PHARMA-CHAP-89

Page 1:

Main Ideas:

• Anti-infective agents are drugs designed to target foreign organisms that have invaded and infected the body.

  • They have selective toxicity, meaning they affect proteins or enzyme systems used only by the infecting organism but not by human cells.

• There are two types of anti-infective agents: bactericidal and bacteriostatic.

  • Bactericidal drugs cause death of the cells they affect.

  • Bacteriostatic drugs interfere with the cells' ability to reproduce or divide, preventing or slowing cell replication.

• The goal of anti-infective therapy is to reduce the population of invading organisms to a point where the human immune response can eliminate them.

• Immunocompromised individuals may have difficulty effectively dealing with invading organisms due to factors such as malnutrition, age, or AIDS.

• Resistance refers to the ability of microorganisms to adapt over time and become unaffected by a particular anti-infective drug.

Page 2:

Main Ideas:

• Gentamicin is an aminoglycoside antibiotic that inhibits protein synthesis in susceptible strains of gram-negative bacteria.

  • It can cause severe renal damage and ototoxicity.

• Meropenem is an IV antibiotic from the carbapenem class that inhibits the synthesis of cell walls in susceptible bacteria.

  • It is used to treat polymicrobial and drug-resistant infections.

  • It can cause uncomfortable gastrointestinal effects.

• Vancomycin interferes with cell wall synthesis in susceptible bacteria.

  • It is used to treat patients who are intolerant or allergic to penicillin.

  • IV vancomycin may be highly toxic and is reserved for serious and severe infections.

• Anti-infective agents can be used for prophylaxis to prevent infections before they occur or to prevent a second infection.

• The treatment of systemic infections involves identifying the pathogen, determining its sensitivity, and using combination therapy.

• Sensitivity testing evaluates pathogens obtained in a culture to determine which anti-infectives will be effective against the organisms causing the infection.

• Anti-infective therapy can have adverse reactions, including kidney damage, gastrointestinal toxicity, neurotoxicity, hypersensitive reactions, and superinfections.

Page 3:

Main Ideas:

• Antibiotics are chemicals that inhibit specific bacteria.

• Bacteria can be categorized based on their types of cell wall using Gram staining.

• Gram-positive bacteria have more peptidoglycan layers in their cell walls and are associated with respiratory tract and soft tissue infections.

• Gram-negative bacteria have a thin layer of peptidoglycan and are associated with genitourinary or gastrointestinal tract infections.

• Aerobic bacteria depend on oxygen for survival, while anaerobic bacteria do not use oxygen.

• Synergistic antibiotics have a combined effect that is greater or can treat more severe infections.

• Aminoglycosides are a group of antibiotics used to treat infections caused by aerobic gram-negative bacilli.

• Aminoglycosides are bactericidal and inhibit protein synthesis in susceptible strains of aerobic gram-negative bacteria.

• They are poorly absorbed from the GI tract, rapidly absorbed after IM injection, and widely distributed throughout the body.

• Contraindications and cautions for aminoglycosides include known allergy, renal disease, preexisting hearing loss, and conditions like myasthenia gravis or parkinsonism.

Page 4

Adverse Effects of Aminoglycosides

• Central Nervous System:

  • Ototoxicity, irreversible deafness

  • Vestibular paralysis

  • Confusion, depression, disorientation

  • Numbness, tingling, weakness

• GI effects:

  • Nausea, vomiting, diarrhea

  • Weight loss

  • Stomatitis

• Cardiac effects:

  • Palpitations

  • Hypotension

  • Hypertension

Clinically Important Drug-Drug Interactions

• Synergistic bactericidal effect with penicillins or cephalosporins

• Increased incidence of ototoxicity when combined with loop diuretics

• Increased risk of nephrotoxicity when combined with vancomycin

• Increased neuromuscular blockade with paralysis when given with anesthetics, nondepolarizing neuromuscular blockers, succinylcholine, or citrate anticoagulated blood

