Antibiotics 2 Flashcards
What 2 classes of Abs are cell wall inhibitors?
penicillins and cephalosporins
What are the 2 classes of protein synthesis inhibitors?
tetracyclines and macrolides
What is the 1 class of DNA synthesis inhibitors?
fluoroquinolones
Targeting the synthesis of _____ is one of the most widely effective and least toxic antibiotic strategies
bacterial cell walls
What are cell wall inhibitors only effective against?
actively growing bacteria
How does penicillin inhibit cell wall synthesis?
it inhibits transpeptidase that forms cross links between peptidoglycan chains that are essential for cell wall integrity
- causes osmotic pressure on the cells resulting in cell lysis
What enzyme does gram positive bacteria product to break down the cell wall?
- produces autolysins
Without active cell wall synthesis ____ can damage the cell
autolysins
What are the 2 examples of penicillinase resistant penicillins
- methicillin and cloxacillin
What are the 2 examples of extended spectrum penicillins
- ampicillin and amoxicillin
Are penicillins bactericidal or bacteriostatic?
Bacteriocidal
Penicillin V and Amoxicillin are only available as ______
oral preparations
Pipercillin must be through the _____ route
IV/IM
Why do penicillins affect the composition of the intestinal flora?
- because they are incompletely absorbed
Absorption of penicillinase resistant antibiotics are ___ by food in the stomach and must be administered ______
reduced
- before a meal or 2-3 hours after
Does penicillin cross the placenta? What abut the bone or CNS?
- does cross the placenta
- does not penetrate the bone or CNS
Where is penicillin excreted?
- in the urine and breast milk
What are the most common adverse effects of penicillins?
- GI effects relatively common but are seldom severe due to the disruption of normal intestinal microflora
- allergy to its metabolite penicilloic acid relatively common (rash, swelling, anaphylaxis)
- cross allergy within the penicillin class
- no negative birth effects
_____ is a concern in patients receiving anticoagulants also also on penicillin
Reduced coagulation
What are the 4 antibiotics that fall under the class of cephalosporins?
cephalxin, cephalothin, cepazolin, cefepime
Which cephalosporins are the only 2 Abs administered orally?
- cephalexin and cefixime
____ penetrates the bone
cefazolin
____ crosses the BBB
cefuroxime
____ and _____ penetrate the cerebrospinal fluid
cefotaxime and ceftriaxone
Where are most cephalosporins excreted?
- most are eliminated in the urine
cefriaxone is excreted in the bile- longest t1/2 of all cephalosporins
How do protein synthesis inhibitors work?
Bind to 70S ribosomes (in bacterial cells) opposed to the 80S ribosomes that are in mammalian cells
- effective against gram positive and gram negative bacteria as well as other micro organisms
What are the 5 classes of antibiotics that fall under the protein synthesis inhibitors class?
- tetracyclines
- amino-glycosides
- macrolides
- chloramphenicol
- clindamycin
How do tetracyclines act as a protein synthesis inhibitor?
- binds irreversible to the 30S ribosome
- blocks acyl-tRNA access to the ribosome
Tetracyclines are considered ____ spectrum and are bacterio____
broad
bacteriostatic
What is the naturally occurring tetracycline?
tetracycline
What is the semi-synthetic tetracyclines?
- doxycycline
- methacycline
- minocycline
Absorption PO of tetracycline is reduced by the consumption of ____ and ____
dairy foods and antacids
Describe the distribution of tetracyclines. Where do they concentrate? What do they cross?
- distribution is throughout the body and body fluids
- concentrates in the liver, kidney, and spleen
- crosses the placenta and penetrates the bone and teeth
Where are tetracyclines excreted?
- metabolized and conjugated to form glucuronides by the liver and secreted in the bile and enters the urine via glomerular filtration
- excreted as well in the breast milk
What are the adverse effects of tetracyclines?
- GI discomfort- overcome by consuming food with the pills
- deposition in bones and teeth of growing children
- hepatotoxicity
- sunburn (increased sensitivity to UV rays)
- dizziness, nausea and vomiting
(minocycline and doxycycline concentrate in the inner ear) - headache/blurred vision
- superinfection: resistance is common
- not recommended or patients with kidney/liver disease or pregnant/lactating women
How do aminoglycosides act as a protein synthesis inhibitor?
