Pharmacology 1: EXAM 2 Liberty University

Antimicrobial Definiton

Used to prevent or treat infection.

Selective Toxicity

The ability of a drug to injure a targeted cell or targeted organism without injuring other cells or organisms.

Three Mechanisms for Selective Toxicity

1.) Disruption of Bacterial Cell Wall.

2.) Inhibits an enzyme unique to bacteria.

3.) Disrupts bacterial protein synthesis.

Inhibition of Bacterial Cell Wall Synthesis

Examples:

1.) Penicillin

2.) Cephalosporins

3.) Imipenem

4.) Vancomycin

Increase Cell Membrane Permeability

Examples:

1.) Amphotericin B

2.) Daptomycin

3.) Ketoconazole

Inhibition of Bacterial Protein Synthesis

Both lethal (Bactericidal) and Non-lethal (Bacteriostatic)

1.) Lethal = Aminoglycosides

2.) Non-Lethal = Tetracycline, Erythromycin, Clindamycin, Linezolid

Inhibition of Bacterial Synthesis of Nucleic Acids

Examples:

1.) Fluoroquinolones

2.) Metronidazole

3.) Rifampin

Inhibition of Specific Biochemical Reactions

Examples:

1.) Sulfonamides

2.) Trimethoprim

Broad Spectrum

Kills a wide spectrum of bacteria. (Extensively effects body flora)

Narrow Spectrum

Specific against few groups of bacteria.

Bactericidal

Kills bacteria directly.

Bacteriostatic

Halts bacterial growth without killing bacteria.

Acquired Resistance to Antimicrobial Drugs

May occur over time. Organisms develop resistance. May have been highly responsive then became less susceptible to one or more drugs.

Microbial Mechanisms of Drug Resistance (Four Basic Actions)

1.) Decrease the concentration of a drug at its site of action.

2.) Inactivate a drug.

3.) Alter the structure of drug target molecules.

4.) Produce a drug antagonist.

Spontaneous Mutation

(Not so bad, usually to one drug)

- Random changes in microbe's DNA.

- Resistance to one drug.

Conjugation

(Very problematic!! Multiple drugs, different classes)

- Extrachromosomal DNA is transferred from one bacterium to another.

- Gram-Negative Bacteria

- Multiple Drug Resistance

How Antibiotic Use Promotes Resistance

Drugs make conditions favorable for overgrowth of microbes that have acquired mechanisms for resistance.

Antibiotics That Promote Resistance

Broad-Spectrum Agents = Do the most to facilitate the emergence of resistance.

The Extent of Antibiotic Use Affects Resistance

The more that the antibiotics are used, the faster drug-resistant organisms emerge.

Nosocomial Infection

Health Care Associated Infections (HAIs):

- MRSA

- VRE

Superinfections

- New infection that appears during course of treatment for a primary infection.

- Because superinfections are caused by drug-resistant microbes, they often are DIFFICULT to treat.

Examples:

1.) Candida

2.) C. Diff

Community Acquired Infection

Infection from community (Strep pneumo).

Delaying Emergence of Drug Resistance

1.) Promote adherence to appropriate prescribing guidelines.

2.) Reduce demand for antibiotics among healthy adults and parents of young children.

3.) Emphasize adherence to prescribed antibiotic regimens.

Selection of Antibiotics

1.) Identify organism

2.) Drug sensitivity of organism

3.) Host factors

4.) Drug may be ruled out owing to:

- Allergy

-Inability to penetrate site of infection

-Patient variables

Empiric Therapy

Antibiotic therapy for patients before causative organism is positively identified.

Drug Selection Based On:

- Clinical evaluation

- Knowledge of microbes that most likely to have caused infection.

