Categories
Chemotherapeutic Agents Nursing Pharmacology

Antiprotozoal Agents

Antiprotozoal Agents

Causes of Protozoal Infections

  • Insect bites
    • Malaria
    • Trypanosomiasis
    • Leishmaniasis
  • Ingestion or contact with the causal organism
    • Amebiasis
    • Giardiasis
    • Trichomoniasis

Protozoal Parasites Identified as Causes of Malaria

  • Plasmodium falciparum
    • Considered the most dangerous type of protozoan
  • Plasmodium vivax
    • Milder form of the disease; seldom results in death
  • Plasmodium malariae
    • Endemic in tropical countries; mild symptoms
  • Plasmodium ovale
    • Rarely seen; in the process of being eradicated

Life Cycle of Plasmodium

Life Cycle of Plasmodium
Life Cycle of Plasmodium

Antimalarials

  • Chloroquine (Aralen)
    • Prevention and treatment of plasmodial malaria; treatment of extraintestinal amebiasis
  • Halofantrine (Halfan)
    • Treatment of plasmodial malaria in combination with other drugs
  • Hydroxychloroquine (Plaquenil)
    • Treatment of plasmodial malaria in combination with other drugs (particularly primaquine)
  • Mefloquine (Lariam)
    • Prevention and treatment of plasmodial malaria in combination with other drugs
  • Primaquine (generic)
    • Prevention of relapses of Plasmodium vivax and Plasmodium malariae infections
    • Radical cure of P. vivax malaria
  • Pyrimethamine (Daraprim)
    • Prevention of plasmodial malaria in combination with other agents to suppress transmission
    • Treatment of toxoplasmosis
  • Quinine (generic)
    • Treatment of chloroquine-resistant plasmodial infections

Antimalarials—Action

  • Interrupt plasmodial reproduction of protein synthesis
  • Agents that do not appear to affect the sporozoites are used for prophylaxis

Antimalarials—Contraindications

  • Known allergy
  • Liver disease
  • Alcoholism
  • Lactation
  • Cautions
    • Retinal disease or damage
    • Psoriasis

Antimalarials—Adverse Effects

  • Headache
  • Dizziness
  • Fever
  • Chills
  • Malaise
  • Nausea
  • Vomiting
  • Hepatic dysfunction

Antimalarials—Drug-to-Drug Interactions

  • Quinine derivatives and quinine create risk for cardiac toxicity
  • Antifolate drugs with pyrimethamine can increase risk of bone marrow suppression

Other Antiprotozoal Drugs

  • Actions
    • Inhibit DNA synthesis
  • Contraindications
    • Known allergy, pregnancy, CNS disease, and hepatic disease
  • Adverse reactions
    • Headache, dizziness, ataxia, nausea, vomiting, and diarrhea

Malaria

  • Signs and symptoms
    • Related to the destruction of red blood cells and toxicity to the liver
  • Treatment
    • Aims at attacking the parasite at the various stages of its development inside and outside the human body

Other Protozoal Infections

  • Amebiasis
  • Leishmaniasis
  • Trypanosomiasis
  • Trichomoniasis
  • Giardiasis
  • Pneumocystis carinii

Risk Factors for Protozoal Infections

  • Unsanitary conditions
  • Poor hygienic practices

Prototype Antiprotozoal Agent

Prototype Antiprotozoal Agent
Prototype Antiprotozoal Agent

Prototype Antifungal Agent

Prototype Antifungal Agent
Prototype Antifungal Agent

Use of Antifungals Across the Lifespan

Use of Antifungal Across the Lifespan
Use of Antifungal Across the Lifespan

Common Antiprotozoal Agents

  • Atovaquone (Mepron)
    • Especially active against PCP
  • Metronidazole (Flagyl, MetroGel, Noritate)
    • Treats amebiasis, trichomoniasis, and giardiasis
  • Pentamidine (Pentam 300, NebuPent)
    • Treats PCP, trypanosomiasis, and leishmaniasis
  • Tinidazole (Tindamax)
    • Treats trichomoniasis, giardiasis, and amebiasis

Nursing Considerations for Antimalarial Agents

  • Assessment (history and physical exam)
  • Nursing diagnosis
  • Implementation
  • Evaluation

