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134 Cards in this Set
- Front
- Back
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Chemotherapy
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Eradication of invading cells or parasites.
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Concentration Dependent Killing
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The more the drug concentration exceeds th MIC the greater the rate of killing
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What two classes of drugs exhibit concetration dependent killing?
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Fluoroquinolones and aminoglycosides
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Time Dependent Killing
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The rate of killing depends on how the long the drug concentration stays above the MIC.
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Post Antibiotic Effect
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How long it takes for a bacterial colony to resume growth once a antibtiotic dips below the MIC.
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Superinfection
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Secondary infetion caused by the use of an antibiotic. i.e. C. diff pseudomembranous colitis.
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Transduction
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Transmission of drug resistance through bacteriophage.
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Transformation
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Uptake of genetic information from the environment that confers drug resistance. Strep. pneumoniae and N. meningitides.
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Conjugation
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Sexual exchange of genetic material.
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What are the 3 major modes of drug resistance to antibiotics?
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1. Decreased entry of the drug into the cell. Change in porin proteins
2. Inactivation by bacterial enzymes 3. Decreased affinity of a receptor for the drug. |
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What is an example of an antagonistic drug effect between antibiotics?
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Tetracycline and Penicillin
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What are some examples of synergistic antiobiotic combinations?
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Cell wall inhibitors + amminoglycosides
Trimethoprim + Sulfamethoxazole. |
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What is the structure of a bacterial cell wall?
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It is composed of alternating units of N-acetylglucosamine and N-acetylmuramic acid. These strands are joined together by crosslinking of glycine and D-alanyl D-alanine.
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What enzyme is responsible for the cross-linking reaction of bacterial cell wall synthesis?
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Transpeptidase.
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What is the mechanism of action of B-lactam antibiotics?
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They are composed of a B lactam ring that binds to PBPs such as transpeptidase. This prevents cell wall crosslinking.
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In addition to preventing cell wall crosslinking, what other antibacterial functions do B-lactams have?
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They activate autolysins which cause a degradation fo the cell wall.
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What are the 3 resistance mechanisms that bacteria have against penicillins?
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1. Production B-lactamase
2. Decreased porin size on gram negative bacteria. 3. Genetic alterations of PBP binding sites. |
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What is the difference between B-lactamases secreted by gram negative vs. gram positive organisms?
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Gram positives have a penicillinase encoded by a palsmid.
Gram negatives have broad spectrum B-lactamases that are encoded in the genome or on plasmids and can be constitutive or inducible. |
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Why are penicillins usually more effective against gram positive organisms?
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The outer membrane of of the gram negatives is hard for the drugs to penetrate.
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What are the four basic components of the structure of penicillin?
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1. Thiazolidine Ring
2. Beta-lactam ring 3. R side chain affecting acid stability 4. Carboxyl group that determines its pharmacokinetic properties. |
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How is penicillin eliminated when given orally and when given IM?
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Oral- 70% destroyed in the stomach
IM- 99% eliminated in the kidney |
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What drug is given simultaneously with penicillin to prolong the duration of action?
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Probenecid (blocks active transport of penicillin in the proximal tubule)
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What form of penicillin is the prefered form to administer orally?
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Penicillin V
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What are the 5 penicillinase resistant penicillins?
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Methicillin
Oxacillin Dicloxacillin Cloxacillin Nafcillin |
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What are the penicillinase resistant penicillins used to treat?
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Penicillinase producing staph.
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What are the two amino penicillins?
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Amoxicillin and Ampicillin
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What is the antibiotice specturm of the amino penicillins?
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They are usefull against gram positvise plus E. coli, H.influenzae, Slamonella, Shigella and Proteus.
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What is the difference between ampicillin and amoxicillin?
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Amoxicillin is more orally active because is is more efficiently absorbed from the gut.
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What are the antipseudomonal penicillins?
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Carbenicillin
Ticarcillin Piperacillin |
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Carbenicillin
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Antipseudomonal.
Used for po treament of UTIs |
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Ticarcillin
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Antipseudomonal
Spectrum of activity similar to ampicillin and is also active against Proteus, Enterobacter and Pseudomonas. |
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Piperacillin
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Antipseudomonal
Active against gram + and gram -. Principle use in Pseudomonas and Klebsiella. |
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What are the B-lactamase inhibitors.
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Clavulanic Acid
Sulbactam Tazobactam |
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What kind of adverse reactions can occur with the use fo penicillins at 0-1hrs, 1-72hrs or >72hrs after administration?
