Flashcards in EXAM #4: REVIEW Deck (235):
What is Peptidoglycan?
A macromolecule of peptides and sugars
What is Lipopolysaccharide?
A macromolecule of phospholipids and polysaccharides
Outline the ESKAPE mnemonic of nosocomial superbugs.
What is the function of Penicillin-Binding Proteins (PBPs) or Transpeptidases?
Cross-linking peptidoglycan in the formation of the bacteria cell wall
How can you group the PCN-type drugs?
- Penicillinase-sensitive PCNs
- Penicillinase-resistant PCNs
List the Beta-Lactamase sensitive PCNs.
PCN G and V
List the Beta-Lactamase resistant PCNs.
Which of the PCNs are "antipseudomonal?"
What are the narrow spectrum PCNs?
PCN G and V
What are the broad spectrum PCNs?
*Remember aminopenecillins are amped up PCNs i.e. ampicillin and broader spectrum*
What is the hallmark 1st generation Cephalosporin?
What is the hallmark 2nd generation Cephalosporin? List the other 2nd generation Cephalosporins.
List the 3rd generation Cephalosporins.
What is the only drug in the Monobactam family?
What type of bacteria can be treated with Aztreonam?
Gram negative (rods) only
What are the two important clinical considerations regarding Aztreonam?
1) Penetrates the BBB
2) Beta-Lactamase resistant
Are the Carbapenams resistant to Beta-Lactamase?
What enzyme are the Carbapenams susceptible to?
What adverse effects are associated with the Carbapenems?
1) GI disturbances (Dr. Henry)
2) CNS toxicity
*Note that it is toxicity that limits their use to life-threatening infections and/or after other drugs have failed*
What is the MOA of Vancomycin?
Inhibits peptidyglycan formation by binding D-ala portion of cell wall precursors
What is Vancomycin generally used to treat?
Serious, multi-drug resistant organisms including:
- C. diff
What is the MOA of Bacitracin?
Blocks incorporation of amino acids and nucleic acids into the cell wall of bacteria
*Remember that Bacitracin is Broad spectrum*
What type of antibiotic is Fosfomycin? What is the MOA?
Cell wall synthesis inhibitor that prevents the synthesis of UDP-NAM (component of peptidoglycan)
What is Fosfomycin commonly used to treat?
What antibiotic class are the Aminoglycosides? What is the MOA?
30S Protein Synthesis Inhibitors
- Prevent charged tRNA from entering the A site
Remember, "Buy AT 30, CELL at 50" (Aminoglycosides and Tetracyclines= 30S inhibitors)
How are the Aminoglycosides commonly administered in the clinical setting?
With Beta-Lactam antibiotics
When are Aminoglycosides commonly used clinically?
Serious gram negative infections
What is the mnemonic to remember many important features of the Aminoglycosides?
"Mean" (i.e. A-mean-oglycodies) GNATS caNNOT kill anaerobes
N= neuromuscular blockade
(CAPITLAL= Dr. Henry)
What is the MOA of the Macrolides?
Blocks translocation of the growing amino acid chain from the A-site to the P-site
What side effect is associated with Macrolides? Use a mnemonic to remember.
Macrolides cause Motility issue i.e. GI disturbances
What is the specific MOA of the Tetracyclines?
Blocks charged tRNAs from entering the A-site
What should not be taken with a Tetracycline?
3) Iron supplements
*Bind divalent cations, which will inhibit absorption from the gut*
In what patient populations are Tetracyclines contraindicated?
2) Pregnant women
*Will prevent/induce bone growth--check ppt*
What type of antibiotic in Clindamycin?
50S Protein Inhibitor
Clinically, what is Clindamycin commonly prescribed for?
Streptococcus and Staphylococcus soft tissue infections
*Thus, it is a NARROW SPECTRUM antibiotic*
What is the MOA of Clindamycin?
Blocks growing amino acid chain transfer from A-site to P-site
What key adverse effect is Clindamycin associated with?
Pseudomembraous colitis i.e. C.diff
What is the MOA of Chloramphenicol?
Blocks peptidyltransferase at 50S subunit i.e. prevents peptide bond formation
What are the adverse effects seen with Chloramphenicol?
2) Aplastic anemia
3) Gray Baby Syndrome
What is Chloramphenicol commonly prescribed for?
Rocky Mountain Spotted Fever
What type of bacteria is Linezolid effective against?
What is the MOA of Linezolid?
50S inhibitor that blocks the A-site
What adverse effect is associated with Linezolid?
