Pharmacology Flashcards
(89 cards)
1
Q
Goals of Immunosuppression include…
A
- To prevent acute rejection
- Improve graft survival
- Improve patient survival
- to maintain good quality of life
2
Q
Immunosuppression is individualized due to…
A
- individual drug toxicity
- to decrease specific side effects changed based on individual immunologic risk t
- provide lowest levels of medication and to wean off steroids
3
Q
Too much medication can cause…
A
- nephrotoxicity
- infection
- malignancy
- neurotoxicity
4
Q
Too little medication can cause…
A
- rejection
- graft loss
5
Q
Induction agents are…
A
intense prophylactic therapy given at time of transplant
6
Q
Induction agents are given when…
A
rejection risk is highest
7
Q
Typical maintenance therapy includes…
A
- CNIs: form the cornerstone of immunosuppressive therapy
- Antimetabolites (AZA, MMF)
- Corticosteroids
8
Q
Adjuvant agents are…
A
medications prescribed in combination with CNI
9
Q
Rescue therapy is…
A
intense therapy utilized in response to a rejection episode
10
Q
Interleukin 1 inhibitors include…
A
Corticosteroids
11
Q
Calcineurin inhibitors include…
A
- tacrolimus
- cyclosporine
12
Q
Antiproliferative agents include…
A
- azathioprine
- mycophenolate mofetil
13
Q
mTOR inhibitors include…
A
- sirolimus
- everolimus
14
Q
Antibodies include…
A
- Atgam
- thymoglobulin
- basilixamab
- rituximab
- alemtuzumab
- IVIG
15
Q
Advantages of induction agents ATG (Polyclonal) include…
A
- stronger
- can be used to treat rejection
16
Q
Disadvantages of induction agents ATG (Polyclonal) include…
A
- common acute side effects
- higher infection (CMV) and malignancy rates
- potential to develop antibodies
17
Q
Advantages of induction agents Basiliximab (Monoclonal) include…
A
- no acute side effects
- not associated with infection and malignancy
18
Q
Disadvantages of induction agents Basiliximab (Monoclonal) include…
A
- weaker
- CANNOT be used for rejection
19
Q
Polyclonal antibodies (ATG): clinical use includes…
A
- intra-op to reduce delayed graft function
- prevention of acute rejection (induction)
- treatment of rejection (rescue)
20
Q
Polyclonal antibodies (ATG): mechanism of action is..
A
- t cell depletion
- cytotoxic activities
21
Q
polyclonal antibodies (ATG): adverse reactions include…
A
- cytokine release syndrome
- leukopenia/thrombocytopenia
- serum sickness
- anaphylaxis
- infection
- malignancies - PTLD
22
Q
Monoclonal antibodies (Basiliximab) adverse reactions include…
A
minimal side effects; well tolerated
23
Q
Maintenance therapy is…
A
- used as primary and chronic immunosuppression
- less potent than induction
24
Q
Maintenance therapy consists of…
A
- calcineurin inhibitor (Tacro OR cyclo)
- +/-corticosteroid (prednisone)
- additional agent: antiproliferative OR mTOR
25
Calcineurin inhibitors inhibit the first phase of…
T cell activation which leads to reduced circulating T cell activators.
