FA Antimicrobial Pharm Flashcards
Which penicillin has best oral availability?
Pen V
Pen G is only IV/IM
How do penicillins work?
D-Ala-D-Ala structural analog
Binds PBP’s (transpeptidase) blocking cross-linking
Clinical use for Penicillins
Mostly G(+) Also G(-) cocci (mainly N meningitidis) and spirochetes
What are the penicillinase sensitive penicillins? (Besides Pen G/V)
Amoxicillin, Ampicillin
MOA of penicillinase sensitive penicillins
Same MOA as Penicillin, but wider spectrum
Often combined with Clavulanic acid
Which of the penicillinase sensitive penicillins has greater oral bioavailability?
Amoxicillin
Use of penicillinase sensitive penicillins
Extended spectrum allows coverage of HHELPSS kill Enterococci H flu H pylori E coli Listeria Proteus Salmonella Shigella Enteroccoci
Adverse effects of penicillinase sensitive penicillins
Pseudomembranous colitis
What are the penicillinase resistant penicillins?
Dicloxacillin, Nafcillin, Oxacillin
MOA of penicillinase resistant penicillins
Same as penicillin
Narrow spectrum
Use of penicillinase resistant penicillins
Staph aureus
What are the antipseudomonal penicillins?
Piperacillin, Ticarcillin
Use of antipseudomonal penicillins
Pseudomonas and G(-) rods
Susceptible to penicillinase so use with beta-lactamase inhibitors
What are the beta-lactamase inhibitors?
Clavulanic acid
Sulbactam
Tazobactam
Which of the Cephalosporins covers MRSA?
5th gen:
Ceftaroline
MOA of Cephalosporins
These are beta-lactam drugs but are less sensitive to penicillinase
Name 2 1st gen Cephalosporins and their use
Cefazolin, Cephalexin
G(+) cocci
Remember 1st gen PEcK
Proteues, E coli, Klebsiella
Which Cephalosporin is used before surgery to prevent S aureus wound infection?
Cefazolin
1st gen
Name 3 2nd gen Cephalosporins and their use
Remember FAke FOX FUR
CeFAclor, CeFOXitin, CeFURoxime
Remember HENS PEcK (in addition to G(+) cocci)
H flu, Enterobacter, Neisseria, Serratia, Proteus, E coli, Klebsiella
Name 3 3rd gen Cephalosporins and use
Ceftriaxone, Cefotaxime, Ceftazidime
Serious G(-) infections resistant to other beta-lactams
Ceftriaxone: meningitis, gonorrhea, disseminated Lyme disease
Ceftazidime: Pseudomonas
4th gen Cephalosporin and use
Cefepime G(-), has increased activity against Pseudomonas and G(+)
5th gen Cephalosporin and use
Ceftaroline
Broad G(+) and G(-) coverage
Includes MRSA
Does not cover Pseudomonas
Adverse effects of Cephalosporins
Disulfiram-like
Vit K deficiency
Increased nephrotoxicity of aminoglycosides
What drugs are Carbapenems?
Imipenem, Meropenem, Ertapenem, Doripenem
MOA of Carbapenems
Beta-lactam like penicillins and cephalosporins, but broader coverage
Less sensitive to common resistance mechanisms
Imipenem must be administered with Cilastatin to inhibit renal dehydropeptidase I
Meropenem is stable to renal enzyme
Use of Carbapenems
Generally only used for MDR bacteria and in patients that are hospitalized because of risk of seizures and to prevent resistance
These are heavy-hitting drugs used often as last resort in life-threatening infections
Cover G(+) cocci, G(-) rods, and anaerobes
Monobactam drug
Aztreonam
Monobactam MOA
Beta lactam, less susceptible to beta-lactamase, synergistic with aminoglycosides, no cross-allergy with penicillins
Monobactam use
G(-) rods only, no G(+) rod or anaerobe coverage
For penicillin allergic patients and those with renal insufficiency that can’t handle aminoglycosides
Is Vancomycin affected by beta-lactamase?
No
Vancomycin use
G(+) only
MRSA, S epidermidis, Enterococcus, C difficile
Adverse effects of Vancomycin
Nephrotoxicity, Ototoxicity, Thrombophlebitis
Diffuse Flushing=Redman Syndrome: can be prevented by pretreatment with antihistamines and slow infusion rate
What are the protein synthesis inhibitors?
