Transplant Nursing Pharmacology FINAL

TRANSPLANT NURSING
Pharmacology
Copyright 2017. OnCourse Learning Corporation. All rights reserved.

Pharmacology
•  What classes of
medications are
routinely used with
transplant patients?
–  Antivirals
–  Antimicrobials
–  Antifungals
–  Immunosuppressive
agents
–  Analgesics

Pharmacology
•  Why are antiviral therapies necessary?

–  Prophylaxis of complications caused by viral infection
–  Treatment of viral complications following transplant in an
immunocompromised host (CMV, reactivation of HSV)

Pharmacology
Acyclovir
Which types of
antivirals are
used often Ganciclovir
with transplant
patients?
Valganciclovir

Pharmacology
•  What are antifungal medications used for?

–  Prevention of oral fungal infection (candidiasis)
–  Systemic fungal infection (aspergillus, cryptococcus)

Pharmacology
•  Which antifungal medications are

used in the transplant population
for treatment or prevention of
oral candidiasis?
–  Clotrimazole
–  Nystatin
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or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons;
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Pharmacology
•  What antifungals are used for treatment of candidiasis,

cryptococcus and aspergillosis?
–  Amphotericin B: (Fungizone, Abelcet, AmBisome) interrupt the
cytoplasmic membrane of the invading fungi leading to fungal
death
•  What side effects of Amphotericin B are important to know?
–  Infusion reactions (fever, rigors, chills)
–  Nephrotoxicity
–  Hepatotoxicity
–  Nausea and vomiting
–  Ability to cause decreased Tacrolimus or Sirolimus levels

Pharmacology
•  Analgesics can be used for:

–  Post-operative pain control
–  Preventative dosing for patients at risk of CVA,
cardiovascular disease
•  Analgesics and post-transplant patients:
–  Acute pain is managed with routine opioid agents
–  NSAIDS should generally be avoided because of increased risk of
toxicities
–  Nonprescription analgesic of choice is acetaminophen

Pharmacology
•  What are immunosuppressive

agents?
–  Medications created to target the
immune system in various areas
resulting in minimal transplant
rejection

Pharmacology
•  What is the goal of immunosuppressive therapy?

–  To maintain graft tolerance using the least amount of drugs
possible
–  Triple therapy (tacrolimus, mycophenolate mofetil and a
corticosteroid) is the most frequently used triple regimen for
solid organ transplant recipients in the United States

Pharmacology
•  What is one category

of immunosuppressive
agents?
–  Small molecule
preparations
•  Corticosteroids
•  Calcineurin inhibitors
•  Antiproliferative agents
•  mTOR inhibitors

Pharmacology
•  What is the second classification of

immunosuppressive drugs?
–  Antibody preparations
•  Treating or preventing acute rejection
•  Either monoclonal or polyclonal antibodies

Pharmacology
•  What is useful about

monoclonal antibodies?
–  Drugs are developed to
target specific antigens or
cell membrane receptors
–  Used in prevention of and
treatment of rejection
–  Two types of mAbs
1.  Depleting
2.  Non-depleting
A general representation of
the method used to produce
monoclonal antibodies
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www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons;
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Pharmacology
What is the difference

between depleting and
non-depleting mAbs?
Non-depleting:
Depleting: Interleukin-2 receptor
Aim to destroy antagonists, not
lymphocytes destroying
lymphocytes

Pharmacology
•  Which drugs are monoclonal antibodies

(mAb)?
–  Depleting mAbs: Alemtuzumab
–  Non-depleting mAbs: Daclizumab (DAC),
Basiliximab (BAS)

Pharmacology
•  What is the mechanism

of action for depleting
mAbs?
–  Alemtuzumab: targets
monocytes, macrophages,
T and B-lymphocytes
By BruceBlaus. When using this image in external sources it can be cited as: Blausen.com staff. "Blausen gallery 2014". Wikiversity Journal
of Medicine. DOI:10.15347/wjm/2014.010. ISSN 20018762. (Own work) [CC BY 3.0 (http://creativecommons.org/licenses/by/3.0)], via
Wikimedia Commons; https://commons.wikimedia.org/wiki/File%3ABlausen_0649_Monocyte.png

Pharmacology
•  What are side effects of Alemtuzumab?

