Microbiology pharm Flashcards
Penicillin: MOA
Pen G= IV, IM
Penicillin V= oral
- Bind PBPs= penicillin binding proteins (transpeptidases)
- Block transpeptidase cross-linking of peptidoglycan
- Activate autolytic enzymes
** Administer with probenecid to decrease renal tubular secretion of penicillin
Penicillin: clinical use
Gram positives:
- Strep pneumo
- Strep pyogenes (prevent endocarditis in child with rheumatic fever history)
- Actinomyces
N. meningitides Treponema pallidum (syphillis prophylaxis)
Gram positive cocci, rods
Gram negative cocci
Spirochetes
Penicillin: toxicity and resistance
Hypersensitivity reactions
Hemolytic anemia
Resistance: beta lactamases cleave beta lactam ring in drug
Oxacillin, nafcillin, dicloxacillin
Penicillinase-resistant penicillins: block beta-lactamase (bacterial enzyme) access to beta-lactam ring
MOA:
- Bind PBPs= penicillin binding proteins (transpeptidases)
- Block transpeptidase cross-linking of peptidoglycan
- Activate autolytic enzymes
Use:
- S. aureus (except MRSA): “Naf for Staph”
Tox:
- Hypersensitivity reactions, interstitial nephritis
Ampicillin, amoxicillin
Aminopenicillins: penicillinase sensitive; combine with clauvanic acid to protect against beta-lactamase
MOA:
- Bind PBPs= penicillin binding proteins (transpeptidases)
- Block transpeptidase cross-linking of peptidoglycan
- Activate autolytic enzymes
- AmOxicillin= more Oral availability
Use: - H. flu - E. coli - **Listeria monocytogenes - Proteus mirabilis - Salmonella - Shigella "Amp/Amox HELPSS kill enterococci" - Combine with gentamicin for UTI ** Group B strep in pregnant women
Tox:
- Hypersensitivity reactions
- Ampicillin rash
- Pseudomembranous colitis (c. diff)
Ticarcillin, Carbenicillin, piperacillin
Ticarcillin, Carbenicillin= carboxypenicillins
Piperacillin= Ureidopenicillin
Antipseudomonals: susceptible to penicillinase; use with clavulanic acid
MOA:
- Bind PBPs= penicillin binding proteins (transpeptidases)
- Block transpeptidase cross-linking of peptidoglycan
- Activate autolytic enzymes
Use:
- Pseduomonas
- Gram negative rods
Tox:
- Hypersensitivity reactions
Beta lactamase inhibitors
CAST:
- Clavulanic Acid
- Sulbactam
- Tazobactam
Add to protect from beta-lactamases
Cephalosporins: MOA
Beta-lactams that inhibit cell wall synthesis
- Less susceptible to penicillinases
- Bactericidal
Not Covered: LAME
- Listeria
- Atypicals (Chlamydia, mycoplasma)
- MRSA *except Ceftaroline
- Enterococci
Toxicity:
- Hypersensitivity reactions
- Vit K deficiency
- low cross-reactivity with penicillins
- Increased nephrotoxicity when combined with aminoglycosides
Cephalosporin: 1st generation
Cefazolin *presurgical prophylaxis
Cephalexin
Covers: PECK
- Proteus mirabilis
- E. coli
- Cocci (Gram positive)
- Klebsiella
Cephalosporin: 2nd generation
fac, fox, fur
Cefoxitin
Cefaclor
Cefuroxime
Covers: HEN PECKS
- Haemophilus influenzae
- Enterobacter aerogenes
- Neisseria
- Proteus mirabilis
- E. coli
- Cocci (gram positive)
- Klebsiella pneumonia
- Serratia marascens
Cephalosporin: 3rd generation
tri, tax, taz
Ceftriaxone: Meningitis, gonorrhea
Cefotaxime
Ceftazidime: Pseudomonas
Covers:
- Serious gram negatives resistant to other beta-lactams
Cephalosporins: 4th generation
Cefepine
Covers:
- Increased activity against pseudomonas, gram-positives
Aztreonam
MOA:
- Monobactam, resistant to beta-lactamases
- Binds PBP3–> blocks peptidoglycan cross-linking
