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PHM 603 > Transplant Drugs > Flashcards

Transplant Drugs Flashcards

1
Q

Pre-Transplant

A

Induction Agent
IV Bolus MEPN
MPA Dose

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2
Q

Post-Transplant (1-7)

A

Few doses of Induction Agent then D/C
IV MEPN converted to PO PRED w/ taper
MPA
Low Dose CNI

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3
Q

Maintenance Therapy

A

MPA
CNI titrated through TDM
PRED taper
Monitor Allograft function

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4
Q

Cyclosporine Therapeutic Trough

A

50-400 ng/ml

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5
Q

Tacrolimus Therapeutic Trough

A

3-20 ng/ml

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6
Q

Factors that affect CNI PK

A 
Fat Content in Meals/Bile
Time post-transplant
Type of Organ Transplanted
Compromised GI Function
Overall Bioavailability
Drug Interactions
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7
Q

Prograf (Astellas)

A 
Tacrolimus IR (Prototype)
Capsules
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8
Q

Astagraf XL (Astellas)

A

Tacrolimus ER
Polymer
1 mg ER: 1 mg IR
Troughs may be lower than IR

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9
Q

Envarsus

A

Tacrolimus ER
Molecular particles w/ meltdose technology (cont. drug release)
70% of IR daily dose

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10
Q

IV Prograf (Astellas)

A 
Tacrolimus ER
Poloxy 60 hydrogenated castor oil with TAC
cont. infusion over 24 hrs
Anaphylaxis may occur; short term use
Glass/Polyethylene Containers
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11
Q

Neoral (Novartis)

A

Modified CYA
Microemulsion capsules and modified emulsion solution
BID (q12h)
May dilute the solution in apple/orange juice only

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12
Q

Gengraf (Abbvie/Abbott)

A

Modified CYA
Emulsion Capsules and modified emulsion solution
Bioequivalent to Neoral

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13
Q

Sandimmune (Novartis/Sandoz)

A 
Non-modified CYA
Castor Oil Capsules and solution
Can flocculate/gel below 20C, use glass to admin
Not bioequivalent to modified CYA
Dosing qd
Erratic Bioavail
May dilute with milk/OJ
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14
Q

IV Sandimmune

A 
Non-modified CYA
Cremophor EL (Castor Oil Complex in CYA)
Anaphylaxis may occur; short term use
Reserved for those who can't do PO
Discard after 24 hrs
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15
Q

Cyclosporine AE

A

Hyperlipidemia, Nephrotoxicity, Tremor, HA, HTN

Hyperglycemia, Gingival Hyperplasia, Hirsutism, Diarrhea, Vomiting

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16
Q

Tacrolimus

A

Diarrhea, Nausea, Nephrotoxicity, Tremor, HA, insomnia

Hyperglycemia, Hyperlipidemia, HTN

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17
Q

Common DDI (Inhibition) w/ CNI

A

CCB, Antifungals, Antibiotics, Protease Inhibitors, Gastric Acid Suppressors, Grapefruit Juice

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18
Q

Common DDI (Induction) w/ CNI

A

Antibiotics, Antifungals, Anticonvulsants, Herbals, Others

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19
Q

Mycophenolic Acid (MPA)

A

Inhibits IMPDH, interfering w/ purine metab needed for lymphocyte development (prevents proliferation of committed T cells)

20
Q

Mycophenolate Mofetil (MMF) - CellCept

A

MPA
Ester pro-drug
Regular Release
1000 mg

21
Q

Mycophenolic Acid Sodium (MPS) - Myfortic

A

MPA
Sodium Salt
Delayed Release (enteric coating)
720 mg

22
Q

Better Biavailability – CYA or MPA?