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0-1 - IgE reaction, ananphylaxis
1-72- Accelerated >72 - Serum sickness, mabilliform rash. |
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Which two antibiotics bind to ADP receptors on platelets and impair aggregation and coagulation?
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Carbenicillin and Ticarcillin
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What is an adverse effect associated with ampicillin and amoxicillin?
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Non-immune medaited rash. Almost all patients with mono receiving these drugs will develop this effect.
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In an allergic reaction to penicillin, what serves as the major hapten and what is the minor hapten?
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Major hapten is the penicillin binding site.
Minor hapten is the protein residue bound to the penicillin. The minor hapten is more immunogenic. |
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Are cephalosporins considered bacteriocidal or bacteriostatic?
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Bacteriocidal.
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Which cephalosporins are resistant to B-lactamase?
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They are all intriniscally resistant to gram + penicillinase but can be metabolized by broad spectrum B-lactamase. With increasing generations the resistance to gram - B-lactamase increases.
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Which cephalosporins can cross the into the CNS?
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The 3rd and 4th generations
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What are the first generation cephalosporins?
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Cephalexin
Cefazolin |
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What is the difference between Cephazolin and Cephalexin?
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Cefazolin is excreted by renal filtration and has a longer half life.
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What is the clinical use of the first gen cephalosporins?
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Gram + cocci
E.coli K. pneumonia Proteus mirabilis |
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What are the second gen. cephalosporins?
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Cefuroxime
Cefaclor Cefoxitin Cefotetan |
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What is the clinical use of the second gen. cephalosporins?
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Not as active against gram + cocci
Good vs. E.coli, Klebsiella, Proteus, H. influenzae, Moraxella. |
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What are the third generation cephalosporins?
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Cefotaxime
Ceftazidime Ceftriaxone |
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What is the clinical use of the thrid gen. cephalosporins?
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Gram - spectrum
Some activity against Strep and Staph Good vs. Enterobacteriacea, Serratis, N. gonorrhoeae. Ceftazidime - best action against pseudomonas |
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What is the fourth generation cephalosporin?
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Cefepime
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What is the clinical use of the cefepime?
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Similar to 3rd gen but with increased resistance to B-lactamase.
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What are the adverse effects cause by the cephalosporins?
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Hypersensitivity reactions
Can be cross-reactive with penicillins in 10% of cases. |
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The methylthiotetrazole side chain on some cephalosporins may lead to which two adverse reations?
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1. Can interfere with vit K metabolism and lead to coagulation problems
2. Can cause disulfuram-like reactions in patients consuming alcoholic beverages. |
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Imipenam
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Carbapenam antibiotic
Broad spectrum. Combined with cilistatin to prevent breakdown in the kidneys by dehydropeptidase. |
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Meropenam, Ertapenam
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Carbapenams. Similar to imipenam but they are not metabolised by dehydropeptidase.
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Aztreonam
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Monobactam antibiotic
Good vs. aerobic gram - organisms. |
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What is the mechaism of action of Vancomycin?
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It binds to the terminal portion of D-alanyl-D-alanine and prevents the transglycosylase crosslinking.
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What is the clinical use of vancomycin?
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Used against gram positives especially MRSA and C.diff.
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How do bacteria become resistant to vancomycin?
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They substitute the D-alanine for D-lactic acid.
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What causes "red man" syndrome and what are its symptoms?
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Vancomycin.
Causes flushing of the skin, urticaria, pruritis, hypotension,wheezing, dyspnea. Caused by release of histamine form mast cells. |
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What are the adverse reactions caused by vancomycin?
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Red man syndrome
Nephrotoxicity Ototoxicity |
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Bacitracin
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Inhibits cell wall synthesis. Only used topically due to nephrotoxicity.
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Cycloserine
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Inhibits cell wall synthesis.
Synthetic analog of serine used to treat TB. Prevents conversion of L-alanine to D-alanine. |
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Fosfomycin
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Inhibits cell wall synthesis.
Used to treat UTIs |
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What is the binding site on the ribosome for the macrolide protein synthesis inhibitors?
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Adenine of domain 5 of the 23S rRNA.
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What are the three ways that bacteria can become resistant to the macrolides?
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1. Increased eflux pump that extrudes the macrolides.
2. Mutation of the ribosomal binding site 3. ermA, ermB coded methylation of the binding sites. |
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What is the clinical use of erythromycin.
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It is used as a substitute in people who have allergies to penicillin G or V. It is useful for Staph, Strep, Mycoplasma and Legionella.
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How is erythromycin removed from the body?
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It is largly degraded in the gastric acid. The rest is concentrated in the liver and excreted in the bile. Can inhibit CYP3A4.
