antiviral

• anti-viral (herpes simplex, herpes zoster)
• -Guanosine analog (no 3'-OH)
• -prodrug-->phos-by host kinase-->phos by viral-Thymidine kinase (TK)-->incorp, terminate DNA chain
• -short half life!

• USE-HSV, VZV, EBV
• -topical, oral, IV (encephalitis)
• -reduce shedding, BUT only works on replicating stage (NOT dormant latency)
• -prophylactic in immunocompromised
• (for Herpes zoster, use similar agent Famciclovir)

• SE- minor with oral , more with IV
• -Crystalluria, neurotoxicity
• -NOT hematotoxic (b/c activated by Herpes-specific TK!)

Resistance- TK negative strains, changes in DNA pol.

• anti-viral (herpes simplex, herpes zoster)
• -Guanosine analog (no 3'-OH)-prodrug-->phos-by host kinase-->phos by viral-Thymidine kinase (TK)-->incorp, terminate DNA chain
• -newer than Acyclovir, longer half life

USE- HSV (acyclovir resistant ones)

Resistance- TK negative strains.

• anti-viral (herpes simplex, herpes zoster)
• -Guanosine analog (no 3'-OH)-prodrug-->phos-by host kinase-->phos by viral-Thymidine kinase (TK)-->incorp, terminate DNA chain
• -newer than Acyclovir, longer half life

USE- HSV (acyclovir resistant ones)

Resistance- TK negative strains.

• anti-viral (herpes simplex, herpes zoster, CMV)
• -Guanosine analog
• -first phos by viral-specific (TK by HSV/VZV or phosphtransferase in CMV)
• -but CAN be phos by cellular kinases
• -similar to Acyclovir, but MORE toxic

USE-CMV prophylaxis for AIDs!!

• SE-dose-limiting hematotoxicity (leukopenia, thrombocytopenia), mucositis, fever, rash, crystalluria
• -seizure in overdose
• -nephrotoxicity

• anti-viral
• -NOT antimetabolite like acyclovir or gnaciclovir
• -inhibit viral DNA and RNA polymerases(bind PPi binding site)
• -does NOT req activation by viral kinase

• USE- CMV retinitis in AIDS when ganciclovir fails.
• -acyclovir-resistant HSV

• SE- nephrotoxicity!!
• do NOT use with Pentamidine (pneumocystis infection in AIDS)- also nephrotoxic so additive!--> ACN, hypocalcemia!!

broad spectrum antiviral Cyt-analog- doesn't need to be phosphorylated

started when paitients present with AIDs defining illness, CD4 < 350 or high viral load

• -3 drugs
• -2 nucleoside reverse transcriptase inhibitors (NRTIs) + 1 protease inhibitor
• OR
• -2 NRTIs + 1 non-nucleoside reverse-transcriptase inhibitor

• Nucleoside reverse transcriptase inhibitors
• -prodrug--> phos by TK (or other)--> competitively inhibit nucleotide binding to reverse transcriptase--> chain termination
• -used w/ protease inhibitors

• SE- marrow suppression! (can be activated by nonspecific kinases)-reverse with GM-CSF
• -peripheral neuropathy, lactic acidosis, megaloblastic anemia.

- Zidovudine, Didanosine, Zalcitabine, Stavudine

• non-nucleoside reverse transcriptase inhibitors
• -NOT prodrug
• -does NOT need to be phos
• -inhibit reverse transcriptase
• -additive/synergistic with NRTIs
• -NOT marrow suppressant!

-Nevirapine, Efavirenz, Declaviridine

• non-nucleoside reverse transcriptase inhibitor
• -NOT prodrug
• -does NOT need to be phos -inhibit reverse transcriptase
• -additive/synergistic with NRTIs
• -NOT marrow suppressant!

• USE- HIV/AIDS
• -decrease vertical transmission by 50%!!

SE-rash, induce CYP3A4, liver toxicity

• non-nucleoside reverse transcriptase inhibitor
• -NOT prodrug
• -does NOT need to be phos
• -inhibit reverse transcriptase
• -additive/synergistic with NRTIs
• -NOT marrow suppressant!

USE- HIV/AIDS

SE- insomnia, night mares!!

• NRTI (anti-HIV)
• -AZT
• -Thymidine analog
• -phos nonspecifically to triphosphate-->inhibit reverse transciptase

• USE- HIV/AIDS
• -prophylaxis dur pregnancy to reduce vertical transmission.

SE- marrow suppression (most severe!),Megaloblastic anemia, myopathy, peripheral neuropathy

Resistance- mutation in pol gene

• NRTI(anti-HIV)
• -ddI
• -Inosine analog (Inosine--> purine (A,G)
• -phos nonspecifically to triphosphate-->inhibit reverse transciptase

USE- HIV/AIDS

SE-pancreatitis, peripheral neuropathy, hyperuricemia, liver toxic

• NRTI (anti-HIV)
• -ddC
• -Cytosine analog
• -phos nonspecifically to triphosphate-->inhibit reverse transciptase

USE- HIV/AIDS

• SE-peripheral neuropathy (major!)
• diarrhea, pancreatitis, neutropenia, rash

• NRTI (anti-HIV)
• -d4T
• -Thymidine analog like zidovudine
• -phos nonspecifically to triphosphate-->inhibit reverse transciptase

USE- HIV/AIDS

• SE-peripheral neuropathy (major!)
• myelosuppression less than Zidovudine
• -do NOT use with Zidovudine!

