Pharm Exam 2 Overview Flashcards
What are the four factors that are unique to chemotherapy
- Selective toxicity
- Selects for resistant strains
- Hypersensitivity and toxicity are potential problems
- Lowers the microorganism load so that the hosts defense mechanism can rid the body of foreign organisms
What type of resistance transmission uses a bacteriophage?
Transduction
What type of resistance transmission uses genetic information from the environment?
Transformation
What type of resistance transmission uses direct contact through a sex pilus?
Conjugation
What is the mechanism of action of all bactericidal agents?
Inhibit cell wall/DNA synthesis
What is the mechanism of action of most bacteriostatic agents?
Inhibit protein synthesis
What is the clinical importance of post antibiotic effect?
Less frequent doses and therefore less potential for side effects
What are the 2 most used natural penicillins?
Penicillin G (IV) Penicillin V (oral)
Natural Penicillins
What is the spectrum of coverage?
What are they DOC for?
G+++
G+ infections
Strep pneumonia
Meningitis
What are the penicillin resistant penicillins?
Nafcillin (IV)
Dicloxacin (oral)
Oxacillin (oral)
Penicillin Resistant Penicillins
What is the spectrum of coverage?
What are they DOC for?
G++/G- (resistant to penicillinase)
MSSA
What are the extended spectrum penicillins?
Ampicillin (oral)
Amoxicillin (oral)
Extended Spectrum Penicillins
What is the spectrum of coverage?
What are they DOC for?
G+/G—
Listeria
H. pylori (or Metronidazole)
Amoxocillin: EARLY stage Borrelia burgdorferi (or doxycycline)
What is a possible side effect of the Extended Spectrum Penicillins? Does it preclude future use?
Ampicillin rash, NOT a hypersensitivity rash and does not preclude future use
What are the antipseudomonal penicillins?
Pipercillin (IV)
Ticarcillin (IV)
Antipseudomonal Penicillins
What is the spectrum of coverage?
What are they DOC for?
G+/G—
P. aeruginosa (in combo with an aminoglycoside), Acinetobacter
Which agents can be combined with b-lactamase inhibitors to extend their spectrum?
Ampicillin, Amoxicillin, Pipercillin, and Ticarcillin
What are the b-lactamase inhibitors that Ampicillin, Amoxicillin, Pipercillin, and Ticarcillin can be combined with to extend their spectrum?
Clavulanic acid, Sulbactam, and Tazobactam
What is the main adverse reaction for all penicillins?
Hypersensitivity
Are penicillins bactericidal or bacteriostatic? What is their MOA?
Bactericidal
B-lactam ring binds to the active site of penicillin binding proteins (PBPs) preventing transpeptidation reaction. Bacteria produces remodeling enzymes called autolysins, which allows their synthesis to proceed without cell-wall repair; eventually leading to lysis
MUST HAVE ACTIVELY GROWING CELLS
Are cephalosporins bactericidal or bacteriostatic? What is their MOA?
Bactericidal
B-Lactam (same as penicillin)
What is an advantage that cephalosporins have over penicillins?
Increased resistance to b-lactamase
What are the 1st generation cephalosporins?
Cafazolin (IV)
Cephalexin (oral)
1st Generation Cephalosporins
What is the spectrum of coverage?
What are they DOC for?
G++/G- (narrow spectrum)
Cafazolin- surgical prophylaxis
Proteus, E. coli, Klebsiella
*PEK
What is the most common 2nd generation cephalosporin?
Cefaclor (oral)
2nd Generation Cephalosporins
What is the spectrum of coverage?
What are they DOC for?
G+/G– (intermediate spectrum)
Proteus, E. coli, Klebsiella (PEK)
Moraxella
What are the 3rd generation cephalosporins?
Ceftriaxone (IV, IM)
Ceftotaximine sodium (IV, IM)
Cefazidime (IV, IM)
Cefixime (oral)
3nd Generation Cephalosporins
What is the spectrum of coverage?
