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Flashcards in Organ Transplantation & Immunosuppressants Deck (20)
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1

Describe donor characteristics for organ transplantation

Donor Characteristics:

Doner has to have respirations and HR intact (may be artificial - on ventilator) 

Kidneys still need to be functioning 

Fixed, dilating pupils; no reflexes; brain dead

No chronic kidney disease

No cancer (except primary brain tumors - bc do not metastasize out of the brain) 

No sepsis or HIV or other infectious processes

2

Describe recipient characteristics for organ transplantation:

Recipient Characteristics

End-stage disease in transplantable organ 

Failure of conventional therapy 

Absence of untreatable malignancy or irreversible infection 

Absence of disease that would attack transplanted tissue 

Ability of patient to survive procedure 

Psychosocial characteristics 

3

  Identify criteria for brain death

What is considered brain dead?

No response to painful stimuli 

No spontaneous movement 

No spontaneous respirations 

No cranial nerve response

EEG, cerebral angiography, apnea test (take patient off ventilator to see if CO2 levels rise and if patient doesn't take breath)

Status unchanged for 6 hours 

4

 Describe absolute  contraindications for transplantation

Active alcohol, drug, or tobacco abuse 

Active infection 

Acute pulmonary embolism 

Bleeding disorders 

AIDS

Psychopathology 

Inability to comply with therapeutic regimen 

Inability to understand risks involved

Recent malignancy 

Severe damage in another organ 

5

Describe relative contraindications for transplantation

 

Cachexia (less than 80% ideal body weight)

HIV 

Lack of functioning psychosocial support 

Morbid obesity (over 140% ideal body weight)

Severe osteoporosis 

6

Understand role of immune system in transplantation

Histocompatibility - minimize rejection 

ABO: blood type 

HLA: human leukocyte antigen 

7

Describe the PRA test

This test is done on patients that are going to be listed on the organ transplant list 

Test detects performed HLA antibodies 

From pregnancy, blood transfusion, previous transplantation - if pt has not had any of these then the body has not been exposed to any other HLA proteins 

The more HLA a patient is exposed to, the more antibodies the body has developed, it could be much more difficult to find an organ 

Can restrict access to transplantation

High PRA means that the body is reacting to a lot of HLA and more likely to reject an organ 

Given as a % - 50% means that the patient's serum reacts with 50% of the donors in the panel 

0-19: means you react with none to very few HLA proteins - that is 60% of patients who waited 490 days 

20-79: means you have preformed antibodies - that is 21% of patients who waited 1042 days

80+: means very restricted to to organs the body can accept - that is 19% of patients who waited 2322 days

8

hyperacute rejection

minutes to hours after transplant.

Kidney is most susceptible. Due to preformed antibodies to organ HLA. Organ must be removed immediately

9

acute rejection

highest risk in the first 3 months, risk declines after 1 year. Must be treated promptly. T-cell mediated. 

10

chronic rejection

long-term loss of organ function due to fibrosis of vasculature, due to poorly understood chronic inflammatory and immune response. 

11

physiologic dosing and effects of glucocorticoids

Metabolic: influence metabolism of carb, proteins, and fats. Elevates blood glucose levels (this is why we check glucose often even if pts are not diabetics), diverts proteins to form glucose 

Cardio: most noticeable when levels are inadequate, capillaries are more permeable, vasoconstriction is suppressed, blood pressure falls 

Stress Response: can be life saving, body produces a large amount of glucocorticoids to prevent bleeding out. Large quantities secreted during physiologic or psychological stress. Help maintain BP, glucose levels 

F&E: similar in structure to aldosterone (mineralocorticoid). Can promote retention of sodium and water, promote excretion of K+. Also, important in maturation of lungs in neonates and premature infants. 

12

 pharmacologic dosing and effects of glucocorticoids

When giving glucocorticoids in super high doses, we are trying to provide anti-inflammatory effects and immunosuppressant 

Inhibit synthesis of chemical mediators that are responsible for inflammation in our immune system 

Suppress infiltration of phagocytes, so damage form release of lysosomal enzymes is averted  

Suppressed proliferation of lymphocytes 

These 3 effects together is what we are trying to achieve 

However, there are really bad side effects with such high doses

13

 Understand the negative feedback loop for endogenous glucocorticoid production

Normally, hypothalamus release CRH to anterior pituitary causing ACTH to release, which stimulates adrenal cortex to release glucocorticoids. Then, when glucocorticoids are at high levels, there will be feedback inhibition that will tell the hypothalamus and anterior pituitary to stop producing hormones related to glucocorticoids because body has enough.

14

Describe side effects of high-dose glucocorticoids

Adrenal insufficiency - adrenal medulla will stop making glucocorticoids because there is so many, there will be atrophy of the adreal cortex. 

Need to taper off so adrenal medulla can start to support the body 

In trauma situation, body won’t be able to pump any glucocorticoids 

Metabolic: increased glucose production; diversion of proteins to make glucose; alteration in fat mobilization and distribution (buffalo hump, moon face) 

Osteoporosis: ribs and vertebrae are most affected, can lead to pathologic fractures 

Suppresses osteoblasts 

Accelerates bone resorption by osteoclasts 

Produce intestinal absorption of calcium - causing hypocalcemia, PTH increases, increased mobilization of calcium from bones

Glucocorticoids = terrible for bones  

15

Describe action and adverse effects of cyclosporine (Sandimmune), 

Class: Calcineurin inhibitor 

MOA: inhibits an enzyme called calcineurin suppresses IL-2 and other cytokines, which is needed for T-cell proliferation. So, basically decreased T-cell production  

AE: nephrotoxicity  (75% of pts), infections (74% of pts), lymphomas, HTN, hirsutism, tremor 

No grapefruit juice 

16

Describe action and adverse effects of tacrolimus (Prograf, FK506)

Class: Calcineurin inhibitor 

MOA: similar to cyclosporine. More effective, more toxic 

AE: nephrotoxicity (40% of pts), neurotoxicity (headache, tremor, insomnia), N/V, HTN, hirsutism, hyperkalemia, hyperglycemia 

No grapefruit juice 

17

Describe action and adverse effects of cytotoxic drugs

Directly kill components of the immune system 

Azathioprine (Imuran) and Mycophenolate (CellCept)

MOA: suppress immune system by killing B and T lymphocytes. Toxic to all proliferating cell

AE: bone marrow suppression 

18

Describe action and adverse effects of antibodies

 

Directed at components of the immune system 

End in -nab or -mab

MOA:

Muromonab-CD3 (Orthoclone OKT3):  Binds to CD3, which blocking T cell function

Basiliximab (Simulect) and daclizumab (Zenapax): bind to receptor for IL-2 on lymphocytes, blocking activation of T cells 

AE: flu-like symptoms

IV only, expensive 

OVERVIEW: of immune system and how it functions and where different drugs work (don’t worry about drugs on here that we didn’t discuss)

19

Describe general concepts for immunosuppression

Will take 2 or 3 different kinds of immunosuppressants at a lower dose instead of one at a higher dose

Prophylaxis: pepcid for stomach ulcer, nystatin to prevent candida and thrush, bacterium to prevent pneumonia 

Generalized increase risk for infections and cancers - pt education 

Lots of drug interactions, especially with cyclosporine and tacrolimus 

20

Predict medications that would be given for acute rejection

Corticosteroid bolus, antibody therapy, and increase immunosuppressant dose 

This is the only one we can treat