- Synergistic with aminoglycosides, no cross-allergenicity with penicillins
Use:
- Gram NEGATIVE RODS only
- Penicillin allergic patients, renal insufficiency patients
Toxicity: GI upset
Imipenem/Cilastin, Meropenem
MOA:
- Broad spectrum beta-lactamase resistant carbapenem
- Imipenem administered with Cilastin to decreased renal dehydropeptidase I (enzyme that breaks down Imipenem)
- “Kill is lastin with cilastin”
Use:
- Gram positive cocci
- Gram negative rods
- Anaerobes
Toxicity: significant, limit use (Meropenem not as toxic)
- GI distress
- Skin rash
- Seizures at high plasma levels
Vancomycin
MOA:
- Inhibits cell wall peptidoglycan formation by binding D-Ala D-Ala portion of cell wall
- Bactericidal
Use:
- Gram POSITIVES only
- Multidrug resistant organisms= MRSA, enterococci, C. diff (oral for pseudomembranous colitis)
Toxicity:
- Nephrotoxicity
- Ototoxicity
- Thrombophlebitis
- Red man syndrome= diffuse flushing, prevent with pretreatment with antihistamines, slow infusion
Resistance:
- D-ala D-ala changed to D-ala D-lac
Protein synthesis inhibitors
MOA: binds smaller bacterial ribosome (70s) subunits (30s and 50s)
30s= AT
Aminoglycosides (bactericidal)
Tetracyclines (bacteriostatic)
50s= CCEL Chloramphenicol (Bacteriostatic) Clindamycin (bacteriostatic) Erythromycin (Macrolides) (bacteriostatic) Linezolid (variable)
Aminoglycosides
GNATS Gentamicin Neomycin Amikacin Tobramycin Streptomycin
MOA:
- Bactericidal
- Binds 30s: Inihibit formation of initiation complex
- Misreading of mRNA
- Block translocation
- Require O2 for uptake (ineffective against anaerobes)
Clinical use:
- Gram-negative rod infections
- Synergistic with beta-lactams
- Neomycin used for bowel surgery
Toxicity:
- Nephro (esp. with cephalosporins)–> ATN
- Neuromuscular blockade
- Otoxicity (loop diuretics)
- Teratogen
Resistance:
- Transferase enzymes that inactivate the drugs via acetylation, phosphorylation, adenylation
Tetracyclines
Tetracycline
Doxycycline
Demeclocycline *used as diuretic in SIADH
Minocycline
MOA:
- Bacteriostatic
- Binds 30s: prevents tRNA attachment
PK:
- limited CNS penetration
- Doxycycline fecally eliminated, can be used in renal failure patients
- Divalent cations (milk, antacids, iron) prevent absorption in gut
Use:
- Borrelia burgdorferi
- Mycobacterium pneumoniae
- Rickettsia, Chlamydia (accumulates intracellularly)
Toxicity:
- GI distress
- Discoloration of teeth, inhibition of bone growth in children
- *Contraindicated in pregnancy= teeth discoloration, inhibition of bone growth**
- Photo-sensitivity
Resistance:
- Plasmid-encoded proton pumps decrease uptake or increase efflux
Macrolides
ACE
Azithromycin
Clarithromycin
Erythromycin
MOA:
- Inhibit protein synthesis: binds 23s rRNA at 50s subunit
- Prevent release of uncharged tRNA
- bacteriostatic
Use:
- Atypicals (mycoplasma, chlamydia, legionella)
- STD (chlamydia)
- Gram positive cocci (strep in penicillin allergic patients)
- Erythromycin ointment in infants: prevent gonococcal, chlamydial conjunctivitis
Tox:
- Motility issues
- Arrhythmia (prolonged QT)
- Cholestatic hepatitis (acute)
- Rash, Eosinophilia
- Increases serum theophyllines, oral anticoagulants
- *Clarithromycin= embrytoxic**
Resistance: methylation of 23s rRNA site
Chloramphenicol
MOA:
- Blocks peptidyltransferase at 50s
- Bacteriostatic
Use:
- Meningitis (H. flu, N. meningitidis, S. pneumo)
- Use limited by toxicity, but inexpensive