Identifying the Infectious Organism

1.) "Match the drug with the bug"

2.) Gram-stained preparation

3.) Determining drug susceptibility:

- Disk diffusion test

- Serial dilution

- Gradient diffusion

Host Factors

1.) Host Defenses

2.) Site of Infection

3.) Previous Allergic Reaction

4.) Genetic Factors

Dosage Size and Duration

-Antibiotic must be present:

a.) At the site of infection

b.) For a sufficient length of time

-Antibiotics must not be discontinued prematurely

-Teach patients to complete full prescription

Antibiotic Combinations

- Antimicrobial effects of antibiotic combinations:

a.) Additive, potentiative, antagonistic.

- Indications:

Mixed infections, prevention of resistance, decreased toxicity, and enhanced bacterial action.

- Disadvantages of Combinations

Prophylactic Use of Antimicrobials

Agents are given to prevent infection rather than to treat an established infection:

- Surgery

- Bacterial Endocarditis

- Neutropenia

- Other indications

Misuses of Antimicrobial Drugs

- Attempted Treatment of Viral Infections

-Treatment of Fever of Unknown Origin

-Improper Dosage

-Treatment in the Absence of Adequate Bacteriologic Information

-Omission of Surgical Drainage

Monitoring of Antimicrobial Therapy

- Monitor clinical responses and lab results.

- Frequency of monitoring should increase with severity of infection.

- Clinical indicators of success =

1.) Reduction of Fever

2.) Resolution of Signs/Symptoms related to the affected organ

- Serum drug levels for toxicity ***

Classification of Anti-Infective Agents

- Penecillins

- Cephalosporins

- Carbapenems

- Aminoglycosides

- Tetracyclines

- Sulfonamides

- Urinary Tract Antiseptics

- Macrolides

- Fluoroquinolones

- Vancomycin

- Antiviral Drugs

- Antifungal Drugs

- Antitubercular Drugs

- Antiparasitic

Gram-Positive

- Staphylococcal

- Streptococcal

- Enterococcus

Gram-Negative

- E. Coli

- Proteus

- Pseudomonas

- Enterobacter

- Klebsiella

- Shigella

Beta-Lactam Antibiotics

- Penicillins

- Cephalosporins

- Carbapenems

- Monobactams

Penicillins

MOA: Inhibits Cell Wall Synthesis

Spectrum:

- Narrow Spectrum PCN - Penicillinase Sensitive

- Antistaphylococcal PCN - Penicillinase Resistant

- Broad Spectrum PCN - Aminiopenicillins

- Antipseudomonal PCN

- PCN plus B-lactamase Inhibitor

Adverse Effects of Penicillin:

- Hypersensitivity: 1-7% of patients, most common problem.

[ RANGES = Minor rash to life threatening anaphylaxis.]

> Allergic response = urticarial rash, flushing, diaphoresis, tachycardia, respiratory difficulties.

> Anaphylactic response = hypotension, severe respiratory distress, laryngeal edema, tachycardia, cyanosis, and seizures.

- Cross-Sensitivity: 1% patients with PCN allergy will also be allergic to Cephalosporins.

- Neurotoxicity: Rare, but PCN can cause convulsions secondary to direct CNS stimulation.

- Nephropathy: Rare, interstitial nephritis can occur. Reactions will go away if the drug stopped.

- Hematological: Rare, Eosinophila, Hemolytic anemia, Leukopenia. Reaction will go away if the drug is stopped.

Narrow Spectrum PCN - Penicillinase Sensitive

PCN G (IV)

- Streptococcus pharyngitis

Other organisms:

- Step. pneumo

- Strep. viridans

- Neisseria species

Antistaphylococcal PCN - Penicillinase Resistant

Methicillin

Oxacillin

- Staphylococcus aureus

Cell Envelope

Gram-Negative Cell Envelope =

- Three Layers

- Thin cell wall and an additional outer membrane that is difficult to penetrate.

Gram-Positive Cell Envelope=

- Only Two Layers

- Relatively thick cell wall that is easily penetrated.

