pharm b7 exam 2

any pt whose Hb is >10g/dl

any pt whose Hb is <7 g/dl. it is better to wait til their Hb is lower such as this to give a transfusion (maintain Hb at 7-9)

accidental transfusion with ABO incompatible RBCs

• leading cause of transfusion-related death
• serious pulmonary reaction possibly associated with leukocyte antibodies/cytokines in donor blood, and recipient’s neutrophil priming and activation
• almost always occurs within 6hrs of transfusion
• Symptoms include bilateral pulmonary edema, dyspnea, hypoxemia, fever, and hypotension

• occurs when immunosupressed/deficient pt is given cellular blood products that possess immunologically competent lymphocytes
• it can be prevented by gamma irradiation og the blood to innactivate the donor lymphocytes

• used to prevent bleeding in pts with thrombocytopenia
• the cut off is:
• 10x10^3 for pts with no other complications
• 20x10^3 with bleeding risk factors
• 50x10^3 if uncomplicated surgery is planned
• 100x10^3 if CNS surgery is planned

Platelet transfusions are no helpful in pts with hemolytic syndromes such as ITP, TTP, HUS, HIS

• must ABO compatible
• coagulation deficiencies
• reversal of warfarin od
• TTP
• replacement of single congenital factor def when specific concentrates are not available

intravascular volume expansion, correction/prevention of protein malnutrition, and when specific concentrates are available

• pathogen transmission
• TRALI
• adverse immune responses

it is precipitate from FFP that contains concentrated levels of factor VIII, factor XIII, vWF, fibronectin, and fibrinogen

• pts with vWF disease who require vWF multimer replacement
• acute bleeding in pts with fibrogenemias

• it is not first line for Hemophilia A or B or vWF dz
• this is because there is no standard concentration of factors in it
• there are better commercial factor concentrates

concentrates of plasma proteins (clotting factors) prepared from large donor pools of plasma or cryoprecipitate--> the specific protein is purified

they are used for tx of hemophilia A or B

significant bleeding in vWF dz

it is used to tx acute bleeding and prohilaxis in hemophilia A and B

it is used for volume expansion but the results of tx with this showed poorer outcomes than using just nml saline

it contains hematopoietic progenitor cells (CD34+) from humancord blood

For use in hematopoietic stem cell transplantation procedures in patients with disorders affecting the hematopoietic (blood forming) system. For example, cord blood transplants have been used to treat patients with certain blood cancers and some inherited metabolic and immune system disorders.

Once these HPCs are infused into patients, the cells migrate to the bone marrow where they divide and mature. When the mature cells move into the bloodstream they can partially or fully restore the number and function of many blood cells, including immune function.

• death
• graft-vs-host dz
• engraftment syndrome
• graft failure
• infusion rxns

• it is a GM-CSF (granulocyte monocyte conlony-stimulating factor)
• it stimulates neutrophil production and enhances neutrophil action
• often used for pts receiving bone marrow or stem cell transplantation
• adverse effects: fever,arthralgias, myalgias, peripheral edema, pleural & pericardial effusion

• CA chemo-associated neutropenia
• congenital neutropenia, aplastic anemia
• mobilization of hematopoetic stem cells (G-CSF)

• it is a recombinant IL-11
• it used to stimulate platelet production
• often used to prevent thrombocytopenia secondary to CA chemo
• adverse effects: fatigue, fluid retention, A-fib

• they are TPO (thrombopoetin) receptor agonists
• used to treat refractory idiopathic thrombocytopenia purpura (ITP)***
• eltrombopag can cause hepatoxicity and increased risk of hematologic malgnancies

• it is a granulocyte colony-stimulating factor
• pegfilgastrim is a pegylated version of filgrastim that has a longer 1/2 life
• it stimulates neutrophil production and enhances neutrophil function (phagocytic activity)
• bone pain is an adverse effect

• certain forms of anemia
• chronic renal failure
• cancer: relative resistance to endogenous EPO, bleeding, poor nutrition, and infiltration of bone marrow by tumor cells)
• chemo
• zidovudine (for HIV)
• Fe supplementation (and sometimes folic acid) may be required with EPO tx

