Infectious Disease Drugs 2 Lecture Notes PDF

**Lecture Notes** **INFECTIOUS DISEASE DRUGS 2** I **Anti-Virals: Non-HIV** A. [Herpes Virus] 1\. Def: Herpes simplex virus (HSV): infections of mouth, face, genitalia Varicella-zoster virus (VZV): chicken pox and herpes zoster (shingles) 2\. [Meds for HSV]: acyclovir/*Zovirax* valacyclovir...

**Lecture Notes** **INFECTIOUS DISEASE DRUGS 2** I **Anti-Virals: Non-HIV** A. [Herpes Virus] 1\. Def: Herpes simplex virus (HSV): infections of mouth, face, genitalia Varicella-zoster virus (VZV): chicken pox and herpes zoster (shingles) 2\. [Meds for HSV]: acyclovir/*Zovirax* valacyclovir/*Valtrex* famciclovir/*Famvir* a\. [Acyclovir/*Zovirax*] MOA: inhibits viral production by suppressing synthesis of viral DNA, activated by enzyme -- enzyme converts acyclovir into a compound that inhibits viral DNA polymerase. IND: oral herpes simplex genital herpes simplex varicella herpes zoster AE: oral: GI upset, HA IV: irritation at site of infusion, nephrotoxicity DI: any nephrotoxic drug Nursing: infuse IV slowly, inc fluid intake B. [Cytomegalovirus] 1\. [Def]: herpes virus family, remains dormant, reactivated in immune compromised pts. Causes infections in GI tract, lungs, eyes. 2\. [Meds for CMV]: ganciclovir/*Cytovene, Vitrasert* valganciclovir/*Valcyte* cidofovir/*Vistide* a\. [Ganciclovir/*Cytovene*] MOA: suppresses synthesis of viral DNA IND: CMV retinitis in immunocompromised pts CMV prevention is transplant pts AE: bone marrow suppression reproductive toxicity Nursing: monitor WBC count, platelet count C. [Hepatitis] 1\. [Def]: inflammation of the liver, viral infection. 2\. [Patho]: widespread inflammation of liver tissue causing hepatic cell scarring, necrosis and degeneration, may also interrupt bile flow. 3\. [Meds for Hepatitis]: interferon alfa/*Intron A, Roferon-A* ribavirin/*Rebetol* lamivudine/E*pivir* adefovir/*Hepsera* simeprevir/*Olysia* sofosbuvir/*Solvaldi* a\. [Interferon alfa] MOA: binds to receptors on host cell membrane and blocks viral entry into cells. Also blocks synthesis of viral mRNA, viral proteins, blocks viral assembly and release IND: chronic hepatitis B and C AE: flu-like symptoms depression heart damage, bone marrow suppression D. [Influenza] 1\. Def: respiratory tract infection - fever, chills, cough, sore throat, muscle aches. 2\. [Meds for Influenza]: Vaccines primary management strategy. oseltamivir/*Tamiflu* zanamivir/*Relenza* amantadine/*Symmetrel* rimantadine/*Flumadine* a\. [Oseltamivir/*Tamiflu*] MOA: stops viral spread by inhibiting enzyme needed for replication IND: prophylaxis/treatment for Influenza A and B treatment of H1N1, H5N1 AE: n/v DI: influenza vaccine II\. **Antivirals: HIV** A. [Def]: causes AIDS. Immune system becomes incompetent due to depletion of T-cells, risk for opportunistic infections. B. [Replication of HIV/Meds sites]: HIV - RNA virus -- retrovirus. 1\. HIV attaches to cell, bind to specific CD4 receptor sites on host cells (CCR5 antagonist, post-attachment inhibitors -- both new) 2\. Once bound virus fuses with host cell membrane and enters cell (fusion inhibitor) 3\. Viral RNA is transcribed into viral DNA with reverse transcriptase. (reverse transcriptase inhibitors) 4\. Viral DNA enters host nucleus, becomes integrated into host DNA with enzyme integrase. (Integrase strand transfer inhibitor) 5\. Viral DNA permanent part of cells genetic structure, cells divide, more HIV production. HIV final maturation under influence of enzyme, protease. (protease inhibitors) C. [Meds for HIV]: ART (anti-retroviral therapy). 1\. Reverse transcriptase inhibitors a\. nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) b\. non-nucleoside reverse transcriptase inhibitors (NNRTIs) 2\. Protease inhibitors 3\. Integrase strand transfer inhibitor 4\. HIV fusion inhibitors D. [Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)] NRTIs first drugs, similar structure to nucleosides, nucleotides that make up DNA Ex: abacavir/*Ziagen* lamivudine/*Epivir* zidovudine + lamivudine/*Combivir* zidovudine + lamivudine + abacavir/*Trizivir* stavudine/*Zerit* didanosine/*Videx* 1\. [Abacavir/*Ziagen* ] MOA: inhibits HIV replication by suppressing synthesis of viral DNA by reverse transcriptase, inhibits activity of viral enzyme -\> premature termination of DNA strand IND: HIV AE: syndrome of lactic acidosis with hepatomegaly hypersensitivity reactions GI MI DI: alcohol Nursing: monitor arterial blood gas if suspect