Penicillinases

- Beta-lactamases

- Enzymes that render penicillin inactive ***

- Bacteria can produce a large variety of these enzymes specific for penicillins (and other beta-lactam antibiotics)

Broad Spectrum PCN: Aminiopenicillins

Ampicillin

Amoxicillin

Activity of PCN G plus:

- Haemophilus influenzae

- Enterococcus

- E. Coli

- Salmonella and Shigella

- Are inactivated by B-lactamases

Antipseudomonal PCN

Piperacillin

Activity of Broad Spectrum PCN: Aminiopenicillin plus:

- Pseudomonas aeruginosa

- Enterobacter

- Proteus

- B. Fragilis

- Klebsiella

- Are inactivated by B-lactamases

PCN plus B-lactamase Inhibitor

Ampicillin + sulbactam (Unasyn)

Piperacillin + tazobactam (Zosyn)

Amoxicillin + clavulanic acid (Augmentin)

Cephalosporins

MOA: Binds to penicillin (PBPs), disrupts cell wall synthesis, and cause cell lysis.

Most effective against cells. undergoing active growth and division.

Resistance: Beta-lactamases (cephalosporinases)

- First: Generation Destroyed

- Second: Generation Less Sensitive

- Third, Fourth, and Fifth: Generation agents are more resistant than first and second generation agents.

Spectrum: Three General Rules of Thumb =

1.) Increasing activity against Gram-NEGATIVE bacteria.

2.) Increased resistance to destruction by beta-lactamases.

3.) Increased ability to reach the cerebral spinal fluid (CSF).

Indications:

- Surgical Prophylaxis

- Respiratory Tract Infections

- Skin/Soft Tissue Infections

- Bones/Joints

- UTI

- Septicemia

Adverse Effects:

- Hypersensitivity = Most Common

> Rash

- Bleeding Disorders =

> Cefotetan interfere with Vitamin K Metabolism.

- Contraindicatons =

1.) Allergy to PCN - Especially Anaphylaxis with PCN.

2.) General Rule of Thumb - If anaphylaxis with PCN do not give Cephalosporin!!! If mild reaction to PCN, can give cephalosporin.

First Generation of Cephaolosporins

Ancef-Cefazolin (IV)

Cefadroxil (PO)

Cephalexin (PO)

Uses = Good for surgical prophylaxis, Cellulitis (GOOD GRAM-POSITIVE)

Second Generation of Cephalosporins

Cefotan-Cefotetan (IV)

Cefoxitin (IV)

Cefuroxime (PO, IV)

Uses = Abdominal surgery (Covers ANAEROBES)

Third Generation of Cephalosporins

Rocephin-Ceftriaxone (IV, IM)

Ceftazidime (IV)

Cefotaxime (IV)

Cefpodoxime (PO)

Uses = Pneumonia

Fourth Generation of Cephalosporins

Maxipime-Cefepime (IV)

Uses = Broad-Spectrum: Febrile Neutropenia

Fifth Generation of Cephalosporins

Teflaro-Ceftaroline (IV)

Uses = Only cephalosporin with activity against MRSA.

Carbapenems

MOA: Binds to PCN Binding Protein and weakens the cell wall.

Spectrum: MOST BROAD-Spectrum of ALL Antibiotics.

Examples: Imipenem and Meropenem

>> Side Effects: GI Upset, Hypersensitivity, and Seizures

Other Carbapenems: Ertapenem (Invanz)

> Weakens bacterial cell wall

> Good for Gram-POSITIVE coverage

> Not quite as Broad-Spectrum as Imipenem and Meropenem

>>Adverse Effects: GI Upset, Headache and CNS Effects, and Seizure

Imipenem

Carbapenem

Side effects:

- GI Upset

- Hypersensitivity

- Seizures

Ertapenem (Invanz)

Carbapenem Antibiotic:

Weakens bacterial cell wall.

Good for Gram-POSITIVE coverage.

Not quite a Broad-Spectrum as Imipenem and Meropenem.

