Anti Inflammatory and Anti Infective Agents

N203 ANTI-INFLAMMATORY AND ANTI-INFECTIVE

AGENTS

Objectives: Upon completion of this class, the student will be able to:

1. identify the five cardinal signs of inflammation;

2. describe the action, indication for use, and potential adverse effects of aspirin

and ibuprofen NSAIDs;

3. describe Gold as the prototype for anti-arthritis;

4. describe allopurinol as the prototype for antigout;

5. explain the mechanisms of action, general adverse effects of antibacterial

drugs;

6. describe the prototypes of each type of antibacterial agents;

7. describe the prototypes of antitubercular drugs, antifungal drugs, and

metronidazole;

8. describe the prototypes of antiviral drugs and urinary antiinfectives;

9. discuss the nursing process with safe administration of these agents.

I. INFLAMMATION

A. Characteristics: cardinal signs; what are they?

B. How can it be prevented?

Inflammation: [heat, redness, swelling, edema, pain, all lead to ‘loss of function’]. Response to tissue injury. Lead to removal of dead cells. Want to stop it when: inappropriate inflammation or chronic painful inflammation. Always means you’re suppressing the immune system: risk for infection.

Tissue damage: arachadonic acid is released from tissue cells, that wakes up the prostaglandins and leukotrienes, and those stimulate nociceptors.

II. ANTIINFLAMMATORY AGENTS

A. How do they work?

B. Prototype: Aspirin:

action: analgesic, antipyretic, prevention of platelet aggregation, and anti-inflammatory by inhibiting prostaglandin synthesis, inhibiting hypothalamic heat-regulating center

caution with renal or hepatic disorders

adverse reactions: tinnitus, ulceration, agranulocytosis, bronchospasm,

thrombocytopenia;

C. Nonnonarcotic Analgesics: NSAIDs: non-steroidal antiinflamatory drugs are things like OTC pain killers: Ibuprofen, naproxen, etc. Good for dull throbbing pain like inflam, headaches, cramps. Act on PNS at pain receptor sites.

NSAIDS: irritate GI, take on full stomach. Reduce inflammation

COX 1&2 inhibitors:

COX-2 inhibitors: “Cyclooxidase-2”. These block the 2 and not the 1—which means less GI upset and GI bleeding.

Ketoralac: [Toradol]

Non-steroid, but severe renal and hepatic impact; should only be used short term. This is about 5x as strong as morphine—it inhibits prostaglandins.

Action: It inhibits synthesis of prostaglandins by inhibiting both COX-1 and COX-2 enzymes. Is a peripherally acting analgesic.

Use: Exhibits analgesic, antiinflammatory, and antipyretic activity. Effective in controlling acute post-operative pain, Short-term management of pain;

Adverse: hemorrhage

Prototype: Celebrex (Celecoxib)

Use; analgesic, nsaid; cyclooxygenase-2 (cox-2 but not cox-1) inhibitor; antiinflammatory;

Action: Although an NSAID, unlike ibuprofen celecoxib inhibits prostaglandin synthesis by inhibiting cyclooxygenase-2 (COX-2)

Adverse: Increased risk of cardiovascular events.

2. Ibuprofen (Motrin)

Class: nsaid, cox-1 and cox-2 inhibitor; analgesic, antipyretic

Action: reduce inflammation and fever by inhibiting prostaglandin synthesis

Caution with bleeding disorders, early pregnancy, SLE

Adverse reactions: GI bleeding, blood dyscrasias, cardiac dysrhythmias,

nephrotoxicity

III. ANTIRHEUMATIC DRUGS

A. NSAIDs

B. Immunosuppressive agents

C. Immunomodulators

D. Chrysotherapy (heavy metal therapy)

2. No longer a prototype: Auranofin (Ridaura)

1. use/action: symptom relief, prevent deformities, depresses migration of

leukocytes, suppresses prostaglandin activity

Contraindication: patients with colitis, SLE, hemorrhagic conditions, renal or

hepatic disorders, HTN, CHF, DM, pregnancy

Adverse reactions: nephrotoxicity, hematuria, thrombocytopenia

IV. ANTIGOUT DRUG

Anti-Gout Drugs: gout is uric acid in the joints that causes burning sensation.

