week 4: Anti-infective_ Protein synthesis Inhibitors Flashcards
Tetracyclines Class/Clinical Indications
Active against gram (+), gram (-), and atypical organisms
Typically, bacteriostatic
1st class of antibiotics to be labeled “broad-spectrum”
Alternatives to beta-lactams
Acne vulgaris
CAP
MRSA (doxy & minocycline)
Tetracyclines Pharmacokinetics
–Absorption improved on empty
Stomach
–Food ↓ absorption along with milk /
dairy Exception: Doxycycline
--Phenytoin and carbamazepine
↓ half -life of doxycycline
Drug Interactions
--Antacids
--Iron
--Cholestyramine
--Sucralfate
--Tetracycline potentiates the effect of
warfarin by impairing vitamin K
production by the intestinal flora
Tetracyclines SE and drawbacks
Hepatotoxicity: rare but potentially fatal
–Increases with use with other
hepatotoxic agents and expired
tetracyclines
Grey-brown discoloration of teeth (permanent)
–Contraindicated in children
< 8 years of age
Tinnitus
Phototoxicity with tetracycline
Dose-related vertigo: minocycline
Nephrotoxix-> Faconi syndrome
Cross placenta; Chelating effect, binds with Ca++ → discoloration of deciduous teeth, enamel hypoplasia, inhibition of fetal skeletal growth.
Greatest risk: middle of 2nd trimester through 6 months of age
Excreted in breast milk in high concentrations
Aminoglycosides Class/Clinical Indications
Bactericidal: Reserved for treatment of serious, resistant G-negative infection
including pseudomonoas
Not normally used in primary care
Narrow therapeutic window
Not effective for anaerobes
Oral preparations: Suppression of bacterial flora, tx for hepatic coma
Aminoglycosides pharmacokinetics
Cross the placenta, but distribution into breast milk is unknown
Patients with impaired renal function are at increased risk for toxicity
Oral aminoglycosides are not absorbed
--Only use is for suppression
of intestinal bacteria
--IM and IV use for treatment
Serum peak (30-45 minutes after IV dosing; 60 minutes after IM) Trough (drawn immediately before dosing) Should be monitored after second or third dose Every 3-4 days, thereafter for duration of therapy
Aminoglucosides SE / Drawbacks
Nephrotoxicity : Acute tubular necrosis, reversible
Ototoxicity,: High frequency loss first. Not reversible
Neuromuscular blockade
Teratogenic
Macrolides/Ketolides Class/Clinical Indications
Bacteriostatic
Gram (+) and Gram (-) aerobes
Atypical organisms: chlamydia, mycoplasma, legionella, rickettsia, mycobacteria, spirochetes
Whooping cough (Pertussis)
Typical and Atypical pneumonia
Not recommended for
Acute bacterial Sinusitis
(even in patients with
allergy to b-lactams) due
to increasing resistance
STIs (Azithro)
Ulcer by H pylori (clarithro)
Macrolides/Ketolides Pharmacokinetics
Minimal protein binding
Good tissue penetration
Improved GI profile and longer half-lives with azithro and clarithro
Half-lives vary: 2 hours –60 hours
Erythromycin compatible with breastfeeding
No alternate birth control method is required
Macrolides/Ketolides SE/Drawbacks
Clarithromycin
–Ototoxicity with extremely high
dose
–Psychosis
All except azithromycin
–Potent inhibitors of CYP 3A4
isoenzyme pathway
–Prolong half-life of cyclosporine,
carbamazepine, theophylline, warfarin
& HMG-CoA reductase inhibitors
(statins)
All have potential to increase QT interval
–Caution when using other agents that
prolong QT interval
what dose of Erythromycin ethylsuccinate = to what erythromycin base?
Due to differences in absorption, 400 mg erythromycin ethylsuccinate = produces the same serum levels as 250 mg erythromycin base or stearate.
