Micro - Antimicrobials Part 2 Flashcards
Patients with what enzyme deficiency can suffer additional toxicities of sulfonamide antibiotics?
People with glucose-6-phosphate dehydrogenase deficiency will get hemolytic anemia
Sulfonamides can cause which renal pathology?
Tubulointerstitial nephritis
What neurologic injury can sulfonamides cause in infants?
Kernicterus
How do sulfonamides affect the plasma concentration of albumin-bound drugs such as warfarin?
The plasma concentration of warfarin and other drugs is raised by displacement from albumin by sulfonamides
What skin condition can sulfonamides cause?
Photosensitivity
Which two drugs inhibit dihydrofolate reductase?
Trimethoprim and pyrimethamine
Which drugs can be dosed with sulfonamides for synergistic inhibition of bacterial DNA synthesis?
Trimethoprim and pyrimethamine
What reaction is catalyzed by dihydrofolate reductase?
The conversion of dihydrofolic acid to tetrahydrofolic acid
Why are trimethoprim and sulfamethoxazole used in combination?
To cause the sequential block of folate synthesis and synergistic inhibition of DNA synthesis
Trimethoprim-sulfamethoxazole is used to treat what pulmonary infection of HIV-positive patients?
Pneumocystis jirovecipneumonia
Trimethoprim-sulfamethoxazole is used to treat which infections?
Recurrent urinary tract infections, Shigella, Salmonella, and (in HIV-positive patients) Pneumocystis jiroveci pneumonia
What part of the body is most affected by the adverse effects of trimethoprim-sulfamethoxazole treatment?
The blood cell precursors in bone marrow (remember: TMP Treats Marrow Poorly)
What hematologic toxic effects are seen with the use of trimethoprim-sulfamethoxazole?
Megaloblastic anemia, leukopenia, and granulocytopenia (remember: TMP Treats Marrow Poorly)
The toxic bone marrow effects seen with the use of trimethoprim-sulfamethoxazole may be alleviated with the administration of what supplement?
Folinic acid
Patients who do not tolerate sulfa drugs should not be given which drugs?
Sulfonamide antibiotics, sulfonylureas, sulfasalazine, and most diuretics (including furosemide, thiazides, and acetazolamide)
Name seven examples of fluoroquinolones.
Ciprofloxacin, norfloxacin, ofloxacin, sparfloxacin, moxifloxacin, gatifloxacin, and enoxacin
Fluoroquinolones inhibit what enzyme?
DNA gyrase (topoisomerase II)
Which organisms are targeted by fluoroquinolones?
Gram-negative rods (in the urinary and gastrointestinal tracts) including Pseudomonas, Neisseria, and some gram-positive organisms
Fluoroquinolones are contraindicated in pregnant women and children because of possible damage to what structure?
The cartilage (remember: fluoroquinoloneshurt attachments to your Bones)
What musculoskeletal adverse effects are seen in adults with fluoroquinolone toxicity?
Tendonitis and tendon rupture
What musculoskeletal complaints do children with fluoroquinolone toxicity have?
Leg cramps and myalgias
What is the mechanism of action of metronidazole?
Toxic metabolites formed in the bacterial cell damage DNA
Metronidazole is used with what two agents as “triple therapy” against Helicobacter pylori?
Bismuth and amoxicillin; another option for triple therapy is omeprazole, amoxicillin, and clarithromycin
What may happen when patients taking metronidazole consume alcohol?
Disulfiram-like reaction
Name two common adverse effects of metronidazole.
Headache and metallic taste
Name six infections that are treated using metronidazole.
Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes, Helicobacter pylori (remember: GET GAP on the Metro)
What is the mechanism of action of polymyxins?
They bind to the cell membrane, disrupting the osmotic properties of the bacterial cell (remember: PolyMYXins MIXup membranes)
Polymyxins are _____ (anionic/cationic) basic proteins that act like _____ (detergents/enzymes).
Cationic; detergents
What kind of infection are polymyxins used to treat?
Resistant gram-negative infections
What are the two major toxicities of polymyxins?
Neurotoxicity and acute renal tubular necrosis
What antimicrobial is used as prophylaxis against Mycobacterium tuberculosis infection?
Isoniazid
What antimicrobial is used as prophylaxis against Mycobacterium avium-intracelulare infection?
Azithromycin
Which drugs can be used to treat Mycobacterium leprae infection?
Dapsone, rifampin, and clofazimine
What are the four medications commonly used to treat Mycobacterium avium-intracellulare infection?
Azithromycin, rifampin, ethambutol, and streptomycin
Name five drugs that are commonly used as first-line antituberculosis treatment.
Isoniazid (INH), Streptomycin, Pyrazinamide, Rifampin, Ethambutol (remember: INH-SPiRE)
All antituberculosis drugs have what potential toxicity?
Hepatotoxicity
Name an important adverse effect of ethambutol.
Optic neuritis causing red-green color blindness
Ketoconazole can be used to treat which four systemic fungal infections?