Adverse Effects:

- GI Effects

- Headache and CNS Effects

- Seizure

Meropenem

Carbapenem

Side effects:

- GI Upset

- Hypersensitivity

- Seizures

Monobactams

MOA: Inhibits cell wall synthesis

Spectrum:

NO Gram-Positive Activity!!

[ Gram-NEGATIVE = Aerobic Bacteria ] *****

Example:

Aztreonam:

- Most Common Side Effect = Allergic reaction

- Can be used with PCN allergy patients.

Aztreonam

Monobactam

- Most Common Side Effect = Allergic reaction

- Can be used with PCN allergy patients.

Vancomycin

MOA: Inhibits cell wall synthesis.

Spectrum:

- Gram-POSITIVE ONLY!!**

- Surgical Prophylaxis for patients with PCN allergy.

>> MRSA, C. Diff (Oral ONLY), Staph and enterococcal infections.

Adverse Effects:

- RED MAN SYNDROME

- OTOTOXICITY

- NEPHROTOXICITY

>> Monitor: Renal Function (Scr), Peak (25-40 mg/l), and Trough Levels (15-20 mg/l).

Today we only do trough levels b/c we know the peak will be high enough.

** Telavancin = Synthetic Derivative

Fosfomycin [Monurol]

- Approved for single-dose therapy of uncomplicated urinary tract infection (UTI) caused by Escherichia coli or Enterococcus faecalis.

- Disrupts the synthesis of peptidoglycan polymer strands that compose the cell wall.

- Side effects

>> Most common: Diarrhea, headache, vaginitis, nausea

Tetracyclines

MOA: Inhibits protein synthesis. Increasing bacterial resistance has emerged.

Spectrum: Broad-Spectrum Antibiotics

Uses =

- Treatment of infectious disease.

- Treatment of Acne

- Peptic Ulcer Disease (ETC.)

Absorption: (Drug-Drug Interactions) (Decreases the drug if give with ===

- Calcium Supplements

- Milk Products

- Iron Supplements

- Magnesium-Containing Laxatives

- Most Antacids

Adverse Effects:

- Gastrointestinal Irritation

- Effects on Bone and Teeth **

- Superinfection

- Hepatotoxcitiy

- Renal Toxicity

- Photosensitivity and Other effects.

Summary:

- Tetracycline and Demeclocycline are eliminated primarily in the urine.

- They accumulate in patients with kidney disease.

- Can cause discoloration of deciduous and permanent teeth.

- Diarrhea may indicate a potentially life-threatening superinfection in the bowel.

- High-does IV Therapy has been associated with severe liver damage.

Tetracycline

Tetracycline

Know MOA, indications, AE, Etc.

Doxycycline

Tetracycline

Know MOA, indications, AE, Etc.

Macrolides

MOA: Inhibits bacterial protein synthesis.

Spectrum:

- Use in place of PCN if PCN allergy.

- Drug of CHOICE for Legionnaires Disease - Erythromycin

- Strep. Pneumonia, Strep. Throat

- Mycoplasma Pneumonia

- Bordetella Pertussis (Whooping Cough)

- Diphtheria

- Prevent gonorrheal eye infections in newborns (Topical)

DO NOT USE IN LIVER FAILURE PATIENTS!!!!*********

Adverse Effects:

- GI Upset

- Liver Injury

- Drug Interactions are Common

- When giving IV - Thrombophlebitis

- Can prolong QT Interval - (Erythromycin and Clarithromycin) - Rare but can happen).

Examples of Drugs:

- Erythromycin

- Clarithromycin (Biaxin)

- Azithromycin (Zithromax)

Erythromycin

Macrolide Antibiotic

Clarithromycin (Biaxin)

Macrolide Antibiotic

Azithromycin (Zithromax)

Macrolide Antibiotic

Clindamycin

MOA: Inhibits protein synthesis.

Spectrum:

- Gram-POSITIVE infections

- Anaerobic infections outside the CNS.

- Aerobes.