True or false, in Azithromycin, ER suspension (Zmax) is not interchangeable with IR formulations.
true
Lincosamides Class/Clinical Indications
Gram (+) & anaerobic infections
Concentration dependent killing
Reversible binding to
50 S ribosome subunits
May be combined with gentamicin to treat mixed aerobic and anaerobic infections
Infections (osteomyelitis and Group A strep, septic arthritis, postpartum endometritis, skin and soft tissue infection more)
Acne
Taste bitter: not for children
Lincosamides Pharmacokinetics
Well absorbed and 90% bioavailable
Penetrates most tissues (including abscesses) & bone
Limited CSF
93% protein-bound
Lincosamides SE / Drawbacks
N/V/abdominal pain
Associated C. difficile colitis (Pseudomembranous colitis)
Metallic taste with IV
What is Fluoroquinolones
Bind to these enzymes and interfere with DNA ligation Increases the number of permanent chromosomal breaks, triggering cell lysis
Fluoroquinolones Class/Clinical Indications
Bactericidal: concentration-dependent oAll have gram (-) activity: Enterobacteriaceae, H. flu, Legionella, Neisseria. Pseudomonas o oNewer FQs have gram (+) coverage --Levofloxacin, moxifloxacin, gemifloxacin --Referred to as “respiratory FQs” --Indicated for Streptococcus pneumoniae --Less effective against pseudomonas oNo effective for MRSA o oUTI: NO longer agent of choice for acute uncomplicated cystitis d/t resistance oProstatitis oPneumonia/Nosocomial pneumonia oSTIs oSkin & soft tissue oGI: combine with an agent covering anaerobic oTravelers diarrhea oOsteomyelitis
Pharmacokinetics Fluoroquinolones
oExcellent bioavailability -- Antacids, sucralfate, Mg,Ca++, or Iron salts by chelation --Decrease absorption of FQs oHalf-life: range 4 – 12 hours oRenal excretion --Exception: moxifloxacin oNot recommended for nursing moms
What are the two distinct topoisomerases are needed for bacteria to replicate in numbers
DNA gyrase (topoisomerase II)
–Responsible for reducing torsional stress ahead of replicating forks by breaking double-strand DNA and introducing negative supercoils
Topoisomerase IV
–Separate daughter chromosomes once replication is completed
What is the black box warning for Fluoroquinolones?
Irreversible tendinopathy, tendon rupture, peripheral neuropathy,
exacerbation of myasthenia gravis
What does Rifampin do?
Inhibitors of RNA Functions or Synthesis:
Bactericidal for both intracellular and extracellular mycobacteria
M. tuberculosis, Mycobacterium avium complex (MAC), M. Leprae
Used as part of treatment for several different bacterial infections
Never given as a single agent in the treatment of active tuberculosis.
Due to resistant strains rapidly emerge during monotherapy
Mechanism of action
Blocks RNA transcription by interacting with the β subunit of mycobacterial DNA-dependent RNA polymerase.
What is the Class/Clinical Indications for Rifampin
Bactericidal :
oGram (+) cocci :
--Mycobacterium tuberculosis
--Staph aureus
oModerate activity against gram (-)
-- Neisseria meningitidis
--Neisseria gonorrhoeae
-- H. influenzae
o1st-line treatment for Active & latent TB
---RIPE (rifamycin (like rifampin), isoniazid,
pyrazinamide, and ethambutol)
o
o
oCombined with other agents
for MRSA or serious gram (+)
infections that fail to respond to other tmt
for synergistic activity to prevent resistance
What is the Pharmacokinetics for Rifampin?
Well absorbed through GI tract
oPenetrates most tissues/fluids including CSF
oHalf-life: 3 hours
oMetabolized by liver and renally excreted
oOK in pregnancy
What is the SE and drawback for Rifampin?
GI: N/V/D
oHeadache
oFever
oChanges bodily fluids to a red-orange color: harmless
oRisk of hepatotoxicity when combined with isoniazid (INH)
-- stop when 3 x> and sx or 5x >
with no sx
oAnemia
oThrombocytopenia
o
Drug Interactions
oPotent inducer of CYP enzyme pathways
--Antiarrhythmics
--Azole antifungals
--Clarithromycin
--OCP
--Most HMG-CoA reductase inhibitors
--Warfarin
--Antiseizure
--HIV medicationsWhat is Folate Antagonist
Inhibitors of Metabolism:
Folic acid
A coenzyme essential in the synthesis of ribonucleic acid (RNA), DNA, and certain amino acids.
No proper growth of cell without folate synthesis
