Step 1 Flashcards
What is the function of apolipoprotein E and what expresses it?
Mediates remnant upake.
Chylomicron
Chylomicron remnant
VLDL
IDL
HDL
What is the function of apolipoprotein A-1 and what expresses it?
Activates LCAT
(LCAT catalyzes esterification of cholesterol, making nascent HDL –> Mature HDL)
HDL
Chylomicrons
What is the function of apolipoprotein C-II and what expresses it?
Lipoprotein lipase cofactor
Required for LPL function on the surface of vascular endothelial cells
Chylomicron
VLDL
HDL
What is the function of apolipoprotein B-48 and what expresses it?
Mediates chylomicron secretion
Chylomicron
Chylomicron remnant
What is the function of apolipoprotein B-100 and what expresses it?
Binds LDL receptro and mediates VLDL uptake in liver
VLDL
IDL
LDL
Penicillin G, V
MOA
Clinical Use
Toxicity
Resistance
MOA: Bind PBP (transpeptidases
Block transpeptidase cross-linking of peptidoglycan
Activagte autolytic enzymes
Clinical Use: Gram+
(S. pneumo, S. pyogenes, actinomyces)
Also, N. meningitidis, T. pall
Toxicity:
Hypersensitivity reactions, hemolytic anemia
Resistance: Penicillinase cleaves b-lactam ring
Ampicillin, Amoxicillin
MOA
Clinical Use
Toxicity
Resistance
MOA: Bind PBP’s and block transpetidase cross-linking of peptidoglycan
Also, combine with clavulanic acid to protect against b-lactamase (augmentin)
Amoxicillin = oral
Ampicillin = IV
Clinical Use: HELPSS
H. influenzae, E. coli, Listeria, Proteus, Salmonella, Shigella, Enterococci
Toxicity: Hypersensitivity, rash, pseudomembranous colitis
Resistance: Penicillinase
Oxacillin, Nacillin, dicloxacillin
MOA
Clinical Use
Toxicity
Resistance
Penicillinase resistant penicillins
MOA: Bind to PBP, block transpeptidase cross-linking of peptidoglycan
Resistant to penicillinase because of bulky R group blocking b-lactam ring
Clinical Use: S. aureus
Use naf for staph
Toxicity: hypersensitivity, interstitial nephritis
Resistance: Modification of PBP’s
Ticarcillin, Piperacillin
MOA
Clinical Use
Toxicity
Resistance
Antispeudomonals
MOA: Binds to PBP’s, inhibits transpeptidases cross-linking of peptidoglycan
Clinical Use: Pseudomonas and gram- rods
Toxicity: Hypersensitivity
Resistance: Penicillinase, use with clavulanic acid, sulbactam, or tazobactam
1st Generation Cephalosporins
MOA
Clinical Use
Toxicity
Resistance
Cefazolin, cephalexin
MOA: b-lactam drugs that inhibit cell wall synthesis, but are less susceptible to penicillinases
Bactericidal
Clinical Use: PECK
Proteus, E. coli, Klebsiella
Toxicity: Hypersensitivity, Vit. K deficiency, low cross-reactivity with penicillins
Increases nephrotoxicity of aminoglycosides
Resistance: modification of PBPs
2nd Generation Cephalosporins
MOA
Clinical Use
Toxicity
Resistance
Cefoxitin cefaclor, cefuroxime
MOA: b-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases
Bactericidal
Clinical Use: HEN PECKS
H. influenzae, Enterobacter, Neisseria, Proteus, E. coli, Klebsiella
Toxicity: Hyeprsensitivity, Vit. K Deficiency, Low cross-reactivity with PCN’s, Increases nephrotoxicity of aminoglycosides
Resistance: Modification of PBP’s and b-lactamases
3rd Generation Cephalosporins
MOA
Clinical Use
Toxicity
Resistance
Ceftriaxone, Cefotaxime, Ceftaxidime
MOA: b-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases. Bactericidal
