antimicrobial Flashcards
Mechanism Mechanism of resistance Clinical use
Mechanism of Penicillin sensitive penicillinase (amoxicillin, ampicillin, aminopenicillin)
- Same as Penicillins; block transpeptidase cross-linkingof peptidoglycan wall.
- Wider spectrum than penicillins
Clinical use of amoxicillen
HHELPSS
H.influenza, H.pylori, E.coli, Listeria, proteus, salmonella, shigella
Mechanism of Penicillin resistant penicillinase (dicloxacillin, nafcillin, oxacilllin
- Same as penicillins
- Narrow spectrum
What makes dicloxacillin
nafcillin, oxacilllin resistent to penicillinase?
Bulky R group blocks access of B-lactamase to B lactam ring.
Clinical use of dicloxacillin
S. Aureus (except MRSA)
Mechanism of resistance of nafcillin
MRSA alters penicillin-binding target site
Oxacillin side effects
Hypersensitivity
Interstitial nephritis
Mechanism of Antipseudomonal penicillins (piperacillin, ticarcillin)
- Same as penicillin
- Extended spectrum
Clinical use of piperacillin
Pseudomonas spp.
Gram - rods
B lactamase inhibitors aka penicillins BFFs
Added to penicillin antibiotics to protect from destruction.
Clavulanic acid, avibactam,sulbactam,tazobactam
Carbapenams
- IV only
- Life threateninig infections
- Given with cilastatin to decrease metaboism of drug (inhibits renal dehydropeptidase l to decrease inactivation of drug)
- SE: seizures
Which carbapenam is stable to dehydropeptidase l and has a decreased risk of seizures?
Meropenam
Monobactams (Aztreonam)
- Prevents cross linking by binding to penicillin-binding protein 3.
- Synergistic with aminoglycosides (mycins)
Clinical use of aztreonam
- Gram negative rods ONLY
- Pts with renal insufficiency who cannot tolerate gentamycin/streptomycin
Vancomycin
- Diffuse flushing
- Prevent side effects by slow infusion rate.
- Drug reaction with eosinophilia
- mechanism of resistance via amino acid modification to D-ALA D-LAC
Neomycin
Streptomycin
- Require O2 for uptake
- inhibit initiation complex by binding to 30s
- Can cause misreading of mRNA.
- Blocks transcription and translocation.
- neomycin for bowel surgery
Streptomycin clinical uses
- Severe gram negative rod infections.
- Synergistic with aztreonam
- Ototoxicity esp when given with loop diurectics like furosemide,bumetanide, torsemide
Streptomycin mechanism of resistance
Drug is inactivated by acetylation, phosphorylation or adenylation.
30s inhibitors
50s inhibitors
30s inhibitos:
aminoglycosides (bacteriocidal)
tetracyclines
50s inhibitors: macrolides (erythomycin) clindamycin, chloramphenicol, lizezolid
Tetracycline;
Doxy
Minocycline
Tertracycline
- Doxy can be used in renal failure and effective agaisnt MRSA
- prevent attachment of aminoacyl-tRNA
- Divalent cations inhibit drugs absorption in gut
Doxycycline mechanism of resistance
Decrease uptake or increase efflux out of bacterial cells by plasmid encoded transport pumps
Glycycycline (tigecycline)
-infections requiring deep tissue penetration.
Chloramphenicol
- Best CNS penetration
- Rapid absorption
- blocks peptidyltransferase at 50s
- Uses meningitis (h.influenza, n. Meningitidis, s. Pneumonia), rickettsial diseases
Chloramphenicol side effects
Side effects are mainly dose dependent (anemia, aplastic anemia)
Chloramphenicol resistance mechanism
Plasmid encoded acetyltransferase inactivates the drug.
Clindamycin
- Blocks peptide transfer at 50s
- Treats anaerobic infections ABOVE the diaphragm (vs metronidazole)
Clindamycin clinical use
Anaerobic infections; (bacteroides, clostridium perfringes) in aspiration pneumonia, lung abscesses and oral infections
-group A srep infection
Oxazolidinones (Linezolid)
- MRSA, VRE
- Inhibit protein synthesis by inhibiting initation complex.