Nursing Considerations for Antiprotozoal Agents

  • Assessment (history and physical exam)
  • Nursing diagnosis
  • Implementation
  • Evaluation
Categories
Chemotherapeutic Agents Nursing Pharmacology

Antibiotics

Antibiotics

Antibiotics

  • Antibiotics are defined as:
    • Chemicals that inhibit specific bacteria

Types of Antibiotics

  • Bacteriostatic
    • Substances that prevent the growth of bacteria
  • Bactericidal
    • Substances that kill bacteria directly

Signs of Infection

  • Fever
  • Lethargy
  • Slow-wave sleep induction
  • Classic signs of inflammation (redness, swelling, heat, and pain)

Goal of Antibiotic Therapy

  • Decrease the population of the invading bacteria to a point where the human immune system can effectively deal with the invaders

Selecting Treatment

  • Identification of the causative organism
  • Based on the culture report, an antibiotic is chosen that is known to be effective at treating the invading organism

Bacteria Classification

  • Gram-positive
    • The cell wall retains a stain or resists decolorization with alcohol
  • Gram-negative
    • The cell wall loses a stain or is decolorized by alcohol
  • Aerobic
    • Depend on oxygen for survival
  • Anaerobic
    • Do not use oxygen

Aminoglycosides

  • A group of powerful antibiotics used to treat serious infections caused by gram-negative aerobic bacilli
  • Common medications:
    • Amikacin (Amikin)
    • Gentamicin (Garamycin)
    • Kanamycin (Kantrex)
    • Neomycin (Mycifradin)
    • Streptomycin
    • Tobramycin (Nebcin, Tobrex)
  • Bactericidal
  • Indications: treatment of serious infections caused by susceptible bacteria
  • Action: inhibit protein synthesis in susceptible strains of gram-negative bacteria causing cell death
  • Pharmacokinetics
    • Poorly absorbed from the GI tract but rapidly absorbed after IM injection, reaching peak levels within 1 hour
    • Widely distributed throughout the body, crossing the placenta and entering breast milk
    • Excreted unchanged in the urine and have an average half-life of 2 to 3 hours
    • Depend on the kidney for excretion and are toxic to the kidney
  • Contraindications
    • Known allergies, renal or hepatic disease, and hearing loss
  • Adverse effects
    • Ototoxicity and nephrotoxicity are the most significant
  • Drug-to-drug interactions
  • Diuretics and neuromuscular blockers

Cephalosporins

  • Similar to penicillin in structure and activity
  • Action
    • Interfere with the cell-wall–building ability of bacteria when they divide
  • Indication
    • Treatment of infection caused by susceptible bacteria
  • Pharmacokinetics
    • Well absorbed from the GI tract
    • Metabolized in the liver, excreted in the urine
  • Contraindications
    • Allergies to cephalosporins or penicillin
  • Adverse effect
    • GI tract
  • Drug-to-drug interactions
    • Aminoglycosides, oral anticoagulants, and ETOH

Fluoroquinolones

  • Relatively new class of antibiotics with a broad spectrum of activity
  • Indications: treat infections caused by susceptible strains of gram-negative bacteria, including urinary tract, respiratory tract, and skin infections
  • Actions: interferes with DNA replication in susceptible gram-negative bacteria, preventing cell reproduction
  • Pharmacokinetics
    • Absorbed in the GI tract
    • Metabolized in the liver
    • Excreted in the urine and feces
  • Contraindications
    • Known allergy, pregnancy, and lactation
  • Adverse effects
    • Headache, dizziness, and GI upset
  • Drug-to-drug interactions
    • Antacids, quinidine, and theophylline

Macrolides

  • Antibiotics that interfere with protein synthesis in susceptible bacteria
  • Indications: treatment of respiratory, dermatologic, urinary tract, and GI infections caused by susceptible strains of bacteria
  • Actions: bind to cell membranes causing a change in protein function and cell death; can be bacteriostatic or bactericidal
  • Pharmacokinetics
    • Absorbed from the GI tract
    • Metabolized in the liver, excreted in the bile to feces
  • Contraindications
    • Allergy and hepatic dysfunction
  • Adverse effects
    • GI symptoms
  • Drug-to-drug interactions
    • Digoxin, oral anticoagulants, theophylline, and corticosteroids