Blastomycosis, coccidioidomycosis, histoplasmosis, and candidal infection
Aside from treating fungal infection, what else can ketoconazole be used to treat?
Hypercortisolism, due to its inhibition of hormone synthesis
What three toxicities are associated with the use of azole drugs?
The inhibition of hormone synthesis (gynecomastia), liver dysfunction (the inhibition of cytochrome P450), and fevers/chills
What two azoles are commonly used to treat topical fungal infections?
Clotrimazole and miconazole
Name six azole antifungal drugs.
Fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole and voriconazole
Flucytosine works by inhibiting _____ synthesis by conversion to 5-fluorouracil, which competes with _____.
DNA; uracil
Clinically, flucytosine is used to treat what broad category of infections?
Systemic fungal infections such as Candida and Cryptococcus
What toxicities are associated with flucytosine treatment?
Nausea, vomiting, diarrhea, and bone marrow suppression; flucytosine is an antimetabolite and has many of the same toxicities as chemotherapy
Which drug is flucytosine frequently paired with to treat systemic fungal infections?
Amphotericin B
How does caspofungin work?
Inhibits the synthesis of -glucan, which inhibits synthesis of the fungal cell wall
Clinically, caspofungin is used when a patient in infected with what organism?
Invasive aspergillus infections
Terbinafine inhibits which enzyme?
Squalene epoxidase
Terbinafine is used as treatment for infection with what organisms?
Terbinafine is used as treatment for infection with what organisms?
Dermatophytoses (onychomycosis)
By interfering with microtubule function, griseofulvin disrupts which biologic process in fungi?
Mitosis
Griseofulvin deposits in which tissues?
Keratin (nails); therefore, it is helpful in treatment of onychomycosis
Griseofulvin is used to treat which infections?
Superficial dermatophyte infection (ringworm, tinea)
Griseofulvin _____ (increases/decreases) warfarin metabolism because it _____ (increases/decreases) the activity of cytochrome P450.
Increases; increases
Name three toxicities associated with griseofulvin.
Headaches, confusion, and carcinogenicity
What patient population should griseofulvin not be given to?
Pregnant mothers (it is teratogenic)
Uncoating of a virus is blocked by which antiviral agent?
Amantadine
Amantadine specifically treats which infection by blocking viral uncoating?
Influenza A
Nucleic acid synthesis is blocked by which two antiviral classes?
Purine/pyrimidine analogs and reverse transcriptase inhibitors; usually antiretroviral drugs
Viral release from cells is blocked by which group of antiviral inhibitors?
Neuraminidase inhibitors (influenza)
What is the mechanism of action of amantadine when used as an antiviral agent?
Blocking viral penetration/uncoating (remember: “a man to dine” takes off his coat)
Amantadine is used to treat which two diseases?
Influenza A and Parkinsons disease
What three toxicities are associated with amantadine?
Ataxia, dizziness, and slurred speech; (remember: Amantadine blocks influenza A, and rubellA and causes problems with the cerebellA)
Which has fewer central nervous system adverse effects, amantadine or rimantidine?
Rimantidine, because it does not cross the blood-brain barrier
What is the mechanism of viral resistance to amantadine?
Mutated M2 protein has made 90% of all influenza A strains resistant to amantadine
In addition to use as an antiviral agent, why is amantadine useful in Parkinsons disease?
It causes release of dopamine from nerve terminals
Which enzymes do zanamivir and oseltamivir (Tamiflu) inhibit?
Influenza neuraminidase, decreasing release of progeny virus
Which strains of influenza do zanamivir and oseltamivir (Tamiflu) inhibit?
Both influenza A and B
The mechanism of action of ribavirin is through inhibiting the synthesis of _____ nucleotides by competitively inhibiting the enzyme _____ _____ _____.
Guanine; inosine monophosphate dehydrogenase
Which two infections is ribavirin used to treat?
Chronic hepatitis C virus and respiratory syncytial virus
What is a potential toxicity of ribavirin use?
Hemolytic anemia
What patient population should ribavirin not be given to?
Pregnant mothers (it is teratogenic)
What is the mechanism of action of acyclovir?
Acyclovir is a guanosine analog that terminates chains of viral DNA into which it is incorporated
Name three viruses for which acyclovir is used.
Herpes simplex virus, varicella zoster virus, and Epstein-Barr virus
Should acyclovir be used to treat herpes zoster?
No; famciclovir is more effective
What is the mechanism of resistance developed by viruses to counteract acyclovir?
Loss of viral thymidine kinase
True or False? Acyclovir is effective against latent herpes simplex virus and varicella-zoster virus infections.
False; it has no effect on latent forms of these infections
Acyclovir is used to treat herpes infections in what areas/organs?
Mucocutaneous (cold sores), genital, herpes simplex virus encephalitis
Why does acyclovir interfere with viral DNA synthesis and not human DNA synthesis?