Carbapenems

• Broad-spectrum beta-lactam antibiotics effective against gram-positive and gram-negative bacteria

• Bactericidal action by inhibiting cell membrane synthesis in susceptible bacteria

• Used to treat serious infections

Page 5

Pharmacokinetics of Carbapenems

• Rapid absorption if given IM, peak levels at the end of IV infusion

• Widely distributed throughout the body

• Varies in ability to cross placenta or enter human milk

• Excreted unchanged in urine, average half-life of 1 to 4 hours IV infusion

Contraindications and Cautions for Carbapenems

• Caution in case of allergy to carbapenems or beta-lactams

• Caution during pregnancy and lactation due to potential adverse effects to fetus

Adverse Effects of Carbapenems

• Toxic effects on the GI tract:

  • Pseudomembranous colitis

  • Clostridium Difficile diarrhea

  • Nausea, vomiting leading to dehydration and electrolyte imbalances

• Superinfections can occur

• CNS effects:

  • Headache, dizziness, altered mental state

  • Seizures reported

Clinically Important Drug-Drug Interactions for Carbapenems

• Decreased serum valproic acid levels and increased risk of seizures when combined with valproic acid

• Increased risk of seizures when combined with ganciclovir

Page 6

Cephalosporins

• Beta-lactam antibiotics similar to penicillins in structure and activity

• Bactericidal or bacteriostatic depending on dose and specific drug

Pharmacokinetics of Cephalosporins

• Primarily excreted unchanged in urine

• Lower doses may be prescribed for patients with renal impairment

Contraindications and Cautions for Cephalosporins

• Allergies to cephalosporins or penicillins, cross-sensitivity may occur

• Caution with hepatic or renal impairment due to kidney toxicity

Clinically Important Drug-Drug Interactions for Cephalosporins

• Increased risk of nephrotoxicity when taken with aminoglycosides

• Increased bleeding when taken with warfarin

Adverse Effects of Cephalosporins

• Common adverse effects involve the GI tract:

  • Nausea, vomiting, diarrhea, anorexia, abdominal pain, flatulence

• Pseudomembranous colitis is a potentially dangerous disorder

• CNS symptoms:

  • Headache, dizziness, lethargy, paresthesia

• Nephrotoxicity associated with use in patients with renal insufficiency

Fluoroquinolones

• Synthetic bactericidal antibiotics with broad-spectrum activity

Therapeutic Actions and Indications of Fluoroquinolones

• Enter bacterial cell and interfere with DNA enzymes necessary for growth and reproduction of bacteria

• Used to treat infections caused by susceptible strains of gram-positive and gram-negative bacteria

Pharmacokinetics of Fluoroquinolones

• Absorbed from GI tract, metabolized in liver, excreted in urine and feces

Contraindications and Cautions for Fluoroquinolones

• Multiple boxed warnings for potential serious adverse effects:

  • Tendinitis, tendon rupture, peripheral neuropathy, CNS effects, exacerbation of muscle weakness in patients with myasthenia gravis

Adverse Effects of Fluoroquinolones

• Serious effects:

  • Tendinitis, tendon rupture, peripheral neuropathy, CNS effects, diarrhea, liver toxicity

• Common effects:

  • Headache, dizziness, insomnia, depression

  • Nausea, vomiting, diarrhea, dry mouth

  • Bone marrow depression

Clinically Important Drug-Drug Interactions for Fluoroquinolones

• Decreased therapeutic effect when taken with iron salts, sucralfate, multivitamins, calcium or magnesium supplements, or antacids

• Increased levels of theophylline when combined with theophylline

• Increased risk of CNS stimulation when combined with nonsteroidal anti-inflammatory drugs

• Increased risk of tendonitis and tendon rupture when combined with corticosteroids

Penicillins and Penicillinase Resistance

• First antibiotic for clinical use, modified to act on resistant bacteria

Therapeutic Actions and Indications of Penicillins

• Bactericidal effects by interfering with cell wall synthesis in susceptible bacteria

