Transplant/ Immunosuppresion Flashcards by Renny Oye

What’s an isograft?

Transplanted organs from GENETICALLY IDENTICAL donor (such as identical twin)

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What’s an allograft/ allogenic transplant/ homograft?

Transplant of an organ or tissue from 1 individual to another of the SAME species with DIFFERENT genotype

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What’s an autograft/ autologous transplant/ autologous stem cell transplant?

Is when a tissue is a transplant from 1 site to another on the SAME patient

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Most commonly used induction agent?

Basiliximab (interleukin-2 (IL-2) receptor antagonist

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What makes up maintenance immunosuppressant therapy?

Calcineurin inhibitor (Tacrolimus is 1st line CNI)
+
Antiproliferative agent (Mycophenolate is 1st line in most protocols), or Everolimus, Sirolimus, Belatacept or Azathioprine
+/-
Steroids (typically prednisone)

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Sx of acute rejection?

Flu-like sx - chills, body aches, nausea, cough & SOB
+
Organ-specific sx -
Heart failure sx with heart transplant
Decrease in urine output/fluid retention/ edema/ BP elevation with kidney transplant rejection

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Which maintenance drugs have highest nephrotoxicity?

Tacrolimus

Cyclosporine

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Which maintenance drugs may worsen DM or cause new onset of DM?

Tacrolimus

Cyclosporine

Steroids

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Which maintenance drugs may worsen lipid parameters?

mTor inhibitors

Steroids

Cyclosporine

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Which maintenance drugs have highest risk for BP elevations?

Steroids

Cyclosporine

Tacrolimus

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Whys other drugs (antiproliferative or antimetabolite) used with CNI?

To reduce nephrotoxicity risk

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List infection risks associated with transplant?

Candida: oral and esophageal - oral Clotrimazole lozenges, nystatin or Fluconazole used commonly 1-3 months post-transplant

Cytomegalovirus - Valganciclovir

Herpes simplex - acyclovir, valacyclovir or Famciclovir

Varicella zoster - vaccine prior to transplant

Pneumocystis jirovecii pneumonia -Bactrim for 3-6 mo post-transplant

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What should pt self-monitor for when on strong immunosuppressants or with any condition that suppresses the immune system?

Self-monitor for sx of infection -

Fever of 100.5 degree F (38 degree C)
Chills
Sore throat
Ear or sinus pain
Cough
More sputum or change in color of sputum
Pain passing urine
Mouth sores
Wound that won't heal
Anal itching or pain

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Infection control in Immunosuppressed pts include:

Air filtration systems

Keeping mouth clean

Keeping away from dusty, crowded areas & sick people

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Can live-vaccines be given post-transplant?

No!

Inactivated vaccines only

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Pneumococcal vaccine in immunocompromised pts?

In adults >= 19 yrs

PCV 13

PPSV23 - at least 8 wks after PCV 13

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List induction agents

Antibodies
- Antithymocyte Globulin (Atgam-Equine; Thymocyte-Rabbit)

Interleukin 2 (IL-2) receptor antagonist
- Basiliximab (Simulect)

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MOA of anitbodies (induction agent)?

Reverse rejection by binding to antigens on T-lymphocytes (killer cells) and interfering with their function

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Drug under antibodies?

Antithymocyte Globulin (Atgam-Equine) (Thymocyte-Rabbit)

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Pre-medication necessary with Antithymocyte Globulin (Atgam-Equine) (Thymocyte-Rabbit)?

May be necessary (diphenhydramine, APAP, steroids)

Epinephrine + resuscitation equipment should be nearby

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MOA of IL-2 receptor antagonist?

Chimeric (murine/human) monoclonal antibody that inhibits IL-2 receptor on the surface of activated T-lymphocytes preventing cell-mediated allograft rejection

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Agents under IL-2 receptor antagonists?

Basiliximab (Simulect)

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SEs of Basiliximab (Simulect) - induction agent?

HTN

Fever

Weakness

Stomach upset/n/v/cramping

Peripheral edema

Dyspnea/upper respiratory irritation/infection

Cough

Tremor

Painful urination

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List maintenance meds

Corticosteroids - prednisone etc

Antiproliferative agents - Mycophenolate Mofetil (CellCept)
Mycophenolic Acid (Myfortic)
Azathioprine (Azasan, Imuran)

Calcineurin Inhibitors - Tacrolimus (Prograf, Astagraf XL)
Cyclosporine (Neoral, Gengraf, SandIMMUNE)

Mammalian target of rapamycin (mTOR)- Everolimus (Zortress, Afinitor)
Sirolimus (Rapamune)
Belatacept (Nulojix)

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MOA of corticosteroids - Prednisone(maintenance medications)?