26
Tacrolimus pharmacokinetics include:
* 0.1-0.15 mg/kd/day divided twice daily
* not removed by dialysis
* decreased absorption with food
* metabolized by liver t
* ransported by cytochrome P450 34A
* elimination half life 12-18 hrs
27
Cyclosporine pharmacokinetics:
* 5-10 mg/kg/day divided twice daily f
* ood alters absorption
* not removed by dialysis
* elimination half life 10-40 hours
28
Adverse effects of CNI's -nephrotoxicity for cyclosporine vs tacrolimus indicates…
* cyclosporine = tacrolimus
* acute toxicity reversible with dose decrease
29
Adverse effects of CNI's -neurotoxicity for cyclosporine vs tacrolimus indicates…
* tacrolimus \> cyclosporine
* tremors, headache, parasthesias, PRES
30
Adverse effects of CNI's - hematology for cyclosporine vs tacrolimus indicates…
* cyclosporine = tacrolimus
* Hemolytic uremic syndrome
* Thrombocytopenia Purpura
* low platelets, high Scr, high LDH, decreased haptoglobin, sometimes decreased platelets
31
Adverse effect of CNI's - hyperlipidemia for cyclosporine vs tacrolimus indicates…
tacrolimus \< cyclosporine
32
Adverse effect of CNI's - hyperglycemia for cyclosporine vs. tacrolimus indicates…
* tacrolimus \> cyclosporine
* tacrolimus higher incidence with higher levels
33
Adverse effect of CNI's - hypertension is…
* most common side effect
* caused by renal vasoconstriction
34
Adverse effect of CNI's - dermatologic include…
* cyclosporine hair growth and gingival hyperplasia
* tacrolimus with hair loss
35
Adverse effect of CNI's - Gastrointestinal for cyclosporine vs tacrolimus indicates…
* tacrolimus \> cyclosporine nausea, vomiting, anorexia, bloating
* bad smell with cyclosporine
36
Target trough time for tacrolimus is…
12 hours after
37
Target trough level for tacrolimus is…
5-15 trough, which is dependent on: organ, time after tx, clinical condition
38
Target trough time for cyclosporine is…
12 hours after
39
Target trough level for cyclosporine is…
100-400 trough, which is dependent on: organ, time after tx, clinical condition
40
Drugs that increase cyclosporine/tacro levels include:
* antifungals (ketoconazole, fluconazole, clotrimazole)
* metoclopramide
* grapefruit/pomegranate juice
* simepravir
* erythromycin, clarithromycin, azithromycin
* diltiazem, verapamil
* amiodarone
41
Drugs that decrease cyclosporine/tacro levels include:
* cholestyramine
* kayexalate
* octreotide
* probucol
* Mg and Al antacids
* rifampin
* herbs
* nafcillin
* phenytoin
* phenobarbital
42
mTOR inhibitors are structurally similar to…
tacrolimus
43
mTOR inhibitors work by …
inhibiting t-cell activation and proliferation
44
Sirolimus therapy is used when…
* used as adjunct to prevent chronic rejection
* used if intolerant to cyclosporine or tacrolimus
* used for steroid free protocols
45
The synergy between Cyclo/tacro and sirolimus allows for…
lower levels of both drugs
46
Sirolimus pharmacokinetics:
* loading dose +/- 6-12 mg
* maintenance 2-5 mg daily
* target trough level 6-12
* 7-12 days to reach steady state
47
Sirolimus side effects - hematologic include…
* neutropenia, thrombocytopenia, leukopenia
* may require dose adjustment
48
Sirolimus side effects - anemia include…
increased incidence when used with mycophenolate
49
Sirolimus side effect - hyperlipidemia and hypertriglyceridemia include…
* may be increased
* may require dose reduction
50
Sirolimus side effect - impaired delayed wound healing due to…
inhibition of cell and muscle proliferation
51
Sirolimus side effect - nausea, vomiting, diarrhea is…
not as bad as with Cellcept
52
Sirolimus side effect -mouth ulcers Include…
* like canker sores, may be painful
* rash may be light or severe
* may need to discontinue drug
53
Sirolimus side effect -interstitial pneumonitis requires…
drug discontinuation
54
Sirolimus other side effects include…
* proteinuria
* lymphocele/lymphedema
* bone pain
55
A black box warning for sirolimus is…
* hepatic artery thrombosis liver patient
* bronchial anastomotic dehiscence lung transplant
56
Everolimus is used for…
* prevention of rejection in low - mod risk renal transplant recipients
* approved for use with basiliximab, low dose cyclosporine and corticosteroids
57
Everolimus pharmacometrics:
* Dosing: 0.75 mg PO BID
* Administer with or without food at the same time as cyclosporine
* Target trough levels 3-8 ng/mL
* Available as 0.25 mg, 0.5 mg, 0.75 mg tabs
58
Everolimus side effects include…
* Hypercholesterolemia
* Hypertriglyceridemia
* Leukopenia
* Anemia
* Mouth ulcers
* Acne
* Impaired wound healing
* Lymphocele
* Proteinuria
* Nephrotoxicity
* Graft thrombosis
* Rash
59
Azathioprine is used when…
* older agent
* adjunct for those who don’t tolerate mycophenolate
* no drug level monitored
60
The mechanism of action for Azathioprine is…
inhibits t-cell proliferation
61
Azathioprine dosing levels:
* 1-3 mg/kg/day
* 50% bioavailability
62
azathioprine - adverse reactions include…
* leukopenia/thrombocytopenia
* pancytopenia
* Nausea vomiting
* macrocytic anemia
* alopecia
* pancreatitis
* hepatotoxicity
* malignancy
* infection
63
Allopurinol and azathioprine drug interactions:
* avoid combination if possible - switch to cellcept, if can't reduce azathioprine dose by 75%
* can cause profound pancytopenia/death
64
Mycophenolate and azathioprine drug interactions:
* do not give together
* separate stopping and starting by 24 hours
65
The most commonly used adjunct agent is…
mycophenolate mofetil
66
Clinical use of mycophenolate mofetil includes...