- Resistance: point mutation of ribosomal RNA.
Linezolid side effects
-Bone marrow suppression;
Decreases platelet count
-Serotonin syndrome
-peripheral neuropathy.
Mechanism of action and mechanism of resistance of Erythromycin,
Clarithromycin
Azithromycin
- Block translocation; bind to 23s of 50s
- mechanism of resistance: methylation of 23s rRNA binding site prevents drug binding.
Azithromycin clinical uses
-Atypical pneumonias; Mycoplasma Chlamydia Legionella -STIs; chlamydia -B.pertussis (whooping cough)
Clarithromycin side effects
MACRO: motility issues, arrhythmia caused by prolonged QT interval, acute cholestatic hepatitis, RASH, eosinophilia
-Clarithromycin and erythromycin inhibit cytochrome p-450; increase serum conc of theophylline and anticoags
Polymyxins (colistin)
- Disrupt membrane integrity of bacterial cell
- leakage of cellular contents =death
Clinical use and adverse effects of colistin
Use: salvage therapy for MDR gram neg bacteria (p.saeruginosa, e.coli, k.pneumoniae.
- polymyxin B is used for superficial skin infections as triple therapy.
- Side effects: neurotoxicity; slurred speech, paresthesias, respiratory failure.
Sulfonamides
-mechanism of resistance: altered enzyme (bacterial dihydropteroate synthase) decrease uptakee of increase PABA synthesis
Dapsone
Uses:
-leprosy
-pneumocystis jirovecci prophylaxis
SE: methemoglobinemia
Trimethoprim
-Prophylaxis for toxoplasmosis
-Prophymaxis and tx for pneumocystis jirovecii
SE: bone marrow suppresion; leukopenia, megaloblastic anemia etc
Fluoroquinolones (ciprofloxacin)
- inhibit top ll (dna gyrase)
- must not be taken with antacids
- cipro is a p-450 inhibitors
Cipro contraindications
- Pregnant/nursing mothers
- children <18 due to possible cartilage damge
- patients taking prednisone
- pts >60 yrs due to tendon rupture.
- leg cramps and myalgias
- superinfections
Ciprofloxacin uses:
- Gram - rods in urinary and GI
- otitis externa
Ciprofloxacin mechanism of resistance:
- Chromosone encoded mutation in DNA gyrase.
- plasmid mediated resistance
- eflux pumps
Daptomycin
- disrupts cell membrane of gram positive cocci
- creates transmembrane channels
- SE: rhabdomyolysis, myopathy
Daptomycin contraindications
Pneumonia (avidly binds to and is inactivated by surfactant,)
Metronidazole
- Damages DNA by creating free radicals
- SE: metallic taste
- Uses: GET GAP giardia, entamoeba, trichomonas, gardenella, anaerobes, h.pylori
Rifampin, rifabutin
- Inihibit DNA dependent RNA plymerase
- increases p-450
- Delay resistance to dapsone when used for leprosy
- Rifabutin preferred iver rifampin in HIV due to less p-450 stimulation.
Rifampin prophylaxis
- Contacts of children with H.influenza type B
- Meningococcal prophylaxis
Rifampin resistance
Mutations reduce drug binding to RNA polymerase. Avoid monotherapy=resistance.
Isoniazid mechanism and resitance
- actually a prodrug
- Needs catalase-peroxidase from the bacteria to activate it.
- encoded by KatG
- decreases mycolic acid synthesis
- Mutations=underexpression of KatG
Isoniazid uses and side effects
- Monotherapy in prophylaxis of TB
- Monotherapy in latent TB
- Inhibits p-450
- anion gap metabolic acidosis
- drug induced SLE
Pyrazinamide
- used in m. TB
- works best in acidic pH in host phagolysosomes.
- SE; hyperuricemia
Ethambutol
- Decreases carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase.