What is the general pattern of bacterial specificity of the protein synthesis inhibitors? Which antibiotic does NOT follow the pattern?
Generally broad spectrum, except for Clindamycin, which is used to treat Streoptoccus and Staphylococcus soft tissue infections
List the Sulfonamides.
What are the key adverse reactions associated with the Sulfonamides? Use a mnemonic to recall these reactions
3) Steven-Johnson Syndrome
What is the bacterial specificity of the Sulfonamides?
What are the two Trimethoprims?
What is the bacterial specificity of the Trimethoprims?
Gram negative bacteria
What is the mnemonic to remember the adverse effects associated with the Trimethoprims?
Treats Marrow Poorly i.e. megaloblastic anemia
List the adverse effects associated with the Fluoroquinolones.
1) GI disturbances
2) Bind divalent cations
3) QT prolongation
4) FluoroquinoLONES hurt attachment to your BONES
- Tendon rupture
What is the Group 1 Fluoroquinolone?
What are the Group 2 Fluoroquinolones? What type of bacteria are these drugs most specific for?
What are the Group 3 Fluoroquinolones? What type of bacteria are these drugs most specific for?
What types of microorgansism can be treated with Metronidazole?
Bacteria AND protozoa
What type of bacteria can be treated with Metronidazole?
Anaerobics ONLY (below the diaphragm)
What is the bacterial specificity of Daptomycin?
What is the bacterial specificity of Polymyxin B?
Gram negatives/LPS i.e. it specifically is a detergent that punches in LPS
How is Polymxyin B administered?
What is a good first choice drug for an uncomplicated skin infection?
1st generation Cephalosporin i.e. Cefazolin
(Treats S. aureus and S. pyogenes that cause uncomplicated skin infections)
What is a good alternative for an uncomplicated skin infection with hypersensitivity to a 1st generation cephalosporin?
What is a good first choice drug for a complicated skin infection?
Ticracillin and clavulanate
(Has anti-pseudomonal activity)
What are good drugs to treat MRSA skin infection?
What two bacteria cause complicated skin infections?
1) P. aeruginosa (Ticracillin has anti-pseudomonal activity)
2) E. coli
What are good first line agents for bone and joint infections?
Vancomycin or Ceftriaxone (3rd/4th generation cephalosporin)
What is the antibiotic of choice for post-op bone/joint infections?
Ticracillin and clavulanate
What is a good antibiotic choice for septic arthritis?
What is the first line antibiotic for acute sinusitis and chronic bronchitis?
Augmentin i.e. Amoxacillin and clavulanate
What is the first line antibiotic for pharyngitis? What organism commonly causes pharyngitis?
What bacteria cause URIs (3)?
1) H. influenza
2) S. pneumonia
3) Moraxella catarrhalis
What is the first line antibiotic for ambulatory pneumonia?
How are patients with pneumonia that have to be hospitalized treated?
Add Beta-Lactam to the Macrolide
How is nosocomial pneumonia treated?
How is pyelonephritis treated vs. a simple UTI?
Pyelo= add Fluoroquinolone
What is the first line antibiotic for intra-abdominal infections? What bacteria cause intra-abdominal infections?
Ticracillin and clavulanate
What is community acquired meningitis treated (older than 2 y/o)?
Ceftriaxone and Vancomycin
How is neonatal meningitis treated?
3) +/- Gentamicin (L. monocytogenes)
What are the first line antibiotics for Endocarditis?
What are the first line antibiotics for neutropenic fever?
Ciprofloxacin and Augmentin
How are enterococci infections treated?
Deptomycin + Tigacycline
How are gram negative ANTIBIOTIC RESISTANT infections treated?
Carbapenam + Carbapenemase
What toxicities are associated with INH?
2) Peripheral neuropathy
What factors increase the risk of peripheral neuropathy with INH therapy?
What is the MOA of Rifampin?
Inhibition of RNA synthesis
(Inhibits bacterial DNA dependent RNA polymerase)
What is the mechanism of Pyrazinamide resistance?
- Pyrazinamide requires Pyrazinamidase to be active (prodrug)
- Mutation in Pyrazinamidase
What adverse effect is associated with Pyrazinamide?
What is the MOA of Ethambutol?
Inhibits arabinosyl transferase needed for mycolic acid synthesis
What adverse effects are seen with Ethambutol?
1) Retrobulbar neuritis
What is a good first line drug to treat disseminated MAC infections in the immunocompromised?
What four drugs are used for MAC combination therapy?
What is the standard drug regimine for Leprosy?
