Antimicrobial Drugs Flashcards
1st line Tuberculosis treatment
**“RIPE” - “4 FOR 2 AND 2 FOR 4”
R**
ifampin
Isoniazide
Pyrazinamide
Ethambutol
Rifampin
- rifampin activated CYP P450
- rifampin bind to bacterial DNA dependent RNA polymerase deactivates it - this is where resistance will develop if used alone.
- Rifampin prophylactic monotherapy in close contacts of H. FLU and N. Meningitides
- Hepatotoxic in RIPE therapy
- Rifampin may produce orange body fluids
Isoniazide
- INH inhibits cytochrome P450
- primary TB (often presents as middle lobe cavity)
- INH can be used alone to treat latent TB infections
- administration of INH and pyridoxine (vitB6) prevents peripheral neuropathy
-INH is activated by catalase-peroxidase (KatG)
(tail makes a G Shape)
- resistance to INH by downregulating KatG
- INH works at the bacterial cell wall inhibiting mycolic acid production
Isoniazide
side effects
- INH promotes excretion of Vit B6 causing peripheral Neuropathy is caused by a Vit B6 deficiency
- INH may cause seizures
- hepatotoxicity associated with all RIPE therapy drugs
- INH causes an asymptomatic rise in aminotransferases
- INH may cause drug induced lupus
- INH may cause anion gap metabolic acidosis
- INH metabolized by the liver enzyme N acetyltransferase – slow acetylators have higher risk of side effects
Ethambutol
- blocks arabinosyl transferase, inhibiting carbohydrate formation at the cell wall
- ethambutol is bacteriostatic
- optic neuritis (red -green blindness)
Pyrazinamide
- moa same as Isoniazide
- pyrazinamide may cause hyperuricemia and needle shaped uric acid crystal formation
Yell ball on toe: pyrazinamide may precipitate gout attacks
- can be hepatotoxic
2nd line treatment
**“C-PEARL” (F)
C**
ycloserine
- *P**as ( para amino salicylic acid)
- *E**thionamide
- *A**mikacin
- *R**ifabutin
- *L**inezolid
Fluoroquinolones
Mycobacterium avium treatment
- a macrolide (azithromycin or clarithromycin) combined with ethambutol for MAC infections
- MAC is a common cause of disseminated disease in AIDS patients
- macrolide prophylaxis for MAC when CD4 <50
-Rifabutin
(may be added as a third agent to combat MAC infections)
- rifampin and rifabutin activate CYP450
Mycobacterium Leprae - LEPROSY
Dapsone
Rifampin
Clofazamine
——————————————————————————-
- agranulocytosis
- hemolytic anemia in G6PD deficiency
- bite cells and Heinz bodies seen in RBC’s
- leonine facies seen in lepromatous leprosy
natural Penicillins
Penicillin G
penicillin V (oral)
(blue)
——————————————————————————–MOA (green)
-Beta Lactam Ring interferes with transpeptidation reaction of bacterial cell wall synthesis
-pBP forms peptidoglycan cross links, penicillin’s will halt peptidoglycan synthesis in the cell walls: bactericidal
Delivery
- penicillin V is acid stable and only used in minor infections due to poor bioavailability (oral)
- administered IV (pen G)
Used to Treat
-against gram (+) organisms (Staph and Strep)
-Oral Penicillin V treats streptococcal pharyngitis
(“Red bandanna”)
- Penicillin G or V treats rheumatic fever
- Strep Viridians endocarditis
-GBS prophylaxis
- Actinomyces Israeli
- Clostridium Perfringens causing gangrene
- pastuerella pen g
- benzathine pen g treats syphilis (spirochete)
- penicillin G - treats Neisseria meningitides
Resistance
Beta Lactamases are immune to penicillin
(“Beta Trooper shooting down a ship”)
-beta lactamases expressed by plasmid genes (“Circular shape”)
Adverse Reactions
Type 1 IgE mediated hypersensitivity reaction