What are they DOC for?
G+/G— (broad spectrum)
Ceftriaxione- CNS penetration, N. gonorrhoeae, LATE stage Borrelia burgdorferi, Salmonella
Ceftotaxime- CNS penetration
Cefazidime- Antipseudomonal with aminoglycosides (IF penicillin allergy)
Moraxella
What are the contraindications of 3rd generation cephalosporins?
Neonates, bilirubin displacement, pseudolithiasis
What is the 4th generation cephalosporin?
Cefepime (IV)
4th Generation Cephalosporin
What is the spectrum of coverage?
What are the DOC for?
G+/G— (Broad spectrum- MOST normal flora changes)
Antipseudomonal
Only used for serious infections
Empirical therapy when B-lactamases are anticipated
What is the 5th generation cephalosporin?
Ceftaroline fosamil (IV)
5th Generation Cephalosporin
What is the spectrum of coverage?
What are the DOC for?
Binds to mutated PBP that other b-lactams cannot bind to; MRSA and VRSA
What are the main adverse reactions for all cephhalosporins (3)?
- Dilsulfiram-like reaction with alcohol consumption (Metronidazole)
- Allergy: 10% cross sensitivity with penicillins
- Does-dependent renal tubular necrosis; do not give to patients with decreased kidney function
What are the four groups of B-lactam agents?
- Penicillins
- Cefalosporins
- Monobactams
- Carbapenems
What class is aztreonam in?
Monobactam
What is the coverage of aztreonam?
ONLY Aerobic G-, including pseudomonas
What is important about the cross sensitivity of aztreonam?
No cross sensitivity with other b-lactam agents (good option for pts with penicillin allergy)
What type of agents are Imipenem + Cilastin and Meropenem?
Carbapenems
What is the coverage of Imipenem + Cilastin and Meropenem?
Anaerobes, G+, G- (broad spectrum)
What are carbapenems DOC for?
Enterobacter
What are contraindications/ possible adverse reactions of carbapenems?
Seizures: do not give to pts with head trauma (meropenem less likely)
Do not give Imipenem to pts with decreased kidney function
Why is imipenem always given with cilastin?
Imipenem is inactivated by renal dihydropepdidases and must be given with cilastatin, a dihydropeptidase inhibitor.
How are monobactams and carbapenems given?
IV
What is MOA of vancomycin?
Binds to D-ala-D-ala (NOT PBPs); cell wall inhibitor= CIDAL
What is the coverage of vancomycin?
ONLY G+
What is IV vancomycin DOC for?
What is oral vancomycin DOC for?
IV: MRSA
Oral: C. diff
Drug of last resort for everything else because of vancomycin resistant enterocooi
What are the main adverse reactions of vancomycin?
Ototoxicity
Nephrotoxicity
Redman syndrome
What is the MOA for Fosfomycin? What is the coverage?
Prevents NAG to NAM reduction; cell wall inhibitor=CIDAL
G+, G-
What is the MOA for Bacitracin?
Interferes with dephosphorylation; prevents NAG-NAM transport; cell wall inhibitor=CIDAL
What is the coverage of Bactracin?
G+
What is Bactracin DOC for?
Combined with polymyxin and neomycin to treat superficial skin infections
What classes of protein synthesis inhibitors bind to the 50S subunit?
Macrolides Ketolides Clindamycin Streptogramins Oxazolidinones Chloramphenicol "50 Men Kiss Cute Strippers On Couches"
How do protein synthesis inhibitor resistant microbes form?
Efflux pumps
Methylation of ribosome binding site
What abx are in the macrolide class?
Erythromycin
Clarithromycin
Azithromycin
What are the macrolides DOC for?
Mycoplasma pneumoniae, Chlamydia
What are the most common adverse reactions of macrolides?