* alternative to azathioprine
* prevent organ rejection
* combination with CsA or tacro +/- steroids
67
Mechanism of action of mycophenolate mofetil includes...
* Inhibits purine synthesis
* Selective to lymphocytes
* Potential for less toxicity
* Ultimately inhibits T and B cell proliferation
68
Mycophenolate absorption is delayed by…
food
69
Mycophenolate side effects include…
* diarrhea
* Nausea/vomiting
* anemia
* Thrombocytopenia
* infections
* CMV tissue invasion
* malignancy
70
Mycophenolate drug interactions include…
* ganciclovir, valganciclovir, acyclovir, sirolimus
* cyclosporine
* azathioprine
* cholestyramine
* aluminum/magnesium containing antacids
71
Mycophenolate drug interactions: ganciclovir, valganciclovir, acyclovir, sirolimus may cause…
increased risk of bone marrow suppression
72
Mycophenolate drug interactions : cyclosporine may cause…
decreased level of MPA
73
Mycophenolate drug interactions : azathioprine may cause…
toxicity additive, need 24hrs between stopping one and starting another
74
Mycophenolate drug interactions : cholestyramine may cause…
cannot be used together, significant decrease in mycophenolate levels
75
Mycophenolate drug interactions : aluminum/magnesium containing antacids may cause…
* may decrease absorption
* separate doses 2-4hrs
76
Corticosteroids (Prednisone/methylprednisone): clinical use includes…
* wide range of doses
* treatment vs induction vs maintenance
* oral doses given with food
* may exacerbate recurrent disease (HBV, HCV)
77
As a treatment of rejection, corticosteroids may be used…
* high dose methylprednisone oral or IV
* if rejection resistant, may consider repeat and add antithymocyte globulin
78
Numerous corticosteroid side effects include:
* euphoria, depression, hypertension, water retention, impaired wound healing, infection
* increased appetite and weight gain, cushingoid face, osteoporosis, high blood sugar
79
A time intensive desensitization method would be performed…
* pre transplant over several weeks
* goal to accept organ in timely manner when antibody level is low
80
A rapid process desensitization method would be performed…
* when donor organ becomes available
* starts immediately pre-transplant and perioperatively
81
Plasmapheresis is…
* the mechanical removal of circulating antibodies
* combined with medications targeting B cells
* does not do anything on the B-cells
82
Intravenous Immune Globulin (IVIG) is used for the..
prevention and treatment of humoral rejection
83
IVIG treatments include…
* Dose of 1-2 mg /kg
* premedicate with Tylenol and Benadryl
* monitor for back pain, headache, chills, fever, hypotension, bronchospasm
84
Rituximab is used for..
* humoral rejection and PTLD
* premedicate with Tylenol and Benadryl
* start at 50 mg/hr, and ramp up as tolerated
* monitor hypotension, chills, fever, bronchospasm, arrythmias
85
Antibody Mediated Rejection treatment includes…
* plasmapheresis
* IVIG
* antithymocyte globulin
* rituximab
* cyclophosphamide
* bortezomib
86
Medications to prevent virus infection include…
* acyclovir
* valganciclovir
87
Medications to prevent fungal infection include…
* clotrimazole troche
* nystatin
* fluconazole
* voriconazole
88
Medication to prevent pneumocystis pneumonia PCP include…
* sulfamethoxazole/trimethoprim
* pentamidine inhalation
* dapsone
* atovaquone
89
Medications to prevent /treat side effects of medications include...
* anti-ulcer
* aspirin
* blood pressure
* stool softener
* insulin
* cholesterol lowering meds
* osteoporosis meds