- SE: optic neuropthy
Which aminoglycoside can be given as second line tx of m. TB?
Streptomycin
Antimicrobials that disrupt membrane by forming pores or channels allowing for leakage of cellular contents.
Amphotericin B
Daptomycin
Polymyxin (colistin)
Amphotericin B protocol
- Supplement K+ and Mg+ because of altered renal tubule permeability
- Hydrate to decrease nephrotoxicity,
- Liposomal amphotericin decreases toxicity.
Azoles
- Voriconazole for mild aspergillus
- Itraconazole for blastomyces, coccidioides, histoplasma
- Isavuconazole for serious aspergillus and Mucor infections.
- Clotrimazole and miconazole for topical infections.
Fluconazole
-INHIBIT ERGOSTEROL BY INHIBITING P-450 THAT CONVERTS LANOSTEROL TO ERGOSTEROL.
Terbinafine
Inhibits squalene epoxidase
- used in dermatophytes esp onychomycosis; fungal infection of finger or toe nail.
- SE: taste disTERBance,
Fungins
Inhibit synth of B-glucan
-uses: invasive aspergillosis/candida
-SE: flushing by histamine release
Griseofulvin
- Interferes with microtubule function
- disrupts mitosis
- Deposits in keratin containing tissues like nails.
- inhibits growth of dermatophytes (tinea, ringworm)
Antiprotozoa
-Pyrimthamine for toxoplasmosis
-Suramin and melarsoprol for trypanosoma brucei
Nifurtimox for T. Cruzi
-Sodium stiboglucnate for leishmenia
Chloroquine
—blocks detox of heme into hemozoin
-heme accumulates and is toxic to plasmodia
-
Antihelminthic therapy
Pyrantel pamoate Ivermectin Mebendazole Praziquantel Diethylcarbamazine “Helminths get PIMP’D”
Antiviral drugs that require kinase activation
Ganciclovir, acyclovir,famciclovir, valacyclovir
Antiviral drug activated by intracellular kinases (rather than viral kinases)
Cidofovir
Acyclovir vs acyclovir in mechanism
Acyclovir does not affect normal host cells whereas ganciclovir does which can lead to bone marrow suppresion.
Cidofovir
- Long half life
- high intracellular drug conc = tubular necrosis
- Activated by intracellular kinases
Foscarnet
- Does not require kinase activation.
- Directly inhibits DNA polymerase
- used in CMV retinitis and acyclovir resistant HSV.
Oseltamivir, zanamivir
Decrease release of progeny virus
-inhibit neurominidase
Tenofovir
- NRTIs
- NucleoTide
- Bone marrow suppression can be reversed by G-CSF and EPO
- lactic acidosis
Zidovudine
- General prophylaxis
- used in pregnancy to decrease fetal transmission
- chain termination
- SE: anemia
Abacavir
-Contraindicated in patients with HLA-B*5701 mutation due to increased risk of hypersensitivity.
Efavirenz
- NNRTI
- Bind to reverse transcriptase at site diff than NRTIs.
- Does not require phosphorylation to be active.
Efavirenz side effects and contraindications
- Contraindicated in pregnancy (along with delavirdine)
- Vivid Dreamse
- CNS symptoms
- Rash/hepatotoxicity
Didanosine
- NRTI
- Terminate DNA chain
- SE: pancreatitis
Atazanavir
- Protease inhibitor
- prevent maturation of new viruses
- interferes with pol gene
Ritonavir
- prevents maturation of new virus
- boosts other drug conc by inhibiting p-450 (vs rifampin which reduces proteus inhibitor conc)
Indinavir
-SE; decrease in platelets
Elvitegravir
- prevent integration of HIV into host DNA (strand transfer of viral DNA is blocked from entering host chromosome)
- SE: increases creatine kinase
Maraviroc
- Binds CCR-5 on T cells/monocytes
- Inhibit gp120 interactions
Enfuvirtide
- Binds gp41
- inhibits viral entry