- Alternative to PCN.

Adverse Effects:

>> Antibiotic Associated Pseudomembranous Colitis - Superinfection (AAPMC) in Bowel with C. Diff.

- Perfuse diarrhea

- Abdominal Pain

- Fever

- Leukocytosis

- Can be deadly - Treat with FLAGYL PO/IV = PO is BEST!

- Can also treat with PO Vancomycin

Linezolid (Zyvox)

Class: Oxaxolidinoes

MOA: Inhibits protein synthesis

Spectrum: Effective Agent Against = VRE, MRSA

Side Effects:

- GI

- Nausea

- Diarrhea

- Headache

- Myelosuppression = Anemia, Leukopenia, Thrombopenia

** Drug interaction with Monoamine Oxidase Inhibitors (MAOIs) **

Chloramphenicol

MOA: Inhibits protein synthesis

Spectrum: Broad-Spectrum Antibiotic

Uses = Only for Life-Threatening infections in which safer drugs are ineffective or contraindicated.

Adverse Effects:

- Reversible Bone Marrow Depression

- Fatal Aplastic Anemia

- Gray Syndrome

- GI Effects

- Peripheral Neuropathy

Mupirocin

Used as a topical antibiotic associated with impetigo and used for MRSA IN NOSTRILS!*

Aminoglycosides

MOA: Disrupts protein synthesis in cells.

Spectrum:

- GOOD for Gram-NEGATIVE Organisms.

- Aerobic Gram-NEGATIVE bacilli.

> E. Coli

> Klebsiella

> Serratia

> Proteus

> Pseudomonas

[ INEFFECTIVE against ANAEROBES!!!**]

Indications:

- Serious systemic infections (pneumonia, sepsis) - NOT!! Absorbed PO - Given Orally.

- Serious nosocomial infections.

- TB resistant to other drug (Steptomycin)

- Given orally to suppress intestinal flora (Neomycin) - GI surgery is the only time this medication is given orally.

Examples:

Tobramycin, Gentamicin, and Amikacin

Adverse Effects:

> Nephrotoxicity = Reversible

> Ototoxicity = Irreversible (Tinnitus, Persistent headache)

Monitoring:

- Renal Function BUN, Scr

- Risk higher in patients with pre-existing kidney disease and other nephrotoxic drugs - Amphotericin B, Cyclosporin, Lasix ..... ELDERLY too!!

General Aminoglycoside Points:

- Narrow therapeutic window

- Levels must be drawn at correct time.

- Adjust dose for renal impairment.

- Once daily (extended-interval) dosing has decreased toxicity.

- Keep patients well hydrated.

- Monitor Renal function

Tobramycin

Aminoglycoside

Gentamicin

Aminoglycoside

Amikacin

Aminoglycoside

Sulfonamides

MOA: Inhibits the synthesis of bacterial FOLIC ACID.

- Bacteriostatic = needs host defenses to help!

Spectrum:

-Gram-POSITIVE and Gram-NEGATIVE

Example:

Trimethroprim/Sulfamethoxazole

** MAJOR drug interactions with Coumadin!! **

Indications:

- UTI

- Acute and Chronic Cystitis

- Bronchitis

- Acute Otitis Media in Children

- Toxoplasmosis and Malaria

- Trachoma

- Topical for Burns

- P. Jiroveci (TMP-SMZ)

Adverse Effects:

- GI Side Effects = MOST COMMON

- Hypersensitivity:

> Rash

> Photosensitivity

> Drug Fever

> ***** Steven-Johnson Syndrome

-Renal Failure = Uncommon today, can occur from Crystalluria

****- Kernicterus: IN NEWBORNS (deposition of bilirubin in brain)

- Hemolytic Anemia: Seen in certain ethinic groups (African Americans and Mediterranean origin)

>>> G-6-PD Deficiency: Anemia can develop from lysis.

Urinary Tract Antiseptics

Used to prevent or treat Urinary Tract Infections.