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Clarithromycin
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Macrolide antibiotic.
More active against Staph and Strep. Less GI side effects |
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What is the major side effect caused by clarithromycin?
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CNS disturbances. Mania
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Azithromycin
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Macrolide antibiotic.
Builds up in tissue reservior -can be given for 5 days instead of 10. Same spectrum as erythromycin + chlamydia and mycobacterium avium. |
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What drug stimulates the motilin receptor and causes increased GI motility.
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Erythromycin
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What drug can cause an increase in QT interval which can be exacerbated when terfenadine is added?
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Erythromycin
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Which drug is know to produce a cholestatic hepatitis after 7-10 days of use?
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Erythromycin
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Telithromycin
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Ketolide antibiotic.
Has binding site on domains 2 and 5 of the 23s subunit - makes it resistant to eflux pump and erm genes. |
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What is the clinical use of telithromycin?
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It is used primarily to treat community aquired pneumonia.
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Clindamycin
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Lincosamide antibiotic
Effective against Staph, Strep, and B. fragilis. |
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What is the major side effect associated with the use of clindamycin?
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Antiobiotic-induced pseudomembranous colitis.
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Quinupristin/Dalfoprsitin
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Streptogramin Antibiotics
Synergistic drug combo that binds to two unique parts of the bacterial ribosome. Used to treat nosocomial Staph, Strep and VREF. |
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Linezolid
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Oxazolidinone Antibiotic
Approved to target methicillin resistant staph. Good vs. gram positive causes of pneumonia and skin structure infections. |
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What are the side effects associated with linezolid?
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Myelosupression
Peripheral neuropathy MAOI activity that can lead to seratonin syndrome. |
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Chloramphenicol
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Nitrobenzene Antibiotic
Works on 50s subunit. Only used when other antibiotics have failed. |
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How is chloramphenicol eliminated from the body?
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It is conjugated in the liver by glucuronosyl transferase to a nontoxic glucuronide.
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What are the major side effects associated with the use of chloramphenicol?
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1. Bone marrow suppresion leading to aplastic anemia.
2. Dose-dependent blood dyscrasias 3. Gray-baby syndrome - cyanosis and vasomotor collapse due to innability glucuronidate the drug. |
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What is the effect of the tetracyclines on bacteria?
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They are bacteriostatic.
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What inhibits the uptake of tetracyclines from the gut?
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Ingesiton of milk or diary products.
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What is the mechanism of action for the tetracyclines?
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They inhibit protein synthesis in both prokaryotic and eukaryotic cells.
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What are the tetracylcines used to treat?
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Rickettisia
Chlamydia Mycoplasma H. pylori S. pneumonia |
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What are the 3 major tetracylcines?
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Tetracylcine
Minocycline Doxycyline |
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Which tetracycline has the longest half life?
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Doxycycline
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What are the adverse side effects of the tetracyclines?
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They cause a phototoxic skin rash.
They can produce hepatic dysfunction, especially during pregnancy. Children may develop teeth discoloration and depressed bone growth. |
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What are the adverse reactions associated with minocycline?
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It causes vestibular ganglion toxicity leading to vertigo and dizziness.
Also causes black iron pigmentation of the skin |
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Tigecycline
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Tetracylcine plus a glycine.
Higher affinity for ribosomal receptor. Prevents binding of the tRNA. Broad spectrum. Good vs. MRSA, VRE, penicillin resistant S. pneumoniae and Acinetobacter. |
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What is required in the environment for bacteria to be susceptible to aminoglycosides?
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Oxygen.
Only effective against aerobic bacteria. |
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Aminoglycosides
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Bacteriocidal antibiotics that bind the the 30S subunit of the ribosome.
Exhibit concentration -dependent killing. |
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Which three aminoglycosides are the most effective at treating systemic infections?
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Gentamicin
Tobramycin Amikacin |
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How are the aminoglycosides administered?
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They are given by IV because they have poor oral absorption.
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What are the 6 aminoglycosides given in class?
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Gentamicin
Tobramycin Amikacin Kanamycin Streptomycin Neomycin |
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What are the two major adverse side effects associated with the use of aminoglycosides?
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Ototoxicity
Nephrotoxicity |
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What is the mechanism of action of the flouroquinolones.
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They inhibit bacterial DNA gyrase of gram negatives and topoisomerase of gram positives.
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What are the four major flouroquinolones given in class?
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Ciprofloxacin
Levofloxacin Gatifloxacin Moxifloxacin |
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What is the clinical use for fluoroquinolones?
