study d1 Flashcards
antibiotic activity
bactericidical:, bacteriostatic, spectrum of antibiotic activity:
bactericidical:
* drug that kills organisms
bacteriostatic:
* drug that prevents the growth of organisms
* it relies on host mechanisms to eliminate the pathogen
spectrum of antibiotic activity:
* range of bacterial species susceptible to the effect of a drug
* can be broad, intermediate or narrow
* drugs with a broad spectrum of activity are active against a wide range of bacteria, usually both Gram-positive and Gram-negative organisms
Gram positive and Gram Negative
Gram staining (positive)
Gram positive (+) staining bacteria have a thick cell wall containing a thick layer of peptidoglycan
Gram staining (negative)
Gram negative (-) staining bacteria have relatively less peptidoglycan
AND
have a third layer (outer membrane) composed of phospholipids
Antimicrobial drug classes
Antimicrobial drug classes
1. Inhibition of bacterial metabolic pathways
2. Inhibition of cell wall synthesis
3. Inhibition of protein synthesis
4. Inhibition of nucleic acid replication and transcription (DNA synthesis inhibitors)
5. Disruption of plasma membrane
Inhibition of bacterial metabolic pathways
folate antagonists, adverse effects
Folate Antagonists
* folate is necessary for the synthesis of DNA and some amino acids
* Bacteria use folic acid in order to synthesize the nucleic acids that make up their DNA –> we dont want that
* bacteria are unable to absorb folate from their environment
* bacteria must therefore synthesize the folate from the precursor PABA (PABA = para-aminobenzoic acid)
* often used to treat urinary tract infections
- Sulfonamides (sulfamethoxazole)
* The structure of sulfonamides resembles that of the natural precursor PABA;
* competition between the drug and PABA thus preventing bacteria from producing folate (DHF) - Trimethoprim
* trimethoprim inhibits a reaction that occurs downstream from the synthesis of folate (DHF), where DHF is converted to tetrahydrofolic acid (THF or activated folate)
* although this activation reaction also occurs in human cells, the drug preferentially targets bacteria
Both drugs are often used in combination
* sulfamethoxazole /trimethoprim = co-trimoxazole
Adverse effects:
* nausea, diarrhea
* hypersensitivity reactions / sulfa « allergies »
* risk of precipitate in urine = crystalluria
(need to drink lots of fluid!)
* well absorbed p.o., except for sulfasalazine (F=0.15)
which is used to treat inflammatory bowel disease and other inflammatory conditions
* must be careful if folate levels are low, especially trimethoprim: –> risk of hyperkalemia
Stevens-Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN
- Drugs associated with SJS are sulfonamides, anti-seizure medications, allopurinol, certain NSAIDS
- typical clinical course of SJS begins within 8 weeks (usually 4 to 30 days) following the first exposure to the causative drug
- patients may initially present with flu-like symptoms (aching joints and muscles, worsening fever)
- patients who develop SJS/TEN can have varying levels of
1. cutaneous (erythematous rash on face, trunk, proximal limbs),
2. extracutaneous (gastrointestinal, respiratory, renal), and
3. mucous membrane manifestations (mouth, eyes, genitals) escalating to rashes, redness, blistering, and peeling of the skin with associated bleeding - possible serious complications include secondary skin infections (cellulitis) and sepsis
B. inhibition of cell wall synthesis
most used antibiotics
effective vs bacteria in growth phase (esp. Gram +)
many share a common chemical structure
= beta lactams: penicillins, cephalosporins, carbapenems
penicillins
B.1.A
Penicillins
* target the peptidoglycan layer of bacteria
* well tolerated overall
* rapid elimination via kidneys
* watch for drug allergy
hypersensitivity reactions (5-10%)
Immediate (3-20 min)
Accelerated (1-2 days)
Delayed (3-10 days)
anaphylactic reactions*(rare), drug rash, serum sickness, nephritis, hemolytic anemia
Natural Penicillins:
* Penicillin G: not stable in gastric acid
(therefore administered parenterally)
* penicillin G benzathine (i.m.): long-acting
* Penicillin V : stable in acidic environment and administered orally
* both are susceptible to degradation by ß-lactamase enzymes contained in some bacteria … highly enriched in staphylococci, for example
Beta lactamases
B.1.A
Beta lactamases
* beta-lactamases are bacterial enzymes that can destroy the beta-lactam structure found in certain antibiotics; this destroys the antibiotic activity of the drug
* bacterial beta-lactamase activity can be reduced by administering a beta-lactamase inhibitor along with a beta lactam antibiotic.
There are two non antibiotic beta lactams that act to poison beta-lactamases
Examples
* clavulanic acid + amoxicillin = CLAVULIN
* tazobactam + piperacillin = TAZOCIN
beta lactam resistant penicillins
broad spectrum penicillins
extended spectrum penicillins
- Beta lactic resistant penicillins
cloxacillin, methicillin - Broad spectrum penicillins
ampicillin (p.o., i.v.) –> gram -
amoxicillin (p.o.) –> gram +/-, + clavulanic acid (ß-lactamase inhibitor) - Extended spectrum penicillins
piperacillin + tazobactam (ß-lactamase inhibitor)
Cephalosporins
B.1.B
Cephalosporins
* chemical structure resembling penicillins
* grouped into five generations,
* according to order of discovery;
* activity versus Gram – increases and Gram + decreases in 1st to 3rd generation
(4th/ 5th generations act as much on Gram + as Gram -)
1st: cefazolin (Ancef) i.v. cephalexin (Keflex) p.o.
2nd: cefprozil, cefuroxime
3rd: ceftriaxone, cefotaxime
4th: cefepime
Adverse effects:
* hypersensitivity reactions
* (cross-reactivity with penicillins <5%)
* nausea, vomiting, diarrhea
* some inhibit the metabolism of alcohol
(disulfiram effect: headaches, flushing, nausea associated with alcohol consumption)
carbapenems and monobacterams
b.1.c and b.1.d
B.1.C —– Carbapenems
meropenem
* resistant to ß-lactamases; controlled use
* certain enterobacteriaceae are resistant (CRE) due to production of an inactivating enzyme first called (NDM-1) / carbapenemase
B.1.D —- Monobacterams
aztreonam
* acts on Gram – aerobic bacteria
* administered inhalation (28 days) for P.aeruginosa for cystic fibrosis patients
* very few cross reactions if patients are hypersensitive to other beta lactams
B.2.A and B.2.B
bacitracin and vancomycin
B.2.A
Bacitracin
* used topically
(skin, nose, eyes)
B.2.b
Vancomycin
* used to treat very resistant or difficult micro-organisms such as Methicillin resistant Staph. aureus (MRSA) and Clostridium difficile (C. difficile)
* normally adminstered i.v.; poor F if given orally can be useful to C. diff. infection
adverse effects: infusion-related flushing, rash, hypotension if administered too quickly; nephrotoxicity;
some resistance in enterococci (VRE)
