Solid Organ Transplant

Pharmacy Practice 3833 with Nola at Lipscomb University

About this deck

By: Joel Daniel
Textbook:

Pharmacotherapy: A Pathophysiologic Approach, Eighth Edition (PHARMACOTHERAPY (DIPIRO))
Created: 2012-02-28
Size: 52 flashcards
Views: 19

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Goals of Induction Immunosuppression

Prevent Hyperacute and Acute Rejection

Minimize AEs of Medications

Goals of Maintenance Immunosuppression

Prevent Acute and Chronic Rejection

Minimize Drug-Related Toxicities

Utilize Lowest Dose Possible

Goals of Immunosuppression in Rejection

Minimize the Intensity of the immune response

Prevent Irreversible Injury

Class (and Place in Immunosuppressant Tx) of RATG

Rabbit Antithymocyte Globulin

Polyclonal Antibody

Induction

Brand Name of RATG

Thymoglobulin

MOA of RATG

Bind to a variety of lymphocyte receptors

Causes complement-mediated lysis and lymphocyte depletion

AE Profile of RATG

Myelosuppression

Anaphylaxis

Infusion related rxns^*

*: Premedicate with APAP, corticosteroids, diphenhydramine

General Dosing Recommendations of RATG

Daily through central line with 0.22-micron filter

Class (and Place in Immunosuppressant Tx) of Alemtuzumab

Antibody against CD52 (expressed on both T and B cells)

Induction Tx that may allow for monotherapy post-transplant

Brand Name of Alemtuzumab

Campath

MOA of Alemtuzumab

Binding to CD52 results in antibody-dependent lysis

Note: B-cells return in 3-12mo; T-cells up to 3 years

AE Profile of Alemtuzumab

Infusion Related Rxns^*

Pancytopenia

Neutropenia

Thrombocytopenia

Lymphopenia

*: Premedicate with APAP, corticosteroids, diphenhydramine

General Dosing Recommendations for Alemtuzumab

May consider second dose 1-5 days later

Class (and Place in Immunosuppressant Tx) of Basliximab

IL-2R Antagonist

Induction Tx that may allow for delayed use or reduced doses of calcineurin inhibitors early post-transplant

Brand Name of Basiliximab

Simulect

MOA of Basiliximab

Binds to IL-2 Receptor

Prevents activation and proliferation of T-cells

AE Profile of Basiliximab

Hypersensitivity Rxns

General Dosing Recommendations of Basiliximab

2 IV Doses

Saturates the IL-2R for 30-45 days

Typical Maintenance Protocol for Immunosuppression Tx

CI (CSA or TAC)

+/- MPA or SRL

+/- Steroids

Names (Trade and Generic) of Calcineurin Inhibitors

Cyclosporine (Sandimmune)

Cyclosporine Modified (Neoral)

Tacrolimus (Prograf)

Place in Immunosuppression Tx of Calcineurin Inhibitors

Maintenance Tx

MOA of Calcineurin Inhibitors

Binds to immunophilin (complex inhibits calcineurin)

Inhibits the activation and cytokine production of T-cells and therefore T-cell proliferation

Absorption Notes of Interest for Calcineurin Inhibitors

Cyclosporin is dependent on bile for absorption

Cyclosporin modified is not as dependent

Distribution Notes of Interest for Calcineurin Inhibitors

Cyclosporine and tacrolimus are highly protein bound

Cyclosporine has large Vd

Tacrolimus has smaller Vd

AE Profile of Calcineurin Inhibitors

Neurotoxicity

HTN/Hyperlipidemia

Hyperglycemia

Hirsutism (cyclosporin)

Alopecia (tacrolimus)

Mechanism of Nephrotoxicity of Calcineurin Inhibitors

Afferent arteriole vasoconstriction

DDIs with Calcineurin Inhibitors

Substrates of 3A4

Inhibitors/Inducers of 3A4

P-gp substrates

MOA of Mycophenolate mofetil

Inhibits nucleotide synthesis via de novo pathway, thereby decreasing nucleotide synthesis and DNA polymerase activity

More specific for T-cells than B-cells

AE Profile of Mycophenolate

GI Sx

Strategies to Reduce

Reduce Dose

Divide into 3-4doses/day

Administer with food

Start low and go slow

DDIs with Mycophenolate

Antacis/Cholestyramine reduce AUC

Acyclovir increases AUC

Brand Name of Azathioprine

Imuran

MOA of Azathioprine

Converted to 6-MP

Disrupts salvage and de novo pathways of DNA/RNA/Protein synthesis

AE Profile of Azathioprine

Myelosuppression

Alopecia

Pancreatitis

Hepatotoxicity

DDIs of Azathioprine

Xanthine Oxidase Inhibitors b/c metabolism into active form is inhibited

Class (and Place in Immunosuppressant Tx) of Sirolimus

mTOR Inhibitors

Maintenance

Brand Name of Sirolimus

Rapamune

MOA of Sirolimus

Inhibits the response of mTOR to cytokines

Reduces T-cell Proliferatin

PK Parmeters of Sirolimus

Low Bioavailability

Large Vd

Metabolized by 3A4

P-gp Substrate

AE Profile of Sirolimus

Myelosuppression

Hypercholesterolemia

Hypertriglyceridemia

Mouth ulcers (oral solution)

DDIs for mTOR Inhibitors

3A4 Inhibitors/Inducers

Cyclosporine and Cyclosporine modified

Class (and Place in Immunosuppressant Tx) of Everolimus

mTOR Inhibitor

Maintenance

Brand Name of Everolimus

Zortress

MOA of Everolimus

Inhibits the response of mTOR to cytokines

Reduces T-cell Proliferatin

PK Parmeters of Everolimus

Low Bioavailability

Large Vd

Metabolized by 3A4

P-gp Substrate

AE Profile of Everolimus

Myelosuppression

Hypercholesterolemia

Hypertriglyceridemia

Mouth ulcers (oral solution)

Brand Name of Belatacept

Nulojix

MOA of Belatacept

Binds to CD80 and CD86 on APCs and prevents interaction with T-cells

FDA Indication for Belatacept

Only indicated for patients who received basiliximab induction and with MPA and Steroids

General Tx for Acute Rejection for Solid Organ Transplant

Pulse dose steroids

Short-term MAB

Increase dose of current Tx

Add another Immunosuppressant

Place in Immunosuppressant Tx of Muromonab-CD3

Typically reserved for Tx of corticosteroid resistant rejection

Brand Name of Muromanab-CD3

Orthoclone OKT3

MOA of Muromanab-CD3

Murine MAB to CD3 (T-cell depletion)

About this deck

By: Joel Daniel
Textbook:

Pharmacotherapy: A Pathophysiologic Approach, Eighth Edition (PHARMACOTHERAPY (DIPIRO))
Created: 2012-02-28
Size: 52 flashcards
Views: 19

About StudyBlue

“Simply amazing. The flash cards are smooth, there are many different types of studying tools, and there is a great search engine. I praise you on the awesomeness.”
Dennis