Infectious Disease - Pharmacology - Immunosuppressives; Antivirals; Antifungals Flashcards
Name a corticosteroid commonly used in preventing transplant rejection.
Prednisone
Name two antimetabolites commonly used in preventing transplant rejection.
Mycophenylate mofetil;
azathioprine
Name two calcineurin inhibitors commonly used in preventing transplant rejection.
Cyclosporine;
tacrolimus
Name two mTOR inhibitors commonly used in preventing transplant rejection.
Sirolimus;
everolimus
What is calcineurin?
A protein phosphatase that activates T cells
What is the mammalian target of rapamycin?
An intracellular serine/threonine protein kinase that serves a critical role in mediating cytokine-mediated stimulation of T cell growth and proliferation
True/False.
IL-2 receptors activate T cell calcineurin.
TCRs activate mTOR.
False.
IL-2 receptors activate T cell mTOR.
TCRs activate calcineurin.
Describe the relationship between T cell receptors, IL receptors, calcineurin, mTOR, and NFAT.
What is cyclosporine’s mechanism of action?
Binds cyclophillins –> inhibits calcineurin in T cells
What is the mechanism of action of anti-thymocyte globulin?
Cytotoxic antibodies bind to molecules on the surface of human T lymphocytes
What is the mechanism of action of basiliximab?
Binding interleukin-2 receptors on activated T cells
What is the mechanism of action of alemtuzumab?
Binds CD52
(found on normal and malignant B cells, T cells, monocytes, macrophages, NK cells, and some granulocytes)
What enzyme does mycophenylate mofetil inhibit?
IMP dehydrogenase
Mr. William Short is a 27 year old stock clerk who you have been treated for the past 2 years after he was diagnosed with CHF caused by a viral cardiomyopathy. After being maintained on drug therapy for a year, Mr Short underwent a heart transplant procedure, and is now being maintained on an immunosuppressive drug regiment consisting of cyclosporine, azathioprine and prednisone. In addition, he is being treated with enalapril (an ACE-inhibitor) & hydrochlorothiazide diuretic, as well as valganaciclovir (an antiviral medication) to alleviate drug-induced side effects. Which drug in this regimen exerts its therapeutic effects by selectively interfering with activation of transcription factors involved in stimulating the transcription and production of IL-2?
A. azathioprine
B. cyclosporine
C. enalapril
D. hydrochlothiazide
E. valganciclovir
F. prednisone
B. cyclosporine
One of the drugs in Mr. Hart’s maintenance drug regimen increases the likelihood for renal toxicity, and should not be combined with other immunosuppressants that also have a high incidence of renal toxicity. Which drug is this?
A. azathioprine
B. cyclosporine
C. enalapril
D. hydrochlothiazide
E. prednisone
B. cyclosporine
Sometimes the level of immunosuppression achieved with a combination of a calcineurin inhibitor and an antimetabolite is not sufficient following an organ transplant. In this case adding an mTOR inhibitor can be beneficial because of their different mechanism of action, which can produce a synergistic effect. An example of this drug class is:
A. alemtuzumab
B. azathioprine
C. everolimus
D. mycophenolate mofetil
E. tacrolimus
C. everolimus (and sirolimus)
Patients who are taking allopurinol, or express a mutation resulting in a non-functional form of thiopurine S-methyltransferase (TPMT), can exhibit extreme bone marrow suppression and other forms of drug toxicity when exposed to:
A. alemtuzumab
B. azathioprine
C. cyclosporine
D. mycophenolate mofetil
E. prednisone
B. azathioprine
The maintenance dose of this immunosuppressant drug is typically tapered down over the first year of therapy because it can cause permanent side effects such as aseptic necrosis of femur heads, cateracts, and other serious side effects including hypertension, ulcers, diabetes & osteoporosis. This agent is:
A. anti-thymocyte globulin
B. azathioprine
C. cyclosporine
D. everolimus
E. prednisone
E. prednisone
A patient on immunosuppresive therapy is given tacrolimus as part of their drug regimen. Which side effect is most likely to occur with this drug?