Pharmacokinetics of Penicillins

• Rapid absorption from GI tract, sensitive to gastric acid levels

• Should be taken on an empty stomach for adequate absorption

Contraindications and Cautions for Penicillins

• Contraindicated in patients with allergies to penicillin or other allergens

• Caution in patients with renal disease, lower doses necessary

• Limited use in pregnancy and lactation due to potential adverse effects on the infant

Adverse Effects of Penicillins

• Major adverse effects involve the GI tract:

  • Nausea, vomiting, diarrhea, abdominal pain, glossitis, stomatitis, gastritis, sore mouth, furry tongue

Clinically Important Drug-Drug Interactions for Penicillins

• Inactivation of aminoglycosides when combined with parenteral penicillins

Sulfonamides

• Inhibit folic acid synthesis

Therapeutic Actions and Indications of Sulfonamides

• Folic acid is necessary for the synthesis of purines and pyrimidines, precursors of RNA and DNA

• Used for cells to grow and reproduce

Pharmacokinetics of Sulfonamides

• Teratogenic, distributed into human milk

• Given orally, absorbed from GI tract

Contraindications and Cautions for Sulfonamides

• Not routinely used during pregnancy due to potential birth defects

• Caution in older adults due to increased incidence of thrombocytopenia, hyperkalemia, and folate deficiency

Adverse Effects of Sulfonamides

• GI tract effects:

  • Nausea, vomiting, diarrhea, abdominal pain, anorexia, stomatitis

• Hepatic injury

Note: This summary includes all the main ideas and supporting details from the given transcript.

Page 7

Adverse Effects of Tetracyclines

• Irritation of the GI tract and death of normal bacteria

  • Renal effects: crystalluria, hematuria, hyperkalemia, proteinuria

  • CNS effects: headache, dizziness, vertigo, ataxia, convulsions, depression

  • Bone marrow depression

  • Dermatological effects: photosensitivity, Stevens-Johnson syndrome

Clinically Important Drug-Drug Interactions

• Increased risk of hypoglycemia when taken with antidiabetic agents glyburide or glipizide

• Increased risk of hyperkalemia when combined with medications like ace inhibitors and potassium sparing diuretics

• Risk of nephrotoxicity when taken with cyclosporine

Therapeutic Actions and Indications of Tetracyclines

• Bacteriostatic, inhibiting protein synthesis in a wide range of bacteria

Pharmacokinetics of Tetracyclines

• Absorbed adequately but not completely from the GI tract

• Absorption affected by food, iron, calcium, and other drugs in the stomach

Contraindications and Cautions of Tetracyclines

• Caution in children younger than 8 years of age due to potential damage to developing bones and teeth

Adverse Effects of Tetracyclines

• Direct irritation of the GI tract and hepatotoxicity

• Damage to teeth and bones

• Dermatological effects: photosensitivity, rash, superinfection

• Local effects: pain and stinging with topical application

• Hematological effects: hemolytic anemia, bone marrow depression

• Hypersensitivity reactions: urticaria to anaphylaxis, intracranial hypertension

Clinically Important Drug-Drug Interactions of Tetracyclines

• Digoxin toxicity increases when taken concurrently

• Decreased absorption when combined with calcium salts, magnesium salts, zinc salts, aluminum salts, bismuth salts, and iron

Clinically Important Drug-Food Interactions of Tetracyclines

• Oral tetracyclines are not effective if taken with food or dairy products

• Should be administered on an empty stomach with water 1 hour before or 2 to 3 hours after any meal or other medication

Page 8

Antituberculosis Drugs

• Tuberculosis can cause serious damage in the lungs, GU tract, bones, and meninges

Leprostatic Drugs

• Dapsone is used to treat leprosy and pneumocystis jirovecii pneumonia in AIDS patients

• Also used for various infections caused by susceptible bacteria and for brown recluse spider bites

• Topical form can be used to treat acne

Thalidomide (Thalomide)

