Chapter 9 anti inflammatory and immunomodulating agents - immunosuppressants and immunostimulants

Question 1

cyclosporin (sandimmune, neoral)

immunosuppressant

Answer 1

inhibits t-cell mediated immunity via
1) decreased production of interleukin-II by activated t helper cells
2) decreased number of interleukin receptors on cytotoxic t cells
3) proliferation of t suppressor cells

**remember interleukin makes inflammation..

indication
* prevent and tx transplanted organ rejection
* graft versus host disease (A condition that occurs when donor bone marrow or stem cells (involving tissues or cells that are genetically dissimilar and hence immunologically incompatible – allogeneic) attack the recipient in bone marrow transplant

effects
1) nephrotoxicity (presentation is similar to kidney rejection)
2) thromboembolism (obstruction of a blood vessel by a blood clot that has become dislodged from another site in the circulation.)
3) neurotoxicity
4) sz
5) reverisble hepatotoxicity
6) HTN

oral – erratic absorption, IV for organ rejection

interactions
* synergistic nephrotoxicity w/
1) amphotericin B (antifungal)
2) aminoglycosides (AB – gentamicin, tobramycin, amikacin, plazomicin, streptomycin, neomycin, and paromomycin)
3) trimethoprim (AB — UTI)

note
* this drug does not inhibit b cell immunity
* pts not at risk for microbial infetions during cyclosporin therapy
* be wary of corticosteroids

Question 2

tacrolimus (prograf)

immunosuppresant

Answer 2

• suppress t-lymphocyte activity
• mech unclear

indication
* transplant organ rejection
* graft vs host

effect
* nephrotoxicity
* neurotoxicity

PO/IV

similar efficacy to cyclosporin; can be effective w/ those that failed with cyclosporin trial and VICE versa

Question 3

azathioprine (imuran)

immunosuppresant

Answer 3

• drug converted to 6-mercaptopurine ribose phosphase (inhibits purine synthesis)
• b/c all proteins need DNA + RNA => all proliferating cells including b, t, and nonimmune cells inhibited

indication
* prevent organ transplant rejection
* also a anticancer agent

effects
* bone marrow depression
* infections
* mild leukopenia and thrombocytopenia

PRODRUG (PO/IV)

interaction
* allopurinol inhibits xanthinse oxidase which converts 6 MP (above) to 6-thiouric acid => renal excretion

Question 4

cyclophosphamide (cytoxan)

immunosuppressant

Answer 4

• prodrug => inside liver => alkylating agent which crosslinks DNA
• b cell prolifeartion inhibited more than t cells
• may also attack immunocompetent lymphocytes

indication
* wegener’s granulomatosis (Granulomatosis with polyangiitis is an uncommon disorder that causes inflammation of the blood vessels in your nose, sinuses, throat, lungs and kidneys. Formerly called Wegener’s granulomatosis, this condition is one of a group of blood vessel disorders called vasculitis. It slows blood flow to some of your organs.)
* severe RA
* autoimmune blood d/o’s

effects
* hemorrhagic cystitis of the bladder (inflammed and bleeds with urinary bladder lining)
* bone marrow depression

PO

encourage those taking this drug to drink plenty of fluids + void to prevent hemorrhagic cystitis

Question 4

lympchote immune-, anti-thymocyte-globulin (afgam)

immunosuppressant

Answer 4

• horse IgG antibodies which selectively suppress t lymphocytes (cell mediated immunity) and humoral immunity

inidcation
* prevent organ transplant rejection
* aplastic anemia (bone marrow cannot make enough new blood cells for your body to work normally.)

effecs
* leukopenia
* thrombocytopenia
* skin rx
* rare – chest + back pain, arthralgia (pain in joint)
* others — night sweats, headache
* anaphylaxis occurs in <1% of pts (ensure airway and appropriat e drugs) // often administered with steroids to prevent risk

IV – must have filter to prevent insoluble material from entering

Question 5

RhoD immune globulin (RhoGAM)

immunosuppresant

Answer 5

• human immune globulin that prevents sensitaztion of Rho negative receipients to rho (D) positive blood
• THEORETICALLY binds to rho (d) antigens masking them from antigen-senstive immune cells

indication
* rho (d) negative mother carrying rho (d) positive fetus or planning abortion
goal — prevent erythroblastosis fetalis (destruction of neonatal red blood cells by maternal immunoglobulin G (IgG) antibodies) in future infants

effect
* well tolerated

contraindicated
* rho(d) positive patients or in rho (d) negative patients who already have anti-rho(d) antibodies

Question 6

interferon b(beta)
1b: (betaeron)
1a: (avonex)

immunosuppressant

Answer 6

• unknown mech
• binds to cell surface => initate several gene products

indication
* relapsing remitting multiple sclerosis
* reduce above exacerbations

effects
* flu like sx
* fever
* headache
* weakness
* pain @ site
* leukopenia

subq

• patients eventually develop AB’s.. not sure about efficacy

Question 7

glatiramer (copaxone)

immunosuppresant

Answer 7

• copolymer of l-alanine, l-glutamate, l-lysine, and l-tyrosine modifies immune sx via unknown mech

indication
* relapsing remitting MS
* reduce above exacerbation

effect
* transient post injection rxn
* transient chset pain

daily injections (SUBQ)

induces IgG levels

Question 8

baslilximab
daclizumab
murmonab-CD3
mycophenolate mofetil

Answer 8

prevent graft rejction in transplant setting

Question 9

levamisole (ergamisol)

immunostimulating agents

Answer 9

• stimulates cell mediated immunity

indication
* colon cancer (duke’s stage C [cancer has spread to at least 1 lymph node close to the bowel]) w/ flourouracil – chemotherapy

effects
* dermatitis
* agranuloycytosis (absolute neutrophil count (ANC) is less than 100 neutrophils per microlitre of blood. People with this condition are at a very high risk of severe infection.)
* malaise

Question 10

interferons

immunostimulating

Answer 10

• enhance activity of cytotoxic — T + NK + macrophages; inhibit proliferation of tumor cells + suppress graft versus host disease

inidcation
* hairy cell leukemia

Is a type of blood cancer that begins in the bone marrow
Is a rare type of chronic leukemia 
Hairy cell leukemia gets its name from the short, thin projections that look like hair on its cells.

• genital warts
• kaposi’s sarcoma (a disease in which cancer cells are found in the skin or mucous membranes that line the gastrointestinal (GI) tract, from mouth to anus, including the stomach and intestines. These tumors appear as purple patches or nodules on the skin and/or mucous membranes and can spread to lymph nodes and lungs.)
• chronic myelocytic leukemia (patients have an abnormal chromosome in their blood cells called the Philadelphia chromosome, which was discovered at Penn. This slow-growing blood cancer takes longer to develop and can progress into acute leukemia, which needs immediate medical attention. )

effects
* fever
* myalgias