Diarrhea
QT prolongation
Drug interactions
Which macrolide does not inhibit CYP3A4? What advantage does this provide?
Azithromycin
Least drug interactions
Which macrolide has the most GI effects?
Which macrolide has the least GI effects?
Most = Erythromycin Least = Clarithromycin
What abx is in the ketolide class?
Telithromycin (oral)
How do ketolides differ from macrolides?
Ketolides bind to two sites on ribosomal RNA
macrolides are used before ketolides because ketolides can cause hepatoxicity
What is clindamycin the DOC for?
Clostridia, streptococcus, staphylococcus, toxic shock syndrome, and osteomyelitis
“Catherine clearly should stop taking opiods”
What is the main adverse reactions of clindamycin?
Pseudomembranous colitis
What should you do if a patient on clindamycin begins to have C. diff symptoms?
Immediately stop clindamycin and initiate oral vancomycin
Which 50S protein synthesis class is synergistically CIDAL?
Streptogramins (Dalfopristin and Quinupristin)
If Dalfopristin and Quinupristin both target the 50S ribosome, why can be administered together?
They work at different times; Dalfopristin binds first and increases the affinity for Quinupristin
What infections are Streptogramins (Dalfopristin and Quinupristin) approved for?
VRE
MSSA
MRSA
What is the most common adverse reaction to Streptogramins (Dalfopristin and Quinupristin)?
Inhibit P450s metabolizing system (CYP3A4) = metabolic interactions (warfarin, diazapam)
What are contraindications to Streptogramins (Dalfopristin and Quinupristin)?
Breast feeding
Children
Hepatic disease
Pregnancy
What abx is in the Oxazolidinones class?
Linezolid
What infections are Oxazolidinones (Linezolid) approved for?
VRE
MRSA
What class of protein synthesis inhibitor works as a reversible, nonselective MAO inhibitor?
Oxazolidinones (Linezolid)
What drug/food interactions should you consider with oxazolidinones (Linezolid)?
MAO inhibitors
Tricyclic antidepressants
SSRIs
Tyramine rich foods (cheese, pork, smoked/picked foods)
What classes of protein synthesis inhibitors bind to the 30S subunit?
Aminoglycosides
Tetracyclines
Glycylcyclines
Which 50S protein synthesis inhibitor class is CIDAL?
Aminoglycosides
What is the MOA for the Aminoglycosides?
Irreversible
Require O2 for active transport into the cell
What abx are in the Aminoglycoside class?
Streptomycin (IV) Gentamicin (IV) Tobramycin (IV) Amikacin (IV) Neomycin (oral)
What is the spectrum of coverage for the Aminoglycosides?
Aerobic G-
What is streptomycin DOC for?
Tularemia
Bubonic Plague
Tuberculosis
Endocarditis
What are Gentamicin, Tobramycin, and Amikacin DOC for?
P. aeruginosa (in combo with Antipseudomonal Pen)
What is neomycin DOC for?
Entercoccus (in combo with pen)
Which Aminoglycosides are DOC for topical wounds and burns?
Neomycin and Gentamicin
How does Aminoglycoside resistance occur?
- Deficiency of ribosomal receptors
- Lack of permeability
- Enzymatic modification
What are possible adverse effects of Aminoglycosides?
Ototoxicity
Nephrotoxicity
(Time and concentration dependent)
How should Aminoglycosides be prescribed and why?
Single large dose! Aminoglycosides have a post abx effect so they work better with a megadose and it reduces toxic side effects
What are the broad spectrum antibiotics?
Chloramphenicol
Tetracyclines
Glycylcyclines
Which abx has the best CNS penetration?
Chloramphenicol
What is Chloramphenicol approved for treatment of?
Typhoid fever Meningitis Rickettsia Brucellosis Bacterial conjunctivitis
What are possible adverse effects of Chloramphenicol?
Fetal aplastic anemia
Gray baby syndrome
Bone marrow supression
How does Chloramphenicol resistance occur?
