Lixin Liu Flashcards
(75 cards)
1
Q
Virus Particle (Virion) Components
A
- Envelope
- Core proteins (capsid)
- RNA or DNA core (nucleois)
- Surface proteins
2
Q
Where do RNA viruses form their mRNA?
A
Cytoplasm except for influenza viruses
3
Q
RNA retroviruses contain which type of DNA?
A
cDNA which are pro viruses that can be transcribed into new viral genomic RNA and mRNA
4
Q
DNA viruses enter where?
A
Enter the nucleus to form viral mRNA
5
Q
Viruses assemble these is the host cell
A
Virions which are released during cell lysis or budding (enveloped viruses)
6
Q
DNA viruses blocking site?
A
Inhibition of viral DNA polymerase
7
Q
RNA viruses blocking sites?
A
Block the uncoating, RNA polymerase, or the release of the virus
8
Q
Neuraminidase inhibitors
A
Remove sialis acid receptors from viral particles and from cell surface, preventing self-aggregation and gluing to infected cell surface
9
Q
Oseltamivir
A
- oral
- active prodrug
- hydrolyses in the liver to active components
- used for influenza A and B
10
Q
Oseltamivir side effects
A
GI discomfort and nausea
11
Q
Zanamivir
A
- inhaled or intranasally or intravenous
- contraindicated in patients with severe respiratory diseases or asthma
- Influenza A and B use
12
Q
Peramivir
A
- intravenous only
- influenza A and B use
13
Q
Peramivir adverse effects
A
Serious skin reactions
14
Q
Amantadine and rimantadine action
A
- blocks viral membrane matrix protein M2
- viral uncoating inhibitors
- Amantadine is effective in treating some Parkinson’s disease
15
Q
Administration of Amantadine and Rimantadine
A
Orally for Influenza A only
16
Q
Ribavirin used to treat
A
- severe RSV in children
- treatment of influenza
- chronic hepatitis C infections
17
Q
Ribavirin action
A
Inhibits GTP formation, viral mRNA capping, and thereby inhibits viral protein synthesis
18
Q
Ribavirin routes of administration
A
- oral
- IV
- aerosol
19
Q
Interferon mode of action (3)
A
- induction of host cell enzymes that inhibit viral RNA translation
- degradation of viral RNA
- stimulation of immune system
- for treatment against hepatic viral infections
20
Q
Interferon route of administration
A
Intralesionally, subcutaneously, or intravenously
21
Q
Interferon adverse effects
A
Flu-like symptoms, bone marrow suppression, neurotoxicity, autoimmune disorders
22
Q
Lamivudine mode of action
A
Inhibits both HBV DNA polymerase and HIV reverse transcriptase
- for treatment of HBV and HIV
23
Q
Lamivudine route of administration
A
Orally
24
Q
Acyclovir treatment of
A
- drug of choice for HSV types 1 and 2 as well as VZV
25
Acyclovir route of administration
IV, oral, and topical
26
Acyclovir mode of action
- competitive inhibition of dGTP for viral DNA polymerase
- binding to DNA template, causing termination of premature viral DNA
- trapping the viralDNA polymerase on acyclovir-terminated DNA chain
27
Adverse effects of Acyclovir
Depends on the route of administration
- Topical: local irritation
- Oral: headache and GI upsets
- IV: transient renal dysfunction at high dose
28
Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NRTI's)
- pro drugs
- convert to the triphosphates in the cell
- incorporated by viral reverse transcriptase into viral DNA to terminate its elongation
- Have much lower affinity to host cell DNA polymerase but affect mitochondria DNA polymerase in certain tissues
29
Zidovudine
Converted by mammalian thymidine kinase to triphosphate introduced by viral reverse transcriptase into viral DNA
- Used in HAART, decreases viral load and increases CD4+ cells. Also used for prophylaxis
30
Zidovudine route of administration
Orally administered, glucuronylated by the liver
31
Zidovudine adverse effects
Toxic to bone marrow, headaches, toxicity can be potentiated by other drugs
32
Nevirapine (NNRTI) adverse effects
Rash can be severe
Fatal hepatotoxicity can occur
Induces CYP3A4 of cytochrome P450 enzymes, and metabolism of a number of other drugs
33
Efavirenz
- only used in combination with other HIV-1 agents
- Very potent against HIV-1
- Preferred treatment with addition of 2 NRTI's.
Efavirenz + Tenofovir + Emitricitabine (once daily co-formulation single pill).
34
Protease inhibitors adverse effects
GI intolerance, disturbances in glucose and lipid metabolism
- diabetes, hypertriacylglycerolemia, hypercholesterolemia, and fat redistribution
35
Ritonavir
- Inhibits CP450 isozymes and is one of the most known potent inhibitors of CYP3A4
- inhibits the metabolism of all current HIV PIs and is frequently used in combinations with most other PIs
- "Pharmacokinetic enhancer"
36
Saquinavir
- poor bioavailability
- must be taken with high fats
- GI upsets are common
37
Viral Entry Inhibitors
Enfuvirtide and Maraviroc
38
Enfurvitide
- inhibits viral fusion
- 36 aa peptide that binds gp41 and prevents its conformational changes that occur when HIV fuses with host cell membrane
- can be combined
- costly and only give subcutaneously twice daily
39
Maraviroc
CCR5 antagonist
| - restricted to use in adults with CCR5-tropic HIV-1
40
CCR5
Major co-receptor involved in viral entry into the cell
41
Integrate inhibitors
Raltegravir, Dolutegravir and Elvitegravir
42
Raltegravir route of admin.
Oral
43
Raltegravir mode of action
Inhibits HIV-1 integrate activity preventing viral DNA from integrating with cellular DNA. It is active against HIV strains resistant to other anti-retroviral drugs.