(Remember: buy AT 30, CCEL (sell) at 50)
30S inhibitors: Aminiglycosides (-cidal), Tatracyclines (-static)
50S inhibitors: Chloramphenicol, Clindamycin (both -static), Erythromycin (Macrolides, -static), Linezolid (variable)
What are the Aminoglycosides?
Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin
Aminoglycoside MOA
Bactericidal
Irreversibly binds 30S subunit preventing initiation complex and causing mRNA misreading
Requires O2 for uptake, therefore ineffective against anaerobes
Aminoglycoside adverse effects
Nephrotoxicity, Neuromuscular blockade, Ototoxicity (especially when used with loop diuretics), Teratogen
Aminoglycoside use
Severe G(-) rod infections
Synergistic with beta-lactam antibiotics
Neomycin for bowel surgery
Tetracycline drugs
Tetracycline, Doxycycline, Minocycline
Tetracycline MOA
Bacteriostatic
Binds 30S subunit preventing attachment of tRNA
Limited CNS penetration
Which of the Tetracyclines can be used in patients with renal failure?
Doxycycline because it is eliminated in the feces
Tetracyclines should not be taken with what because it inhibits absorption from the gut?
Milk, Antacids, iron containing preps because divalent cations inhibit absorption
Tetracycline use
Borrelia burgdorferi, M pneumoniae, Rickettsia, Chlamydia, acne
Tetracycline adverse effects
Teeth discoloration, inhibits bone growth in kids, photosensitivity
CI in pregnancy
Chloramphenicol MOA
Blocks peptidyltransferase at 50S ribosomal subunit
Bacteriostatic
Chloramphenicol use
Meningitis: H flu, N meningitidis, S pneumo
RMSF
Limited use in US because of toxicity, but used abroad because of low cost
Chloramphenicol adverse effects
Anemia, aplastic anemia, gray baby syndrome in premature infants because lack liver UDP-glucuronyl transferase
Clindamycin MOA
Blocks peptide transfer at 50S
Bacteriostatic
Clindamycin use
Anaerobe infections like Bacteroides and Clostridium in aspiration pneumonia, lung abscesses, oral infections
Also effective against invasive GAS infection
Treats anaerobes above the diaphragm whereas Metronidazole treats anaerobes below the diaphragm
Clindamycin adverse effects
Pseudomembranous colitis, fever, diarrhea
Linezolid MOA
binds 50S
Linezolid use
G(+) including MRSA and VRE
Linezolid adverse effects
Bone marrow suppression (especially thrombocytopenia), peripheral neuropathy, serotonin syndrome
What are the Macrolides?
Azithromycin, Clarithromycin, Erythromycin
Macrolide MOA
Prevents translocation by binding the 23S rRNA of 50S
Bacteriostatic
Macrolide use
Atypical pneumonia (Mycoplasma, Chlamydia, Legionella)
STI’s (Chlamydia)
G(+) cocci (strep infections in patients allergic to penicillin)
B pertussis
Macrolide adverse effects
GI motility problems Arrhythmia from prolonged QT Acute cholestatic hepatitis Rash Eosinophilia All but Azithromycin inhibit P450
Sulfonamide MOA
Inhibits folic acid synthesis by Dihydropteroate Synthase inhibition
Sulfonamide use
G(+), G(-), Nocardia, Chlamydia, SMX for simple UTI
Sulfonamide adverse effects
Hypersensitivity, hemolysis if G6PD deficient, nephrotoxicity, photosensitivity, displaces drugs form albumin like warfarin
Inhibit P450
Dapsone MOA, Use, and Adverse effects
Similar to sulfonamide in function, used for Leprosy and prophylaxis for Pneumocystis jirovecii
Hemolysis in G6PD deficiency
Trimethoprim MOA
Inhibits folic acid synthesis by inhibiting Dihydrofolate reductase
Trimethoprim use
In combination with sulfonamides to cause sequential block of folate synthesis
UTI’s, shigella, salmonella, Peumocystis jirovecii treatment and prophylaxis, Toxoplasmosis prophylaxis
Trimethoprim adverse effects
Bone marrow suppression: megaloblastic anemia, leukopenia, granulocytopenia
What are the Fluoroquinolones?