A. hypoglycemia
B. hypokalemia
C. hypotension
D. profound myelosuppression
E. renal toxicity
E. renal toxicity
IL-2 is a cytokine that is produced by T cells, and also exerts autocrine effects to stimulate T cell replication. Which of the following agents is a selective antagonist for the IL-2 receptor expressed on the cell surface of T cells?
A. aldesleukin
B. alemtuzumab
C. basiliximab
D. etanercept
C. basiliximab
There are several general principles that must be considered when designing an immunosuppressive drug regimen for a patient undergoing an organ transplant. Which of the following is a side effect common to all immunosuppressant drugs that limits the dosages that can safely used for long term maintenance therapy?
A. hypertension
B. hip fractures
C. increased risk of infections and neoplasia
D. osteoporosis
E. pancreatitis
C. increased risk of infections and neoplasia
One of the drugs Mr. Short was taking to suppress organ rejection was azathioprine. Which of the following describes its mechanism of action?
A. blockade of leukocyte adhesion to endothelial cells
B. conversion to 6-mercaptopurine, a purine antimetabolite toxic to stimulated lymphocytes
C. decreased prostaglandin production due to inhibition of phospholipase A2
D. inhibition of TNF-alpha
B. conversion to 6-mercaptopurine, a purine antimetabolite toxic to stimulated lymphocytes
A prodrug that is converted to a metabolite that is a selective inhibitor of inosine monophosphate dehydrogenase, and is a selective inhibitor of lymphocyte proliferation. It can be combined with cyclosporine in kidney, liver and heart transplants. It has a relatively minimal toxicity apart from some GI effects.
A. azathioprine
B. cyclophosphamide
C. cyclosporine
D. mycophenolate mofetil
D. mycophenolate mofetil
A goal of the actue phase of induction immunotherapy following an organ transplant is to deplete circulating lymphocytes, which are the primary mediators of rejection. One drug that is commonly used for this purpose consists of a mixture of antibodies that bind to the surface of T lymphocytes and induce a cell-mediated and complement-induced cytotoxicity. Which of the following drugs has this mechanism of action?
A. aldesleukin
B. antithymocyte globulin (ATG)
C. daclizumab
D. natalizumab
B. antithymocyte globulin (ATG)
A patient was given a combination of immunosuppressant drugs following a liver transplant. Six months after his transplant his lab results indicate a 20 mm Hg increase in mean arterial blood pressure, elevated fasting blood glucose, hyperkalemia, and elevated serum creatinine. Which drug is most likely responsible for these side effects?
A. azathioprine
B. everolimus
C. mycophenolate mofetil
D. sirolimus
E. tacrolimus
E. tacrolimus
Name some of the various points in which viral replication can be inhibited by pharmacologic agents.
The drug amantadine has antiviral properties because it inhibits what normal viral function?
Uncoating
The drug rimantadine has antiviral properties because it inhibits what normal viral function?
Uncoating
Name two medications that can be used to prevent viral uncoating after penetration of host cells.
Amantadine;
rimantadine
What medication can be used to prevent viral penetration into host cells after attachment?
Interferon α-2b
(also, other smaller roles in preventing uncoating and translation)
The drug oseltamivir has antiviral properties against the flu because it inhibits what viral activity?
Neuraminidase activity
Name two antiviral medications that interfere with neuraminidase activity.
Oseltamivir;
zanamivir
The drug zanamivir has antiviral properties against the flu because it inhibits what viral activity?
Neuraminidase activity
The drugs rimantadine and amantadine are primarily used against what infectious agent?
The drugs oseltamivir and zanamivir are primarily used against what infectious agent?
Influenza;
influenza
Blocking influenza neuraminidase inhibits what process?
Release of daughter virions
(cannot cleave sialic acid)
Describe the differences between influenza types A - D according to which are most severe, how they move through populations, etc.
Why is amantadine no longer typically used against influenza?
Increasing influenza resistance
Tamiflu is the brand name of what medication?