A

MPA

23
Q

Factors affecting MPA PK

A 
Time After Transplantation
DI
Enterohepatic Circulation
Concurrent Disease States
Food
Ethnicity
Gender
Genetic Polymorphorphisms
24
Q

MPA DI (EHC)

A

CYA, Tacrolimus, Cholestyramine and Bile Acid Resins, Antibiotics

25
Q

MPA DI (Renal Elim)

A

Acyclovir/Ganicyclovir, Co-trimoxazole

26
Q

MPA DI (COC)

A

Use barrier method

27
Q

MPA DI (Protein Binding)

A

Alters binding of Phenytoin and ASA

28
Q

MPA DI (Inc Metab)

A

Glucocorticoids

29
Q

MPA AE

A

GI (N/V, Diarrhea, dyspepsia), Hematologic (Leuko/Neutro/Thrombocytopenia, Anemia), Opportunistic Infections, CNS (dizziness, insomnia, HA), Cardiovascular

30
Q

MPA Dosing w/ declining renal function

A

Use lower dose w/ a longer interval based upon the patient’s ADE response

31
Q

Equivalents to Cortisone Dosage (25 mg)

A

Prednisone (5 mg)

Methylprednisolone (4 mg)

32
Q

Glucocorticoid Usage

A

Lowest Dose for Shortest Duration

33
Q

Metabolic Inhibition of Glucocorticoids

A

Oral Contraceptives, Conjugated Estrogens, Macrolide Antibiotics, Ketoconazole, Isoniazid, Naproxen, Cyclosporine

34
Q

Metabolic Induction of Glucocorticoids

A

Phenytoin, Phenobarbital, Rifampin, Carbamazepine, Ephedrine (dexameth)

35
Q

Metabolic Induction BY Glucocorticoids

A

Tacrolimus, CYA (high dose MePn), MPA

36
Q

Decrease Steroid Absorption

A

Cholestyramine and Antacids

37
Q

Maintenance Glucocorticoid AE

A

Adrenal Atrophy, Cushing’s Syndrome, Dyslipidemia, HTN, thrombosis, Vasculitis, Changes in Behavior/Cognition/Memory/Mood, Cerebral Atrophy, GI bleeding, Pancreatitis, Peptic Ulcer, Broad Immunosuppression, Activation of Latent Viruses, Delayed Wound Healing, Dermatitis, Bone Necrosis, Muscle Atrophy, Osteoporosis, Cataracts, Glaucoma

38
Q

Post Transplant Complications

A

HTN, Opportunistic Infections, Diabetes, Hyperlipidemia, Osteoporosis, Lymphoproliferative Disorder

39
Q

We use multiple drugs with different MOA to

A

use lower doses and minimize AE

40
Q

Induction Immunosuppression

A

More intense immunosuppression initiated just prior and during the acute post-transplant phase

41
Q

Role of Induction Therapy

A

Avoid Full Dose CYA/TAC (result in renal vasconstriction/slower function of renal graft), block Tcell/immunologic activation at time of graft placement

42
Q

Disadvantage of Induction Therapy

A

Increased Costs, Increased risk of Cytomegalovirus (CMV) infection and post-transplantation lymphoproliferative disease (PTLD)

43
Q

Induction Therapy Drug Plan

A

ONE Induction Agent, Mycophenolate mofetil (MMF), Glucocorticoids (at high doses with rapid dose tapering)

44
Q

ATG (Anti-thymocyte Globulin)

A

Depleting Induction
Polyclonal Antibodies
4-6 hours IV for 2-4 doses
Coat T cells, opsonization of donor tissue
AE: flu-like symptoms (fever, chills, N/V) on 1st dose; leukopenia, lymphopenia, thrombocytopenia, pruritis, erythema, serum sickness
Premedicate w/ Diphenhydramine and APAP

45
Q

Alemtuzumab (Campath)

A

Depleting Induction
Monoclonal Antibody against CD52 surface antibody
2 doses OR 1 Dose IV
Precede each dose by IV MePn, use anti-infective agent for at least 2 mo after d/c
Causes prolonged lymphocyte depletion (up to 3 years)
AE: HAMA, GI (N/V, diarrhea), lymphopenia, neutropenia, thrombocytopenia

46
Q

Basiliximab (Simulect)

Daclizumab (Zenapax)

A

Non-Depleting
Monoclonal Antibodies
Against CD25 portion of the IL-2 receptor which prevents T cell proliferation
ADE: GI (N/V, diarrhea - minimal)

47
Q

possible drug use to decrease CNI dosage

A

Verapamil

PHM 603 (4 decks)

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