(“Astronaut shutting eyes w/ IgE missiles on ship”)
-drug-induced autoimmune hemolytic anemia
(+ direct coombs test) (“Exploding asteroids w/ IgG”)
-drug induced interstitial nephritis
(“Kidney shaped nebula”)
anti staph penicillin
Nafcillin
Oxacillin
Dicloxacillin
- bulky R-groups prevent beta-lactamase binding
- Narrow spectrum, only activity against staphylococci
- empiric treatment for skin and soft tissue infections (folliculitis, abscesses)
Tricuspid pyramids: treatment for staph endocarditis
Fish bones: treatment for Staph osteomyelitis
broad spectrum penicillins
+beta lactamase inhibitors
- *Amoxicillin**
- amoxicillin – oral bioavailability
amoxicillin and ampicillin to treat strep throat
- amoxicillin treats otitis media and sinusitis caused by strep pneumoniae, Haemophilus influenza, moraxella catarrhalis
- amoxicillin and ampicillin treat pneumonia caused by strep pneumoniae, H. influenza
H Wing ship: activity against Haemiphilus influenza
-amoxicillin is part of the triple therapy (with clarithromycin and a PPI) for helicobacter pylori infection
- amoxicillin treats Lyme Disease caused by Borrelia burgdorferi
- amoxicillin prophylaxis against encapsulated bacteria (s. pneumo, H. Flu) in asplenic patients
- Amoxicillin prophylaxis before dental procedures in patients at high risk for endocarditis
Ampicillin
–IV administration
- ampicillin treats anaerobic infections (enterococcus)
- Gram Positive enterococcus
- ampicillin resistant strains of Enterococcus due to beta-lactamase production
- ampicillin treats meningitis caused by Listeria monocytogenes
- activity against gastrointestinal and urinary tract gram (-) rods
-sensitive to beta-lactamases
(typically used with clavulanate)
Piperacillin/Ticarcillin
- Paired with beta lactamase inhibitors to prevent cleavage of beta lactamases
- piperacillin and ticarcillin treat anaerobic infections,
- active against pseudomonas
**Beta lactamase inhibitors
Sulbactam
Tazobactam
Calvulanate**
1st generation cephalosporins
(“LEX”)
Cephalexin
- *Cefazolin
- ——————————————————————————-**
- activity against gram( +)organisms (staph and strep)
- treats cellulitis, abscesses caused by staph and strep
- treats S. pyogenes
- activity against gram (-) UTI bugs (Proteus, E Coli, Klebsiella) 1st gen
- cefezolin for surgical prophylaxis
2nd generation cephalosporins
**Cefoxitin
Cefuroxime
Cefotetan
——————————————————————————–**
-same coverage as 1st gen with extended gram (-) coverage (2nd Gen)
-activity against H. flu, Neisseria, Serratia (HENS)
3rd generation cephalosporins
Ceftriaxone
Cefotaxime
Ceftazidime
——————————————————————————-
-extended gram negative coverage beyond 2nd gen
- ceftriaxone and cefotaxime empiric treatment for meningitis
- activity against H Flu
- treats community and hospital acquired pneumonia
- ceftazidime treats pseudomonas infections
- ceftriaxone treats endocarditis caused by Strep Viridians and HACEK organisms
- activity against gram (-) G.I. bugs
- single dose of IM ceftriaxone is first line txt for gonorrhea
- ceftriaxone treats Lyme disease caused by Borrelia burgorferi
4th generation cephalosporins
(“prime”)
- *Cefepime
- ——————————————————————————-** -broad spectrum
- *- Pseudomonas** coverage
- *-G+ / G- broad spectrum
- cefepime treatsbacterial meningitis**
5th generation cephalosporins
Ceftaroline
-broad spectrum
- Beta-lactamases ineffective against cephalos
cephalo’s have same adverse effects as penicillin
nephritis
hemolytic anemia
hypersensitivity reaction