Ciprofloxacin, Norfloxacin, Levofloxacin, Ofloxacin, Moxifloxacin, Gemifloxacin, Enoxacin
Fluoroquinolone MOA
Inhibits prokaryote DNA gyrase (topoisomerase II and IV)
Fluoroquinolone use
G(-) rods of urinary and GI tracts including Pseudomonas
Neisseria and some G(+)
Fluoroquinolone adverse effects
CI in pregnant and nursing women and kids under 18 because can damage cartilage
May prolong QT
May cause tendonitis and tendon rupture in those over 60 and in patients taking prednisone
Daptomycin MOA
Lipopeptide that disrupts cell membrane of G(+) cocci
Daptomycin use
S aureus skin infections (especially MRSA), bacteremia, endocarditis, VRE
Not used for pneumonia because inactivated by surfactant
Daptomycin adverse effects
Myopathy, rhabdomyolysis
Metronidazole MOA
Forms toxic free radicals that damage DNA
Antiprotozoal also
Metronidazole use
Treats anaerobes below the diaphragm whereas Clindamycin treats them above
Giardia, Entamoeba, Trichomonas, Gardnerella, Anaerobes like bacteroides and C difficile
Used with PPI and clarithromycin for triple therapy against H pylori
Prophylaxis and treatment for M avium-intracellulare
Prophylaxis: Azithromycin, rifabutin
Treatment: Azithromycin or Clarithromycin + ethambutol
Can also add rifabutin or ciprofloxacin
Of the TB drugs, which work by inhibiting mycolic acid synth, araginoglycan synth, mRNA synth, and which have unclear mech?
Isoniazid: mycolic acid synthesis
Ethambutol: arabinoglycan synthesis
mRNA synthesis: Rifabutin and Rifampin
Unclear: Pyrazinamide
What are the Rifamycins?
Rifampin, Rifabutin
Rifamycin MOA
Inhibits DNA dependent RNA polymerase
Rifamycin use
TB, delay resistance to dapsone in Leprosy, meningococcal prophylaxis
What are Rifampin’s 4 R’s?
RNA polymerase inhibitor
Ramps up P450
Red/orange body fluids
Rapid resistance if used alone
How are Rifampin and Rifabutin different?
Rifampin ramps up P450 and Rifabutin does not and is therefore preferred for use in HIV patients
How is MRSA treated?
Vancomycin, Daptomycin, Linezolid, Tigecycline, Ceftaroline
How is VRE treated?
Linezolid, Streptogramins
How are MDR P aeruginosa and Acinetobacter baumannii treated?
Polymyxins B and E
Amphotericin B MOA
Binds ergosterol and creates pores in fungal membrane
AmphoTEARicin
Amphotericin B use
Serious systemic mycoses
Cryptococcus, Blastomyces, Coccidioides, Histoplasma, Candida, Mucor
Intrathecally for fungal meningitis
Supplement K+ and Mg+ because of altered renal tubule permeability
Amphotericin B adverse effects
Fever/Chills, hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis
Hydration decreases nephrotoxicity
Nystatin MOA and use
Same MOA as Amphotericin B but topical only
Used most often for candida (oral, diaper, and vaginal)
Flucytosine MOA
Inhibits DNA and RNA biosynthesis by conversion to 5-FU by cytosine deaminase
Flucytosine Use
Systemic fungal infections (especially meningitis from Cryptococcus) in combo with Amphotericin B
Flucytosine adverse
Bone marrow suppression
What are the azoles?
Clotrimazole, Fluconazole, Itraconazole, Ketoconazole, Miconazole, Voriconazole
Azole MOA
Inhibit fungal sterol synthesis by inhibiting P450 that converts lanosterol to ergosterl
Azole use
Local and less serious systemic fungal infections
Fluconazole: chronic suppression of cryptococcal meningitis in AIDS and candidal infections of all types
Itraconazole: Blastomyces, Coccidioides, Histoplasma
Clotrimazole and Miconazole: topical fungal infections
Azole adverse
Testosterone synth inhibition causing gynecomastia especially with ketoconazole
Liver dysfunction from P450 inhibition
Terbinafine MOA, Use, Adverse
Inhibits fungal squalene oxidase preventing ergosterol synth
Dermatophytoses especially onychomycosis
Gi upset, headaches, hepatotoxicity, taste disturbance
Name the echinocandins
Anidulafungin, Caspfungin, Micafungin
Echinocandins MOA, Use
Inhibits fungal cell wall synth by inhibitingsynth of beta glucan
Invasive aspergillosis, candida
Griseofulvin MOA
Microtubule function of fungus disrupts mitosis
Deposits in keratin-containing tissues
Griseofulvin use
Oral treatment of superficial infections, inhibits growth of dermatophytes
Griseofulvin adverse
Teratogenic, carcinogenic, confusion, headaches, induces P450 and warfarin metabolism
Anti-mite and louse therapy
Permethrin: blocks Na channels
Malathion: AChE inhibitor
Lindane: Blocks GABA channels
Chloroquine use
Treats Plasmodium except for P falciparum
Causes retinopathy and puritis
How is P falciparum treated?