• Immunomodulatory drug used to treat cutaneous reactions due to leprosy

• Dosage: 100-300 mg/d PO, up to 400 can be administered

Erythema Nodosum Leprosum

• Complication of leprosy that causes inflammatory skin nodules and systemic symptoms like fever, malaise, and neuritis

Therapeutic Actions and Indications of Antimycobacterials

• Acts on the DNA and RNA of bacteria, leading to lack of growth and bacterial death

Rifadin, Rimactane

• Bactericidal drugs mostly active against mycobacteria

• Resistance to rifampin develops quickly if used as monotherapy

Adverse Effects of Antimycobacterials

• CNS effects: neuritis, dizziness, headache, malaise, drowsiness, hallucinations

Clinically Important Drug-Drug Interactions of Antimycobacterials

• Concurrent use of isoniazid, rifampin, and pyrazinamide increases the risk of hepatotoxicity

• Eating foods with tyramine and taking isoniazid can cause histamine reaction

• Taking isoniazid with alcohol can increase liver damage

Lincosamides

• Similar to macrolides, bacteriostatic drugs that interfere with protein synthesis of gram-positive bacteria

• Examples: clindamycin (Cleocin), lincomycin (Lincocin)

Therapeutic Actions and Indications of Lincosamides

• React at the same site in bacterial protein synthesis and are effective against the same strains of bacteria

• Used to treat infections caused by gram-positive and some anaerobic bacteria

Pharmacokinetics of Lincosamides

• Absorbed rapidly from GI tract or from IM injections, typically administered IV

• Metabolized in the liver and excreted in the urine and feces

• Cross the placenta and enter human milk

Page 9

Contraindications and Cautions

• Caution with hepatic impairment

  • Interference with metabolism and excretion of the drug

• Dose adjustment recommended for renal impairment

Adverse Effects

• Severe GI reactions, including fatal pseudomembranous colitis

• Drug of choice for serious infections caused by susceptible bacteria

Lipoglycopeptides

• Class of antibiotics introduced in 2010

• Includes Telavancin, Dalbavancin, Oritavancin, and Vancomycin

Therapeutic Actions and Indications

• Inhibit bacterial cell wall synthesis

• Bind to bacterial membrane and disrupt membrane barrier function

• Treat complicated skin and skin structure infections in adults

Pharmacokinetics

• Available as IV drugs, only Vancomycin has an oral form

• Oral Vancomycin poorly absorbed and not used for systemic infections

• Lipoglycopeptides reach peak levels at the end of infusion

Adverse Effects

• Toxic effects on GI tract: nausea, vomiting, taste alterations, diarrhea, loss of appetite

• Risk of C. difficile diarrhea

• Nephrotoxicity

Clinically Important Drug-Drug Interaction

• Increased risk of prolonged QT interval and arrhythmias with Telavancin and other drugs known to prolong QT interval

• Increased risk of nephrotoxicity with Telavancin and Vancomycin when combined with other nephrotoxic drugs

Macrolides

• Antibiotics that bind to the ribosome and interfere with protein synthesis in susceptible bacteria

• Includes Erythromycin, Azithromycin, Clarithromycin, and Fidaxomicin

Therapeutic Actions and Indications

• Bactericidal at high doses or bacteriostatic

• Bind to ribosomes and change protein synthesis, preventing cell division or causing cell death

• Treat various bacterial infections

Pharmacokinetics

• Widely distributed throughout the body

• Cross the placenta and enter human milk

• Erythromycin and Azithromycin primarily metabolized in the liver, excreted in bile to feces

• Half-life of Erythromycin is 1.6 hours

Page 10

Clarithromycin

• Partially excreted unchanged in the urine

• Half-life of Azithromycin is 68 hours, useful for patients with trouble remembering