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They are broad spectrum agents that exhibit concentration-dependent killing
They are good drugs of choice for prostatitis because they concentrate in tissues. |
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What are the adverse reactions associated with the use of fluoroquinolones?
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GI disturbance
Rash Headache and vertigo Major effect is tendon rupture following vigorous exercise. Damage to cartilage in children. |
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Rifampin
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Inhibits DNA-dependent RNA polymerase. Used primarily to treat TB.
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What are the adverse reactions associated with rifampin?
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It is a potent inducer of CYP3A4 and can lead to drug-drug interactions.
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What is the mechanism of action of the sulfonamides?
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They inhibit dihydropterate synthase. They act as structural analogs of PABA. Inhibits the synthesis of DNA and RNA.
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What are the 4 sulfonamide antibiotics mentioned in class?
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Sulfisoxazole
Sulfacetamide Silver Sulfadiazine Sulfasalazine |
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What are the adverse reactions associated with the sulfonamide antibiotics?
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Skin rashes
Drug fever Blood dyscrasias Eosinophilia Crystalluria Hepatitis Kernicterus |
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Trimethoprim
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Inhibits bacterial dihydrofolate reductase. Leads to decreased synthesis of DNA and RNA.
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TMP-SMX
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Combination drug that is used to treat bronchitis, otitis media and pneumonia due to P. jeroveci.
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Nitrofurantoin
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Antibiotic that is used to treat E. coli urinary tract infections.
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What is the major adverse effect associated with nitrofurantoin?
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Acute allergic reaction with pulmonary infiltrates.
Chronic use can produce irreversible pulmonary fibrosis. |
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Methenamine
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Used for prophylaxis against recurrent UTIs. Produces ammonia and formaldehyde.
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Fosfomycin
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Cell wall synthesis inhibitor that is used to treat UTIs.
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Daptomycin
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Lipopeptide antibacterial.
Used to treat gram positives. Similar spectrum as vancomycin Cna be used against soft tissue infections from MRSA,VRSA and VRE. |
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What is the mechanism of action of daptomycin?
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It has a lipohilic tail that inserts into bacterial cell walls. Creates a pore that allows K and other electrolytes to leak out.
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Colistin,Colistimethate, Polymyxin B.
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Cationic detergents that destroy bacterial cell membranes.
Only used in treatment of Pseudomonas and other gram negatives that are resistant to other drugs. Causes severe nephrotoxicity. |
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Metronidazole
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Useful against anaerobic bacteria. Creates free radicals that damage bacteria.
Good vs. C.diff, H.pylori, B.fragilis and other protozoals. |
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What are the side effects caused by metronidazole?
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It causes a disulfuram-like reaction when patients consume alcohol.
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Spectinomycin
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Used to treat penicillinase-producing strains of N. gonorrhea.
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What is Multi Drug Resistant TB?
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TB that is resistant to at least two of the primary drugs.
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What is Extra Drug resistant TB?
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TB that is resistant to at least 2 primary and 1 secondary drugs.
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What are the primary TB drugs?
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Isoniazid
Rifampin Ethambutol Streptomycin Pyrazinamide |
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What are the secondary TB drugs?
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Cycloserine
Capreomycin P-aminosalicylic acid |
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What is the only drug approved for single drug prohylaxis of TB?
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Isoniazid
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Isoniazid
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Primary TB drug.
Used for prophylaxis Inhibits synthesis of mycolic acids. |
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How does TB develop resistance to isoniazid?
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A mutation occurs in the catalase/peroxidase enzyme that is required to activate the drug.
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What is the rate-limiting step in the metabolism of isoniazid?
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Acetylation.
Varied elimination occurs among rapid and slow acetylators. |
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What are the side effects associated with isoniazid?
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Peripheral neuropathy due to depletion of pyridoxine.
Isoniazid-induced hepatitis. |
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Rifampin
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Second most important drug in the treatment of TB.
Inactivates RNA polymerase in bacteria. |
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What are the side effects associated with rifampin?
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GI or hepatic reactions
Oragne body fluids Induces CYP3A4 and can cause drug interactions. |
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Ethambutol
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Primary TB drug.
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What are the side effects of ethambutol?
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Causes a retrobulbar neuritis and loss of vision.
Causes hyperuricemia which can lead to gout. |
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Pyrazinamide
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Primary TB drug.
May cause dose related hepatotoxicity and hyperuricemia. |
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Streptomycin
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Primary TB drug
Aminoglycoside Must be injected |
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What drugs are used to treat leprosy?
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Dapsone and Clofazimine.
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