NOT used in systemic infections.

Nitrofurantoin

Bacteriostatic drug.

Used to treat uncomplicated UTI's.

Side Effects: GI Upset Common

Pyridium

Analgesic! NOT AN ANTIBIOTIC!

Used only for pain.

Can cause discoloration of urine and sweat.

Fluroquinolones

MOA: Inhibits bacterial DNA gyrase and topoisomerase IV - BACTERICIDAL

Spectrum: BROAD-SPECTRUM

Coverage:

- Ciprofloxacin (Mainly GRAM-NEGATIVE)

- Levofloxacin (Good for nosocomial pneumonia) [ Also has GRAM-POSITIVE

DOES NOT COVER ANAEROBES!!!

Therapeutic Uses:

- Resp., GU, and GI Infections

- Intra-abdominla infections.

- Bones, skin, and soft tissue

- Multi-drug Resistant TB

- Anthrax

Adverse Effects of Fluroquinolones:

- CNS = Dizziness, Confusion, HA

- GI Upset

- Photosensitivity = LESS COMMON

- Tendon Repture!

- QT interval prolongation (Watch with certain cardiac drugs!!)

Contraindications:

- DO NOT give to children, pregnant, or breastfeeding mothers.

- DO NOT give with Ca, MG, Zn, Multivitamins.

Drug Interactions:

- Avoid antiacids, dairy products

- Can interact with COUMADIN (Warfarin)

Has GREAT bioavailability: CAN BE GIVEN PO OR IV **

Metronidazole [Flagyl]

MOA: Inhibits nucleic acid synthesis: Bacteriostatic

Antimicrobial Spectrum:

- Anaerobes only (C. Difficile, Bfrag)

Uses =

- Pseudomembranous Colitis

- Prophylaxis for surgery (HIGH risk of infection from anaerobes)

- H Pylori Infections

Adverse Effects =

- Nausea and vomiting

- Diarrhea

- CNS Effects

- Metallic Taste

Daptomycin (Cubicin)

NEW CLASS: Cyclic Lipopeptide

MOA: Kills virtually ALL GRAM-POSITIVE bacteria including MRSA *****

Uses =

- Bloodstream infection with S. aureus and complicated skin and skin structure caused by susceptible strains of gram-POSITIVE bacteria.

NO SIGNIFICANT DRUG INTERACTIONS.

Adverse Effects:

- Possible muscle injury (Monitor CPK Levels (Creatine Phosphokinase)

- Given only once daily by IV: No laboratory work needed.

Do NOT Give FATS to Pregnant Women

F = Fluoroquinolones

A = Aminoglycosides

T = Tetracyclines

T = Tigecycline

S = Sulfa Drugs

Treatment of Myobacterial Infections

- Slow-growing microbes

- Require prolonged treatment

- Drug toxicity and poor patient adherence

- Promotes emergence of drug-resistant myobacteria

Tuberculosis (TB)

Treatment =

- More effective drugs make hospitalization generally unnecessary.

- Always treat with two or more drugs!!!**

- Direct observation of drug administration is considered standard of care.

- Treatment is considered effective when no mycobacteria are observed in sputum or no colonies are present in culture.

Multi-Drug Resistance in Tuberculosis:

- Multidrug-Resistant TB (MDR TB):

>> Resistant to both Isoniazid and Rifampin

Extensively Drug-Resistant TB (XDR TB):

Resistant to =

- Isoniazid (INH) and Rifampin

- All Fluoroquinolones

- At least one of the injectable second-line drugs

Treatment =

- Drug-sensitive tuberculosis

- Isoniazid-resistant OR Rifampin-resistant tuberculosis

- MDR TB and XDR TB

- Patients with TB and HIV Infection

- Duration of Treatment:

>> Minimum of 6 months for Drug-Sensitive TB

>> Up to 24 months (2 years) for MDR TB or HIV/AIDS

First-Line Drugs for Tuberculosis (TB)

- Isoniazid

- Rifampin

- Pyrazinadmide

- Ethambutol

Isoniazid

Used for = Primary agent for the treatment and prophylaxis of TB.

