Antifungal Drug Classes Quiz

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15 Questions

Which drug can cause increased creatinine without renal failure?

Tenofovir (TDF)

What is the mechanism of action of protease inhibitors in HIV treatment?

Blocks protease cleavage of viral gag and gag-pol polyproteins

Which drug induces CYP3A4 and may interact with statins, rifampin, and fluticasone?

Lopinavir

What side effect is commonly seen with HIV protease inhibitors?

Hyperlipidemia

Which drug is a safer version with minimal side effects but can still cause neural tube defects if given during conception?

Dolutegravir

Which drug class does Tenofovir (TDF) belong to?

NRTI

What is the mode of action of integrase inhibitors like Raltegravir?

Prevents insertion of linear HIV-1 DNA into host DNA

Which drug may cause lipodystrophy, renal stones, gallstones, and insulin resistance?

Dolutegravir

What is the mechanism of action of entrivirine?

Reversible noncompetitive inhibitor of HIV reverse transcriptase > binds to an allosteric site (not RT active site)> blocks RNA-/DNA-dependent DNA polymerase action

Which antifungal drug class binds to ergosterol in the fungal cell membrane?

Polyene antifungal

What is the most common side effect associated with Isoniazid use in treating Mycobacterium tuberculosis?

Hepatitis

Which HIV drug class interferes with HIV entry into cells by blocking the CCR5 receptor?

CCR5 inhibitor

What is the mechanism of action of Enfuvirtide, an HIV Fusion Inhibitor?

Inhibits fusion with CD4+ cell membrane

Which nucleotide reverse transcriptase inhibitor causes lipodystrophy/fat atrophy, especially in the face and arms?

Didanosine (ddl)

Which antifungal drug class is least effective against cryptococcus and mucorales?

Echinocandins

Study Notes

Antifungal Agents

  • Polyene antifungal: Amphotericin B
    • Binds to ergosterol in fungal cell membrane, creating pores
    • Side effects: anemia, nephrotoxicity, infusion-related reactions
    • Lipid formulations are less nephrotoxic
  • Antimetabolite antifungal: 5-flucytosine (5-FC)
    • Blocks fungal DNA synthesis
    • Works synergistically with amphotericin B
    • Side effects: bone marrow suppression, hepatitis
  • Azole antifungals:
    • Ketoconazole (Imidazole)
      • Inhibits lanosterol demethylase, reducing membrane structure integrity
      • Side effects: increased liver function tests (LFTs), endocrine abnormalities, gynecomastia, menstrual irregularities, impotence
    • Fluconazole (Triazole)
      • Inhibits lanosterol demethylase, reducing membrane structure integrity
      • Side effects: increased LFTs, endocrine abnormalities, alopecia, hepatitis
    • Itraconazole (Triazole)
      • Inhibits lanosterol demethylase, reducing membrane structure integrity
      • Side effects: increased LFTs, endocrine abnormalities, CHF, GI upset
    • Voriconazole (Triazole)
      • Inhibits lanosterol demethylase, reducing membrane structure integrity
      • Side effects: increased LFTs, endocrine abnormalities, visual disturbances, skin photosensitivity
    • Posaconazole (Triazole)
      • Inhibits lanosterol demethylase, reducing membrane structure integrity
      • Side effects: increased LFTs, endocrine abnormalities, N/V/D
  • Echinocandins:
    • Caspofungin, Micafungin, Anidulafungin
      • Block fungal enzyme glucan synthase, leading to cell wall leakage
      • Side effects: allergic reactions, anaphylaxis, fever, accumulation in liver disease

Anti-Tuberculosis Agents

  • Rifampin:
    • Inhibits DNA-dependent RNA polymerase
    • Side effects: orange body fluids, nephritis, skin rash, thrombocytopenia, liver dysfunction, GI distress
  • Isoniazid:
    • Inhibits synthesis of mycolic acid, disrupting cell wall
    • Side effects: hepatotoxicity, abnormal LFTs, jaundice, hepatitis, peripheral neuritis, CNS effects
  • Pyrazinamide:
    • Deaminates to pyrazinoic acid, converting to a lipid-soluble form that enters the bacillus
    • Side effects: hepatotoxicity, 40% of patients develop nongouty polyarthralgia, hyperuricemia, polyuria, GI irritation
  • Ethambutol:
    • Inhibits arabinosyl transferases, involved in synthesis of arabinogalactan, a component of mycobacterial cell walls
    • Side effects: dose-dependent visual disturbances, always given in combination with other drugs