Tox:
- Anemia (dose-dependent)
- Aplastic anemia (dose-independent)
- Gray baby syndrome (premies lack UDP-glucuronyl transferase)
Resistance:
- Plasmid-encoded acetyltransferase (inactivates drug)
Clindamycin
MOA:
- Blocks peptide transfer (transpeptidation) at 50s subunit
- Bacteriostatic
Use:
- Anaerobes (B. fragilis, c. perfringens) in aspiration pneumonia, lung abscess
- Oral infections with anaerobes
- Anaerobes ABOVE the diaphragm (vs Metronidazole)
Toxicity:
- Pseudomembranous colitis (c. diff overgrowth)
- Fever
- Diarrhea
Sulfonamides
Sulfamethoxazole (SMX= UTI)
Sulfisoxazole
Sulfadiazine
MOA:
- PABA antimetabolites–> block dihydropteroate synthase (precursor to folic acid)
- Bacteriostatic
Use:
- Gram positive
- Gram negative
- Nocardia, Chlamydia
- Triple sulfa or SMX for simple UTI
Tox:
- Hypersensitivity reaction (serum sickness= Type III hypersensitivity reaction)
- G6PD deficiency–> hemolysis
- Nephrotoxic (tubulointerstital nephritis)
- Photosensitivity
- Kernicterus in infants
- Displaces protein-bound drugs (Warfarin)
Resistance:
- Altered enzyme (dihydropteroate synthase), decreased uptake, increased PABA
Trimethoprim
MOA:
- Inhibits dihydrofolate reductase
- Bacteriostatic
Use:
- Combination with SMX= Sequential block of folate synthesis
- UTIs
- Shigella
- Salmonella
- Pneumocystis jirovecii pneumonia (tx and prophylaxis- CD4+ < 200)
Tox:
- Megaloblastic anemia
- Leukopenia
- Granulocytopenia
- Leucovorin (folinic acid) may alleviate
- Stevens-Johnson/TEN
Fluoroquinolones
-Floxacins
Nalidixic acid= quinolone
MOA:
- Inhibit DNA gyrase (topo II) and topo IV
- Bactericidal
- Do not take with antacids**
Use:
- Gram-negative rods in urinary, GI tract (pseudomonas)
- Neisseria
- some Gram positives
- Ciprofloxacin= Meningococcal prophylaxis in adults
Tox:
- GI upset
- Superinfections
- skin rashes
- H/A
- Dizziness
- Tendonitis, tendon rupture, myalgia, leg cramps (esp older pts on prednisone): “Fluoroquinolones hurt your bones”
- Contraindicated in pregnancy damage to cartilage
- Prolong QT interval
Resistance:
- Chromosome-encoded mutation in DNA gyrase
- Plasmid mediated–> efflux pumps
Metronidazole
MOA:
- Forms free radical metabolites–> damage bacterial DNA
- Bactericidal, antiprotazoal
Use:
- GET: Giardia, Entamoeba, Trichomonas
- GAP: Gardnerella, Anaerobes (bacteroides, c. diff), h. Pylori (triple therapy
- treats anaerobe infections BELOW the diaphragm (vs clindamycin)
Tox:
- Disulfiram-like reaction with alcohol
- H/A, metallic taste
Isoniazid (INH)
Decreases mycolic acid synthesis
- Bacterial catalase-perozidase (Kat-G) needed to convert to active metabolite
Use:
- TB (solo prophylaxis)
Tox:
- Neurotoxicity, hepatotoxicity (INH Injures Neurons and Hepatocytes)
- Pyridozine (Vit B6) prevents neurotoxicity, lupus (INH chemically similar to B6–> depletes B6 levels)
Resistance:
- Decreased catalase-peroxidase (Kat-G) enzyme (INH not converted to active metabolite)
- Modification of protein target binding site
Rifampin
MOA:
- Inihibits DNA-dependent RNA polymerase
Use:
- TB
- Delays resistance to Dapsone in leprosy
- Meningococcal prophylaxis in children
- Chemoprophylaxis in H. flu type B
Tox:
- Minor hepatotoxicity (increased p450)
- Orange urine
4Rs:
- RNA polymerase inhibitor
- Revs up p450
- Red/orange body fluids
- Rapid resistance if used alone
Pyrazinamide
MOA:
- Uncertain (acidify intracellular environment)