- binds irreversibly to the 30S ribosome
- blocks functional assembly of the ribosome
Amino glycosides are effective against _______
aerobic gram negative bacteria
Is aminoglycosides bacteriocidal or bacteriostatic
bacteriocidal
What Abs are derived from streptomyces?
streptomycin
kanamycin
What Abs are derived from micromonospora?
gentamicin
amikacin
Molecular properties of aminoglycosides prevent ____ absorption
oral
Describe the distribution of aminoglycosides in the body?
- levels achieved in most tissues are low
- concentrates in the renal cortex and the inner ear
- low penetration into the cerebrospinal fluid
- crosses the placenta and enters the fetal circulation
Where are aminoglycosides excreted?
the urine
What are the adverse effects associated with aminoglycosides?
- nephrotoxicity - retention of aminoglycosides by proximal tubular cells disrupts calcium mediated transport
- ototoxicity - deafness caused by the destruction of hair cells within the inner ear (fetuses and elderly are the most susceptible)
- neuromuscular paralysis- high dose toxicity from injections
- allergic reactions
How do macrolides act as protein synthesis inhibitors?
- bind irreversibly to the 50S ribosome
- blocks peptidyl transfer
Macrolides are ____ spectrum and effective against gram ___ bacteria
broad
positive
What macrolide Abs are derived from streptomyces
- erythromycin
- clarithromycin
- azithromycin
What macrolides are derived from the synthetic ketolides?
telithromycin
Macrolides are ____ administered
orally
___ interferes with the absorption of macrolides.
food
What is one method of ensuring that erythromycin does not get destroyed in the gastric acid of the stomach?
can enteric coat the tablets
Describe the distribution of macrolide Abs?
- distributes throughout the body
- does not penetrate the cerebrospinal fluid
- concentrates in the liver
Where are macrolide Abs excreted? What about their inactive metabolites?
- excreted in the bile
- inactive metabolites are secreted in the urine
What are the adverse effects associated with using macrolides?
- GI problems
- jaundice
- ototoxicity (associated with high doses of erythromycin)
- prolonged QT c interval- patients with existing arrhythmia (erythromycin, clarithromycin)
- myopathy - interactions with statins due to the inhibition of CYP 3A4
In what case would we use Quinupristin/Dalfopristin (synercid)?
- reserved for the treatment of vancomycin resistant enterococcus
- mixture of 2 drugs in a ratio of 70:30
- binds to separate sites on the ribosome (Quinupristin binds to the 50S subunit preventing peptide elongation while dalfopristin binds to the 23S subunit preventing peptide transfer
- tx of gram + cocci
- bactericidal with a long post Ab effect
What is the administration route of synercid
IV/IM
What is the distribution of synercid?
- penetrates macrophages and polymorphonucleosites- VREs grow intracellularly
- low levels in the cerebrospinal fluid
Where is synercid excreted?
in the bile
- secondarily excreted in the urine
What are the adverse effects of synercid?
- venous irritation when given IV
- joint/muscle ache in patients given high doses
- hyperbilirubinemia (bilirubin is elevated in about 25% of patients)
- causes inhibition of P450
What are the two enzymes that are inhibited by DNA synthesis inhibitors?
- bacterial topoisomerase
- DNA gyrase
What are two examples of DNA synthesis inhibitors?
- fluorowuinolones
- rifamycin
What enzyme does fluoroquinolones inhibit?
- DNA gyrase
What route of administration are fluoroquinolones given?
- via the oral/IV route
What mineral interferes with oral absorption of fluoroquinolones?
- dietary calcium
What is the distribution of the fluoroquinolones?
- distributes well throughout the tissues
- levels are high in the bones, kidney and prostate
- low penetration into the cerebral spinal fluid
- crosses the placenta and enters fetal circulation
Where are fluoroquinolones excreted?
the urine
List the adverse effects of fluoroquinolones?
- GI disturbances
- CNS - light headed, dizziness
- phototoxicity
- cartilage erosion (should not be administered to pregnant or nursing women)
What is the most commonly prescribed fluoroquinolone?
- ciprofloxacin
What infections is ciproflxacin generally used to treat?
- infections of the bones/joints
- infections of the respiratory tract
- infections of the urinary tract
Administration of fluoroquinolones at the same time as ____substantially reduces absorption
calcium, antacids, zinc, magnesium
What are the drug interactions that ciproflaxacin has?