Naturally occurring hormones that prevent or suppress inflammation and humoral immune responses

MOA of Antiproliferative Agents (maintenance medications)?

Inhibit T-lymphocyte proliferation by altering purine synthesis

List Antiproliferative Agents (maintenance medications)?

Mycophenolate Mofetil (CellCept) Mycophenolic Acid (Myfortic) Azathioprine (Azasan, Imuran)

Brand name of Mycophenolate Mofetil (Antiproliferative Agents used for maintenance medications)?

CellCept

Brand name of Mycophenolic Acid (Antiproliferative Agents used for maintenance medications)?

Myfortic

Brand name of Azathioprine (Antiproliferative Agents used for maintenance medications)?

Azasan Imuran

BBW of Mycophenolate Mofetil (CellCept) & Mycophenolic Acid (Myfortic) - (Antiproliferative Agents used for maintenance medications)?

Increased risk of inf Increased development of lymphoma and skin malignancies Increased risk of congenital malformations and spontaneous abortions when used during pregnancy

SE of Mycophenolate Mofetil (CellCept) & Mycophenolic Acid (Myfortic) - (Antiproliferative Agents used for maintenance medications)?

Diarrhea GI upset Vomiting Hypo- & hypertension Edema Tachycardia Pain Hyperglycemia Hypo- & hyperkalemia Hypo- magnesemia; calcemia; cholesterolemia Tremor Acne Infections

Monitoring parameters of Mycophenolate Mofetil (CellCept) & Mycophenolic Acid (Myfortic) - (Antiproliferative Agents used for maintenance medications)?

CBC Renal, liver, signs of infection

Difference btw Mycophenolate Mofetil (CellCept) & Mycophenolic Acid (Myfortic) - (Antiproliferative Agents used for maintenance medications)?

Myfortic is enteric coated, which helps to reduce diarrhea T4 Myfortic and CellCept are NOT interchangeable

What can be done to avoid variability in absorption of Mycophenolate Mofetil (CellCept) & Mycophenolic Acid (Myfortic) - (Antiproliferative Agents used for maintenance medications)?

Take on empty stomach

MOA of Calcineurin Inhibitors?

Suppresses cellular immunity by inhibiting T-lymphocyte activation

Calcineurin Inhibitors agents?

Tacrolimus (Prograf, Astagraf) Cyclosporine (Neoral, Gengraf, SandIMMUNE)

Brand name of Tacrolimus - CNI used for maintenance meds?

Prograf Astagraf XL

What's Protopic (Topical Tacrolimus) used for?

Topical for Eczema

Brand name of Cyclosporine - CNI used for maintenance meds?

Neoral Gengraf SandIMMUNE

What's Restasis (Ophthalmic Cyclosporine) used for?

Dry eyes

BBW of Tacrolimus (Prograf) - CNI used for maintenance meds?

Increased susceptibility to infection

SE of Tacrolimus (Prograf) - CNI used for maintenance meds?

HTN Nephrotoxicity Hyperglycemia Tremor Hyperkalemia QT prolongation

Monitoring of Tacrolimus (Prograf) & Cyclosporine (Neoral, Gengraf, SandIMMUNE) - CNI used for maintenance meds?

Trough levels Serum electrolytes Renal fxn Hepatic fxn, if liver transplant BP BG Electrolytes ( esp, K) Lipid profile

How should Tacrolimus (Prograf) be used - CNI used for maintenance meds?

On an empty stomach (to avoid variability in absorption)

How do u dose Cyclosporine (Neoral, Gengraf, SandIMMUNE) - CNI used for maintenance meds?

Dose depends on transplant type & formulation

How do u dose modified Cyclosporine (Neoral, Gengraf) - CNI used for maintenance meds - in Renal transplant?

9 +/- 3 mg/kg/day, divided twice daily

How do u dose modified Cyclosporine (Neoral, Gengraf) - CNI used for maintenance meds - in Liver transplant?

8 +/- 4 mg/kg/day, divided twice daily

How do u dose modified Cyclosporine (Neoral, Gengraf) - CNI used for maintenance meds - in Heart transplant?

7 +/- 3 mg/kg/day, divided twice daily

How do u dose non-modified Cyclosporine (SandIMMUNE) - CNI used for maintenance meds?

3 - 10 mg/kg/day

For Neoral/Gengraf/SandIMMUNE...When can nephrotoxicity occur? Trough level?

