Q.692. Many drugs can ppt. ARF in R.Tx., discuss?
﴾﴾III. Transplantation and Medications ﴿﴿
 |
Allograft of the Renal transplantation |
Q.692. Many drugs can ppt. ARF in R.Tx., discuss?
A. The following
drugs 👉 are accused:
1. NSAID 🠞Functional pre-renal, esp. é hopovolemia,
RAS… Avoid. 2. ACE/ARB🠞Functional pre-renal, esp. é hopovolemia,
RAS… Avoid early use. 3. SMX/TMP: High dose TMP🠞🠟tub. Cr. secretion (no effect é GFR), well tolerated.
4.
Acyclovir/foscarnet🠞Tubular crystal deposition🠞Obstruction🠞ttt: good hydration. 5. INFa 🠞Immune
stimulatory effect 🠞Ac. Rj. 🠞use cautiously. 6. Verapamil, Diltiazem, erythromycin, ketokenazol🠞🠟CNI metb.🠞🠝s. level.
7. CNI: 🠞🠝Statin
level 🠞Rhbdo. risk🠞use CNI
é lower dose. Monitor C.K., .. Pravastatin & Fluvastatin are less affected.
Q.693. Give general
idea about the current immunosuppression?
A. I. Anti-T-cell receptor A.B.
II. Glucocorticoids.
III. Calcineurin inhibitors (C.N.I.s) : Csp. (Neural ) & Tacrolimus (Prograf ).
IV. Target of Rapamycin, m(TOR) inhibitors, Sirolimus
(Rapamycin).
IV. Antiproliferative Ag.: MMF(Sp. Purine inhibitors)& Aza.(Non-sp. purine
inhibitors).
Q.694. Specify anti-“T” cell receptor A.B.?
A. Two ✌ main groups: I. Anti-lymphocytes A.B. targeting All T-cells 🠞 Non sp., targeting All T-cell, not just those reacting é allograft, it incl. two ✌ main preparations:
i. OKT3 (Orthoclone) 🠞 Mouse monoclonal A.B. agnst CD3 receptor Cx. on T-cells.
ii. Polyclonal A.B.🠞 Rabbit (thymoglobin, rATG) or Horse (ATGAMأنغام الحصان), immunized é human lymphoid cells 🠞 multiple. A.B. agnst multiple leukocyte Ag.
Both i. & ii. are equally effective, but Polyclonal esp. (Rabbit thymoglobin) are most effective/tolerated due🠞 more sustained depletion of reciptor lymphocytes.
* Indications:
v Induction: additional
initial im/m. thpy (1st 5-14 d.) e.g.
DGF & high risk ptn.
v Reversal of Ac. Rejection.
II. Humanized/Chimeric Anti-IL2 receptors [monoclonal A.B.]: more specific im/m.,
because full IL2 receptors only expressed on👉 activated T. cells.
Humanization or Chimerization of A.B.🠞 minimize recipient generation of anti-mouse A.B.
(a problem in O.K.T3)🠞 prolongation of ½
life & drug efficacy.
* Indications: Only as initial im/m. (induction thpy), Not for Ac. Rj..
* Members: Anti-CD 25 (anti IL2) recep. A.B.🠞
Basileximab. (Simulect).
Daclizumab. (Zanapax).
…. Well 😊 tolerated é minimal S.E. é induction thpy.
Q.695. How can Corticosteroids exert their action? What is the impact of glucocorticoid-free immunosuppression?
A. They’re the cornerstone in im/m. therapy.
Tapering of the initial dose is continued until reaching a maintenance of 5-10 mg/d.
* Mechanism of
action: “Anticytokine” (incl. IL.2) + Antinflammatory effects.
* S.E. : [Glucose intolerance- H.T.- Hyperlipidemia-
Osteoporosis & necrosis -Myopathy- Growth retardation in children- cosmetic
& neuropsychiatric effects].
A.The 10-y. outcomes
of a glucocorticoid avoidance strategy foll.