Microbe produces acetyl transferase
What abx are in the Tetracycline class?
Tetracycline (oral)
Doxycycline (oral)
Minocycline (oral)
What are the Tetracyclines DOC for?
Cholera Mycoplasma pneumonia (or erythro) Chlamydia (or azithro) Rickettsia EARLY stage Borrelia burgdorferi (or amoxicillin) Vibrio species
What are possible adverse effects of Tetracyclines?
Chelation with Ca, Fe, Al (no milk or multivitamin)
Deposit in bone and teeth
Normal flora changes
Photosensitivity
What are contraindications of Tetracyclines?
Pregnancy
< 8 years old
What abx is in the Glycylcycline class?
Tigecycline (IV)
What is an advantage of the Glycylcyclines over the Tetracyclines?
Glycylcyclines have activity against Tetracycline resistant organisms
What is Tigecycline approved for treatment of?
MRSA
MRSE
PRSP
VRE
How does resistance to Tetracycline occur? How does this effect Doxycycline and Minocycline?
Efflux pumps
No cross resistance with doxycycline or minocycline
What abx are in the Fluoroquinolone class?
Ciprofloxacin (oral) Ofloxacin (oral) Levofloxacin (oral) Moxifloxacin (oral) Gemifloxacin (oral) Gatifloxacin (solution)
What is the coverage of the Fluoroquinolone class?
Aerobic G-, Good G+
What Fluoroquinolone abx also has coverage against pseudomonas?
Ciprofloxacin (oral)
What Fluoroquinolone abx also have coverage against anaerobes?
Moxifloxacin (oral)
Gemifloxacin (oral)
What is the MOA for the Fluoroquinolone class?
Inhibit DNA synthesis via inhibition of DNA gyrase
How does resistance to the Fluoroquinolone class occur?
DNA gyrase mutation
Reduced membrane permeability
Is the Fluoroquinolone class CIDAL or STATIC?
CIDAL
What is Ciprofloxacin (oral) DOC for?
Anthrax
2nd DOC for UTI
What is Ofloxacin (oral) DOC for?
Prostatis
What is Levofloxacin (oral) DOC for?
Community acquired pneumonia
What are possible adverse effects of the Fluoroquinolone class?
QT prolongation
Tendon rupture
Photosensitivity
What are contraindications of the Fluoroquinolone class?
Pregnancy
Breast feeding
Children <18
What is the MOA for Metronidazole?
Inhibit DNA synthesis
What is the coverage of the Metronidazole class?
Anaerobe G+, G-
What is Metronidazole DOC for?
H. pylori (extended spec pen)
2nd DOC for C. diff (oral vancomycin)
What are possible adverse reactions to Metronidazole?
Disulfiram-like reaction (cephalosporins)
Disgeusia
What are the UTI specific drugs?
Nitrofurantoin (oral)
Methenamine (oral)
What is the MOA of Nitrofurantoin (oral)?
Damages bacteria DNA
What is the MOA of Methenamine (oral)?
Decomposes formaldehyde and ammonia
What is unique about resistance to Methenamine (oral)??
Bacterial resistance to formaldehyde does not develop
What is the coverage of the UTI specific drugs, Nitrofurantoin and Methenamine?
G+, G-
The UTI specific drugs, Nitrofurantoin and Methenamine, are ___ dependent and are only therapeutic in the ____.
Concentration
Urine
What are possible adverse reactions to Nitrofurantoin?
Colors urine brown
Hemolytic anemia (G6PD deficiency)
Pulmonary fibrosis
What are contraindications to Nitrofurantoin?
Decreased kidney function
Pregnancy
Neonates
What are contraindication to Methenamine?
Decreased kidney function
Decreased liver function
What is the coverage of Streptogramins?
ONLY G+ aerobic
What is the coverage of Oxazolidinones?
ONLY G+ aerobic
What classes work on anaerobes?