Nephrotoxicity can occur at ANY level Trough 100-400 ng/mL

BBW of Cyclosporine (Neoral/Gengraf/SandIMMUNE)?

Renal impairment (with high doses) Modified cyclosporine (Neoral, Gengraf) & Non-modified cyclosporine (SandIMMUNE) cant be used interchangeably

SE of Cyclosporine (Neoral/Gengraf/SandIMMUNE)?

HTN Nephropathy Hirsutism Gingival hyperplasia Edema Hyperglycemia QT prolongation

Cyclosporine (Neoral/Gengraf/SandIMMUNE) & other meds?

Most drugs will affect the cyclosporine level, cuz its a CYP 450 3A4 and P-gp substrate Avoid alcohol

MOA of Mammalian target of Rapamycin (mTOR) kinase inhibitor?

Inhibits T-lymphocyte activation and proliferation May be synergistic with CNIs

Agents under Mammalian target of Rapamycin (mTOR) kinase inhibitor?

Everolimus (Zotress, Afinitor) Sirolimus (Rapamune) Belatacept (Nulojix)

BBW of Everolimus (Zostress, Afinitor) - mTOR?

Increased risk of infection Increased Risk of lymphoma & skin cancer

Everolimus (Zostress, Afinitor) & Cyclosporine (Neoral, Gengraf, SandIMMUNE)?

Reduced doses of cyclosporine when used concomitantly

SEs of Everolimus (Zostress, Afinitor)?

Peripheral edema Constipation HTN Hyperglycemia Hyperlipidemia Delayed wound healing Pneumonitis

Trough levels for Sirolimus (Rapamune)? When should it be collected?

Loading dose: 3-4 days after LD Maintenance dose: 7-14 days after dosage adjustments 4-12 ng/mL

SEs of Sirolimus (Rapamune)?

Delayed wound healing Pneumonitis/bronchitis Cough Hyperglycemia Hyperlipidemia

How should calculated dose of Belatacept (Nulojix) be rounded up?

To nearest 12.5mg

Effect of cyclosporine on Mycophenolate, Sirolimus, Everolimus?

Cyclosporine will DECREASE Mycophenolate levels Cyclosporine will INCREASE Sirolimus and Everolimus levels

Xtics of Tacrolimus & Cyclosporine? Substrates, inh or inducers?

Tacrolimus & Cyclosporine are CYP 450 3A4 & P-gp substrates Both will interact with the majority of drugs

Mycophenolate and hormonal contraceptions?

Mycophenolate can reduce levels hormonal contraceptions (making OCPs less effective)

Which immunosuppressants should caution be taken when used with other drugs that are nephrotoxic?

Tacrolimus Cyclosporine

Which immunosuppressants should caution be taken when used with other drugs that are raise BG?

Tacrolimus Steroids Cyclosporine mTor inhibitors (Everolimus/ Sirolimus)

Which immunosuppressants should caution be taken when used with other drugs that worsen lipids?

mTor inhibitors (Everolimus/ Sirolimus) Steroids Cyclosporine

Which immunosuppressants should caution be taken when used with other drugs that raise BP?

Steroids Cyclosporine Tacrolimus

How should immunosuppressants be used?

Take EXACTLY as prescribed Stay consistent on how u take ur medication

What should pt on immunosuppressant monitor and recorded on a daily basis?

Temperature Weight BP Glucose (if pt has DM)

What meds should be avoided with immunosuppressants use?

NSAIDs (Advil, Naprosyn, Aleve) cuz they can harm the kidney OTC, herbal or alternative meds

When should pt use meds if having blood drawn?

Take meds AFTER blood is drawn, not b4

How should Mycophenolate be taken? Main SE?

Empty stomach Diarrhea

What meds should be avoided with Mycophenolate use?

Antacids or multivitamin (separate by 2 hrs) Bile acid resins - avoid completely

Mycophenolate use and sun exposure?

Limit time spent in sunlight Use SPF 30 or higher Those who take this med have a higher risk of getting skin cancer

Are the 2 brand (Myfortic & CellCept) of Mycophenolate interchangeable?

Missed doses for Mycophenolate, Tacrolimus and Cyclosporine?

< 4 hrs after missed scheduled dose - take missed dose and continue as usual > 4 hrs after missed scheduled dose - skip missed dose

What medical condition can Tacrolimus cause?

DM Talk to doctor if u experience any of the following symptoms of high BG: increased thirst/hunger or freq urination

What medical condition can Cyclosporine cause?

High BP and kidney problems Swelling and growth of gums (gingival hyperplasia)