• Contraindications: Allergy, pregnancy because tooth color affected- dont children

Anti-biotics Clindamycin

• Cleocin and Bastectoic
• Admin IV
• Causes coltis Module 2A