Without: Anaerobes a CAR: Carbapenems (c)LINDA: Clindamycin PENS: Penicillin her GEMini: Gemifloxacin sign on the MOving: Moxifloxacin METRO: Metronidazole Door: Daptomycin
What is the MOA of the Sulfonamide class?
Compete with PABA to inhibit Folic Acid Synthesis
Are Sulfonamides STATIC or CIDAL?
STATIC
***Except Sulfamethoxazole + Trimethoprim (Bactrim) are CIDAL in the urine
How does resistance to the Sulfonamide class occur?
- Increased PABA production
- Efflux pumps
- Alternative pathway for synthesis of folic acid
What is the coverage of the Sulfonamide class?
G+, G-
What is Sulfamethoxazole + Trimethoprim (Bactrim) DOC for?
First attack UTI
What are secondary options for UTI treatment?
Ciprofloxacin
Nitrofurantoin
Methenamine
Fosfomycin
What are the Sulfonamides in gereneral DOC for?
Moraxella PEK Samonella Vibro species Burkholderia Nocardia
What are possible treatment options of CAP
Penicillin Levofloxacin Macrolides Tetracyclines Ketolides
What are possible adverse effects of the Sulfonamide class?
Aplastic anemia (G6PD deficiency) Photosensitivity Hypersensitivity Drug sensitivity SJS Kernicterus
What are contraindication to the Sulfonamide class?
Pregnancy
Breast feeding
Jaundiced infants
<2 months
Which classes cause anemias (3)?
Sulfonamide and Chloramphenicol= Aplastic anemia
Nitrofurantoin= Hemolytic anemia
Which classes cause ototoxicity and nephrotoxicity (2)?
Aminoglycosides and Vancomycin
Which classes cause hypersensitivty (2)?
Penicillins and Sulfonamides
Which classes are contraindicated in decreased kidney function (5)?
Imipenem Vancomycin Aminoglycosides Nitrofurantoin Methenamine Cephalosporins
Which classes cause photosensitivity (3)?
Tetracyclines
Fluoroquinolones
Sulfonamides
Which classes are contraindicated in pregnancy (5)?
Tetracyclines Nitrofurantoin Fluoroquinolones Streptogramins Sulfonamides
Which classes are contraindicated in children (3)?
Streptogramins (children)
Tetracyclines (<8 yrs)
Fluoroquinolones (<18 yrs)
Which classes cause QT prolongation (2)?
Macrolides and Fluoroquinolones
What is the MAO for Daptomycin (IV)?
Bind to membrane causing rapid depolarization; CIDAL
What is the coverage of Daptomycin (IV)?
G+ aerobic and anaerobic
What is Daptomycin (IV) used for?
Empiric therapy for serious G+ infections (alternative to vancomycin)
What is the MAO for Mupirocin (topical)?
Binds to Isoleucyl-tRNA synthetase to inhibit protein and RNA synthesis
What is the coverage of Mupirocin (topical)?
G+, G-
What is Mupirocin (topical) used for?
Impetigo
Intranasal for MRSA
What is the MOA for Polymyxin B/E?
Bind to cell membrane phospholipid (lipid A endotoxin)
What is the coverage of Polymyxin B/E (topical)?
G-
What can be used to treat VRE?
Streptogramins (Dalfopristin + Quinupristin)
Oxazolidinones (Linezolid)
Glycylcylines (Tigecycline)
Which classes are contraindicated in infants (4)?
3rd Gen Cefalosporins (neonates- bilirubin displacement)
Nitrofurantoin (<1 month)
Sulfonamides (<2 months)
Chloramphenicol (grey baby syndrome)
If a patient doesn’t want a ceftriaxone injection for N. gonorrhoeae, what can you give them?
Cefixime (oral)
What classes absorption can be effected by Ca, Fe, Al, or Mg?
Tetracyclines and Fluoroquinolones