Note that these drugs are taken for YEARS****
What is the MOA of Dapsone?
PABA analog that inhibits folate synthesis
What adverse effect is associated with Dapsone?
What is Clofazamine?
*Associated with skin pigmentation changes
What drugs are used to follow-up Metronidazole treatment for Amebiasis?
Iodoquinol or Paromomycin
What are halogenated Hydroxyquinolone and Paromomycin good drugs for?
BOTH forms of Entameba histolytica
What are the three parasites cause major opportunistic infections of AIDS patients/immunocompromised?
1) Cryptosporidium parvum
2) Pneumocystis jiroveci
3) Toxoplasma gondii
How is Cryptosporidosis treated?
What is the MOA of NItazoxanide?
Inhibits PFOR to disrupt the energy metabolism of the parasite
How are pneumocystis jiroveci and toxoplasma gondii treated? What adverse reaction is common with these drugs?
Inhibitors of folate synthesis i.e.
What enzyme is specifically inhibited by the Sulfonamides?
What enzyme is inhibited by the diaminopyrimidines?
What is the adverse effect of TMP-SMX treatment?
What is the adverse effect of Pyrimethamine-Sulfadiazine?
Folic acid deficiency leading to megaloblastic anemia
What adverse effect is highly associated with Mefloquine?
Recall, malaria prophylaxis that causes SEVERE NEUROPSYCHIATRIC symptoms
*So bad it can lead to suicide
What is the MOA of Primaquine?
Prodrug that gets activated to interfere with electron transport
What species of malaria is Malarone specific to treating?
What is Malarone?
Atoaquone and Proguanil
What is the MOA of Proguanil?
What drugs fall into the Benzimidazole class?
What side effects are associated with Thabendazole?
CNS disturbances i.e. delirium and hallucinations
What infections are Albendazole and Mebendazole prescribed for?
What is Thiabendazole prescribed for?
1) Cutaneous larval migrans
2) Strongyloidiasis (2nd line)
What infections is Ivermectin the drug of choice for?
1) First line for Strongloidiasis
2) Tissue dwelling nematodes
- O. volvulus
- Loa loa
- W. bancrofti
What infection is Pyrantal Pamoate used to treat?
What is the MOA of Praziquantel?
- Increased Ca++ permeability of cuticle covering Flukes and Tapeworms
- Leads to depolarizing NM blockade
List the three major opportunistic fungal infections.
3) Cryptococcus neoformans
List the drugs that inhibit ergosterol synthesis.
What major anti-fungal works by inhibiting fungal membrane function?
What drug inhibits fungal cell wall function?
List the four drugs or drug classes that can be used to treat systemic fungal infections.
1) Polyenes i.e. Amphotericin B
What is the mechanism of resistance to Amphotericin B?
Decreased membrane ergosterol
What are the adverse reactions seen with Amphotericin B administration?
1) Infusion site reaction
What is the packaging of Amphotericin B in a lipid micelle called?
List the imidazoles.
List the triazoles.
What is the MOA of the azoles?
Inhibit the enzyme that produces ergosterol
Name three mechanisms of resistance to the azoles.
1) Decreased membrane ergosterol
2) Efflux pumps
3) Mutations in the target enzyme
List three reasons that Fluconazole is the first line agent for systemic fungal infections.
1) Safe--highest TI
2) Well distributed to the CNS
3) Few drug-drug interactions
List the infections that Fluconazole is the first line agent for.
1) Systemic Candidiasis
What is Itraconazole the drug of choice for?
What is Voriconazole the drug of choice for?
What adverse effect is associated with Voriconazole?
*Think Voriconazole= Visual*
What is Posconazole used to treat?
How is Flucytosine used clinically?
Part of combination therapy for severe Cryptococcal infections
List the Echinocandins.
What infections are the Echinocandins commonly used to treat?
What is Griseofulvin? What is it used to treat?
This is an ORAL antifungal used to treat the Dermatophyte infections
*Note that it concentrates in Keratin precursors*
What class of drug are the Allylamines? What is the MOA?
- Antifungals that inhibit ergosterol synthesis
- Specifically inhibit SQUALENE EPOXIDASE
What is Terbinafine a first line agent for?
List the topical antifungals and their drug class.
What is Nystatin used to treat?
This is a topical agent used to treat Candida infections i.e.
- Oral candidiasis
- Vaginal candidiasis
What are Clotrimazole and Miconazole used to treat?
Topical agents for:
- Vulvovaginal candidiasis
- Oral thrush
2) Dermatophyte infections
What are the topical Allylamines used to treat?