–  Fever/chills
–  Increased risk of opportunistic infection
–  Hyper or hypotension
•  What is the mechanism of action for non-depleting

mAbs?
–  Basiliximab inhibit interleukin-2 activation of lymphocytes
within the cellular immune response

Pharmacology
•  Which side effects might you encounter with infusion of

non-depleting mAbs (BAS)?
–  Generally well tolerated medications
–  Possible fever and chills
–  Rare anaphylactic reactions

Pharmacology
When are depleting

mAbs administered?
Alemtuzumab:
30 mg as a single dose
at the time of transplant

Pharmacology
When are non-depleting

mAbs administered?
BAC: 20 mg IV over 15-30

minutes on day 0 and day 4
post-transplant

Pharmacology
•  How are mAb medications

monitored?
–  CBC, platelet counts

Pharmacology
•  What is a costimulation inhibitor?

–  Belatacept
•  Used in patients who are poor candidates for CNI-based
immunosuppression or who are intolerant of CNI-based
immunosuppression after renal transplantation

Pharmacology
•  What are adverse effects of Belatacept?

–  GI-nausea, diarrhea
–  Infusion-related reactions
–  Peripheral edema
–  Infections, particularly fungal infections

Pharmacology
•  What is useful about

polyclonal antibodies?
–  Medications used as
induction therapy for
immunosuppression prior
to solid organ transplant
and treatment of acute
rejection
Polyclonal Antibody
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https://commons.wikimedia.org/wiki/File%3AAntibody1.jpg

Pharmacology
•  Which drugs are classified as polyclonal antibodies?

–  Atgam
–  Thymoglobulin
–  ATG Fresenius
•  Not available for use in the United States
•  What is their mechanism of action?

–  Prevention of B-cell proliferation
–  Induce depletion of T-cells and clearing them from circulation
–  Cytotoxic activity
–  Unknown

Pharmacology
•  What monitoring is necessary in

patients taking these medications?
–  WBC 2,000-3,000 = dose reduction
–  Platelets < 75,000 = dose reduction
–  CD3 counts to monitor level of T-cell
depletion
Giemsa-stained peripheral
blood smear showing
platelets (blue dots)
surrounded by red blood
cells (pink and circular)
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4.0-3.0-2.5-2.0-1.0)], via Wikimedia Commons; https://commons.wikimedia.org/wiki/File%3APlatelets2.JPG

Pharmacology
•  What side effects may appear with infusion of Atgam

or ATG?
–  Fever, chills
–  Leukopenia
–  Nausea/vomiting
–  Myalgia and dyspnea *ATG only

Pharmacology
•  Which side effects are

specific to
thymoglobulin?
–  Hypertension
–  Thrombocytopenia
–  Abdominal pain
–  Increased risk of CMV
infection

Pharmacology
One hour prior to infusing Atgam or Thymoglobulin,

to prevent side effects during infusion, the nurse
needs to premedicate the patient with…
Acetaminophen Antihistamine Corticosteroids

Pharmacology
•  How are corticosteroids used in the transplant setting?

–  1st immunosuppressive drugs introduced in organ
transplantation
–  Used along with CNIs for maintaining immunosuppression

Pharmacology
•  What side effects of

corticosteroids are important to
know?
–  Increased risk of hypertension
–  Development of diabetes
–  Increased risk for infection
–  Fluid and electrolyte abnormalities

Pharmacology
•  What is a calcineurin inhibitor?

–  Medications given to patients that have had solid organ transplants
for prevention of allograft rejection
–  Standard medications for initiating immunosuppression
•  Tacrolimus (TAC)
•  Cyclosporine (CsA)

Pharmacology
•  What is the mechanism of action of CNIs?