- TB phagocystosed by macrophage–> activates drug
Use:
- TB
Tox:
- Hyperuricemia, hepatotoxicity
Ethambutol
MOA:
- Decreased carbohydrate polymerization of mycobacterium cell wall–> blocks arabinosyltransferase
Use: TB
Tox: Optic neuropathy
HIV prophylaxis for CD4 < 200
TMP-SMX
- Pneomocystis jirovecci pneumonia
HIV prophylaxis for CD4 < 100
TMP-SMX
- Pneuomcystis jirovecci
- Toxoplasmosis
HIV prophylaxis for CD4 < 50
Azithromycin
- Mycobacterium avium complex
Treatment of very resistant enterococci
Linezolid (50s inhibitor) and streptogramins (quinupristin/dalfopristin)
Amphotericin B
MOA:
- Binds ergosterol (unique in fungi)–> membrane pores–> leak electrolytes
Use: Serious, systemic mycosis:
- Cryptococcus (+/- flucytosine for meningitis)
- Blastomyces
- Coccidioides
- Histoplasma
- Candida
- Mucor
Tox:
- Shake and bake (fever and chills)
- Hypotension
- Nephrotoxicity (supplement K and Mg due to renal tube changes, hydrate)
- Arrhythmias
- Anemia
- Phlebitis
Nystatin
MOA:
- Binds ergosterol (unique in fungi)–> membrane pores–> leak electrolytes
- TOPICAL (too toxic for systemic use)
Use:
- Oral candidiasis: swish and swallow
- Diaper rash, vaginal candidiasis
Azoles
Fluconazole Ketoconazole Clotrimazole Miconazole Itraconazole Voriconazole
MOA:
- Inhibit p450 enzyme converting lanosterol to ergosterol (fungal sterol)
Use:
- Local, less serious mycoses
- Fluconazole= Candidiasis; chronic suppression of cryptococcus in AIDS
- Itraconazole= blastomyces, coccidioides, histoplasma
- Clotrimazole, miconazole for topical fungal
Tox:
- Testosterone synthesis inhibition
- Liver dysfunction (p450): avoid with Warfarin, Cyclosporine, Tacrolimus, phenytoin, INH, rifampin, oral hypoglycemics
Flucytosine
MOA: cytosine deaminase converts to 5-FU–> inhibit DNA and RNA biosynthesis
Use:
- Systemic fungal infections (Cryptococcus meningitis) + Ampho B
Tox:
- Bone marrow suppression
Capsofungin, Micafungin
MOA: Inhibits Beta-glucan–> blocks cell wall synthesis
Use:
- Invasive aspergillosis
- Candida
Tox:
- GI upset
- flushing
Terbafine
MOA:
- Inhibits fungal enzyme squalene epoxidase
Use:
- Dermatophytosis (onchomycosis)
Tox:
- Visual disturbances, abnormal LFTs
Griseofulvin
MOA:
- Interferes with microtubule function–> disrupts mitosis (keratin tissue)
Use:
- Oral treatment for superficial infections (dermatophytes)
Tox:
- Teratogen, Carcinogen
- Confusion, H/A
- Increased p450, Warfarin metabolism
Pyrimethamine
Toxoplasmosis tx
Suramin, melarsoprol
Trypanosoma brucei tx
Nifurtimox
Trypanosoma cruzi
Sodium stibogluconate
Leishmaniasis treatment
Chloroquine
MOA:
- Blocks detox of heme–> hemozoin–> heme accumulation toxic to plasmodia
Use:
- Plasmodia EXCEPT falciparum (resistant due to membrane pump decreasing conc)
- treat falciparum with artemether/lumifantrine or atovaquone/proguanil
Tox: retinopathy
Helminth tx
Mebendazole Pyrantel pamoate Ivermectin Diethylcarbamazine Praziquantel
ALL immobilize helminths
Praziquantel
Anti-helminthic
Anti-trematode (Schistosoma)
Zanamivir, oseltamivir
MOA:
- Inhibit influenza NA–> decreased release of virus
Use:
- Prevent/treat influenza A, B
Ribavirin
MOA:
- Inhibit IMP dehydrogenase–> prevent synthesis of guanine nucleotides
Use:
- RSV
- Chronic Hep C
Tox:
- Hemolytic anemia
- Severe teratogen
Acyclovir
MOA:
- Viral thymidine kinase monophosphorylates drug–> acyclo GMP
- Host cell forms triphosphate–> acyclo GTP
- Inhibits DNA polymerase via chain termination