Lincosamides

  • Similar to macrolides but more toxic
  • Action
    • Similar to macrolides
  • Indications
    • Severe infections
  • Pharmacokinetics
    • Well absorbed from the GI tract or IM
    • Metabolized in the liver and excreted in the urine and feces
  • Contraindications
    • Hepatic or renal impairment
  • Adverse effects
    • GI reactions

Monobactams

  • Unique structure with little cross-resistance
  • Action
    • Disrupts bacteria cell wall synthesis, which promotes the leakage of cellular content and cell death
  • Indications
    • Treatment of infections caused by susceptible bacteria; UTI, skin, intra-abdominal, and gynecologic infections
  • Pharmacokinetics
    • Well absorbed from the IM injection
    • Excreted unchanged in the urine
  • Contraindications
    • Allergy
  • Adverse effects
    • GI and hepatic enzyme elevation

Penicillins

  • First antibiotics introduced for clinical use
  • Action
    • Inhibit synthesis of the cell wall in susceptible bacteria, causing cell death
  • Indications
    • Treatment of infections caused by streptococcal, pneumococcal, staphylococcal, and other susceptible bacteria
  • Pharmacokinetics
    • Well absorbed from the GI tract
    • Excreted unchanged in the urine
  • Contraindications
    • Allergy
    • Caution in patients with renal disease
  • Adverse effects
    • GI effects
  • Drug-to-drug interactions
    • Tetracyclines and aminoglycosides

Sulfonamides

  • Drugs that inhibit folic acid synthesis
  • Action
    • Interfere with the cell-wall–building ability of dividing bacteria
  • Indications
    • Treatment of infections caused by gram-negative and gram positive-bacteria
  • Pharmacokinetics
    • Well absorbed from the GI tract
    • Metabolized in the liver and excreted in the urine
  • Contraindications
    • Allergy and pregnancy
  • Adverse effects
    • GI symptoms and renal effects related to the filtration of the drug
  • Drug-to-drug interactions
    • Cross sensitivity with thiazide diuretics
    • Sulfonylureas

Tetracyclines

  • Developed as semisynthetic antibiotics based on the structure of a common soil mold
  • Action
    • Inhibit protein synthesis in susceptible bacteria, preventing cell replication
  • Indications
    • Treatment of various infections caused by susceptible strains of bacteria and acne, and when penicillin is contraindicated for eradication of susceptible organisms
  • Pharmacokinetics
    • Adequately absorbed from the GI tract
    • Concentrated in the liver and excreted unchanged in the urine
  • Contraindications
    • Allergy, pregnancy, and lactation
  • Adverse effects
    • GI, skeletal: damage to bones and teeth
  • Drug-to-drug interactions
    • Penicillin G, oral contraceptive therapy, methoxyflurane, and digoxin

Antimycobacterials

  • Contain pathogens causing tuberculosis and leprosy
  • Action
    • Act on the DNA of the bacteria, leading to lack of growth and eventual bacterial death
  • Indication
    • Treatment of acid-fast bacteria
  • Pharmacokinetics
    • Well absorbed from the GI tract
    • Metabolized in the liver and excreted in the urine
  • Contraindications
    • Allergy and renal or hepatic failure
  • Adverse effects
    • CNS effects and GI irritation
  • Drug-to-drug interactions
    • Rifampin and INH can cause liver toxicity

