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What is the therapeutic goal of antimicrobials?
Clear tissue of infecting organism
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What are the 6 actions that are used to classify antibiotics?
- 1. inhibits bacterial cell wall synthesis
- 2. inhibits protein synthesis
- 3. inhibits nucleic acid synthesis
- 4. interrupts metabolic pathways
- 5. disrupts cell membrane permeability
- 6. inhibits enzyme important in microbe’s function
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What is the difference b/w bacteriocidal and bacteriostatic?
- Bacteriocidal kills bacteria
- Bacteriostatic inhibits reproduction so host can kill
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What is antimicrobial resistance?
Microorganism no longer affected by a particular antimicrobial that was once effective
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What mechanisms cause antimicrobial resistance?
- Production of drug-inactivating enzyme
- Change in receptor structure
- Change in structural features of microbe that affects permeability
- Development of alternate metabolic pathways
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What 2 ways can antimicrobial resistance be conferred on a particular bacterium?
- Spontaneous mutation
- Conjugation
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What are 3 factors that promote antimicrobial resistance?
- Administration of antimicrobial when not needed
- Lack of/improper adherence to regiment
- Dosing that does not maintain adequate drug levels
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What are 5 common resistant microbes?
- MRSA
- Penicillin-resistant S. pneumoniae
- VRE
- Multi-drug resistant TB
- HIB
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What are 6 principles of antimicrobial selection and administration?
- 1. Match drug with bug
- 2. Consider Drug Spectrum
- 3. Consider combo therapy
- 4. Consider site of infection
- 5. Maintain adequate blood levels
- 6. Antibiotic combination when needed
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What is suprainfection?
Infection with a second organism that occurs while on antibiotic therapy
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Which organisms have additional component on their cell wall that most beta-lactam antibiotics cannot penetrate?
Gram negative bacteria
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What are 4 beta-lactam antibiotics?
- Penicillins
- Cephalosporins
- Carbapenems
- Azetronam
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What kind of bacteria are penicillins used to treat?
Gram positive and some gram negative, some anaerobes
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Why don’t penicillins pass blood brain barrier?
Because they are bound to plasma proteins
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How are penicillins eliminated?
Excreted by kidneys
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What can overdose of penicillins cause?
Neurologic problems (seizures)
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What are Beta-Lactamases?
Enzymes that cut the beta-lactam ring, inactivating beta-lactam antibiotics
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What are beta-lactamase inhibitors?
Drugs that bind to beta-lactamases and keep them from cutting the beta-lactam ring.
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What are four penicillin-beta-lactamase inhibitors?
- Augmentin
- Unasyn
- Timentin
- Zosyn
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What two drugs make up Augmentin?
Amoxicillin and clavulanic acid
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What two drugs make up Timentin?
Ticarcillin and clavulanic acid
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What two drugs make up Unasyn?
Ampicillin and sulbactam
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What two drugs make up Zosyn?
Piperacillin and tazobactam
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How are cephalosporins similar to penicillins?
Structure and activity
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What are possible problems with cephalosporins?
- Chance of increased bleeding with warfarin
- Disulfram-like reaction if used with alcohol
- Resistant bacteria, use 3rd or 4th generation with serious infection
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What beta-lactam antibiotics have an extremely broad spectrum?
Carbapenems
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What kind of antibiotic is vancomycin?
Non-Beta-Lactam antibiotic affecting bacterial cell wall
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What are adverse effects of vancomycin?
- Ototoxicity and nephrotoxicity
- Drug interactions
- Rapid infusion causes severe reaction
- Irritating to veins
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What kind of drug is tetracycline?
Bacteriostatic inhibitors of protein synthesis
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What kind of drug are macrolides?
Bacteriostatic inhibitors of protein synthesis
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What kind of drug is clindamycin?
Bacteriostatic inhibitors of protein synthesis
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What kind of drug is chloramphenicol?
Bacteriostatic inhibitors of protein synthesis
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What are three main problems with tetracycline?
- Poor absorption of some
- Bind to calcium in developing teeth
- Suprainfection
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What are 3 common macrolides?
- Erythromycin
- Clithromycin
- Azithromycin
-
What is the drug of choice for Legionella and Chlamydia?
macrolides
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What are 2 booby traps for macrolides?
- Hepatotoxicity
- P450 inhibition
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What type of antibiotics are aminoglycosides?
Bacteriocidal antibiotics that alter protein synthesis
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Which class of antibiotics are tobramycin, gentamycin and amakacin?
Aminoglycosides
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What do aminoglycosides NOT work on?
