Micro - Antimicrobials Part 2 Flashcards by Krishnaa Pandya

Patients with what enzyme deficiency can suffer additional toxicities of sulfonamide antibiotics?

People with glucose-6-phosphate dehydrogenase deficiency will get hemolytic anemia

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Sulfonamides can cause which renal pathology?

Tubulointerstitial nephritis

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What neurologic injury can sulfonamides cause in infants?

Kernicterus

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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

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What skin condition can sulfonamides cause?

Photosensitivity

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Which two drugs inhibit dihydrofolate reductase?

Trimethoprim and pyrimethamine

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Which drugs can be dosed with sulfonamides for synergistic inhibition of bacterial DNA synthesis?

Trimethoprim and pyrimethamine

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What reaction is catalyzed by dihydrofolate reductase?

The conversion of dihydrofolic acid to tetrahydrofolic acid

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Why are trimethoprim and sulfamethoxazole used in combination?

To cause the sequential block of folate synthesis and synergistic inhibition of DNA synthesis

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Trimethoprim-sulfamethoxazole is used to treat what pulmonary infection of HIV-positive patients?

Pneumocystis jirovecipneumonia

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Trimethoprim-sulfamethoxazole is used to treat which infections?

Recurrent urinary tract infections, Shigella, Salmonella, and (in HIV-positive patients) Pneumocystis jiroveci pneumonia

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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)

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What hematologic toxic effects are seen with the use of trimethoprim-sulfamethoxazole?

Megaloblastic anemia, leukopenia, and granulocytopenia (remember: TMP Treats Marrow Poorly)

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The toxic bone marrow effects seen with the use of trimethoprim-sulfamethoxazole may be alleviated with the administration of what supplement?

Folinic acid

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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)

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Name seven examples of fluoroquinolones.

Ciprofloxacin, norfloxacin, ofloxacin, sparfloxacin, moxifloxacin, gatifloxacin, and enoxacin

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Fluoroquinolones inhibit what enzyme?

DNA gyrase (topoisomerase II)

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Which organisms are targeted by fluoroquinolones?

Gram-negative rods (in the urinary and gastrointestinal tracts) including Pseudomonas, Neisseria, and some gram-positive organisms

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Fluoroquinolones are contraindicated in pregnant women and children because of possible damage to what structure?

The cartilage (remember: fluoroquinoloneshurt attachments to your Bones)

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What musculoskeletal adverse effects are seen in adults with fluoroquinolone toxicity?

Tendonitis and tendon rupture

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What musculoskeletal complaints do children with fluoroquinolone toxicity have?

Leg cramps and myalgias

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What is the mechanism of action of metronidazole?

Toxic metabolites formed in the bacterial cell damage DNA

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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

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What may happen when patients taking metronidazole consume alcohol?

Disulfiram-like reaction

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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

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