–  Block production of cytokines
–  Interrupt IL-2 causing inactivation of cytotoxic T-cells response
to non-self antigens
–  Suppression of the immune system activation of T-lymphocytes

Pharmacology
Dosing of cyclosporine is specific to type

of organ transplanted:
Cyclosporine
Heart: 3 mg/kg/day p.o., in 2 divided doses
Kidney: 3 mg/kg/day p.o., in 2 divided doses
Liver: 4 mg/kg/day p.o., in 2 divided doses
IV dosing infused over 4-6 hours, 1/3 oral dose

Pharmacology
•  Cyclosporine formulations
–  Nonmodified (Sandimmune)
–  Modified, as microemulsion (Neoral, Gengraf)
–  There are generic equivalents for both formulations
–  These formulations are not easily interchangeable

Pharmacology
Dosing of Tacrolimus is specific to

solid organ transplanted:
Adult Heart: 0.075 mg/kg/day po, in 2 divided doses
Adult Kidney: 0.2 mg/kg/day po, in 2 divided doses
Adult Liver: 0.10 - 0.15 mg/kg/day po in 2 divided doses
Pediatric Liver: 0.15 – 0.20 mg/kg/day po, in 2 divided doses

Pharmacology
•  IV Tacrolimus
–  IV dosing continuous
infusion 0.03-0.05mg/
kg/day
–  Typically 1/3 of oral
dose per day

Pharmacology
•  How are therapeutic drug levels monitored?

–  Cyclosporine
•  Serum trough and peak
•  12 hour trough therapeutic 100-400ng/mL
•  2 hour peak therapeutic 800-1200ng/mL
–  Tacrolimus
•  12 hour trough therapeutic 5-20ng/mL

Pharmacology
•  What drugs / food may

interact with CsA or TAC
causing increased drug
levels?
–  Calcium channel blockers
–  HMG-CoA reductase inhibitors
–  Antifungal medications
–  Antigout angents
–  Grapefruit juice/pomegranate
–  Antibiotics-macrolides

Pharmacology
•  Which medications may decrease CsA or TAC drug level

concentration?
–  Herbal preparations, over the counter
–  Antibiotics
–  Antituberculins
–  Anti-epileptic medications

Pharmacology
•  Adverse effects of CsA and TAC can include the following:

–  Diabetes mellitus
–  Gastrointestinal distress
–  Hirsutism (CsA)
–  Hypertension
–  Hyper K+, hypo Mg+, Phos (TAC)
–  Tremors

Pharmacology
•  What medications may be used in combination with CNIs

(CsA, TAC)?
–  Antiproliferative agents (antimetabolites)
•  CellCept (MMF)
•  Imuran (azathioprine, AZA)
•  Myfortic
•  Rapamune (Sirolimus, SRL)

Pharmacology
•  What is different about Sirolimus?

–  mTOR inhibitor-Mammilian target of rapamycin (inhibits a
kinase necessary for cell division)
–  Only approved for use with kidney transplant patients
–  Used in conjunction with cyclosporine or Tacrolimus therapy

Pharmacology
•  What is an additional proliferation signal inhibitor?

–  Everolimus (Zortress)
•  Similar to sirolimus
•  Has a black box warning against use in heart transplantation

Pharmacology
•  How are Sirolimus levels monitored?

–  Serum trough values at initiation of administration
between 4-12ng/mL
–  Concurrently with withdrawal of CsA, levels should
maintain 12-24ng/mL

Pharmacology
•  What are adverse effects

of Sirolimus?
–  Anemia
–  Diarrhea
–  Delayed wound healing
–  Hypertension
–  Increased cholesterol,
glucose
–  Pneumonitis
–  Thrombocytopenia
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Commons; https://commons.wikimedia.org/wiki/File%3APneumonitis.png

Pharmacology
•  What are other antimetabolites used in solid organ

–  CellCept(MMF) used in combination with Sirolimus, TAC, CsA,
prevention of B and T-cell proliferation
–  AZA use reduced secondary to creation of MMF
–  Myfortic

Pharmacology
•  What is the recommended

oral dosing of Cellcept?
–  2 g/day in kidney, liver,
pancreas, and lung given
twice daily
–  3 g/day in heart given
twice daily
–  IV dose is the same as
oral dose, usually infused
over 2 hours

Pharmacology
•  What is the mechanism of action of Myfortic?