Anaerobes
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What is sulfamethoxazole-trimethoprim?
Bactrim
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What is Bactrim’s MOA?
Blocks enzymes that help build DNA/RNA/proteins
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What drug causes kidney stones, blood dysacrasias, psychosis and Stevens-Johnson Syndrome?
Bactrim
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What is MOA of Fluoroquinones?
Inhibit enzymes that replicates DNA (DNA gyrase)
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What are fluoroquinones active against?
Aerobic organism (both gram + and gram -)
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What should you not take with fluoroquinones?
Aluminum, iron, calcium, iron or zinc supplements
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Which antibiotic causes irreversible join disease in children, photosensitivity, candid suprainfections, and tendon rupture in adults?
Fluoroquinones
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Which antibiotic targets anaerobic organisms, including parasites and bacteria?
Flagyl
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Which antibiotic can cause darkening of urine, CNS effects, and interacts with P450s?
Flagyl
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Which infection is always treated with 2 or more drugs to avoid emergence of resistant strains?
TB
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What kinds of patients are extremely succeptible to TB?
HIV patients
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What are 4 TB drugs?
- Isoniazid
- Rifampin
- Pyrazinamide
- Ehambutol
-
Which TB drug is used alone to treat latent TB?
Isoniazid
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Which TB drug is NOT hepatotoxic?
Ethambutol
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Which TB drug decreases levels of birth control pills and turns body fluids red?
Rifampin
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What kind of drugs are Amphoteracin B and Ketaconazole?
Antifungals
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Which antifungal is a strong inhibitor of P450?
Ketaconazole
-
Which antifungal is toxic to mammalian cells?
Amphoteracin B
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Which antifungal can be used topically?
Ketaconazole
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Which antiviral is active against all herpes viruses?
Acyclovir
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Which antiviral has serious toxicities?
Ganciclovir
-
What is a prodrug of acyclovir?
Valtrex
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What is the MOA of antivirals?
Suppress synthesis of viral DNA
-
What drugs are used as prophylaxis during flu epidenmics?
Amantadine and Rimantadine
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Why is it important to look up HIV drugs?
They may have overlapping toxicities
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What is ARV?
Anti-retrovirals
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What is ART?
Anti-retroviral therapies
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What is HAART?
Highly active antiretroviral therapy
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Why is multiple therapy used for HIV?
To avoid resistance
-
What are 5 classes of HIV drugs?
- NRTIs
- NNRTIs
- PIs
- Attachment inhibitors
- Integrase inhibitors
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What are NRTIs?
Nucleoside reverse transcriptase inhibitors
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What are NNRTIs?
Non-nucloside reverse transcriptase inhibitors
-
What are PIs?
Protease inhibitors
-
What are two types of attachment inhibitors?
-
What are PMTCT programs?
Prevention of mother to child transmission
-
What drugs are given during and after labor to reduce HIV transmission to baby?
RT inhibitors
-
Which RT inhibitor does not affect human DNA polymerase?
NNRTIs
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What is the MOA of NRTIs?
Inhibit viral reverse transcriptase by terminating growing DNA strand
-
What is the MOA of NNRTIs?
Bind to active site of reverse transcriptase
-
Which class of HIV drugs are AZT, ddi, ddc, 3tc, d4t?
NRTIs
-
Which HIV drug causes lipoatrophy?
NRTIs
-
Which drugs have negative interaction with St. John’s wart?
NNRTIs and PIs
-
What is the MOA of PIs?
Inhibit viral protease
-
What kind of HIV drugs are indinavir, ritonavir, sauinavir, nelfinavir, amprenavir, foamprenair, atazanavir, tipronavir and lopinavir?
PIs
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Which HIV drugs cause hyperglcemia, fat redistribution, hyperlipidemia, increased bleeding in hemopheliacs, reduced bone density, elevation of liver enzymes and ECG changes?
Protease Inhibitors
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What is the MOA of fusion inhibitors and attachment inhibitors?
Inhibits the entry of HIV into CD4 positive cells
-
What is the only fusion inhibitor currently on the market?
Enfurvitide
-
Which HIV drugs block the CCR5 receptor so HIV does not attach to the CD4 cell?
Atatcment inhibitors
-
What kind of drug is Maraviroc?
Attachment inhibitor
-
What is the only approved integrase inhibitor?
Raltegravir
-
What is the MOA of Integrase inhibitors?
Prevents integration of viral DNA into host DNA
-
What is the daily replication rate of HIV?
Between 1 and 10 billion virons per day
-
What percent of adherence is recommended to prevent HIV resistance?
Greater than 95%
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