- alters level of drugs metabolized by the cytochrome P450 enzyme
- warfarin levels can be dangerously increased
- increased seizure risk when combines with NSAIDS
- affects the renal clearance of other drugs such as methotrexate
What infections is moxiflaxacin used to treat?
- respiratory tract infections
- endocarditis
- meningitis
- conjunctivitis
Concurrent administration of moxifloxacin along with ____ significantly reduced absorption
- aluminum or mangesium
What is moxifloxacin’s adverse drug reactions?
- ## may prolong the QTc interval - should not be used in patients with cardiac arrhythmias
What drug interactions are associated with moxifloxacin?
- does not inhibit the cut p450 enzyme
- may interact with warfarin
What antibacterials ball under the category of metabolite synthesis inhibitors?
- sulfonamides
- trimethoprim
Sulfonamides inhibit the synthesis of bacterial _____ acid
dihydrofolic acid
What bacteria are sulfonamides active against?
- most gram positive and many gram negative bacteria - broad spectrum
Bacteria that _________ are inherently resistant for sulfonamides
obtain folate from the environment
What is considered a short acting sulphonamide?
- sulfamethazole
- sulfadiazine
What is considered an intermediate acting sulfonamide?
- sulfacetamide
- sulfadoxine
What is considered to be a long acting sulfonamide?
sulfadimethoxine
Where are sulfonamides absorbed?
- in the small intestine
Describe sulfonamide distribution
- crosses the BBB and penetrates the CSF
- crosses the placenta and gets into fetal circulation
Where are sulfonamides excreted?
- active and inactive metabolites secreted in the urine
- secreted into the breast milk
What are the adverse effects of sulfonamides?
- allergies common
- kernicterus- sulfonamide displaces bilirubin from binding albumin causing free bilirubin to cross the undeveloped BBB and pass into the CNS
- nephrotoxicity (solubility of sulfonamides is low)
- hemolytic anemia
What are the drug interactions associated with sulfonamides?
- potentiate the hypoglycaemia effect of tolbutamide
- potentiate the anticoagulant effect of warfarin
Trimethoprim inhibits the synthesis of bacterial ______
tetrahydrofolic acid
What is trimethoprim active against?
- against most gram positive and many gram negative bacteria
- broad spectrum
Trimethoprim is used in the treatment of what?
- urinary tract infections
- vaginal infections
- bacterial prostatitis
- prophylaxis
Absorption of trimethoprim is where?
in the small intestine
Where is trimethoprim distributed?
- penetrates CSF
- crosses the placenta and affects fetal folate metabolism
- distributed widely throughout the body
Where is trimethoprim excreted?
- in the urine
What are the adverse effects of trimethoprim?
- contraindicated in pregnancy (doubling of miscarriage rates)
- thrombocytopenia (low levels of platelets, pregnant women and those with poor diets are at a higher risk
What does trimethoprim interact with?
- potentiates the anticoagulant effects of warfarin
What 2 medications make up cotrimoxazole?
- composed of both trimethoprim (more lipid soluble) and sulfonamethazole in a 1:5 ratio
There is _____ activity in cotrimoxazole from the sequential inhibition of ______
synergistic
folate synthesis
What is the advantage of using cotrimoxazole over other sulfonamides?
- broader spectrum
Cotrimoxazole is used generally in the treatment of what infections?
- urinary tract infections
- respiratory tract infections
- kidney infections
- GI tract infections
- septicemia
- prophylaxis in HIV patients
Where is cotrimoxazole absorbed?
in the small intestine
Cotrimoxazole is distributed where in the body?
- throughout the body
- crosses the BBB very slowly
- crosses the placenta and affects fetal folate metabolism
Where is cotrimoxazole excreted?
in the urine
What are the adverse effects associated with cotrimoxazole use?
- contraindicated for pregnant women
- hematologic (thrombocytopenia, anemia, leukopenia)
- skin rashes are common and can be severe in the elderly
- nausea/vomiting
- jaundice, renal damage/ failure
- rashes/diarrhea (common along immunocompromised patients)
What are the drug interactions that are associated with cotrimoxazole?
- potentiate the anti-coagulant effect of warfarin
- methotrexate is displaced for albumin binding sites
Normal GI and vaginal flora are disrupted with antibiotic use, contributing to 4 major side effects
nausea, vomiting, diarrhea and yeast infections