A. Prototype: allopurinol (Zyloprim)

1. action: reduces uric acid synthesis

Use: Antigout

2. caution with renal and hepatic disease

3. adverse effects: retinopathy, cataracts, bone marrow disorders

IV. ANTIBACTERIAL DRUGS

A. Mode of action

Either bacteriostatic [prevent multiplication] or bacteriocidal [destroy pathogenic cells]

1. inhibit bacterial cell wall synthesis

2. alter membrane permeability

3. inhibit protein synthesis

4. inhibit synthesis of bacterial RNA and DNA

5. interfere with metabolism within bacterial cell

Modes of action: need to know in general how these drugs work. Some are both types, depending on the dose.

B. Body defenses

1. nutrition

2. age

3. immunoglobulins

4. WBCs

5. organ function

6. circulation

C. Resistance to antibacterials

1. MRSA

2. VRE

D. General adverse reactions to antibacterials

1. allergic reactions

2. superinfections: esp fungal, and superinfections are likely when someone has been on antibiotics for more than 1 week.

3. organ toxicity

4. The worst adverse reaction: anaphylactic shock. Lots of people are allergic to penicillin, and that means they are likely to be allergic to cephalosporins. A lot of people are also allergic to sulphanomides.

5. Also heavy renal and hepatic impacts with these.

E. Nursing Responsibilities

Patients w/ infections: maintain skin integrity—when skin breakdown occurs, it is harder to repair in patients with infections.

We don’t culture people’s pneumonia too often any more: RBP says if someone got their illness in the community, it’s probably a gram positive, so we treat them one way until we get back a culture that says to switch meds.

V. PENICILLINS AND CEPHALOSPORINS

Penicillin has been around forever. Unfortunately they’ve been overused.

A. PCN prototype: amoxicillin (Amoxil)

1. contraindication: PCN allergy

Use: Good for both gram negative and gram positive infections. Who gets it: kids with ear infections, UTI’s, etc.

2. action: inhibits enzyme in cell wall synthesis, bactericidal

3. adverse reaction: superinfections, blood dyscrasias, respiratory distress

B. Cephalosporins

1. 1-4 generations: stronger and broader

2. prototype: cezazolin (Ancef), 1st generation

Use: Preop prophylaxis, UTI, bone, joint, soft tissue infections, bacteremia.

Action: Inhibits cell wall synthesis, destroys cell

caution: renal disease and PCN allergy

adverse reactions: superinfections, seizures, anaphylaxis

We prefer to use our ‘little guns’; our 1^st generation antibiotics, before we use our 4^th generation antibiotics.

VI. MACROLIDES, TETRACYCLINES, AMINOGLYCOSIDES,

FLUOROQUINOLONES

A. Macrolides: azithromycin (Zithromax)

1. indication for use: gm-positive and some gm-negative, with clients allergic to

PCN, respiratory infections, gonorrhea

2. action: inhibits steps of protein synthesis, bactiostatic or cidal

3. adverse reaction: superinfections, hepatoxicity

B. Tetracycline: Tetracyclines: Vibramycin: can have more adverse effects. Given when you need to step up the antibiotics b/c you have an uncommon bacteria or unresponsive strain.

Doxycycline (Vibramycin)

1. caution: with alcoholism, hypokalemia, bradycardia

2. action: inhibits steps of protein synthesis, cidal or static

3. use: treat infections by uncommon bacteria

4. adverse: blood dyscrasias, hepatoxicity, CNS toxicity

C. Aminoglycosides: Aminoglycosides: these are super nephrotoxic. Gentamycin. They are for super sepsis situations. There are protocols to check BUN and Creatinine, etc, the pharmacy manages it based on body weight, etc.