Antibiotic Use Across the Lifespan

  • Pediatric population
  • Adult population
  • Geriatric population

Comparison of Prototype Antibiotics

Drug/ Classification Indication Action Route Onset Peak Pharmacokinetics Adverse Effects
Gentamicin/ Aminoglycosides Treatment of serious infections caused by susceptible bacteria Inhibits protein synthesis in susceptible strains of gram negative bacteria IM Rapid 30-90 min T½  – 2-3 h Sinusitis, dizziness, rash, fever, risk of nephrotoxicity
IV Metabolized in the liver,
excreted in the urine
Cefaclor/ Cephalosporins Treatment of respiratory, dermatological, urinary tract, and middle ear infections Inhibits synthesis of bacteria cell wall Oral 30-60 min 8-10 h T ½ 30-60 min Nausea, vomiting, diarrhea, rash, superinfections, bone marrow suppression, risk for pseudomembranous colitis
Excreted unchanged in the urine
Ciprofloxacin/ Fluoroquinolones Treatment of respiratory, dermatological, urinary tract, ear, eye, bone, and joint infections Interferes with DNA replication in susceptible gram negative bacteria Oral Varies 4-5 h T ½  – 3.5-4 h Headache, dizziness, hypotension, nausea, vomiting, diarrhea, fever, and rash
IV 10 min 4-5 h Metabolized in the liver,
excreted in bile and urine
Erythromycin/ Macrolides Treatment of respiratory, dermatological, urinary tract, and GI infections Binds to cell membrane causing change in protein function and cell death Oral 1-2 h 1-4 h T ½ – 3-5 h Abdominal cramping, vomiting, diarrhea, rash, superinfections, liver toxicity, potential for hearing loss
IV Rapid 1h Metabolized in the liver, CONTINUED ON NEXT SLIDE
excreted in bile and urine
Treatment of serious infections caused by susceptible strains of bacteria Inhibits protein synthesis in susceptible bacteria Oral Varies 1-2 h T ½ – 2-3 hours Nausea, vomiting, diarrhea, pseudomembranous colitis, bone marrow suppression, hypotension, cardiac arrest
IV Immed. Min Metabolized in the liver, excreted in bile and urine
IM 20-30 min 1-3 h
Aztreonam/ Treatment of lower respiratory, dermatological, urinary tract, intra-abdominal, and GYN infections Interferes with bacterial cell wall synthesis IM Varies 60-90 min T ½ – 1.5-2 h Nausea, vomiting, diarrhea, rash, superinfections, anaphylaxis, local discomfort at injection site
Monobactams IV Immed. 30 min Excreted in unchanged urine
Amoxicillin/ Treatment of infections caused by susceptible strains of bacteria Inhibits synthesis of the cell wall, causing cell death Oral Varies 1 h T ½  – 1-1.4 h Nausea, vomiting, diarrhea, glossitis, stomatitis, bone marrow suppression, rash, fever, lethargy
Penicillins Excreted unchanged in urine
Sulfasalazine/ Treatment of rheumatoid arthritis, arthritis, and ulcerative colitis Clindamycin/ Oral Varies 1.5-6 h T ½ – 5-10 h Nausea, vomiting, hepatocellular necrosis, hematuria, Stevens-Johnson syndrome, rash, photophobia, fever
Sulfonamides Lincosamides 6-24 h – metab. Metabolized in the liver, excreted in urine
Tetracycline/ Treatment of various infections caused by susceptible bacteria Inhibits protein synthesis in susceptible bacteria Oral Varies 2-4 h T ½ – 6-12 h Nausea, vomiting, diarrhea, discoloration of teeth, bone marrow suppression, photosensitivity
Tetracyclines Excreted unchanged in urine
Isoniazid/ Treatment of tuberculosis Interferes with lipid and nucleic acid synthesis in actively growing tubercle bacilli Oral Varies 1-2 h T ½  – 1-4 h Peripheral neuropathies, nausea, vomiting, hepatitis, bone marrow suppression, fever, gynecomatia, lupus syndrome
Antimycobacterials Metabolized in the liver, excreted in urine

Nursing Considerations—Aminoglycosides

  • Assessment and history
  • Nursing diagnosis
  • Implementation
  • Evaluation

Nursing Considerations—Cephalosporins

  • Assessment and history
  • Nursing diagnosis
  • Implementation
  • Evaluation

Nursing Considerations—Fluoroquinolones

  • Assessment and history
  • Nursing diagnosis
  • Implementation
  • Evaluation

Nursing Considerations— Macrolides & Lincosamides

  • Assessment and history
  • Nursing diagnosis
  • Implementation
  • Evaluation

Nursing Considerations—Monobactam

  • Assessment and history
  • Nursing diagnosis
  • Implementation
  • Evaluation

Nursing Considerations—Penicillins

  • Assessment and history
  • Nursing diagnosis
  • Implementation
  • Evaluation

Nursing Considerations—Sulfonamides

  • Assessment and history
  • Nursing diagnosis
  • Implementation
  • Evaluation

Nursing Considerations—Tetracyclines

  • Assessment and history
  • Nursing diagnosis
  • Implementation
  • Evaluation

Nursing Considerations—Antimycobacterials

  • Assessment and history
  • Nursing diagnosis
  • Implementation
  • Evaluation
Categories
Chemotherapeutic Agents Nursing Pharmacology

Anti-infective Agents

Anti-infective Agents

Drug Therapy Across the Lifespan

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
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