cross reactivity with penicillin allergies
cephalosporin’s Resistance is gained by altered PBP’s and extended spectrum beta lactamases
Monobactam
(“AZ-3M”)
- *Aztreonam**
- has activity against aerobic gram negative rods
-monobactams and carbapenems treat Pseudomonas infections
-monobactam treats serious systemic infection with gram negative pathogens
(meningitis, pneumonia, sepsis)
- monobactams can be used in patients with a H/O penicillin allergy
- monobactams are resistant to beta-lactamases, ring shape on gun to remind us that beta lactamases are encoded by plasmid genes. they cleave beta lactams
Carbapenems
(“hover car”)
Doripenem
Imipenem
Meropenem
Ertapenem
monobactams and Carbapenems treat pseudomonas infections
-broad spectrum carbapenems
-carbapenems treat anaerobic infections
(aspiration pneumonia, intra-abdominal infections)
“when others fail we get the job done”:
use of carbapenems with bugs resistant to other available treatments
-monobactam treats serious systemic infection with gram negative pathogens
(meningitis, pneumonia, sepsis)
- imipenem inactivated by dehydropeptidase in renal tubules
- cilastin inhibits dehydropeptidase in the renal tubules preventing degradation of imipenem
-GI side effects of carbapenems
- carbapenem may cause skin rash
- imipenem lowers the seizure threshold
- monobactams are resistant to extended spectrum beta-lactamases
B-Lactamase inhibitors
Tazobactam
Sulbactam
Calvulanic acid
Chloramphenicol
- binds reversibly to 50s ribosome, inhibiting peptide bond formation and halting translation
- bacteriostatic
- empiric treatment for meningitis in developing countries (S. Pneumo, H Flu, N Meningitidis)
- alternative agent in serious rickettsial infections (rocky mountain spotted fever) useful in pregnant women
- anemia due to dose related reversible suppression of RBC production
- aplastic anemia
-accumulation of the drug in newborns-grey baby syndrome
(due to ineffective glucuronic acid conjugation system)
-causes flaccidity, hypothermia, shock (floatation device looks like a liver)
Antifolate drugs
Sulfamethoxazole (SMX)
Trimethoprim (TMP)
- Bactrim = SMX/TMP
PABA → Dihydrofolate →tetrahydrofolate → purines → DNA
-SMX is a PABA analog that blocks dihydropterate synthetase
- TMP /Pyrimethamine blocks **dihydrofolate reductase
- ——————————————————————————--1st linetreatment forUTI**
- Treats acute prostatitis
- activity against gram (-) GI and urinary tract bacteria
- activity against MRSA
activity against nocardia
activity against gram positives
-treats pneumocystis jirovecii pneumonia (PJP)
- PJP prophylaxis for cd4<200
- toxoplasmosis prophylaxis with TMP/SMX for CD4 <100
-Pyramethamine/sulfadizine treat toxoplasmosis caused by toxoplasma gondii
Antifolate drugs
side effects
- pancytopenia
- megaloblastic fireworks
- teratogen in the 1st trimester anti-folate effects cause neural tube defects
- sulfa allergy – fever, urticarial, rash
- Hemolytic anemia in G6PD deficiency
- Bite cells and Heinz bodies seen in RBC’s
- stevens-johnson syndrome
type IV renal tubular acidosis →hyperkalemia
-interstitial nephritis
-photosensitivity
-kernicterus in the neonate
(sulfonamides when used in the lath month of pregnancy displace bilirubin in the neonate)
- sulfonamides displace warfarin from albumin causing over anticoagulation and bleeding
- inhibition of cytochrome 450
- causes drug induced lupus
Polymyxins
bind LPS in the outer membrane of Gram-negative and disrupt both the outer and inner membranes.