• recombinant human EPO
• binds to EPO receptors on red cell progenitors and stimulates erythroid proliferation and differentiation

they are modified or pegylated to have a longer than normal 1/2 life

increased risk of HTN, stroke, MI, and heart failure

Fe, vit B12, folic acid

EPO, GM-CSF, G-CSF, TPO, interleukins (IL-11), others

• iron sulfate, iron fumarate, and iron gluconate
• mainly cause GI sx such as epigastric pain, n/v, diarrhea and consitpation

• iron dextran, iron-sucrose complex, iron sodium gluconate complex
• these should only be used for pts that cannot tolerate oral Fe, or absorb oral Fe, or extensive chronic blood loss that cannot be maintained with oral Fe
• it is common for pts with chronic renal dz on dialysis to need this

• cyanocobalamin and hydroxocobalamin (has longer 1/2 life)
• these can be given IM
• folate can also help correct anemia caused by B12 def but only B12 def causes neurological problems

• it is used to tx sickle cell anemia
• it works by increasing HbF to almost 20%

• 5-azacytidine is a demethylating agent
• and they both increase HbF

• down regulates the expression of many inflammatory cytokines (TNF-alpha, IL-1, and IL-2)
• blocks the synthesis of araihadonic acid metabolites (prostaglandins, leukotrienes, and thromboxanes)
• indicated to prevent solid organ rejection and chronic graft-vs-host dz

• hyperglycemia, diabetes
• osteoporosis
• HTN
• adrenal suppression
• susceptibility to infection
• muscle wasting

• calcineurin inhibitors
• this stops activation of NFATc which leads to IL-2 not being transcribed***
• they are used to prevent rejection in kidney, liver and cardiac transplants
• CsA: also used for RA, psoriasis, and chronic dry eyes
• they are metabolized by the CYP3A4 enzyme***

nephrotoxicity***

• mTOR inhibitors (mammalian target of Rapamycin)
• blocks T cell proliferation (does not effect IL-2 but inhibits cellular response to IL-2)
• used for prophylaxis of organ transplant rejection (everolimus esp for kidney)
• also used for drug-eluting stents in CAD
• metabolized by CYP 3A4

• hyperlipidemia
• anemia, leukopenia, thrombocytopenia
• HA, nausea, diarrhea

• anti-metabolite-->prodrug of purine analog 6-mercaptopurine
• used to prevent transplant rejection with glucocorticoids and calcineurin inhibitors
• major adverse effect is bone marrow suppression
• metabolism inhibited by allopurinol so must be reduced by 60-75% when used together

• antimetabolite--> inhibits dihydrofolate reductase which inhibits pruine and thymidine synthesis
• indicated for graft-vs-host dz in bone marrow/stem cell transplantations and some inflammatory dz such as RA, crohn's and psoriasis
• major adverse effects = myelosupression, gut disorders, hepatotoxicity, and renal toxicity

• inhibitor of inosine monophosphate dehydrogenase (IMPDH), the rate limiting enzyme in the formation of guanosine
• indicated for prevention of rejection in kidney, heart, and liver transplants and some autoimmune dz
• adverse effects: leukopenia, diarrhea, vomiting
• these are very specific to lymphocytes!

• caused by activation of T cells by antibody binding and release of T cell cytokines
• symptoms: Fever, chills, headache, myalgias, tremor, weakness
• more serious ones include--pulmonary edema, hypotension with CV collapse, cardiac arrhythmia
• prevent with premedication of glucorticoids and acetominophen

• targets all T cells resulting in broad immunosupression
• indications are acute renal transplant rejection and severe rejection episodes
• adverse effects inslude cytokine release syndrome and susceptibility to infection

• monoclonal antibody to human T cell CD3
• binds to CD3 antigen which results in disruption of T cell function and depletion of T cells
• indications are acute renal transplant rejection and glucocorticoid resistant acute rejection
• adverse reactions include cytokine release syndrome

• monoclonal antibodies to CD25 receptor (IL-2 receptor) on activated T cells
• blocks proliferation of T cells mediated by IL-2
• indicated for acute organ rejection
• NOT used for ongoing rejection
• adverse effects include GI sx

• MOA: binds to B7 molecules on APCs and blocks interaction between B7 and CD28 (costimulatory)
• indicated in prevention of kidney transplant rejection
• adverse effects include anemia, n/v, diarrhea, constipation, peripheral edema, UTI, HTN