Adverse Effects:

-- Peripheral Neuropathy

- Dose Related

- Signs:

> Tingling, Numbness, Burning, and Pain.

> REVERSAL AGENT: Pyridoxine (Vitamin B6)

--Heptatoxicity:

> Results from toxic metabolites.

--Others:

> CNS (Seizures, Dizziness)

> Anemia

> GI Upset

> Depression

> Dry Mouth

Drug-Drug Interactions: STRONG INHIBITOR = CYP2C9, CYP2C19, CYP2E1

Rifampin (Rifadin)

Used For =

Treatment and Prevention of TB

- Equal to INH in importance!!

Adverse Effects:

- Hepatotoxicity = Signs of Toxicity

- Discoloration of Body Fluids:

>> Red to Orange Fluids: Sweat, Urine, Tears, Etc.

- Others:

>> GI Upset

>> Cutaneous Reactions (Flushing, Itching)

Accelerates the metabolism of other drugs = STRONG INDUCER***

- Also, can be used for prophylaxis of Meningitis

Rifabutin (Mycobutin)

Used For =

Used in HIV Patients with TB (alternative to Rifampin)

Adverse Effects =

1.) Rash

2.) GI Upset

3.) Hepatotoxic

4.) Red Discoloration of Body Fluids

Pyrazinamide

Used for =

Prevention and Treatment of TB

- Used in combination with INH and Rifampin

Adverse Effect =

1.) Hepatoxicity

2.) Nongouty Pararthralgia

3.) Hyperuricemia

4.) GI Disturbances

5.) Photosensitivity

Ethambutol (Myambutol):

Used For = Prevention and Treatment of TB

- Used for resistant cases (resistance to INH and Rifampin)

- Initial treatment of TB and treatment of patients who have received therapy previously.

- Always used as part of a multi-drug regimen.

Adverse Effects =

- Optic Neuritis:

>> Dose Related - Routine Monitoring

-- Blurred Vision

-- Constriction of Visual Field

-- Color Disturbances

- Allergic Reactions

- GI Upset

- Confusion

Amphotericin B

"AmphoTerrible"

Mechanism of Action/Use =

- Binds to the fungal cell membrane

>> Used in severe systemic fungal infections

Adverse Effects:

- Infusion Reaction =

>> Fever

>> Chills

>> Nausea

>> HA ("Shake and Bake") [ Fever and Chills ]

- Nephrotoxicity =

>> Very toxic, keep patient well hydrated.

- Electrolyte Changes =

>> Hypokalemia

>> Hypomagnesemia

- Bone Marrow Suppression

- Infusion Reaction Again =

>> Fever

>> Chills

>> Rigors

>> Nausea

>> Headache

>> Caused by release of pro-inflammatory cytokines.

>> Symptoms begin to 1 and 3 hours after the start of infusion and last for about 1 hour.

>> Less intense with lipid-based Amphotericin B formulations.

>> Mild Reactions: Pretreatment Options

- Diphenhydramine + acetaminophen

- Aspirin can help but may increase renal damage.

>> IV meperidine or dantrolene can be given if rigors occur.

>> Hydrocortisone can be given with caution.

>> Amphotericin infusion produces as high incidence of phlebitis.

- This can be minimized by changing peripheral venous sites often and administering Amphotericin through a large central vein while also pretreatment with Heparin. ( GIVE WITH HEPARIN TO DECREASE PHELIBITIS)

Azole Antifungals

Cannot be used in pregnancy.

Mechanism of Action/Use =

- Inhibits ergosterol in membrane

- Used for systemic and non-systemic fungal infections.

- ALTERNATIVE to Amphotericin B

Examples: "If Victor Fails Pre-K."