Acyclovir requires monophosphorylation by herpes simplex virus/varicella zoster virus thymidine kinase and formation of a triphosphate form by cellular enzymes
How do viruses develop resistance to acyclovir?
Lack of thymidine kinase
How does ganciclovir work?
Ganciclovir is a guanosine analog that inhibits viral DNA polymerase
Which viral infection is ganciclovir used to treat?
Cytomegalovirus (in immunocompromised patients)
What four toxicities are associated with ganciclovir use?
Leukopenia, neutropenia, thrombocytopenia, and renal toxicity
Leukopenia, neutropenia, thrombocytopenia, and renal toxicity
Mutated viral DNA polymerase, lack of viral kinase
Which drug is more toxic, acyclovir or ganciclovir?
Ganciclovir
What modifications must ganciclovir undergo before becoming active?
Formation of a 5’ -monophosphate by either herpes simplex virus/varicella zoster virus thymidine kinase or cytomegalovirus viral kinase and a triphosphate by cellular kinases; this process ensures that it targets viral replication and spares human cells.
Foscarnet ____ (does/does not) require activation via phosphorylation by viral kinase.
Does not
Foscarnet inhibits viral _____ (DNA/RNA) polymerase by binding to the _____ binding site of viral kinase.
DNA; pyrophosphate (remember: FOScarnet is a pyroFOSphate analog)
For which two infections is foscarnet used?
Cytomegalovirus retinitis in the immunocompromised and acyclovir-resistant herpes simplex virus
What is the major toxicity of foscarnet?
Nephrotoxicity
Mutation in which enzyme allows cytomegalovirus or herpes simplex virus to be resistant to foscarnet treatment?
DNA polymerase
Protease inhibitors end in which suffix?
-navir (remember: NAVIR [never] Tease a ProTEASEinhibitor)
Name five protease inhibitors.
Saquinavir, ritonavir, indinavir, nelfinavir, and amprenavir
What are the major toxicities of most protease inhibitors?
Gastrointestinal intolerance (nausea, diarrhea), hyperglycemia, and lipid abnormalities
What adverse effect is specific to indinavir?
Thrombocytopenia
Name six nucleoside reverse transcriptase inhibitors.
Zidovudine, didanosine, zalcitabine, stavudine, lamivudine, and abacavir (remember: Have YOU DINED[vudine] with my NUCLEAR family?)
Name three nonnucleoside reverse transcriptase inhibitors.
Nevirapine, Efavirenz, Delavirdine (remember: Never Ever Deliver nucleosides)
Reverse transcriptase inhibitors prevent which viral process from occurring?
Incorporation of viral DNA into the host genome
What toxicities are associated with both nucleoside and nonnucleoside reverse transcriptase inhibitors?
Neutropenia, anemia, and peripheral neuropathy
Which cause lactic acidosis: nucleoside reverse transcriptase inhibitors or nonnucleoside reverse transcriptase inhibitors?
Nucleoside reverse transcriptase inhibitors
Which cause rash: nucleoside reverse transcription inhibitors or nonnucleoside reverse transcriptase inhibitors?
Nonnucleoside reverse transcriptase inhibitors
What nucleoside reverse transcriptase inhibitor used to treat HIV can cause a megaloblastic anemia?
Zidovudine
What is the name of the combination therapy that is used to treat HIV and that includes a cocktail of protease inhibitors and reverse transcriptase inhibitors?
Highly active antiretroviral therapy
Which nucleoside reverse transcriptase inhibitor is used for general prophylaxis and during pregnancy to reduce fetal transmission risk?
Zidovudine
At what point should highly active antiretroviral therapy be initiated in an HIV-positive individual?
When the viral load is high or when CD4+ cell count is < 500 cells/mm³
In the treatment of HIV infection, what viral process does enfuvirtide inhibit?
Fusion
What toxicities are associated with enfuvirtide?
Hypersensitivity reactions, subcutaneous injection site reaction, increased risk of bacterial pneumonia
How does enfuvirtide block entry and replication of viruses?
Binding the gp41 subunit, inhibiting the conformational shift required for CD4 cell fusion
When is enfuvirtide used clinically?
It is added to other antiretroviral drugs when standard regimens have failed
How can the bone marrow suppression associated with reverse transcriptase inhibitors be reduced?
By treatment with granulocyte-macrophage colony-stimulating factor and erythropoietin
What viral process is blocked by enzyme inhibition with protease inhibitors?
Maturation of new viruses
What are interferons?
Endogenous human glycoproteins that induce an anti-viral state in cells
What two clinical conditions are treated by interferon therapy?
Chronic hepatitis B and C virus infections and Kaposi sarcoma
What clinical condition is treated by interferon beta-1a therapy?
Multiple sclerosis
What clinical condition is treated by interferon γ therapy?
Nicotinamide adenine dinucleotide phosphate oxidase deficiency
What is the major toxicity of the interferons?
Neutropenia
In addition to blocking viral DNA and RNA synthesis, interferons also induce what enzyme to encourage viral mRNA degradation?
Ribonuclease
