Combined_Exam 1 (Study Guides) Final

What are the first gen cephalosporins?

-Cefazolin

-cephalexin

-cefadroxil

What are the first gen cephalosporins used for?

Surgical prophylaxis

What are the gen 2 cephalosporins?

-Cefuroxime

-Cefotetan

Cefuroxime (does/does not) cross the BBB, which means it (can/cannot) treat meningitis due to H. influenza

Does, can

What are the most notable AEs with cefotetan?

-Disulfiram like reaction with alcohol

-Hypoprothrombinemia - deal with vitK expoxide reductase → bleeding

What is the spectrum of cefotetan?

Anaerobic coverage

What are the gen 3 cephalosporins?

-Ceftriaxone

-Cefotaxime

-Ceftazidime/Avibactam

Ceftriaxone and cefotaxime (can/cannot) cross the BBB which makes them (effective/ineffective) at treating meningitis

Can, effective

• all 3rd gen cephs can cross

What bugs cause meningitis that can be treated by ceftriaxone and cefotaxime?

-E. coli

-S. agalactiae

-H. influenzae

-S. pneumoniae

What is the spectrum of ceftazidime/avibactam?

-Pseudomonas

-MDR G-s

What bugs does ceftazidime/avibactam NOT cover?

-MRSA

-Enterococci

-Acinetobacter

What are the gen 4 cephalosporins?

Cefepime

What does cefipime cover?

-Pseudomonas

-Broad spectrum G+/G-

What does cefipime NOT cover?

-MRSA

-Enterocci

-Limited acinetobacter

What is the MOA of cefiderocol?

-Siderophore cephalosporin

-Uses siderophore transport (iron channels) to access the bacteria

What does cefiderocol cover?

-Pseudomonas

-Acinetobacter

-Carbapenem-resistant G-

What does cefiderocol NOT cover?

-MRSA

-Enterococci

-Anaerobes

What are the gen 5 cephalosporins?

-Ceftaroline

-Cetrobiprole

-Ceftolozane/Tazobactam

What does ceftaroline cover?

MRSA

What does ceftaroline NOT cover?

-Pseudomonas - only ceftobiprole can cover pseudo

-Enterococci

-Anaerobes

-Acinetobacter

What does ceftobiprole cover?

-MRSA

-Pseudomonas

What does ceftopibrole NOT cover?

-Enterococci

-Acinetobacter

What does ceftolozane/tazobactam cover?

-MDR pseudomonas

-Anaerobes

What does ceftolozane/tazobactam NOT cover?

-MRSA

-Enterococci

-Acinetobacter

What is the MOA of fluoroquinolones?

-Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV

-Direct nucleic acid synthesis inhibitor

-Bactericidal

What drugs are fluoroquinolones?

-Ciprofloxacin

-Ofloxacin

-Levofloxacin

-Moxifloxacin

-Gemifloxacin

-Delofloxacin

“circling often, leaves move, descent gently”

What are the uses of fluoroquinolones?

-UTIs

-STDs/PID due to gonorrhea or chlamydia

-Shigella

-Salmonella

-E. coli

-Campylobacter

-Skin/soft tissue/bone infections

What are the respiratory fluoroquinolones?

-Levofloxacin

-Moxifloxacin

-Delafloxacin

-Gemifloxacin

What do the respiratory fluoroquinolones cover?

-Strep

-Chlamydia

-Mycoplasma

-Legionella

What is the PK behind fluoroquinolones?

-Oral absorption decreased by antacids

-Mostly renally cleared

What are some AEs associated with fluoroquinolones?

-GI upset

-Rash

-Phototoxicity

-Tendinitis

-Tendon rupture

-CNS effects

-QT prolongation

Why are fluoroquinolones CI in pregnancy/kids?

Affected cartilage growth (tendon rupture risk)

What MOR was developed against fluoroquinolones?

-Mutations in DNA gyrase/topoisomerase IV

-Efflux pumps

-Decreased outer membrane permeability

What is the MOA of clindamycin?

-Binds 50s

-Inhibits translocation (like macrolides)

What is the spectrum of clindamycin?

-Narrow

-G+ cocci

-Some anaerobes “CANCUN”

-MSSA

What does clindamycin NOT cover?

-G-

-Salmonella

-Pseudomonas

What are some side effects of clindamycin?

High risk of C. diff pseudomembranous colitis

What is the MOA of the oxazolidinones?

-Bind 50s

-Inhibit formation of initiation complex

What are the oxazolidinones?

-Linezolid

-Tedizolid

What is the spectrum of the oxazolidinones?

-MRSA

-VRSA

-VRE

-Resistant strep pneumonia

What do the oxazolidinones NOT cover?

-G-

-Anaerobic coverage

What are some side effects of oxazolidinones?

-BMS

-MAO inhibition → Serotonin syndrome risk increased with SSRIs

What is the MOA of sulfonamides?

-Indirect inhibition of nucleic acid synthesis

-Compete with PABA

-Inhibit dihydropteroate synthase

-Decrease DHF

-Bacteriostatic

What is the MOA of trimethoprim/pyrimethamine?

-Inhibits DHFR

-Used with sulfas to increase synergy and decrease resistance

What is TMP/SMZ used for?

-DOC for nocardia

-E. coli

-Salmonella

-Shigella

-H. influenza

What opportunistic infection does SMZ/TMP treat?

