Antiobiotics Flashcards
What is the mechanism of action for penicillins?
interfere w/ formation of peptidogylcan layer. and prevent cross linking of Nam and Nag
What are penicillin binding proteins?
they are transpeptidases that bind penicillin, binding activates autolytic enzymes in the cell wall that cause lesions resulting in bacterial death
What are the 4 ways that bacteria become resistant to penicillin?
- modify their PBPs
- Active pumping of drugs back out of the cell
- Cleavage of the beta-lactam ring via beta-lactamases
- Altered porins (only gram -) if present
What are important drug interactions involved with penicillin?
- For them to be effective, microorganisms should be actively growing and dividing. So avoid taking w/ bacteriostatic drugs.
- may be taken w/ irreversible beta-lactamases inhibitors
What penicillins are used to treat gram negative bacteria?
Aminopenicillins and Antipseudomonal
What penicilins are used to treat gram + bacteria?
Natural and penicillinase-resistant
What are examples of natural penicillins?
Penicillin G and V
How does one take penicillin G?
IV or IM b/c destroyed in acidic environment
How does one take penicillin V?
Orally but on a empty stomach
What are examples of Aminopenicillins?
Ampicillins and amoxcillins
How does one take ampicillin?
orally on empty stomach
How does one take amoxcillin?
w/ or w/out food
How can aminopenicillins be taken?
parenterally or enterally
What are examples of Penicillanse-resistant penicillins?
methicillin, oxacillin, and nafcillin, dicloxacillin
Which penicillinase-resistant drugs can bebe taken parenterally?
Methicillin, Nafcilin, and Oxacillin (MNOP)
Which penicillinase-resistant drugs can be taking orally?
Dicloxacillin
What is the function of cabencillin?
used to treat UTIs
What are examples of irreversible beta-lactamase inhibitors?
Clavulanic acid, sulbactam, and tazobactam
What is unique about beta-lactamase inhibitors activity?
have no activity on their own and need to be combined w/ penicillins for expanded coverage
What are examples of antipseudomonal penicillin drugs?
cabencillin, tircarcillin, mezlocillin, piperacillin
How are most antipseduomonal drugs taken? except?
parenterally except Cabencilin is taken orally
What is the mechanism of action for penicillinase-resistant drugs?
Have a side group that protects the drugs from being inactivated by beta-lactamases
What do cephalosporins resemble?
penicillin, possess beta-lactam backbone
Are cephalosporins unstable or stable to pH changes?
stable, thus may be taken w/ or w/out food
What are the 6 adverse effects of cephlosporins?
- Penicillin-allergic patients may also be hypersenitive
- GI irritation is common so take w/ food
- Parenterally administered can cause local irritation at sire of injection
- Renal toxicity possible if excretion problems exist. Avoid giving to patients w/ preexisting renal disease.
- Newer ones may cause seizures but usually only concern those w/ impaired kidney causing drug to accumulate
- Secondary infections may occur due to disruption of normal flora
What are examples of Carbapenems?
imipenem, cilastatin, doripenem, ertapenem, and meropenem
What is the mechanism of action for carbapenems?
Bactericial, have different stereochemical structure in their Beta-lactam ring that renders them resistant to Beta-lactamases
What is the mechanism of action of telavancin and vancomycin?
Block polymerization and cross-linking of peptidoglycan by binding to D-Ala terminal pair
What additional mechanism of action does telavancin have?
disrupts membrane potential and changes in cell permeability
What is cycloserine used for?
treat TB infections resistant to first line antitubercular drugs
What is polymyxin B used to treat?
nearly all gram negative except Proteus
How does polymyxin B work?
cationic detergent disrupts lipoproteins in bacterial cell wall resulting in increased membrane permeability
What are aminoglycosides used to treat?
mainly gram negative bacteria
What are examples of aminoglycosides?
amikacin, gentamicin, kanamycin, netilmicin, streptomycin, tobramycin, and neomycin
What are the 3 ways that aminoglycosides interfere w/ 30 S ribosomal subunit?
- formation of initiation complex
- Misread mRNA and miscode AA in growing peptide chain
- Cause ribosomes to separate from mRNA
How are aminoglycosides administered and why?
Parenterally b/c really water soluble
Where do aminoglycosides accumulate?
inner ear and renal cortex leading to nephrotoxicity and orotoxicity
what is unique about aminoglycosides’ pharmacokinetics?
translational mechanism of action causes microorganisms to continue to die as plasma levels of drug declines – known as postantiobiotic effect
How do bacteria resist aminoglycosides?
- alter receptor proteins on their ribosomes so prevents binding
- may enymatically/posttranslationally alter drugs inhibiting efficient binding
What are examples of tetracyclines?
tetracyclin, minocyclin, doxycyclin, demeclocyclin, oxytetracycline
What is the mechanism of action for tetracycline?
Bacteriostatic. Reversible binding of 30 S subunit. Prevent binding of new incoming AA and interfere w/ peptide growth
What is a 1st glycycline antiobiotic?
Tigecycline, It overcomes 2 mechanisms of resistance: efflux pumps and ribosomal protection
What is mode of penetration for tetracycline in the two types of bacteria?
negative = passive diffusion positive = active transport
Why is it best to administer tetracyclines on an empty stomach?
B/c divalent cation chelators or bile acid resin inhibit gastric absorption
Why is it good to use doxycycline?
undergoes hepatic metabolism and excreted in feces so safest option in patients w/ renal dysfunction
What is the resistance for tetracyclines?
Gram positive use efflux pumps
Gram negative alter their outer membrane protein
What is the mechanism of action for chloramphenicol?
Bacteriostatic
Binds to 50S subunit and block linkage of incoming AA by interfering w/ peptidyl transferase
How are chloramphenicols metabolized?
In the liver via glucuronidation
What are the consequences of using chloramphenicols in patients w/ hepatic disease?
Drug accumulates resulting in grey adults/babeis.
Signs: pale/cyanosis, abdominal distention, may die of respiratory or vasomotor collapse
What is the common drug for lincosamides?
clindamycin
How lincosamides work?
prevents translocation of incoming AA from ribosomal A site to P site by binding to 50S subunit
What are examples of macrolides?
erthyromycin bases, estolates, stearates, ethylsuccinates; clarithromycin, acithromycin
What is the mechanism of action for macrolides?
Bind to 50 S subunit, prevents translocation from site A to site P,
Bacteriostatic or bacteriocidal depending on drug [ ]
What other drugs are involved in cross-resistance w/ macrolides?
clindamycin and cloramphenicol
How do bacteria become resistant to macrolides?
- permeability is altered
- methylate bacterial 50 S subunit
- enzymatically destroy the drug
What are adverse effects of erythrymycin?
Associated w/ GI distress so take w/ food
Inhibit P450 3A4 and can prolong QT interval on ECG
What are adverse effects of carithrymycin?
Inhibit P450 3A4 and prolong QT interval
What are adverse effects of azithromycin?
minimal incidence of diarrhea
What are adverse effects of estolate salt?
May cause cholestatic hepatitis, elevated liver enzymes, malaise, nausea, vomiting, abdominal cramps, jaundince, and fever
What is the role of liver function test?
to monitor if hepatotoxicity is suspected w/ estolate salts
What is the key ketolide?
telithromycin - poor substrate for bacterial efflux pumps
What is the mechanism of action for ketolides?
- Inhibit 50 S subunit by binding to 2 separate domains
Why is it harder to form resistance to ketolides?
2 different mutations are needed to over ketolides mechanism of action