causing membrane damage, suggesting a detergent-like mode of action. bactericidal
Polymyxin B- IV, otic, ophthalmic, topical
- G (-)
- *Pseudomonas **
Polymyxin E (colistin) -IV, aerosol
- Pseudomonas (Cystic fibrosis) → given aerosol
- do not enter CNS
- Neuro/nephro toxicity
Tetracyclines
**Tetracycline
Oxytetracycline
Doxycycline
Minocycline
——————————————————————————–**
- bind irreversibly to 30s ribosomal subunit
- broad spectrum
- activity against MRSA
-activity against tick borne bacteria
(Rickettsia, Erlichia, Francisella, Borrelia)
- activity against Brucella
- treats culture negative endocarditis caused by coxiella
- activity against yersenia
- treats chlamydial cervicitis and urethritis
- treats chlamydial pelvic inflammatory disease
- treats chlamydial bronchitis and atypical pneumonia
- treats atypical “walking” pneumonia by Mycoplasma
- treat acne
- Causes tooth discoloration in young children
- deposits in fetal teeth and **bone
- ——————————————————————————-**
- multivalent cations (calcium, iron, magnesium) decrease absorption
- GI side effects (nausea, vomiting, diarrhea)
- Photosensitivity
- Fanconi syndrome (type 2 RTA) associated with use of expired tetracycline’s
- resistance via efflux pumps, and alteration of ribosome
- eliminated fecally, safe in renal failure patients
Fluoroquinolones
- *Nor** floxacin
- *Cipro** floaxcin
- *Levo** floxacin
- *Moxi** floxacin
- mainly indicated for gram negatives
- Unwinding braid: inhibit bacterial DNA gyrase (Topoisomerase)
- treat gram negative UTI’s (E. coli and proteus)
- elevating (levo) and sipping (cipro) from Bladder cup: Complicated UTI’s, levofloxacin and ciprofloxacin treat UTI caused by Pseudomonas
- empiric treatment for pyelonephritis
- treat acute prostatitis
- treat gram negative causes of gastroenteritis (shigella, E. Cola, Salmonella)
- treat salmonella gastroenteritis
- treat anthrax caused by B. Anthracis
- treat gram negative salmonella osteomyelitis
- respiratory quinolones treat community acquired pneumonia (s. Pneumonia)
- respiratory quinolones treat atypical “walking “ pneumonia caused by mycoplasma pneumonia (levofloxacin and moxifloxacin)
- respiratory quinolones treat atypical pneumonia caused by Legionella
- *-not recommended for children under 10 years of age
- ——————————————————————————**
-sickle cell patients are at increased risk of Salmonella osteomyelitis
-divalent and trivalent cations
(calcium, iron, magnesium, decrease absorption
- risk of prolonged QT interval
- GI Side effects N/V
- risk of tendon and cartilage damage in the elderly
- risk of tendon rupture in steroid users
- teratogenic – damage to growing cartilage
Aminoglycosides
Neomycin
Paromycin
Streptomycin
Gentamicin
Tobramycin
Amikacin
——————————————————————————–
-binding to the 30s ribosomal subunit
-activity against aerobic gram negatives, actively transported cell membrane
-coupled with cell wall active drugs
(beta-lactams, vancomycin) to allow entry into the cell
-transported into bacteria via an oxygen dependent process (aerobic bacteria)
- *-ivy administration**
-Neomycin remains active in the GI tract until secreted with feces
- neomycin used in bowel prep before colorectal surgery
- Paromycin, luminal agent active against parasital infections
- ——————————————————————————–streptomycin treats tularemia caused by Francisella tularensis
- streptomycin treats the plague caused by Yersinia pestis
- gentamycin treats resistant gram negative infections (Enterobacter, serratia, Klebsiella)
-systemic gram negative infections
(septicemia, nosocomial RTI, complicated UTI, intra-abdominal infection)
- activity against pseudomonas (aerobic gram negative)
- tobramycin -activity similar to gentamycin
- activity against enterococcus when coupled with a cell wall active agent (penicillin, vancomycin)
-inactivated by an acetylation enzyme
(E. faecium against tobramycin)
- Amikacin Activity against E. faecium w/ acetylation enzymes
-Activity against pseudomonas
(gentamycin, tobramycin, amikacin)
———————————————————————————