Clinical Use:
Serious Gram - infections
Ceftriaxone for CSF penetration
Toxicity: Hypersensitivity, Vit. K Def., low cross-reactivity with PCN’s increases nephrotoxicity of aminoglycosides
Resistance: Modification of PBP’s
4th Generation Cephalosporins
MOA
Clinical Use
Toxicity
Resistance
Cefepime
MOA: b-lactam drugs taht inhibit cell wall synthesis but are less susceptible to penicilinases
Bactericidal
Clinical Use: Pseudomonase and gram + organisms
Toxicity: Hypersensitivity, Vit. K def., low cross-reactiity with PCN’s, increased nephrotoxicity of aminoglycosides
Resistance: Modification of PBP’s
5th Generation Cephalosporins
MOA
Clinical Use
Toxicity
Resistance
Ceftaroline
MOA: b-lactam drugs taht inhibit cell wall synthesis but are less susceptible to penicilinases
Bactericidal
Clinical Use: Broad Gram+/- coverage, including MRSA
No pseudomonal coverage
Toxicity: Hypersensitivity, Vit. K def., low cross-reactiity with PCN’s, increased nephrotoxicity of aminoglycosides
Resistance: Modification of PBP’s
Aztreonam
MOA
Clinical Use
Toxicity
Resistance
MOA: Monobactam, resistant to b-lactamases
Prevents peptidoglycan from cross-linking by binding to PBP 3
Clinical Use: Gram - Rods only
For PCN allergic patients or those with renal insufficiency who cannot tolerate aminoglycosides
Toxicity: Occassional GI upset
Resistance: modification of PBP
Carbapenems
MOA
Clinical Use
Toxicity
Resistance
Imipenem, meropenem, ertapenem, doripenem
MOA: broad-spectrum, b-lactamase-resistant
Binds to PBP to inhibit cell wall synthesis
Clinical Use:
Imipenem is administered with cilastatin to reduce deactivation of drug in renal tubules
Gram+ cocci, Gram- rods, and anaerobes
Toxicity: GI distress, skin rash, CNS toxicity/seizures at high plasma levels (Meropenem has less CNS toxicity)
Vancomycin
MOA
Clinical Use
Toxicity
Resistance
MOA: inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors
Bactericidal
Clinical Use: MRSA, enterococci, C. diff
Gram+ ONLY
Toxicity: NOT many issues
Nephrotoxicity
Ototoxicity
Thrombophlebitis
Red Man Syndrome (pretreat with antihistamines and slow infusion rate)
Resistance: Amino acid modification of D-ala D-ala to D-ala D-lac
What antibiotics target protein bacterial ribosomes/protein synthesis and how?
Buy AT 30, CCEL at 50
- *30**s ribosome:
- *A**minoglycosides (cidal)
- *T**etracyclines (static)
- *50**s ribosome:
- *C**loramphenicol (static)
- *C**lindamycin (static)
- *E**rythromycin (macrolides = static)
- *L**inezolid (variable)
Aminoglycosides
MOA
Clinical Use
Toxicity
Resistance
Mean GNATS caNNOT kill anaerobes
Gentamycin, Neomycin, Amikacin, Tobramycin, Streptomycin
MOA: Inhibit formation of initiation complex and cause misreading of mRNA. Also, blocks translocation
Requires O2 for uptake
Clinical Use: Gram- Rods
Synergistic with b-lactams
Neomycin for bowel surgery
Toxicity:
- *N**ephrotoxicity (esp. w/Cephalosporins)
- *N**euromuscular blockade
- *O**totoxicity (esp. w/loop diuretics)
- *T**eratogen
Resistance: Anearobes
Bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation or adenylation
Tetracyclines
MOA
Clinical Use
Toxicity
Resistance
Tetracycline, Doxycycline, Minocycline
MOA: Bind to 30s and prevent attachment of aminoacyl-tRNA.