Atovaquone/Proguanil
How is life-threatening malaria treated?
Quinidine in US
Quinine elsewhere
Oseltamivir and Zanamivir MOA and use
Inhibit influenza neuraminidase preventing release of progeny virus for influenza A and B
Acyclovir, Famciclovir, Valacyclovir MOA
Guanosine analogs
Monophosphorylated by HSV and VZV thymidine kinase in infected cells only so few side effects
Inhibits viral DNA polymerase by chain termination
Acyclovir, Famciclovir, Valacyclovir use
HSV and VZV Weak against EBV and no effect in CMV No effect on latent viruses Valacyclovir has better oral availability Famciclovir best for herpes zoster
Acyclovir, Famciclovir, Valacyclovir adverse
Obstructin crystalline nephropathy and acute renal failure if not adequately hydrated
Ganciclovir MOA and use
Guanosine analog activated by viral kinase in CMV inhibits DNA polymerase
Used for CMV especially in immune compromised
Valganciclovir better oral availability
Ganciclovir adverse
Bone marrow suppression and renal toxicity
Foscarnet MOA
Viral DNA/RNA polymerase inhibitor and HIV reverse transcriptase inhibitor
Binds to pyrophosphate-binding site of enzyme
Does not require kinase activation
Foscarnet use
CMV retinitis in immune compromised when ganciclovir fails
Acyclovir-resistant HSV
Foscarnet adverse
Nephrotoxicity
Seizures form electrolyte abnormalities
Cidofovir
Similar to Foscarnet
DNA polymerase inhibition
Does not require phosphorylation
Used in CMV retinitis and acyclovir-resistant HSV
Has a long half-life
Adverse: nephrotoxicity–coadminister probenecid and IV saline to reduce toxicity
How do the -navir HIV drugs work?
Protease inhibitors
How do the HIV -TEGRavir drugs work?
InTEGRase inhibitors
NRTI’s MOA and Drugs
Nucleot(s)ide Reverse Transcriptase Inhibitors
Abacavir, Didanosine, Emtricitabine, Lamivudine, Stavudine, Tenofovir, Zidovudine
Tenofovir is a nucleotide, all others are nucleosides and require phosphorylation before being active
ZDV can be used for general prophylaxis and in pregnancy to decrease risk of passing on virus
NRTI’s adverse
Bone marrow suppression (can be reversed with G-CSF and EPO)
NNRTI’s MOA and Drugs
Inhibit reverse transcriptase at a different place than NRTI’s and don’t require phosphorylation to be active.
Delavirdine, Efavirenz, Nevirapine
Many CI in pregnancy
HIV protease inhibitors MOA and drugs
Inhibit HIV-1 protease
All end in -navir
Atazanavir, Darunavir, Fosamprenavir, Ininavir, Lopinavir, Ritonavir, Saquinavir
Ritonavir can boost other drug concentrations by inhibiting P450
Rifampin is CI with all these drugs because it induces P450
HIV integrase inhibitors
Inhibits HIV viral integration into host genome
All end in -tegravir
Raltegravir, Elvitegravir, Dolutegravir
HIV fusion inhibitors
Enfuvirtide: Binds gp41 inhibiting viral entry
Maraviroc: Binds CCR-5 on surface of T-cells/monocytes inhibiting interaction with gp120
What are interferons?
Glycoproteins usually synthesized by viral-infected cells that exhibit a range of antiviral and antitumoral properties
What is IFN-alpha used for?
Treat chronic Hep B and C, kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, renal cell carcinoma, malignant melanoma
What is IFN-beta used for?
Multiple Sclerosis
What is IFN-gamma used for?
Chronic granulomatous disease
What are the adverse effects of treatment with interferons?
These are normally made by viral infected cells so you will have Sx of a viral infection: flu-like Sx, depression, neutropenia, myopathy
What drugs are used in Hep C treatment?
Ribavirin, Sofosbuvir, Simeprevir
Which antimicrobials should be avoided during pregnancy?
Remember: SAFe Children Take Really Good Care Sulfonamides–kernicterus Aminoglycosides–ototoxicity Fluoroquinolones–cartilage damage Clarithromycin–embryotoxic Tetracycline–discolored teeth, inhibits bone growth Ribavirin–teratogenic Griseofulvin–teratogenic Chloramphenicol–gray baby