Gentamicin (Garamycin)

1. action: inhibits bacterial synthesis, cidal effect

2. use: serious infections from gram-negative bacteria, PID, MRSA

3. adverse: oliguria, superinfection, ototoxicty, nephrotoxicity, liver damage

D. Fluoroquinolones: Levofloxacin (Levaquin)

1. action: interferes with DNA enzyme, cidal effect

2. use: lower respiratory tract, renal, bone, joint infections

3. adverse: encephalopathy, seizures, dysrhythmias

VII. SULFONAMIDES: may potentiate sulfonylurea-induced hypoglycemia

Co-trimoxazole/tmp-smz (Bactrim): combination of sulfamethoxazole (SMZ), a sulfonamide, and trimethoprim (TMP)

A. action: inhibits protein synthesis, cidal effect

B. use: complex UTI, bronchitis, PCP [Pneumocystis carinii pneumonitis most common death in AIDS patients], burns.

C. adverse: bone marrow disorders, renal failure. If you have a diabetic, toxic epidermal necrolysis. hepatitis, stomatitis, crystalluria. megaloblastic anemia, hypoprothrombinemia, allergic myocarditis.

Drug: Coumadin interference: sulpha’s cause clotting

VIII. ANTITUBURCULAR & ANTIFUNGAL AGENTS

A. Anti-tuburcular agents:

1. TB: pathology & symptoms: Symptoms; coughing, hacking, night sweats.

Tuberculosis bacteria and illness is back on the rise due to cramped populations, Russian prisons, highly resistant strains, etc. Combination therapies for 6-24 months is the usual treatment. Not just a lung disease, although mostly a lung disease. Droplet/airborne spread

2. Prototype Isoniazid (INH)

action: inhibits cell-wall synthesis

use: TB treatment and prophylaxis

adverse: blood dyscrasias, hepatoxicity

Nursing Process

B. Antifungal Drugs

1. Causes of fungal infections: Usually fungal infections are super infections; can be focal or systemic.

2. Prototype: Fluconazole (Diflucan)

use: treat candida infections and meningitis

action: increases permeability of cell membrane

adverse: none known, No adverse [really?] but not for renal/hepatic impaired pts. N/V

IX. ANTIVIRAL NON-HIV DRUGS & UTI DRUGS

Viruses are tricky b/c: they’ve already invaded our cells, and don’t do their own metabolism, so they are difficult targets

A. Non-HIV Anti-Viral Prototype: Acyclovir sodium (Zovirax)

1. caution: electrolyte imbalance, children

2. use: treat HSV-2 and HSV-2

3. action: interferes with viral DNA synthesis

4. adverse: nephrotoxicity, bone marrow depression, renal failure

Acyclovere: HSV ½ [herpes] Serious adverse effects: renal, bone marrow, etc.

UTI drugs: UTI symptoms: fever, burning, frequency, discharge, etc. Elderly: confusion—oddly enough old people don’t have the burning sensation but they get altered LOC.

B. UTI Drugs: Nitrofurantoin (Furalan)

1. use: treat acute and chronic UTIs

2. action: inhibits bacterial enzymes and metabolism

3. adverse: superinfection, hepatotoxicity

C. Nursing Process

X. CASE SCENARIOS

A. Migrant laborer with chronic cough, night sweats

Community nursing: migrant worker w/ nightsweats and cough. Think: TB. Get an interpreter, figure out how to get the meds paid for. Test the family and give them prophylactic drugs.

B. 85 yo hospitalized female with MRSA in her sputum

85 yo F w/ MRSA in her sputum. Vancomycin or Gentomycin. Contact precautions, handwashing, etc. Don’t let your RN manager give you this pt and a post op pt in the same rotation.

C. 55 yo with pneumonia

55 yo with pneumonia: assess lung sounds, adequate hydration, sitting up, drugs are good. Supplemental O2.

Fluid in the pleural space: pleural effusion; why Margi couldn’t hear anything in the right base.

D. 74 yo with UTI admitted from SNF

74 yo w/ UTI admitted from a SNF. High risk, elderly, needs antibiotics.