• NRTI (anti-HIV)
• -3TC
• -Cytosine analog
• -phos nonspecifically to triphosphate-->inhibit reverse transciptase

USE-HIV/AIDS, Hepatitis B!!

• SE- least toxic! so least potent
• GI effects, neutropenia.

• NRTI (anti-HIV)
• -ABC
• -phos nonspecifically to triphosphate-->inhibit reverse transciptase

USE- HIV/AIDS

SE-allergies!

ddI+ ddC- additive toxicity of peripheral neuropathy and pancreatitis

d4T + AZT- competition b/c both Thymine analogs

• protease inhibitor (anti-HIV)
• -inhibit aspartate protease (pol gene encoded- cleave precursor viral protein to active ones)
• -inhibit unique dipeptide structure on aspartate protease (absent in us)

USE-HIV/AIDS

• SE-least toxic, but very low bioavailability. TOO much resistance now, so doens't work..
• -Hyperglycemia, DM, nausea, diarrhea

Resistance-point mutation in pol gene

• protease inhibitor (anti-HIV)
• -inhibit aspartate protease (pol gene encoded- cleave precursor viral protein to active ones)
• -inhibit unique dipeptide structure on aspartate protease (absent in us)

USE- HIV/AIDS

• SE-CYP activate, inhibit!! so much drug interactions!!
• Hyperglycemia, nausea, diarrhea

• protease inhibitor (anti-HIV)
• -inhibit aspartate protease (pol gene encoded- cleave precursor viral protein to active ones)
• -inhibit unique dipeptide structure on aspartate protease (absent in us)

USE- HIV/AIDS

SE-Hyperglycemia, crystalluria, thrombocytopenia

• protease inhibitor (anti-HIV)
• -inhibit aspartate protease (pol gene encoded- cleave precursor viral protein to active ones)
• -inhibit unique dipeptide structure on aspartate protease (absent in us)

USE- HIV/AIDS

SE-Hyperglycemia, nausea, diarrhea

• protease inhibitor (anti-HIV)
• -inhibit aspartate protease (pol gene encoded- cleave precursor viral protein to active ones)
• -inhibit unique dipeptide structure on aspartate protease (absent in us)

USE- HIV/AIDS

SE-Hyperglycemia, diarrhea, nausea

• protease inhibitor (anti-HIV)
• -inhibit aspartate protease (pol gene encoded- cleave precursor viral protein to active ones)
• -inhibit unique dipeptide structure on aspartate protease (absent in us)
• newer! NO hyperglycemia DM SE!

USE- HIV/AIDS

• Fusion inhibitor (anit-HIV)
• -bind, inhibit gp41-->steric hindrance so gp120 cannot bind CD4
• -gp120 mutates much more frequent than gp41

USE-early HIV/AIDS drug!

SE-hypersensitivity, increase risk of bacterial pneumonia

• Fusion inhibitor (anit-HIV)
• -block CCR5 on Tcell

USE-early HIV/AIDS drug!

SE-hypersensitivity, increase risk of bacterial pneumonia

Integrase inhibitor (anti-HIV)

• DA-reuptake blocker+releaser+ antimuscarinic+ anti-viral!!
• -block attachment, penetration, uncoating of Influenza A

• USE- Prophylaxis for Influenza A
• Parkinson's disease

• SE-Ataxia, dizziness, slurred spech
• nervousness, insomnia
• -atropine-like, livedo reticularis~!!

Resistance-mutated M2 (most Influenza viruses are resistant!)

• derivative of Amantadine with fewer SE
• -does NOT cross CNS, so less atropine-like CNS effects

• antiviral
• -inhibit neuraminidase of Influenza A,B
• (decrease relesase of progeny of virus)

USE- prophylaxis

SE- flu-like symptoms!

• antiviral
• -nucleoside analog
• -mono-phos form-->inhibit IMP dehydrogenase (block Guanine syn)
• -tri-phos form-->inhibit RNA pol

USE- RSV (infant bonchiolitis!) , Hep-C (w/ alpha-IFN)

SE-Hemolytic anemia, upper airway irrtation, teratogen!!

antiviral

• USE- Hepatitis B, C, D
• -Kaposi sarcoma, CML, renal cell carcinoma

note- Lamivudine also used for Hep B

SE- neutropenia

immunoregulatory

USE- Multiple sclerosis

SE- neutropenia

USE- NADPH oxdiase deficiency (chronic granulomatous disease)

SE- neutropenia

• Sulfonamides--> kernicterus
• Aminoglycosides--> ototoxcity
• Fluoroquinolones--> cartilage damage
• Erythromycin-->acute cholestatic hepatitis in mom
• Clarithromycin-->embryotoxic
• Metronidazole-->mutagenesis
• Tetracyclline-->discolor teeth, inbibit bone growth
• Ribavirin-->teratogenic
• Griseofulvin-->teratogenic
• Chloramphenicol-->"gray baby"