Pneumocystis jirocecii pneumomia (CD4 < 200)

What DHFR is used to treat toxoplasma gondii (CD4 < 50)?

Pyrimethamine = for protozoa (toxaplasma is protozoa)

What is SSD used to treat?

Burns

What is sulfasalazine used for?

-IBD (Colitis)

-RA

What is the PK behind sulfonamides?

-Hepatic acetylation, renal excretion (crystalluria)

-High protein binding --> drug interactions, kernicterus in neonates

What are some AEs associated with sulfonamides?

-SJS

-GI upset

-Kernicterus in neonates

-Photosensitivity

-Hemolysis in G6PD deficiency

What is a notable side effect of the DHFRs?

BMS

What is the MOR against sulfonamides?

-Increased PABA production

-Altered DHFR

-Efflux pumps

What is the MOA of chloramphenicol?

-Binds 50s subunit

-Inhibits peptidyl transferase

→ Blocks peptide bond formation

What is the spectrum of chloramphenicol?

-Broad

-Meningitis due to H. influenza

True or False: Chloramphenicol crosses the BBB

True

Chloramphenicol is (water/lipid) soluble due to (hepatic/renal) metabolism

Lipid, hepatic

What are some AEs with chloramphenicol?

-Gray baby syndrome (immature liver --> accumulation)

-Dose dependent BMS

-CYP450 inhibitor --> DDIs

What drugs are pleuromutilins?

-Lefamulin

-Reptamulin

What is the MOA of the pleuromutilins?

-Bind 50s subunit

-Inhibit peptide bond formation

What is the ROA of lefamulin?

-PO

-IV

What is the spectrum of lefamulin?

-CABP

-ABSSSI

-MRSA

-G+

-Atypicals

What is reptamulin used for?

Impetigo (topical)

What are some AEs associated with pleuromutilins?

-C. diff colitis (pseudomembranous)

-QT prolongation

What is the MOA of macrolides?

-Bind 50s subunit

-Block translocation

-Bacteriostatic

What is the spectrum of macrolides?

-G+ infections in PCN allergies

-Legionella

-Chlamydia

-Mycoplasma

-H. pylori

-MAC (HIV)

What opportunistic infections are macrolides good for?

Mycobacterium avium intracellulare (MAC)

Which macrolides are lipid soluble and inhibit CYP450?

-Erythromycin

-Clarithromycin

True or False: Azithromycin is preferred in HIV patients/pregnancy because it is renally excreted and does not inhibit CYP450

True

Put the macrolides in order from most likely to cause GI distress to least likely to cause GI distress

Erythromycin --> Azithromycin --> Clarithromycin

most → least

Why do macrolides cause GI distress?

Stimulate motilin receptors

What is the MOR against macrolides?

Methylation of 23s rRNA

What is the MOA of tetracyclines?

-Bind 30s subunit

-Block aminoacyl tRNA binding at A site

-Inhibits elongation

-Bacteriostatic

What is the spectrum of tetracyclines?

-Broad

-H. pylori

-Chlamy6dia

-Mycoplasma

-Rikettsia

-Borellia

-Brucella

-Vibrio

-Some protozoa

What tetracycline is DOC for lyme?

Doxycycline

What else is doxycycline used for?

Prostatitis caused by chlamydia

Doxycycline is eliminated by the (liver/kidneys)

Liver

What is minocycline used for?

Meningococcal carrier state

Minocycline is (widely/narrowly) distributed

Widely

What is demeclocycline used for?

SIADH

What does eravacycline cover?

-Complicated intra-abdonimal infections

What does omadacycline cover?

-CABP

-ABSSSI

What is sarecycline used for?

Non-nodular acne vulgaris

What does tigecycline cover?

-MRSA

-VRE

-ESBL

-Complicated skin/intra-abdominal infections

-CABP

True or False: Dairy, antacids, iron, and magnesium all chelate with tetracyclines which increase the absorption of tetracyclines

False - decrease absorption

What are some AEs associated with tetracyclines?

“BLAST”

-Tooth discoloration

-Bone dysplasia (avoid in kids and pregnancy)

-Photosensitivity

What is the most notable AE with minocycline?

Vestibular toxicity

What MOR was developed against tetracyclines?

-Efflux pumps

-Ribosomal protection proteins

What are the cell membrane inhibitors?

-Daptomycin

-Polymyxin B

-Polymyxin E

What is the MOA of daptomycin?

-Forms pores using Ca2+

-Causes excessive K+ efflux

What does daptomycin cover?

-MRSA

-VRE

True or False: Daptomycin has coverage against respiratory infections because surfactant has a synergistic effect

False - surfactant inhibits daptomycin

What should you monitor in a patient taking daptomycin?

CPK for rhabdomyolysis

“dance until muscles get tired/weak”

What is the MOA of polymyxin B?

-Binds LPS

-Causes a leaky membrane (increased permeability of cell membrane)

What are the ROAs of polymyxin B?

-Topical

-IV

What is polymyxin B used for?

Resistant G-

What are the ROAs for polymyxin E?

-IV

-Inhaled

What does polymyxin E cover?

-Pseudomonas

-Acinetobacter

-Enterobacteriaceae

How is polymyxin E excreted?

Renally