ID Exam 2

HBV replication cycle

endocytosis, enter nucleus, repair, cccDNA, pregenome RNA, reverse transcription→ DNA, exocytosis

HCV replication cycle

endocytosis, uncoating, RNA translation→polyprotein, cleavage, web formation, assembly, exocytosis

HBV therapeutic strategies

Nucleoside or nucleotide analogs (ex. tenofovir) (may be lifelong), Interferon-alpha (48-52 weeks), complete cure cannot be obtained, only functional cure

HCV therapeutic strategies

DAA, Ribavirin

DAA (direct-acting antiviral therapy)

NS5B RNA polymerase inhibitors (nucloside/tide analog inhibitors & nonnucleoside analog inhibitors), NS5A protein (affects virion assembly), NS3 protease inhibitors, used in combination for 8, 12 or 24 weeks

Interferon-alpha MOA

-cytokine produced in response to viral infection by many cells

-stimulate lymphocytes, NK cells, & macrophages

-stimulate expression of antiviral enzymes→ degrade RNA & inhiit viral protein synthesis

Interferon-alpha adverse effects

Flu-like symptoms, neurotoxicity, myelosuppresion, autoimmune disorder symptoms, CV effects

Tenofovir MOA

competitor w/ cellular nucleotides for viral DNA polymerase & reverse transcriptase

Tenofovir warning

risk of lactic acidosis

Sofosbuvir MOA

pro-drug, Uridine analogue – Is converted into uridine tri-phosphate analogs by cellular kinases

Inhibits HCV RNA polymerase – Inhibits RNA replication by chain termination – Does not inhibit host RNA polymerase, DNA polymerase or mitochondrial RNA polymerase

HIV replicative cycle

fusion of virus to host cell, RNA/reverse transcriptase/integrase enter host cell, viral DNA formed by reverse transcriptase, new viral RNA formed, new virus formed, virus matures by protease

gp120

allows HIV to bind to CD4 on host cell

gp41

A transmembrane glycoprotein of HIV that mediates fusion of the viral envelope

protease

enzyme that cleaves viral proteins during HIV maturation, essential for forming infectious viral particles.

reverse transcriptase

enzyme that is responsible for converting the viral RNA into DNA

integrase

enzyme in HIV responsible for integrating the viral DNA into the host cell's DNA

HIV therapeutic approach

combine 3 drugs

treatment: Highly Active Anti-Retroviral Therapy

start treatment ASAP

HAART

Highly Active Anti-Retroviral Therapy

NRTI

nucleoside reverse transcriptase inhibitor

NNRTI

non-nucleoside reverse transcriptase inhibitor

Maraviroc MOA

Entry inhibitor, bind to and block CCR5 interaction w/ gp120, does not bind to CXCR4

Zidovudine MOA

NRTI, mono-phosphorylated by TK, di-phosphorylated by TK, tri-phosphorylated by nucleoside diphosphate kinase

Efavirenz MOA

NNRTI, bind outside the active site of HIV-1 reverse transcriptase, trigger changes in enzyme, reduce activity of reverse transcriptase

Efavirenz adverse effects

CNS (dizziness, abnormal dreams, insomnia), rashes

Efavirenz drug interaction

inducer of CYP3A4

Ritonavir MOA

protease inhibitor, inhibits proteolytic cleavage of: HIV gag polyprotein (essential structural proteins) and HIV pol polyprotein (reverse transcriptase, protease, integrase)

Ritonavir adverse effects

GI, peripheral and perioral neuropathy, elevation of cholesterol and triglycerides

Ritonavir drug interaction

inhibit CYP450s

Raltegravir MOA

Integrase inhibitor that prevents integration of viral DNA into the host genome

Plasmodium life cycle

mosquito bites, sporozoites enter the bloodstream, infect liver cells, replicate, and release merozoites that infect red blood cells

Liver stage- 2 species that stay dormant

P. vivax and P. ovale

Erythrocytic stage

phase in the Plasmodium cycle where the merozoites invade red blood cells, replicating asexually and leading to symptomatic infection.

ACT treatment (malaria)

Artemisinin-based combination therapy

Toxoplasmosis therapeutic strategy

Trichomoniasis therapeutic strategy

Artemether MOA

Chloroquine MOA

accumulates in digestive vacuoles of plasmodium, inhibit heme sequestration in vacuoles and hemozoin formation

Chloroquine severe adverse effects w/ IV

higher risk of toxicity

-CV: hypotension, vasodilation, cardiac arrhythmias, cardiac arrest

-Neurological: confusion, convulsions, coma

Primaquine MOA

induces formation of reactive oxygen species, interferes w/ electron transport on the parasite

Primaquine adverse effects for patients w/ G6PDH deficiency

acute hemolysis

G6PDH significance

protects red blood cells from damage caused by reactive oxygen species

Metronidazole MOA

Metronidazole serious adverse effects