44
Immunosuppressive Drugs
Are used to dampen the immune response in organ transplantation and autoimmune diseases, and to suppress inflammatory reactions
45
Immunostimulatory Drugs
Applicable to the treatment of infection, immunodeficiency, cancer
46
Cardinal signs of Acute Inflammation
```
Redness (rubor)
Heat (calor)
Swelling (tumor)
Pain (dolor)
Loss of function
```
47
Cellular events in inflammation
1. Leukocyte extravasation
2. Cell activation, exocytosis, and phagocytosis
3. Release of leukocyte products and leukocyte-induced tissue injury
- lysosomal enzymes
- reactive oxygen intermediates
- products of arachidonic acid metabolism
48
Cytokines include:
- Interleukins
- Interferons
- Tumor necrosis factors
- Transforming growth factors
- Colony-stimulating factors
- Chemokines
49
Glucocorticoids mechanism of action
- regression of lymphoid tissues
- enhance destruction of lymphocytes (especially T lymphocytes)
- interfere with the cell cycle of activated lymphoid cells
- inhibit leukocyte functions
- inhibit antibody formation
- inhibit inflammatory mediators
50
Prednisone mechanism of action
- represses COX-2 gene and enzyme expression
- represses the expression of cytokines that activate COX-2
- blocking the function of Phospholipase A2 therefore limiting the availability of arachidonic acids
51
Glucocorticoids clinical uses
- organ and tissue transplantation
- autoimmune diseases (drug of choice)
- inflammatory diseases (allergies, arthritis, bowel disease)
52
Glucocorticoids Adverse Effects
Suppression of pituitary-adrenal axis
Increased susceptibility to serious infection
Peptic ulcer
53
Cyclosporine action
- binds to cyclophiln, inhibits calcineurin, which inhibits NFAT from going into the nucleus to produce IL-2
- inhibits cytokines production
54
Cyclosporine AE's
- Nephrotoxicity
- Hepatotoxicity
- Prédispose to infections
- lymphoma may occur
- hypertension, hyperkalemia, tremor, hirsutism, glucose intolerance, and gum hyperplasia
- causes little bone marrow toxicity
55
Tacrolimus action
- more potent and allows lower dose of glucocorticoids to be used
- binds to different immunophilin (FKBP-12)
56
Sirolimus action
- also binds FKBP-12 forming a complex with mTOR
- Sirolimus binding to mTOR blocks the progression of activated T cells from the G1 to the S phase of cell cycle, consequently the proliferation of these cells
57
Methotrexate mechanism of action
- antagonist by inhibiting dihydrofolate reductase which converts folic acid into tetrahydrofolic acid
- decreases biosynthesis of A, T, C, G and eventual death of the cell
- Immunosuppressive antimetabolite
58
Leflunomide mechanism of action
- reversible inhibits dihydroorotate dehydrogenase and deprives the cells of the precursor for uridine monophosphate
- reduces pain and inflammation associated with the disease, slows the progression of structural damage
- immunosuppressant antimetabolite
59
Mechlorethamine mechanism
- causes lymphocytopenia
- alkylate the N-7 nitrogen of a guanine residue in one or both strands of DNA
- largely replaced by cyclophosphamide
- Immunosuppressive alkylating agents
60
Cyclophosphamide
- the most commonly used alkylating agent
- biotransformed into the active compound, phosphoramide mustard, which alkylate DNA.
- Immunosuppressive alkylating agent
61
Types of Antibodies (4)
1. Polyclonal antibodies
2. Monoclonal antibodies
3. Humanize antibodies
4. Chimeric antibodies
62
Antithymocyte globulins
- purified polyclonal Abs from rabbit
- treat acute renal transplant rejection
- depletion of T cell responses
- humoral antibody mechanism remains active
63
Muromonab-CD3
- murine mAbs, for the depletion of human T cells
- used in autoimmune disorders and renal, cardiac and hepatic transplant as well as depletion of T cells from the donor bone marrow
64
Antithymocyte globulins and Muromunab-CD3 adverse effects
- Cytokines release syndrome
| - using humanize anti-CD3 mAb can minimize this effect
65
Intravenous Immunoglobulins treatment
- treats Ig deficiencies, AIDS, autoimmune disorders, and bone marrow transplants
- prepared as IgG
66
Hyperimmune Immunoglobulins
- treatments against viruses or toxins
- syncytial virus, cytomegalovirus, varicella zoster virus, human herpesvirus type 3, HBV, rabies, tetanus, and digoxin overdose
67
Omalizumab mechanism
- anti-IgE recombinant humanize mAb blocking the binding of IgE to Fce receptor
68
Omalizumab treatment
- allergic asthma patients whose symptoms are refractory to inhaled corticosteroids
69
Basiliximab and daclizumab
- humanized mAbs
- use with CSA and glucocorticoids
- both are anti-CD25 mAbs (bind to alpha chain of the IL-2 receptor on activated T cells).
- Are used for prophylaxis of acute organ rejection in adult patients
70
Infliximab
Chimeric antibody
| TNFalpha antagonist
71
Adalimumab
Humanized antibody
| TNFalpha antagonist
72
Etanercept
- fusion protein comprising part of TNF p75 receptor and the Fc portion of human IgG.
- Binds to TNFalpha and lymphotoxin
- TNFalpha antagonist
73
Anti-TNF AE's
- reaction at injection site
- infections
- malignancies
- cardiac failure
74
Anakinra
- recombinant form of IL-1 receptor antagonist
| - differs by a methionine residue
75
Anakinra AE's
- similar to TNFalpha antagonists
- asthma may be a co-morbid risk factor for serious infections
- use of anakinra and etanercept increases risk of neutropenia and serious infections
