Transplant/ Immunosuppresion Flashcards
What’s an isograft?
Transplanted organs from GENETICALLY IDENTICAL donor (such as identical twin)
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
Most commonly used induction agent?
Basiliximab (interleukin-2 (IL-2) receptor antagonist
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)
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
Which maintenance drugs have highest nephrotoxicity?
Tacrolimus
Cyclosporine
Which maintenance drugs may worsen DM or cause new onset of DM?
Tacrolimus
Cyclosporine
Steroids
Which maintenance drugs may worsen lipid parameters?
mTor inhibitors
Steroids
Cyclosporine
Which maintenance drugs have highest risk for BP elevations?
Steroids
Cyclosporine
Tacrolimus
Whys other drugs (antiproliferative or antimetabolite) used with CNI?
To reduce nephrotoxicity risk
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
TB
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
Infection control in Immunosuppressed pts include:
Air filtration systems
Keeping mouth clean
Keeping away from dusty, crowded areas & sick people
Can live-vaccines be given post-transplant?
No!
Inactivated vaccines only
Pneumococcal vaccine in immunocompromised pts?
In adults >= 19 yrs
PCV 13
PPSV23 - at least 8 wks after PCV 13
List induction agents
Antibodies
- Antithymocyte Globulin (Atgam-Equine; Thymocyte-Rabbit)
Interleukin 2 (IL-2) receptor antagonist - Basiliximab (Simulect)
MOA of anitbodies (induction agent)?
Reverse rejection by binding to antigens on T-lymphocytes (killer cells) and interfering with their function
Drug under antibodies?
Antithymocyte Globulin (Atgam-Equine) (Thymocyte-Rabbit)
Pre-medication necessary with Antithymocyte Globulin (Atgam-Equine) (Thymocyte-Rabbit)?
May be necessary (diphenhydramine, APAP, steroids)
Epinephrine + resuscitation equipment should be nearby
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
Agents under IL-2 receptor antagonists?
Basiliximab (Simulect)
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
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)
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?
No
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)
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