Oseltamivir
Tamiflu (oseltamivir) is most effective if given within what timeframe following the onset of symptoms?
48 hours
How is Tamiflu (oseltamivir) administered?
PO
(good absorption)
At what phase of viral replication do antivirals targeting Herpes viruses function?
Why?
Nucleic acid synthesis;
the long latency period means it is not reasonable to target entry and egress of the virion to the host cell
What medications (2) can be given for HHSV infection?
What stage of viral replication do they block?
Acyclovir, valacyclovir;
nucleic acid synthesis
What medications (2) can be given for non-resistant CMV infection?
What stage of viral replication do they block?
Ganciclovir, valganciclovir
(valacyclovir can also be used);
nucleic acid synthesis
What medications (2) can be given for VZV infection?
What stage of viral replication do they block?
Acyclovir, valacyclovir;
nucleic acid synthesis
What medication can be given for herpes labialis infection?
What stage of viral replication does it block?
Valacyclovir;
nucleic acid synthesis
What topical medications can be given for HSV infection?
These are analogs of what?
Idoxuridine, trifluridine;
thymidine
Acyclovir, valacyclovir, ganciclovir, and valganciclovir are all analogs of what?
Guanosine
Why is acyclovir called acyclovir?
It is acyclic — it is analogous to guanosine but has no cyclic ribose
(thus inhibiting nucleic acid synthesis)
How are acyclovir and ganciclovir activated within the human body?
Why are they specific to virally infected cells?
Viral thymidine kinase activity
Why are higher acyclovir dosages needed for treating herpetic encephalitis?
Only 50% enters the CSF
Ture/False.
TTP and HUS are adverse reactions sometimes seen with valacyclovir use.
True.
True/False.
Valacyclovir is a prodrug similar in effect to acyclovir.
Valganciclovir is a prodrug for ganciclovir.
True.
Which has a higher oral bioavailability, acyclovir or valcyclovir?
Valcyclovir
What medication is used in treating resistant herpetic infections?
What is its mechanism of action?
Foscarnet;
inhibition of viral DNA polymerase
True/False.
Foscarnet has a high oral bioavailability.
False.
Foscarnet has a low oral bioavailability and is given IV.
Interferon α-2b is used in treating which viral infections?
HBV, HCV
Interferon α has ________-spectrum activity against viral infections.
Interferon α has broad-spectrum activity against viral infections.
__________ is a riboside analog used in treating RSV and HCV.
Ribavarin is a riboside analog used in treating RSV and HCV.
Name some of the viral enzymes inhibited by ribavarin (a riboside analog).
IMP dehydrogenase (IMP –> GMP);
RNA polymerase (in HCV)
(it also activates T cells and is an RNA mutagen)
What medication is used to treat RSV infections?
What medication combo is used to treat HCV infections?
Ribavarin;
ribavarin + interferons
Ribavarin is pregnancy category ___.
Ribavarin is pregnancy category X.
(Absolutely contraindicated for pregnant women and their partners.)
Describe the general mechanisms by which antifungals work.
- Inhibiting ergosterol synthesis (membrane)
- Inhibiting glycan synthesis (cell wall)
Which antifungals target fungal membranes?
Azoles;
polyenes;
allylamines
Which antifungals target fungal cell walls?
Echinocandins
Which antifungal targets fungal DNA/protein synthesis?
Flucytosine
Name two antifungals in the polyene class.
Amphotericin B;
nystatin
What is the potential major negative side effect of amphotericin B?
Nephrotoxicity
How can amphotericin B be prepared so as to only be active when fungal infections are present, thus decreasing the risk of negative side effects?
Coupling with liposomal preparations
What is the mechanism of action of -azoles such as ketoconazole, fluconazole, itraconazole, clotrimazole, and miconazole in fighting fungal infections?
Inhibition of ergosterol synthesis
(membrane damage)
Name three negative potential effects of ketoconazole.
Hepatotoxicity;
antiandrogenic effects;
strong C-P450 inhibition