Topical agents for:
1) Tinea curis (jock-itch)
2) Tinea corporis (ringworm)
What is the MOA of Acyclovir?
This is a nucleoside analog that:
1) Competitive inhibitor of viral DNA polymerase
2) Causes chain termination via incorporation into the viral genome
What are the indications for oral Acyclovir?
1) Genital herpes (HSV-2)
List four indications for IV Acyclovir.
1) Severe/ disseminated HSV
2) Neonate infections
3) HSV encephalitis
4) VZV in the immunocompromised
What major toxicity is associated with Acyclovir?
What are the clinical indications for Valacyclovir?
1) Genital Herpes (HSV-2)
2) Oral Herpes (HSV-1)
How does Foscarnet compared to Acyclovir?
Does NOT require thymidine kinase activation
What are the clinical indications for Foscarnet?
1) HSV/VZV infections resistant to Acyclovir
What are the adverse effects associated with Foscarnet?
2) Changes in blood chemistry
What activates Ganciclovir?
Viral CMV kinase
What are three adverse effects associated with Ganciclovir?
2) CNS toxicity
3) Injection site reaction
What are the two indications for Valganciclovir?
1) CMV Retinitis
2) Prophylaxis against CMV in transplant patients
What is the MOA of Trifluridine?
1) Prodrug that gets activated by phosphorylation
2) Competitive inhibition of thymidine incorporation into DNA
What are the indications for Trifluridine?
HSV-1 and 2 associated:
What is the difference between Oseltamivir, Zanamivir, and Peramivir?
Oseltamivir= Oral and 1+ y/o
Zanamivir= inhaled and 7+ y/o
Peramivir= IV, think "Parenteral"
What are the adverse effects associated with Peramivir?
1) Neuropsychiatric sx.
- Neurominidase inhibitors cause Neuropsychiatric symptoms
2) Steven Johnson's Syndrome
What is the MOA of Ribavirin?
Remember, RSV= Ribavirin
1) Phosphorylated by ADENOSINE KINASE
2) Interferes with GTP/ mRNA capping
What can Ribavirin be used to treat aside from RSV?
What adverse effect is associated with Ribarivin?
When is Ribavirin contraindicated?
3) Ischemic vascular disease
4) Severe renal disease
What are the two HCV DAA Protease Inhibitors?
What are the two HCV DAA RNA Polymerase inhibitors?
1) Sofosbuvir- nucleoside
2) Desabuvir- non-nucleoside
What are the two HCV DAA NS5A inhibitors?
What should you avoid giving Sofosbuvir with?
List the NRTIs.
Aside from HIV, what can the NRTIs be used to treat?
What adverse effects are seen with the NRTIs?
1) Lactic acidosis
3) Fatty Liver Disease
What specific adverse reaction is associated with Abacavir?
*Think "A" for allergic reaction/ hypersensitivity
What polymorphism is associated with hypersensitvity to Abacavir? Why is this important?
*Need to test for this prior to administration*
What is unique about the toxicity profile of Lamivudine?
Least toxic of the antiretrovirals
What unique adverse effect is seen with Emtricitabine?
Hyperpigmentation of the palms and soles
Name three contraindications for Emtricitabine.
2) Young children
3) Hepatic or renal failure
What unique adverse effects are seen with Tenofivir?
1) Bone marrow--> "Faconi anemia"
2) Decreased bone density/ fetal growth
What unique adverse effect is seen with Zidovudine?
List the adverse effects common to the NNRTIs.
2) Steven Johnson Syndrome
4) Drug-drug interaction
List the two most clinically important NNRTIs.
What unique toxicities are associated with Efavirenz?
2) CNS toxicity
3) CYP p450 inducer
What unique toxicity is associated with Nevirapine?
What is the unique clinical utility of Nevirapine?
Can prevent VERTICAL TRANSMISSION
List the adverse effects common to the protease inhibitors.
3) GI intolerance
5) Increased bleeding risk
6) Drug-drug interactions
What drugs are contraindicated with Atazanavir? Why?
PPIs b/c they require acidic GI pH for proper absorption
*Think Ataznavir needs Acid*
What specific adverse effects are associated with Ataznavir?
1) Peripheral neuropathy
3) Adverse cardiac effects
What effect does Ataznavir have on the CYP p450 system?
What is the clinical utility of Darunavir?
Pharmacologic booster like Ritonavir
What specific adverse effects are associated with Darunavir?
1) Increased liver enzymes
2) Increased serum amylase
What is the specific indication for Darunavir?