Use:
- HSV: lesions, encephalitis, prophylaxis
- VSV
- Weak EBV activity
- NO CMV activity
- *Valacyclovir= better oral bioavailability
- Famciclovir= Herpes zoster
Tox: few
Resistance: mutated viral thymidine kinase
Ganciclovir
MOA:
- Viral kinase–> 5’ monophosphate–> GMP
- Host cell–> triphosphate–> GTP
- Inhibits viral DNA polymerase
Use:
- CMV (esp. immunocompromised)
- Valganciclovir= better oral bioavailability
Tox:
- Leukopenia, neutropenia, thrombocytopenia, renal (more toxic than acyclovir)
Resistance: Mutated viral DNA pol or no viral kinase
Foscarnet
MOA:
- Binds pyrophosphate binding site of viral DNA polymerase–> inhibition (no activation needed)
Use:
- CMV retinitis in immunocompromised
- Ganciclovir failure
- Acyclovir-resistant HSV
Tox: Nephrotoxic
Resistance: DNA polymerase mutation
Cidofovir
MOA:
- Inhibits viral DNA polymerase
- No P-tion by viral kinase
Use:
- CMV retinitis in immunocompromised
- Acyclovir-resistant HSV
- long half-life
Tox:
- Nephrotoxic (use probenecid, IV saline to reduce toxicity)
HIV therapy principles
2 Nucleoside reverse transcriptase inhibitors (NRTIs) PLUS 1 of following:
- non-nucleoside reverse transcriptase inhibitor (NNRTI)
- protease inhibitor
- integrase inhibitor
Protease inhibitors
-navir (“Navir tease a protease”)
MOA:
- HIV-1 protease (pol gene)–> cleaves polypeptide product of HIV mRNA
- PI prevents maturation of new viruses
- Ritonavir= boost other drug concentrations by inhibiting CYP450
Tox:
- Hyperglycemia
- Lipodystrophy
- GI intolerance (N/V/D)
- Nephropathy, hematuria (indinavir)
Nucleoside Reverse Transcriptase Inhibitors (NRTI)
Tenofovir Emtricitabine Abacavir Lamivudine Zidovudine Didanosine Stavudine
MOA:
- Binds to reverse trascriptase–> terminates DNA chain (missing 3’OH group)
- Requires activation= phosphorylation (except tenofovir)
Zidovudine (ZDV) used for general prophylaxis in pregnancy (reduce fetal transmission)
Tox:
- Bone marrow suppression (reverse with G-CSF and Epo)
- Peripheral neurpoathy
- Lactic acidosis (nucleosides)
- Anemia (ZDV)
Tenofovir
Nucleoside Reverse Transcriptase inhibitor (NRTI)
- Nucleotide analog= does NOT require activation
- Binds to reverse trascriptase–> terminates DNA chain (missing 3’OH group)
Tox:
- Bone marrow suppression (reverse with G-CSF and Epo)
- Peripheral neurpoathy
- Lactic acidosis (nucleosides)
Non-nucleoside reverse transcriptase inhibitors (NNRTI)
Nevirapine
Efavirenz
Delavirdine
MOA:
- Bind to reverse transcriptase (different site from NRTI)
- Do not require phosphorylation to be activated
- Do no compete with nucleotides
Tox:
- Bone marrow suppression (reverse with G-CSF and Epo)
- Peripheral neurpoathy
- Rash (non-nucleosides)
Raltegravir
Integrase inhibitor
MOA:
- Inhibits integrase: blocks HIV genome integration into host cell DNA
Tox:
- Hypercholesterolemia
Interferons
MOA:
- Glycoproteins synthesized by virus-infected cells–> block RNA/DNA viral replication
Use:
- IFN alpha= Chronic Hep B, C, Kaposi’s
- IFN beta= MS
- IFN gamma= NADPH oxidase deficiency
Tox:
- Neutropenia
- Myopathy
Enfurvitide
Fusion inhibitor
MOA: binds heptad repeat 1 (HR1) of gp41
- Blocks membrane fusion
Linezolid
50S subunit inhibitor
Tox: mild MAO-I function–> lead to serotonin sickness when dose with SSRIs
Dapsone
Used for topical M. Leprae threatment (tuberculoid and lepromatous)
Toxicity: agranulocytosis (need CBC during administration)
