antibacterials Flashcards
invaders
- bacteria (protozoa- no nuclei)
- fungi (eukaryote)
- protozoa (eukaryote)
- helminth (eukaryote)
- viruses
chemotherapy
drugs selectively toxic to invader
- minimal effect on host
bacterial infection example
necrotizing fasciitis (flesh eating disease)
necrotizing fasciitis
- break in skin, nutrients, warm and moist environment for bacteria
- bacteria release chemicals that kill human cells
- antibiotic treatment
prokaryotic cells
- DNA not in nucleus
- adaptable
- wide range of environments like temps and levels of oxygen(diff types)
- pathogenic and non-pathogenic
what is infection
invasion and multiplication of organisms that lead to untoward consequences
- from foreign bacteria or normal flora
colonization
- normal flora that live on/in our body
- non-pathogenic
- if circumstances change in person, colonization can become infection
bacteria shapes
- cocci (circle)
- bacilli (rods)
- strepto (chains)
- staphylo (clumps)
bacterial cell wall
- outside plasma membrane
- structural support (internal osmotic pressure)
- protection
- gram positive or gram negative (key difference for drug therapy)
gram positive cell wall
- thick peptidoglycan layer (50%)
- gram stain trapped in wall, gram stains purple
gram negative cell wall
- thin peptidoglycan layer (5%)
- has outer membrane
- less gram stain trapped
- harder to treat bc outer membrane is a barrier to antibiotics
gram positive bacteria example
staphylococcus aureus
gram negative bacteria example
escheria coli
narrow spectrum antibacterials
selective against one class of bacteria
- ex. only gram positive
broad spectrum antibacterials
effective against both classes of bacteria (g-ve and g+ve)
- can affect healthy bacteria you do not want to get rid of
bactericidal
directly lethal to bacteria (kill)
bacteriostatic
slow bacterial growth
- host immune system helps body control/eliminate bacteria
superinfection (suprainfection)
- new microbes take over when antibacterials kill normal flora
- new microbes are resistant to drug action and difficult to treat
opportunistic infections
- infections that would normally not harm person
- existing colonization become infections
- antibiotic took out normal flora so new infections have no competition
- common in immunocompromised
antibacterial drug resistance
bacteria less susceptible to drug action
- bacteria pumps drugs out
- enzymes break down/change drug
what causes drug resistance (mutation)
- choosing wrong antibiotic
- dose too low
- dose not taken long enough
- improper use (treat virus)
- prophylactic use (animal feed)
host factors affecting drug choice
age, allergies, organ health, pregnancy, site of infection, general health
antibacterials mechanism of action
- disruption of metabolic reactions
- interference with cell wall synthesis
- interference with protein synthesis
- interference with DNA replication/transcription mechanisms
antimetabolite example
sulfonamides
- sulfamethoxazole
sulfonamide characteristics
- broad spectrum
- bacteriostatic
-prevent synthesis of folic acid
sulfonamide (sulfamethoxazole) mechanism of action
inhibit enzymes so bacteria can’t make folic acid (DNA/RNA), cells can’t replicate
sulfonamide (sulfamethoxazole) indications
- UTI
- otitis media
- upper resp tract infections
- malaria
- chlamydia
what drug is sulfamethoxazole combined with? why?
trimethoprim
- makes more effective bc stops at 2 spots in folic acid pathway
contraindications
- allergies (to all sulfa drugs)
- pregnancy (birth defects, increase fetal bilirubin)
- breastfeeding
- infants < 2 mths
sulfonamide adverse effects
- skin allergies (hypersensitivity, steven-johnson syndrome, photosensitivity)
- bone marrow depression (agranulocytosis, thrombocytopenia, aplastic anemia)
- nausea and vomiting
steven-johnson syndrome
swelling and rash of mucosal membranes
sir alexander fleming findings
mold growing on growth plate made chemical that kept bacteria away (starting point of antibacterial drugs)
beta lactam antibacterial characterstics
- inhibit cell wall enzyme responsible for peptidoglycan synthesis (stop cell wall)
- bactericidal
- beta lactam ring is effective part of drug
groups of beta lactam drugs (4)
- penicillins
- cephalosporins
- monobactams
- carbapenems
penicillins categories
- naturally occuring
- semi-synthetic
naturally occuring penicillins
- penG (IM, IV)
- pen V (PO)
- narrow spectrum
- sensitive to beta lactamase (drug resistance)
semi-synthetic penicillins
- beta-lactamase resistant (cloxacillin)
- broader-spectrum/aminopenicillins (ampicillin, amoxicillin (PO)
- extended spectrum/antipseudomonal penicillins (ticarcillin, piperacillin)
penicillin mechanism of action
- inside cell bind to proteins
- normal cell wall synthesis disrupted
- bacterial cells rupture
drug resistance to penicillin
- enzymes (beta lactamases) can split beta lactam ring so drug ineffective
how to stop penicillin resistance
b-lactamase inhibitors
- stop enzymes
- ex. clavulanic acid
penicillin indications
g+ve bacteria
- broad/spectrum spectrum types kill g-ve
penicillin adverse effects
- GI problems (disturb normal gut flora)
- allergic reactions (rashes, edema, can be fatal)
cephalosporin characteristics
- semisynthetic
- b-lactam
- bactericidal
- divided into groups (generations)
changes in cephalosporin generations
- increased permeability to g-ve cell wall
- increase stability against b-lactamases
1st gen
- for surgical prophylaxis, UTIs, otitis media
- cefazolin: good for g+ve (IV)
- cephalexin (PO)
- cefadroxil
2nd gen
- good g+ve coverage
- better g-ve coverage than 1st gen
- cefuroxime (po) (surgical prophylaxis)
- cefoxitin (IV & IM)
3rd gen
- broader spectrum (better against g-ve)
- cefotaxime (IV & IM) (passes meninges and diffuses into CSF to treat CNA infections like meningitis)
- cefixime (PO - best oral cephalosporin against g-ve)
4th gen
broader spectrum
- especially g+ve
- cefepime
5th gen
ceftaroline
- MRSA infections
cephalosporin adverse effects
- similar to penicillins
- patients with history of allergy to penicillin may have cross hypersensitivity
carbapenems characteristics
- broad spectrum
- good for mixed infections
- not MRSA
- last resort drug!!!