Drug resistant HIV-1
What is the CCR5 antagonist?
What specific adverse effect is associated with Maraviroc?
Cardiac events in those with underlying cardiac disease
What is the fusion inhibitor? What is unique about the administration of this drug?
Enfuvritide -- given SubQ!
What specific adverse effects are associated with Enfuvritide?
1) Injection site reaction
2) Allergy to drug
3) Increased risk of bacterial pneumonia
What suffix is associated with the Integrase Inhibitors.
What specific adverse effects are associated with Raltegravir?
What specific adverse effects are associated with Elvitegravir?
Note that this is given orally with Ritonavir
What specific adverse effects are associated with Dolutegravir?
2) Elevation of liver enzymes
List the non-selective COX inhibitors.
List the selective COX inhibitors.
What is the MOA of Colchicine?
Inhibition of leukocyte migration and phagocytosis
What is the MOA of Probenecid and Sulfinpyrazone?
- Inhibit tubular absorption of uric acid
- Increase renal clearance of uric acid
What is the MOA of Methotrexate in the treatment of RA?
1) Inhibits AICAR transformylase
2) Increases extracellular adenosine
3) Inhibits T-cell activation
4) Cytotoxic to lymphocytes
List the synthetic DMARDs.
What is the MOA of Leflunomide?
Inhibits ribonucleotide synthesis
What are the biologic DMARDs?
List the drugs used to PREVENT migraines.
What are the antiemetics used to treat migraines?
List the antimetabolite immunosuppressants.
List the biological immunosuppressants.
1) Antithymocyte globulin
What are the non-genomic effects of the glucocorticoids?
1) Alternation of signaling pathways
2) Insertion into cell membrane to alter ion transport
Name four effects of glucocorticoid administration.
1) Decreased peripheral lymphocytes
2) Decreased pro-inflammatory cytokines
3) Inhibition of IL-2
4) Reduced neutrophil chemotaxis
List the pro-inflammatory cytokines.
List four clinical indications for the glucocorticoids.
1) Prevent transplant rejection
3) Autoimmune disease
4) Prevention of cytokine storm with biological immunosuppressants
What adverse effects are associated with the glucocorticoids?
1) Growth retardation
2) Poor wound healing
7) Adrenal crisis with d/c
Outline the MOA of Cyclosporine.
- Complexes with Cyclophillin in the cytosol
- That complex binds Calcineurin
- Calcineurin complex prevents dephosphorylation of NAFT
- NAFT cannot translocate to the nucleus
No NAFT= NO IL-2
What is the grapefruit juice/ cyclosporine interaction?
- Grapefruit juice inhibits CYP p450
- Increased concentrations of cyclosporine-->toxicity
What does Azathioprine ultimately block?
De novo purine synthesis
List three indications for Azathioprine.
1) Prevent transplant rejection
2) Severe RA
3) Glucocorticoid resistant autoimmune disease
What adverse effects are associated with Azathioprine?
What the MOA of Mycophenolate Mofetil?
1) Prodrug metabolized to MPA
2) MPA blocks IMP in de novo purine synthesis
What are the clinical indications for Mycophenolate Mofetil?
1) Prophylaxis for transplant rejection
What adverse effects are associated with Mycophenolate Mofetil?
2) GI upset
3) CMV infections
What is the MOA of Sirolimus?
What is the specific utility of Sirolimus?
Renal transplant that cannot tolerate nephrotoxocity of Cyclosporine
What are the indications for antithymocyte globulin?
1) Induction immunosuppression
2) Treatment of ACUTE transplant rejection
What adverse reactions are associated with Antithymocyte Globulin?
1) Cytokine storm
2) Serum sickness
What are the indications for antithymocyte globulin?
Glucocorticoid resistant transplant rejection
What drawback is associated with Muromonab-CD3?
Mouse antibody that can only be used once
What are the three anti-TNF-a biologicals? What are the used to treat?
How does Echinacea reduce the duration and intensity of a cold?
1) Increased cytokine production
2) Anti-inflammatory/ COX inhibitor
3) Increased immunological blood cells
What two major side effects are associated with Gingko Biloba?
2) Seizure induction
How does garlic lower blood pressure?
1) ACE inhibitor
2) Increased NO bioavalibility
3) Increased H2S production
*Decrease vasoconstriction and increase vasodilation
What drug-drug interaction is associated with Glucosamine and Chondroitin?
Enhanced anticoagulant effects of Warfarin
List the intended uses of CoQ10.
1) Reduction of statin-induced myopathy
4) Neurodegenerative Disease