R.Tx. have been reported. Among 1241 low-risk adult Tx. recipients receiving
allografts betw. 1999 & 2010, in whom prednisone ws discontinued within one
w. after Tx., both ptn. & graft survival were comparable to
national data rep. by the Scientific Registry of Tx. Recipients in 2009.
Q696. Describe the role
& S.E. of calcineurin inhibitors (CNIs.)?
A. Calcineurin
inhibitors (CNIs.):
I. Csp 🠞🠋 CALCINEURIN (Key enzyme for T-cell activation) 🠞🠋of IL2. & other molecules
necessary for “T cell” activation.
S.E.: [Nephrotoxicity, Ac. & ch. Rj., G.H.H. (Glucose intolerance- H.T.- Hyperlipi-demia)-
Cosmetic effects (Hirsutism). ].
II. Tacrolimus: Same mechanism & S.E. as Csp, but More diabetogenic
& Less [ H.T.- Hyper-lipidemic & cosmetic effects].
Disadv.: More
(Nephrotoxic
& neurotoxic)- more D.M. , more
G.I. esp. é MMF.
Q.697. What about antiproliferative
group?
A. Antiproliferative agents:
i.
Aza: a
purine analogue 🠞🠟DNA & RNA synthesis🠞🠟“T”-cell & “B” lymphocytic replication. S.E.: 🠞[B.M.
suppression- rarely hepatitis & pancreatitis.]. N.B.:
Concurrent “Allopurinol” use 🠞 Fatal B.M.
suppression.,💀 as Xanthi-ne Oxidase, responsible
for Aza metab., will be suppressed by Allopurinol 🠞🠝🠝s. level of Aza🠞 Sev. B.M.
suppression… So, Reduce Aza dose by 75 %.
ii.
MMF: Inhibit De Novo pathway
of purine biosynthesis (more selective) 🠞
🠋🠋 Lymphocytic
replication. It hs the foll.
effects:
1) Block T & B
cell proliferation.
2) Inhibit A.B.
formation.
3) Dcr. expression
of “adhesion molecules”.
4) Reversible
inhibition of “Inosine monophosphate dehydrogenase”. S.E.:Ö[n. & v.-
G.I. upset.- B.M. suppression- more CMV. tissue invasion].
Q.698. What
are m. T.O.R.s.?
A. Sirolimus (Rapamycin):[Siriolimus-F.K.B.P.(f.
k.- binding protein) Cx.], binds & inhibits a
kinase called (T.O.R.)=target
of rapamycin🠞🠋lymphocytic proliferation.
Both CNIs & Siros 🠞 are mtb.by “Cytochrome P 450” 🠞 many drug interactions. “Rapamycin” most appropriately used ✌ as:
1) CNIs-sparing drug: (stopping CNIs improves GFR) & in
2) Ptn é Neoplasia.
Q.699.What are the
possible side effects?
S.E.🠞[B.M. suppression-Hyperlipidemia-Interstitial
pneumonitis-🠝Csp. toxicity.].
Q.700. How to start induction
immunosuppressive therapy in R.Tx. in adults?
A. Im/m.
for R. allog. recipientis recommended but optimal reg. is unclear. Induction:is
recomm. for R. allograft, it consists of: [A.B.+standard im/m.] rather
thn standard im/m. thpy alone. Caucasian recip. of two haplotypeidentical
L.R.A. don’t require induction thpy
é A.B. thpy given the dcr. immunologic risk of Ac. Rj.. A.B.s incl. [rATG- thymoglobulin,
ATGAM, alemtuzumab,
OKT3
& two IL-2 receptor A.B.: basiliximab & daclizumab]. Ptns at incr. risk of Rj., start of rATG-thymoglobulin rather thn IL-2
receptor antagonist
is recommended. Ptns not at
increased risk of Rj., giving of rATG-thymoglobulin rather thn IL-2 receptor antagonist is suggested. If rATG-thymoglobulin cannot
be administered, IL-2 receptor A.B. is recommended.
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