- all parenterally given
carbapenems example
imipenem
imipenem combination drug
imipenem-cilastatin
- inhibits breakdown of imipenem in kidney
carbapenems drug resistance
- carbapenem-resistant bacteriaceae
- enzymes: klebsiella pneumoniae caarbapenemase and new dehli metallo beta lactamase)
macrolides (large molecules) example
- erythromycin
- azithromycin
- clarithromycin
macrolides mechanism of action
inhibit protein synthesis
- 50s ribosome
macrolides characteristics
- broad spectrum
- bacteriostatic (some bactericidal with higher concentration)
macrolides indications
- patients allergic to b-lactam antibacterials
- penicillin resistant bacteria
- opportunistic infections - HIV/AIDs (azithromycin and clarithromycin)
- infections of respiratory, skin, soft tissue
macrolides adverse effects
- GI disturbances
- provoke cardiac dysrhythmia (long Q-T)
- narrow therapeutic index of azithromycin and clarithromycin (fwer drug-drug interactions, little to no inhibition of CYP enzymes = increased concentration)
tetracylines (group)
- tetracycline
- doxycycline
- minocycline
- demeclocycline
tetracyclines charactersitics
- very broad spectrum coverage (first drug to be broad spectrum!)
- bacteriostatic
- PO
tetracycline mechanism of action
inhibit protein synthesis (30s ribosome)
tetracycline interactions
- bind to metal ions (Ca, Mg, iron, aluminum)
- milk products, supplements, laxatives, antacids, iron salts
- form insoluble complexes = chelation which cannot be absorbed
tetracycline contraindications
- pregnancy
- breastfeeding
- children < 8
tetracycline adverse effects
- strong affinity to calcium (bind to and discolour teeth)
- slow fetal skeletal development
- GI disturbances (alterations in GI flora)
alteration of intestinal flora may result in:
- superinfection
- diarrhea
- c difficile/colon infection (fecal transplant)
- photosensitivity
- can be antagonist to bacteriocidal antibacterials
aminoglycosides (amino + sugar) characteristics
- natural and semisynthetic
- produced from streptomyces
- first antibacterial against g-ve
- bactericidal
aminoglycosides mechanism of action
- inhibit protein synthesis (30s)
aminoglycoside example
gentamicin
aminoglycoside indications
- g-ve
- often used synergistically with another antibacterial
aminoglycoside administration route
- poorly absorbed through GI tract (IV mainly or IM)
- only give po to treat GI infection
how to minimize aminoglycoside toxicities?
- do not give next doses until plasma concentration levels very low
- blast to high concentration then wait until low concentration to do it again
- check with blood test
aminoglycoside adverse effects
- irreversible ototoxicity (inner ear)
- reversible nephrotoxicity (kidney) (extreme in neonates and pre-existing kidney problems)
aminoglycoside interactions
increased nephrotoxicity risk when taken with:
- vancomycin (antibiotic)
- cyclosporine (immunosuppressant)
amphotericin B (antifungal)
quinolones/fluoroquinolones example
ciprofloxacin (very effective - PO)
quinolones characteristics
- bactericidal
- broad spectrum
quinolones mechanism of action
alter bacteria DNA
- transcription inhibitors
quinolones indications
- UTI (e coli)
- anthrax
quinolones adverse effects
- GI: nausea, vomiting , diarrhea
- skin: rashes
- CNS: headache, dizziness
quinolones interactions
- drug-drug: cyp inhibition means less drug metabolism and higher level of drug concentration (theophylline, warfarin)
- oral absorption reduced by: antacids, iron, zinc, calcium
vancomycin mechanism of action
inhibit cell wall synthesis
vancomycin characteristics
- bactericidal
- drug resistance increasing
- last resort drug
vancomycin administrations
- IV: MRSA and g+ve bacteria
- PO: GI problems like c diff
vancomycin adverse effects
- flushing syndrome (rly red face and chest from IV too fast)
- nephrotoxicity
- ototoxicity
- phlebitis (inflamed vein at injection)