–  Inhibit purine synthesis
–  Inhibit B and T cell proliferation
–  Enteric coated for release in small intestine to reduce GI side
effects
–  Least side effects of nephrotoxicity, alteration in glucose levels

Pharmacology
•  What are most common side effects of antimetabolites?

–  Bone marrow suppression
–  Higher frequency of CMV infection
–  GI upset (constipation, diarrhea, n/v)

Pharmacology
•  Why are antimicrobials necessary in transplantation?

–  Transplant patients are at great risk for:
•  Post-operative infection
•  Opportunistic infection (2-6 months post-transplant)
•  Nosocomial infection
•  Community or hospital acquired infection
•  Infection related to immunosuppressive medication

Pharmacology
•  Which types of antimicrobials are used often with

–  Trimethoprim (TMP) / Sulfamethoxazole (SMX):
•  Prevention and treatment of Pneumocystis carinii
–  Metronidazole: treatment of clostridium difficile
–  Cefazolin, Vancomycin: post-operative infection

Pharmacology
What time line for development of infection is

followed closely with post-transplant patients?
Late >6 months

Early infection (community
(nosocomial) acquired/latent)
Mid 2-6 months

(opportunistic
infections)

Pharmacology
•  When is there a need for cardiovascular medications post-

transplant?
–  Hypertension is the most common development in patients
post-solid organ transplant
–  CsA most common drug with side effect of hypertension

Pharmacology
•  Which drugs of choice are utilized

in the transplant setting to treat
hypertension?
–  ACE inhibitors
–  Angiotensin II blockers
–  Calcium channel blockers

Pharmacology
•  Pharmacological treatment of organ transplant patients

can be complex:
–  Monitoring medication interactions
–  Development of opportunistic infections
–  Drug toxicity development

Pharmacology
•  Medications to manage GI
symptoms:
–  Peptic ulcers and GERD are very
common in the transplant
population
–  Prophylactic therapy is
commonly prescribed post-
transplant
–  Use proton pump inhibitors with
caution with MMF, may lower
levels of mycophenolic acid
By BruceBlaus (Own work) [CC BY-SA 4.0 (http://creativecommons.org/licenses/by-sa/4.0)], via Wikimedia Commons;
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Pharmacology
•  Diabetes Mellitus medications:

–  Occurs in up to 50% of solid organ transplant recipients
within first 3 months
–  Treatment options include
•  Dietary and lifestyle modifications
•  Pharmacotherapy

Bibliography
•  Chandraker, Anil & Yeung, Melissa. Overview of care of the adult

kidney transplant recipient. In D. Brennan (Ed.), UpToDate; 2017.
Retrieved from http://www.uptodate.com/home/index.html
•  Golan DE, Tashjian AH, Armstrong E, Armstrong AW. Principles of
Pharmacology: The Pathophysiologic Basis for Drug Therapy. 2nd
Ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2007.
•  Hanaway MJ, Woodle ES, Mulgaonkar S, et al, “Alemtuzumab
Induction In Renal Transplantation,” N Engl J Med, 2011,
364(20):1909-19. [PubMed 21591943]
•  Hardinger, Karen & Brennan, Daniel. Maintenance
immunosuppressive therapy in renal transplantation in adults. In
B. Murphy (Ed.), UpToDate; 2017. Retrieved from http://
www.uptodate.com/home/index.html