HIV Agents

  • CCR5 inhibitor: Maraviroc
    • Blocks CCR5 receptor, interfering with HIV entry into cells
    • Side effects: allergic reactions, rash, hepatotoxicity, substrate of CYP3A4
  • Fusion inhibitor: Enfuvirtide
    • Binds to gp41, inhibiting fusion with CD4+ cell membrane
    • Side effects: injection site reactions, bacterial pneumonia, hypersensitivity
  • NRTIs (Nucleoside Reverse Transcriptase Inhibitors):
    • Lamivudine (3TC), Emtricitabine (FTC)
      • Cytidine analog triphosphorylation to active form, shutting down HIV reverse transcriptase
      • Side effects: lipodystrophy, fat atrophy, bone marrow suppression, peripheral neuropathy, lactic acidosis, pancreatitis
    • Zidovudine (ZDV), Stavudine (d4T)
      • Thymidine analog triphosphorylation to active form, shutting down HIV reverse transcriptase
      • Side effects: anemia, bone marrow suppression, peripheral neuropathy, lactic acidosis, pancreatitis
  • NRTIs (Nucleotide Reverse Transcriptase Inhibitors):
    • Didanosine (ddl), Tenofovir (TAF)
      • Adenosine analog triphosphorylation to active form, shutting down HIV reverse transcriptase
      • Side effects: pancreatitis, bone marrow suppression, peripheral neuropathy, lactic acidosis, kidney toxicity
  • Integrase inhibitors:
    • Dolutegravir, Bictegravir, Elvitegravir
      • Prevents insertion of linear HIV-1 DNA into host DNA, preventing formation of HIV-1 provirus
      • Side effects: minimal, can cause increased creatinine without renal failure
  • Protease inhibitors:
    • Darunavir, Atazanavir, Fosamprenavir, Lopinavir, Indinavir, Saquinavir, Ritonavir, Tipranavir
      • Prevents protease cleavage of viral gag and gag-pol polyproteins, forming immature noninfectious viral particles
      • Side effects: lipodystrophy, hyperlipidemia, renal stones, gallstones, insulin resistance, CV effects

Diabetes and Hypertension Agents

  • Metformin:
    • Decreases hepatic gluconeogenesis, enhances insulin sensitivity in muscle and adipose tissue
    • Side effects: GI upset, gas
  • Sulfonylureas:
    • Glipizide
      • Increases insulin secretion from pancreatic beta cells
      • Side effects: hypoglycemia, weight gain
  • GLP-1 agonists:
    • Exenatide
      • Stimulates GLP-1 receptor, prolonging activity, decreasing glucagon secretion, and increasing insulin secretion and sensitivity
      • Side effects: delayed gastric emptying, nausea, pancreatitis
  • TZDs (Thiazolidinediones):
    • Pioglitazone
      • Increases insulin sensitivity in muscle and adipose tissue
      • Side effects: cannot be used in HF, decreases hepatic gluconeogenesis
  • Meglitinides:
    • Repaglinide
      • Increases insulin secretion from pancreatic beta cells in the presence of glucose
      • Side effects: hypoglycemia, weight gain
  • SGLT-1 inhibitors:
    • Canagliflozin
      • Inhibits glucose reabsorption in the proximal tubule of the kidney, enhancing glycosuria
      • Side effects: UTIs, GU infections, hypovolemia, AKI
  • DPP-4 inhibitors:
    • Sitagliptin
      • Increases GLP-1 through inhibition of DPP-IV, decreasing glucagon and increasing insulin secretion
      • Side effects: minimal, 0.7-1% risk of pancreatitis
  • Alpha-glucosidase inhibitors:
    • Acarbose
      • Inhibits carbohydrate absorption in the small intestine
      • Side effects: GI upset, 0.3-1% risk of pancreatitis

Other Agents

  • GABA analog:
    • Gabapentin
      • Binds to the alpha2delta subunit of voltage-gated calcium channel, reducing calcium entry into the neuron and glutamate release
      • Side effects: somnolence, dizziness, ataxia, respiratory depression, increased agitation
  • ACE-i/ARBs:
    • Lisinopril, Captopril, Losartan, Candesartan
      • Reduce effects of angiotensin II
      • Side effects: cough, angioedema, hyperkalemia, prevention of diabetic retinopathy and nephropathy
  • Statins:
    • -statin
      • Inhibition of HMG-CoA reductase
      • Side effects: muscle weakness, rhabdomyolysis, management of diabetic HLD and prevention of STEMI

SLE Agents

  • Antimalarial:
    • Hydroxychloroquine
      • Inhibits phagosome function, reducing TLR activity, downregulating IFNa, and reducing antigen processing on APCs
      • Side effects: ocular exam required, first-line drug, used in combination with steroids/NSAIDs
  • Corticosteroids:
    • Prednisone
      • Reduces proinflammatory genes, affecting innate and acquired immunity
      • Side effects: long-term toxicities, mainstay SLE flare treatment
  • Chemotherapy:
    • Cyclophosphamide
      • Alkylation of DNA
      • Side effects: extremely toxic, small, short doses, standard of care for lupus nephritis, often with steroids
  • Inosine monophosphate dehydrogenase inhibitor:
    • Mycophenolate mofetil (MMF)
      • Inhibits Inosine monophosphate dehydrogenase, disrupting de novo synthesis of guanosine nucleotides, reducing T and B cell proliferation
      • Side effects: will decrease steroid requirements for patients treated with higher-than-

Test your knowledge on antifungal drug classes, including polyene antifungals and antimetabolite antifungals, their mechanisms of action, indications, and common side effects.

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