• Half-life of Clarithromycin is 3 to 7 hours

Fidaxomicin

• Minimally absorbed systemically, acts in the GI tract

• Metabolized in the GI tract and excreted in the feces

• Half-life of 9 hours

Contraindications and Cautions

• Contraindicated in patients with allergy that can cause cross-sensitivity

• Caution with hepatic dysfunction

• Caution with lactating mothers, except for Fidaxomicin which is not absorbed systemically

• Caution with pregnant women, potential adverse effects on fetus or infant

Adverse Effects

• GI tract effects: abdominal cramping, anorexia, diarrhea, vomiting, pseudomembranous colitis

• Neurological symptoms: confusion, abnormal thinking, uncontrollable emotions

• Hypersensitivity reactions ranging from rash to anaphylaxis and superinfection

Clinically Important Drug-Drug Interactions

• Increased serum levels of digoxin when taken with macrolides

• Increased metabolic changes in the liver when taken with oral anticoagulants, carbamazepine

Clinically Important Drug-Food Interactions

• Food in the stomach decreases absorption of oral macrolides, except for Azithromycin

• Antibiotics should be taken on an empty stomach with a full 8-oz glass of water 1 hour before or 2 to 3 hours after meals

Oxazolidinones

• Class: Tedizolid and Linezolid

Therapeutic Actions and Indications

• Interfere with protein synthesis on the bacterial ribosome

• Act as MAO inhibitors

• Effective against vancomycin-resistant strains of MRSA and penicillin-resistant pneumococci

• Tedizolid FDA approved for skin and skin structure infections, diabetic foot infections without osteomyelitis

Pharmacokinetics

• Tedizolid available for oral or IV use, half-life of 12 hours, metabolized in liver and excreted in urine and feces

• Linezolid available for oral or IV use, half-life of 5 hours, metabolized in liver and excreted in urine

Page 11

Contraindications and Cautions

• Allergy to drug

• Caution with phenylketonuria (oral suspension of Linezolid)

• Caution with patients taking MAO inhibitors

• Caution with pregnant and lactating patients

• Caution with hepatic impairment, pheochromocytoma, hypertension, hyperthyroidism, and bone marrow suppression

Adverse Effects

• CNS effects: headache, insomnia, dizziness

• GI tract effects: dry mouth, nausea, vomiting, diarrhea, potential for pseudomembranous colitis

• Optic neuritis, thrombocytopenia, bone marrow suppression, hypertension

Drug-Drug Interactions

• Risk of hypertension when combined with drugs that increase blood pressure

• Risk of bleeding and thrombocytopenia when combined with NSAIDs and platelet inhibitors

• Potential for serious serotonin syndrome if used with serotonergic drugs

Drug-Food Interactions

• Potential for serious to life-threatening hypertension when combined with large amounts of tyramine-containing foods

Monobactam Antibiotic

• Aztreonam

Therapeutic Actions and Indications

• Effective against gram-negative enterobacteria

• No effect on gram-positive or anaerobic bacteria

• Disrupts bacterial cell wall synthesis

• Indicated for the treatment of urinary tract, skin, intra-abdominal, and gynecological infections

Pharmacokinetics

• Available for IV and IM use only

• Reaches peak effects levels immediately if administered IV, slower if administered IM

• Half-life of 1.5 to 2 hours

Contraindications and Cautions

• Caution with history of acute allergic reaction to penicillins or cephalosporins

• Caution with renal dysfunction

• Caution with pregnant and lactating mothers

Adverse Effects

• Local GI tract effects: nausea, GI upset, vomiting, diarrhea

• Hepatic enzyme elevations

• Inflammation, phlebitis, and discomfort at injection sites

• Anaphylaxis

Page 12: Clinically Important Drug-Drug Interactions

• Aztreonam and aminoglycosides may have a synergistic effect when used together to treat certain organisms.

End of Transcript

• This note is transcribed from a pharmacology midterm coverage lecture.

• The instructor is Joel F. Defensor, RN, MAN, USRN.

• The transcription was done by Braille Justine T. Boncales, SN.

• The lecture refers to Sir Joel's PowerPoint presentation and discussion.