-myasthenia gravis is an absolute contraindication to aminoglycoside use, due to post NMJ Blockade
-Teratogenic – deafness in newborn
ototoxicity (vestibular or cochlear damage)
- nephrotoxicity (due to acute tubular necrosis)
- acute tubular necrosis (brown casts)
Peaks and troughs in undulating terrain: monitoring of serum drug levels
Macrolides
“FACES”
Fidaxomycin
Azithromycin
Clarithromycin
Erythromycin
Spiramycin
———————————————————————————acts on bacterial 50s ribosomal subunit, Irreversible inhibition of translocation
- bacteriostatic
- treats Bordetella pertussis
- prophylaxis for Bordetella pertussis for family members
- Azithromycin treats atypical pneumonia caused by M. Pneumoniae
- treats walking pneumonia caused by legionella
- Azithromycin treats atypical chlamydia pneumoniae, and urethritis and cervicitis caused by Chlamydia
- Azithromycin treats infections with Bartonella
- Azithromycin and clarithromycin have activity against mycobacterium avium
- Azithromycin prophylaxis for patients **CD4<50
- ——————————————————————————--oral Erythromycin treatsneonatal conjunctivitiscan pneumonia caused bychlamydia trachomatis**
- Erythromycin drops treat neonatal conjunctivitis caused by N. Gonorrhea
- Erythromycin treats **diphtheria
- ——————————————————————————-**
- Azithromycin and clarithromycin treat community acquired pneumonia caused by Strep pneumoniae
-Clindamycin + atovaquone treats babesiosis
- *-**Clarithromycin, amoxicillin, and PPI are triple therapy for **H. Pylori
- ——————————————————————————-**
- increased GI motility
- Acute cholestatic jaundice
- prolonged QT interval
- CYP450 inhibit
Clindamycin
bacterial 50s ribosomal subunit, inhibiting translocation
Bacteristatic
- Activity against staph and strep
- treats S.Pyogenes (GAS) and soft tissue infections (cellulitis)
Activity against MRSA
-Anaerobe activity
Lung stains with holes: excellent penetration into abscesses
treats oral infections and aspiration pneumonia caused by Bacteroides fragilis
activity against clostridium perfringens
topical clindamycin treats moderate to severe inflammatory acne
Uterus Machine: clindamycin plus gentamicin (gently cleaning the uterus) treats polymicrobial female genital tract infection.
Judo practitioner with Sai: gentamicin paired with clindamycin for broad coverage
-treats bacterial vaginosis from gardenella vaginallis
causes pseudomembranous colitis caused by C.Diff
Oxazolidinones
Linezolid
- binds reversibly to 50s ribosome, inhibiting peptide bond formation and halting translation
- activity against gram positive bacteria (staph, strep, enterococcus)
- MRSA activity
- treats nosocomial MRSA infections (hospital acquired pneumonia)
- activity against vancomycin resistant bacterial strains
- activity against **vancomycin enterococcus
- ———————————————————————————**
Broken plates: thrombocytopenia
Cut security camera wire: optic neuropathy ( and peripheral neuropathy)
-stocking-glove peripheral neuropathy
Happy face: serotonin syndrome
(weak inhibitor of MAOI, so can cause serotonin syndrome)
Glycopeptides
Vancomycin
-inhibition of cell wall synthesis by directly binding
D-ALA-D-ALA oligopeptides
- activity against gram (+) bacteria
- activity against methicillin resistant Staph aureus (MRSA)
- CNS penetration – activity against penicillin-resistant strep pneumo /meningitis
- Bone penetration–treats MRSA osteomyelitis
- activity against nosocomial MRSA infections (hospital acquired pneumonia, lung stains on her uniform)
- activity against S. epidermidis
- empiric treatment of endocarditis
- activity against Enterococcus
- oral vancomycin treats Clostridium difficile colitis
- IV administration
- altered PBP’s ineffective against vancomycin
- beta-lactamases ineffective against vancomycin
- altered peptidoglycan structure (D-ALA-D-LAC) confers resistance to vancomycin
——————————————————————————-
Vancomycin
Side effects
- red man syndrome due to histamine release
- thrombophlebitis at injection site
- ototoxicity
- nephrotoxicity
- Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome
Fusidans
Protein synthesis inhibitor
-Gram (+) (staphylococci!!)