Bibliography
•  Martin ST, Roberts KL, Malek SK, et al. Induction treatment

with rabbit antithymocyte globulin versus basiliximab in renal
transplant recipients with planned early steroid withdrawal.
Pharmacotherapy 2011; 31:566.
•  Ohler L, Cupples S. Core Curriculum for Transplant Nurses.
Second Ed. St. Louis, MO: Mosby; 2016.
•  Simulect (basiliximab) [product monograph]. Dorval, Quebec,
Canada: Novartis Pharmaceuticals Canada Inc; July 1014.
•  Susssman, Norman & Vierling, John. Liver Transplantation in
adults: Overview of immunosuppression. In R. Brown (Ed.),
UpToDate; 2017. Retrieved from http://www.uptodate.com/
home/index.html

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TRANSPLANT NURSING

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• Why are antiviral therapies necessary?

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• What are antifungal medications used for?

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• Which antifungal medications are

By James Heilman, MD (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• What antifungals are used for treatment of candidiasis,

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• Analgesics can be used for:

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• What are immunosuppressive

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• What is the goal of immunosuppressive therapy?

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• What is one category

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• What is the second classification of

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• What is useful about

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

What is the difference

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• Which drugs are monoclonal antibodies

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• What is the mechanism

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• What are side effects of Alemtuzumab?

• What is the mechanism of action for non-depleting

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• Which side effects might you encounter with infusion of

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

When are depleting

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

When are non-depleting

BAC: 20 mg IV over 15-30

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• How are mAb medications

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• What is a costimulation inhibitor?

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• What are adverse effects of Belatacept?

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• What is useful about

By Gentaur (Gentaur) [Public domain], via Wikimedia Commons;

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• Which drugs are classified as polyclonal antibodies?

• What is their mechanism of action?

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• What monitoring is necessary in

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• What side effects may appear with infusion of Atgam

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• Which side effects are

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

One hour prior to infusing Atgam or Thymoglobulin,

Acetaminophen Antihistamine Corticosteroids

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

• How are corticosteroids used in the transplant setting?

Copyright 2017. OnCourse Learning Corporation. All rights reserved.

•  Why are antiviral therapies necessary?

•  What are antifungal medications used for?

•  Which antifungal medications are

•  What antifungals are used for treatment of candidiasis,

•  Analgesics can be used for:

•  What are immunosuppressive

•  What is the goal of immunosuppressive therapy?

•  What is one category

•  What is the second classification of

•  What is useful about

•  Which drugs are monoclonal antibodies

•  What is the mechanism

•  What are side effects of Alemtuzumab?

•  What is the mechanism of action for non-depleting

•  Which side effects might you encounter with infusion of

•  How are mAb medications

•  What is a costimulation inhibitor?

•  What are adverse effects of Belatacept?

•  What is useful about

•  Which drugs are classified as polyclonal antibodies?

•  What is their mechanism of action?

•  What monitoring is necessary in

•  What side effects may appear with infusion of Atgam

•  Which side effects are

•  How are corticosteroids used in the transplant setting?

•  What side effects of

•  What is a calcineurin inhibitor?

•  What is the mechanism of action of CNIs?

•  How are therapeutic drug levels monitored?

•  What drugs / food may

•  Which medications may decrease CsA or TAC drug level

•  Adverse effects of CsA and TAC can include the following:

•  What medications may be used in combination with CNIs

•  What is different about Sirolimus?

•  What is an additional proliferation signal inhibitor?

•  How are Sirolimus levels monitored?

•  What are adverse effects

•  What are other antimetabolites used in solid organ

•  What is the recommended

•  What is the mechanism of action of Myfortic?

•  What are most common side effects of antimetabolites?

•  Why are antimicrobials necessary in transplantation?

•  Which types of antimicrobials are used often with

•  When is there a need for cardiovascular medications post-

•  Which drugs of choice are utilized

•  Pharmacological treatment of organ transplant patients

•  Diabetes Mellitus medications:

•  Chandraker, Anil & Yeung, Melissa. Overview of care of the adult

•  Martin ST, Roberts KL, Malek SK, et al. Induction treatment