Do not take with Ca, Mg, or Fe containing foods; they inhibit resorption
Clinical Use: Borrelia burgdorferi (Lyme dz), M. pneumoniae, Rickettsia (RMSF), Chlamydia, and acne
Toxicity: GI distress, discolorationo f teeth, inhibition of bone growth (chelates to Ca), photosensitivity. Contraindicated in pregnancy
Resistance: Decreased uptake or increased efflux by plasmid-encoded transport pumps
Macrolides
MOA
Clinical Use
Toxicity
Resistance
ACE
Azithromycin,Clarithromycin,Erythromycin
MOA: Inhibits protien synthesis by blocking translocation (“macroslides”); bind to the 23s rRNA of 50s ribosome
Clinical Use: Atypical pneumonias, STD (chlamydia), Gram+ cocci (Strep ifnxn if allergic to PCN)
Toxicity: MACRO
Gastrointestinal Motility issues, Arrhythmia/prolonged QT, acute Cholestatic hepatitis, Rash, eOsinophilia. Increases [] of theophyliines, oral anticoags
Resistance: Methylation of 23s rRNA-binding site prevents drug binding
Chloramphenicol
MOA
Clinical Use
Toxicity
Resistance
MOA: blocks peptidyltransferase at 50s ribosomal subunit
Clinical Use: Meningitis (H. influenzae, N. meningitidis, S. penumo) and Rickettsia rickettsii (RMSF)
Toxicity: Anemia (dose dependent), aplastic anemia (dose independent), gray baby syndrome (premies lack UDP-glucuronyl transferase)
Resistance: Plasmid-encoded acetyltransferase inactivates drug
Clindamycin
MOA
Clinical Use
Toxicity
Resistance
MOA: Blocks peptide transfer (translocation) at 50s subunit
Clinical Use: Treats anaerobes above the diaphragm Anaerobic infxns (Bacteroides, C. perfringens) in aspiration pneumonia, lung abscesses, and oral infections
Affective against invasive GAS
Toxicity: C. diff colitis, fever, diarrhea
Resistance: active transport out of cells
Sulfonamides
MOA
Clinical Use
Toxicity
Resistance
Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine
MOA: Inhibit folate synthesis. PABA antimetabolites inhibit dihydroperoate synthesis
Clinical Use: Gram+, Gram-, Nocardia, Chlamydia, simple UTI
Toxicity: Hypersensitivity, hemolysis of G6PD deficient, Interstitial nephritis, photosensitivity, kernicterus in infants, displace other drugs from albumin (i.e. warfarin)
Resistance: Altered enyzme (bacterial dihydropteroate synthase), decreased uptake, or increase PABA synthesis to overcome drug competitively
Trimethroprim (TMP)
MOA
Clinical Use
Toxicity
Resistance
MOA: Inhibits bacterial dihydrofolate reductase
Clinical Use:
TMP-SMX = UTI, shigella, salmonella, pneumocystis jirovecii tx and prophy, toxoplasmosis prophy
Toxicity: TMP: Treats Marrow Poorly
Megaloblastic anemia, leukopenia, granulocytopenia
Fluoroquinolones
MOA
Clinical Use
Toxicity
Resistance
Ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, sparfloxacin, moxifloxacin, gemifloxacin, enoxacin, nalidixic acid
MOA: Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV. Must not be taken with antacids
Clinical Use: Gram- rods of urinary and GI tracts (including pseudomonas), Neisseria, some Gram+
Toxicity: Fluoroquinolones hurt attachments to your bones
GI, upset, superinfections, skin rashes, headache, dizziness. Tendonitis, tendon rupture, leg cramps, myalgias. Prolonged QT
Resistance: Chromosome encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps
Metronidazole
MOA
Clinical Use
Toxicity
Resistance
MOA: Forms free-radical toxic metabolites in the bacterial cell to damage DNA
Bactercidal, antiprotozoal
Clinical Use: GET GAP on the metro!
- *G**iardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes, H. Pylori
- *Treats anaerobic infxn below the diaphragm**
Toxicity: Disulfiram-like rxn with alcohol, headache, metallic taste
Treatment for M. tuberculosis
Prophy: Isoniazid
Treatment: RIPE
Rifampin, Isoniazid, Pyrazinamide, Ethambutol (+Vit B6)
Treatment for M. avium-intracellulare
Prophy: Azithromycin, rifabutin
Treatment: Azithromycin or Clarithromycin + Ethambutol
Can add rifabutin or ciprofloxacin
Treatment for M. leprae
Tuberculoid form: Dapsone and Rifampin
Lepromatous form: Clofazimine
Isoniazid
MOA
Clinical Use
Toxicity
Resistance
MOA: Decreased synthesis of mycolic acids
Bacterial catalase-peroxidase needed to convert INH to active metabolite
Clinical Use: M. tuberculosis
Toxicity: INH Injures Neurons and Hepatocytes
Neurotoxicity, hepatotoxicity.