- not into the CNS
- Serious staphylococci infection
- *-MRSA-endocarditis
- Corynebacterium endocarditis**
Lipopeptides
Daptomycin
-activity against gram positive cell wall
(staph, strep, enterococcus)
Taser: inserts lipid tail into membrane to depolarize cell
- Activity against vancomycin resistant bacterial strains
- activity against enterococcus
- activity against methicillin resistant S. Aureus (MRSA)
“its in our blood”: treats MRSA bacteremia
Tricuspid peaks: treats Staph endocarditis
——————————————————————————–-ineffective for pneumonia
- myopathy and rarely rhabdomyolysis
- monitor creatine phosphokinase (CPK) levels
Mupirocin
Protein synthesis inhibitor - Inhibits isoleucyl tRNA synthesis
-Gram (+)positive bacteria (resistant staphylococci)
-Topical
-Dermatology (impetigo)
Metronidazole
-free radical metabolites disrupt bacterial DNA
(form free radicals) Bactericidal
- Coverage of polymicrobial anaerobic infections (intra-abdominal infections)
- activity against Entamoeba histolytica (liver abcess)
- activity against giardia
- treats vaginitis and cervicitis caused by protozoal infection(treat both patient and partner)
- treats bacterial vaginosis caused by gardenella
- substitute for amoxicillin in the triple therapy for helicobacter pylori infection in penicillin allergic patients
- activity against anaerobic bacteria
(bacteroides, prevotta, fusobacterium, clostridium) - treats pseudomembranous colitis caused by clostridium
- Clindamycin above the diaphragm, metronidazole below
Aciclovir MOA
guanosine nucleoside analog
(“Purine shaped luggage”)
-converted to acyclovir monophosphate via virus encoded thymidine kinase
(“Hermes with “P” luggage tag”)
→ converted to acyclovir triphosphate by cellular kinases
(“Bag checkers with P tags”)
→acyclovir triphosphate incorporates into replicating DNA, halting synthesis
(“Baggage jam”)
Cidofovir/Foscarnet
MOA
directly inhibit viral DNA polymerase
(“Conveyer belt stop switch”)
Cidofovir/Foscarnet are active against …
they don’t require phosphorylation by the viral kinase
- active against aciclovir/ganciclovir VZV resistant HSV, CMV,
(“Luggage car net”) - This may be important with immunocompromised patients
(““P”access badge”)
what is the major benefit of Valciclovir over Aciclovir ?
valcyclovir has improved oral bioavailability
- suppressive therapy for yearly multiple episodes of recurrence
(“Daily rate for frequent flyers”)
(“Open mouth”)
What is the treatment for serious HSV and VZV infections?
IV acyclovir treats HSV encephalitis
(“Red winged helmet”)
(“ivy”)
IV acyclovir treats neonatal infection
(“Baby Hermes helmet”)
(“ivy”)
preferred treatment for varicella zoster virus and shingles ?
Famciclovir and Valaciclovir are preferred over acyclovir due to superior activity and less frequent dosing for VZV
(“Family value”)
(“Zues”)
IV Aciclovir is used as a prophylactic treatment of HSV in which cases ?
in immunocompromised states
(“Cane”)
important in pregnant women with active recurrent genital herpes
(“Pregnant”)
IV aciclovir Side effects
can cause interstitial nephritis crystalline nephropathy
(“Kidney sharps”)
-delirium, confusion, vertigo, hallucinations
Ganciclovir MOA
Is a guanosine analog,
(“G purines in the background”)
→converted to ganciclovir monophosphate by a virus encoded kinase (UL97)
(“Market worker with P label gun”)
→converted to ganciclovir triphosphate by cellular kinase
(“Customers with p label guns”)
→Ganciclovir triphosphate incorporates into replicating viral DNA, halting synthesis
(“Grocery jam”)
Valganciclovir benfit over Ganciclovir …
has better oral bioavailability
(“Open mouth”)
Valganciclovir /Ganciclovir are indicated when
in high-risk solid organ and bone transplant recipients
(“Organs on ice”)
Valganciclovir /Ganciclovir side effect
are associated with bone marrow suppression
(“Eaten marrow”)
-
myelosuppression may be additive in patients receiving zidovudine
(“Princess Izoide”)
Foscarnet Side Effects
may induce renal insufficiency
(“Spilled kidney beans”)
may cause hypocalcemia
(“Broken milk bottle”)
may cause hypomagnesium
(“Falling magnets”)
may cause hypokalemia
(“Banana peel”)
may cause siezures
(“Shaking”)
Cidofovir Side Effects
nephrotoxicity, leading to proteinuria, azotemia, and metabolic acidosis
- probenecid blocks the tubular secretion of cidofovir, limiting its toxic effects
(“Probation officer cid stoping the kidneys from falling and preventing the drug punk from getting alcohol”)
(“Broken kidney”)