acidosis monitor liver function E. [Non-nucleoside reverse transcriptase inhibitors (NNRTIs)] NNRTIs not structurally related to nucleosides. Ex: efavirenz/*Sustiva, EPV* nevirapine/*Viramune* delavirdine/*Rescriptor* 1\. [Efavirenz/*Sustiva*] MOA: binds directly to HIV reverse transcriptase, suppresses enzyme activity IND: HIV -- usually used in combo with zidovudine and another NRTI AE: CNS symptoms rash liver damage teratogenic DI: competes with other drugs for metabolism by P450 induces P450 Nursing: empty stomach, high fat meals inc plasma levels, monitor liver fxn F. [Protease Inhibitors] not used alone, risk of drug resistance. Combine with reverse transcriptase inhibitors. Ex: darunavir/*Prezista* ritonavir/*Norvir* indinavir/*Crixivan* saquinavir/*Invirase, Fortovase* nelfinavir/*Viracept* atazanavir/*Reyataz* 1\. [Darunavir/*Prezista* ] MOA: binds to HIV protease, prevents enzyme from cleaving HIV polyproteins - virus remains immature and noninfectious IND: HIV AE: hyperglycemia fat maldistribution hyperlipidemia reduced bone mineral density hepatotoxicity DI: P450 inhibitors: grapefruit juice, ketoconazole P450 inducers: rifampin, antiseizure meds Nursing: monitor blood sugar, teach pt S&S of hyperglycemia, monitor LFT G. [Integrase strand transfer inhibitor] Ex. raltegravir/*Isentress* dolutegravir/*Tivicay* 1\. Raltegravir/*Isentress* MOA inhibits viral enzyme integrase, prevents integration of viral DNA into host DNA AE headache, insomnia hypersensitivity reactions -- skin, liver DI minimal H. [HIV Fusion Inhibitors] 1\. [Enfuvirtide/*Fuzeon, T-20*] MOA: prevents HIV from fusing with cell membrane of CD4 cells. blocks entry IND: HIV infections that are resistant to other antiretrovirals AE: injection site reaction pneumonia hypersensitivity reaction hypersensitivity reaction DI: minimal III\. **Anti- Fungals** A. [Types of Infections]: 1\. [Systemic infections:] a\. opportunistic: candidiasis, aspergillosis, cryptococcosis, mucormycosis. b\. non-opportunistic: sporotrichosis, blastomycosis, histoplasmosis, coccidioidomycosis 2\. [Superficial infections]: a\. candidiasis b\. dermatophytic infections tinea pedis, tinea corporus, tinea cruris, tinea capitis B. [Types of Antifungals]: 1\. Polyenes: amphotericin B/*AmBisome, Amphotec* nystatin/*Mycostatin* 2\. Azoles: itraconazole/*Sporanox* fluconazole/*Diflucan* ketoconazole/*Nizoral* clotrimazole/*Mycelex, Gyne-Lotrimin* C. [Polyenes] 1\. [Amphotericin B] MOA: binds to ergosterol -- component of the fungal cell membrane, causes inc in cell permeability, cells leak intracellular components, no longer viable IND: broad spectrum for systemic fungal infections AE: infusion reactions nephrotoxicity hypokalemia bone marrow suppression DI: other nephrotoxic agents Nursing: monitor creatinine, K level, I&O, RBC count 2\. [Nystatin] IND: candidiasis oral, esophageal: suspension, lozenges, tablets skin: cream, ointments, powder vaginal: vag tablets AE: oral topical D. [Azoles:] 1\. [Itraconazole] MOA: inhibits synthesis of ergosterol. Without ergosterol, leakage of cellular components. IND: broad spectrum for systemic fungal infections. Alt to Ampho B AE: hepatotoxicity cardiac suppression DI: warfarin, digoxin, oral hypoglycemic agents antacids IV\. **Meds for Tuberculosis** A. [Def]: Infectious disease caused by Mycobacterium tuberculosis B. [Patho]: Airborne droplets. Bacillus inspired into lung \--\> inflammation. Inflammation causes neutrophil and macrophage activity. Engulf bacilli, sealed off, forming tubercle lesion. Infected tissue within tubercle dies, scar tissue grows around lesion. C. [Meds for TB]: Ex. First line isoniazid/*INH* rifampin/*Rimactane* pyrazinamide/*PZA* ethambutol/*Myambutol* rifabutin/*mycobutin* Second line streptomycin ethionamide/*Trecator* amikacin/*Amikin* kanamycin/*Kantrex* cycloserine/*Seromycin* levofloxacin/*Levaquin* 1\. [Isoniazid/*INH*] MOA: may inhibit synthesis of mycolic acid IND: used as single drug for prophylaxis of TB used in combo with other anti-TB drugs for treatment AE: hepatotoxicity peripheral neuropathy DI: dilantin, warfarin alcohol, rifampin Nursing: teach pt about signs of liver disease, monitor liver enzyme levels 2\. [Rifampin/*Rimactane*] MOA: inhibits mycobacterial protein synthesis IND: treatment of active TB in combination with another drug AE: hepatotoxicity discoloration of body fluids DI: oral contraceptive, warfarin, dilantin alcohol, isoniazid: inc risk of liver injury