1.) Itraconazole (Sporanox) - IV, PO, Topical

2.) Voriconazole (Vfend) - IV or PO

3.) Fluconazole (Diflucan) - IV or PO

4.) Posaconazole - PO

5.) Ketoconazole (Nizoral) - IV or PO

Itraconazole (Sporanox)

Azole group of antifungal agents.

Lower toxicity level.

Mechanism of Action =

- Inhibits the synthesis of ergosterol.

- Inhibits fungal cytochrome P450 - Dependent Enzymes

Used For =

- Systemic mycoses (alternative to Amphotericin B)

Side Effects =

- Cardiosuppression:

>> Transient decrease in ventricular ejection fraction.

- Liver Damage:

>> Watch for signs of liver dysfunction

- Can inhibit drug-metabolizing enzymes

- GI Effects:

>> Nausea

>> Vomiting

>> Diarrhea

Fluconazole (Diflucan)

- Azole group of anti-fungal agents.

- Fungistatic

- Good PO Absorption!!

>> IV and PO dosage is the SAME!!!

Mechanism of Action =

- Inhibits the synthesis of ergosterol.

- Inhibits fungal cytochrome P450 - Dependent Enzymes

Adverse Effects =

- Nausea

- Headache

- Vomiting

- Abdominal Pain

- Diarrhea

Voriconazole (Vfend)

Azole group of Anti-fungal agents

Mechanism of Action =

- Suppresses synthesis of ergosterol.

Spectrum =

- BROAD-spectrum of fungal pathogens

Used For =

- Candidemia

- Invasive Aspergillosis = Drug of Choice

- Esophageal Candidiasis

- Scedosporium Apiospermum - Resistant Infection

Adverse Effects =

- Hepatotoxicity [Monitor Trough Levels]

- Visual Disturbances, Hallucinations

- Changes in Color Perception (Photopsia)

- Teratogenic = DO NOT GIVE IN PREGNANCY!

- Hypersensitivity Reactions

- Nausea, Vomiting, and Abdominal Pain

- Headache

- Drug Interactions

Ketoconazole

- Azole group of Anti-Fungal Agents

Mechanism of Action =

- Inhibits ergosterol

Used For =

- Alternative to Amphotericin B for Systemic Mycoses

>> Less toxic and only somewhat less effective.

>> Slower effects.

>> More useful in suppressing chronic infections than in treating severe, acute infections.

Adverse Effects:

- GI =

>> Can be reduced if given with food.

>> Rare, but potentially fatal hepatic necrosis.

- Effect on Sex Hormones =

>> Can inhibit steroid synthesis in humans

- Other =

>> Rash

>> Itching

>> Dizziness

>> Fever

>> Chills

>> Constipation

>> Diarrhea

>> Photophobia

>> Headache

*** Must be in an acid environment.

*** Can be given with Prostate Cancer.

*** May cause Gynecomastia.

Posaconazole

** Newest member of azole family.

** Binds with ergosterol in the fungal cell membrane, thereby compromising membrane integrity.

** Only by mouth.

- Narrow therapeutic index

- Monitor trough levels.

Nystatin

Used For =

- Oral Candidiasis

- Skin Candidiasis

Adverse Effects:

- No absorption from PO or Topical Route

- Nausea

- Vomiting

- Diarrhea

Viruses

- Viruses are parasites that only reproduces inside a living cell.

- Antivirals prevent the reproduction of the virus.

- Viruses are very difficult to treat.

- Antimicrobials are not effective against viruses.

Antivirals

"A Great Cyclovir Family"

Mechanism of Action =

- DNA Polymerase Inhibitors

Acyclovir (Zovirax) - IV, PO, Topically

Used For =

Herpes Simplex and Varicella Zoster

** Given 5 Times A Day!!

Adverse Effects:

- Phlebitis = Infuse Slowly to Prevent!

- Nephrotoxicity = Renal Failure (IV)

- Oral

>> Nausea

>> Vomiting

>> Diarrhea