Use with Pyridoxine (Vit. B6) to prevent neurotoxicity, lupus
Rifamycins
MOA
Clinical Use
Toxicity
Resistance
Rifampin, rifabutin
4 R’s:
RNA polymerase inhibitor
Ramps up microsomal cytochrome (P450)
Red/orange body fluids
Rapid resistance if used alone
Rifampin ramps up CYP450, but rifabutin does not
MOA: Inhibits DNA-dependent RNA polymerase
Clinical Use: M. tuberculosis. Delays resistance to dapsone when used for leprosy. Meningococcal prophylaxis and chemoprophylaxis when in contact with those with H. flu type B
Toxicity: Hepatotoxicity and drug interxns
orange body fluids
Pyraxinamide
MOA
Clinical Use
Toxicity
Resistance
MOA: Mechanism uncertain. Acidiy intracellular environment via conversion to pyrazinoic acid? Effective in phagolysosomes
Clinical Use: M. tuberculosis
Toxicity: Hyperuricemia, hepatotoxicity
Ethambutol
MOA
Clinical Use
Toxicity
Resistance
MOA: Decrease carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase
Clinical Use: M. tuberculosis
Toxicity: optic neuropathy (red-green color blindness)
Eyethambutol
Amphotericin B
MOA
Clinical Use
Toxicity
Resistance
MOA: Bidns ergosterol; forms membrane poors that allow leakage of electrolytes
“Amphotericin ‘tears’ holes in the fungal membrane”
Clinical Use: Systemic mycoses
Cryptococcus, Blastomyces, Coccidioides, Histoplasma, Candida, Mucor
Administer intrathecally for fungal meningitis
Toxicity: Fever/chills (“Shake and Bake”), hypotension
Nephrotoxicity, arrhythmias, anemia, IV phlebitis. Hydration decreases nephrotoxicity. Supplement K and Mg because of altered renal tubule permeability
Nystatin
MOA
Clinical Use
Toxicity
Resistance
MOA: Binds ergosterol; forms membrane pores that allow leakage of electrolytes
Clinical Use: Oral candida (“swish and swallow”), diaper rash or vaginal candida
Toxicity: Topical only - too toxic for systemic use
Azoles
MOA
Clinical Use
Toxicity
Resistance
Fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole
MOA: Inhibit fungal sterol synthesis by inhibiting
lanosterol –> ergosterol
Clinical Use:
Local and less serious systemic mycoses
Fluconazole for chronic suppression of cryptococcal meningitis in AIDS pts and candida of all types
Itraconazole for blastomyces, coccidioides, Histoplasma
Clotrimazole and miconazole for topical fungal infections
Toxicity: Testosterone synthesis inhibition (gynecomastia, esp. ketoconazle) Liver dysfunction (inhibits CYP450)
Flucytosine
MOA
Clinical Use
Toxicity
Resistance
MOA: Inhibits DNA and RNA biosynthesis by conversion to 5-fluorouracil by cytosine deaminase
Clinical Use: Systemic fungal infections (Cryptococcal meningitis) in combo with amphotericin B
Toxicity: Bone marrow suppression
Echinocandins
MOA
Clinical Use
Toxicity
Resistance
Caspofungin, micafungin, anidalafungin
MOA: Inhibits cell wall syntehssis by inhibiting syntehsis of b-glucan
Clinical Use: Invasive aspergillosis, candida
Toxicity: GI upset, flushing (histamine release)
Terbinafine
MOA
Clinical Use
Toxicity
Resistance
MOA: inhibits fungal enzyme squalene epoxidase
Clinical Use: Dermatophytoses (esp. onychomycosis)
Toxicity: GI upset, headaches, hepatotoxicity, taste disturbance
Griseofulvin
MOA
Clinical Use
Toxicity
Resistance
MOA: Interferes with microtubule fxn; disrupts mitosis. Deposits in keratin-containing tissues (i.e. nails)
Clinical Use: Oral Tx of superficial infections; inhibits growth of dermatophytes (tinea, ringworm)
Toxicity: Teratogenic, carcinogenic, confusion, headaches, Induces CYP450 and wafarin metabolism
