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77 Cards in this Set
- Front
- Back
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What kind of things do we think about with transplant drugs
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large doses early
multidrug regimens trying to prevent acute allograph rejection |
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Induction immunosuppression therapy
-how work -what does -SE |
antibodies against T cells
may decrease acute rejection risk infections and malignancy |
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different lvls of immune supression
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maintence
rejection |
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transplant agents classes
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Depleting antibodies
IL-2 receptor antibodies calcineurin antagonists antiproliferation agents |
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Depleting antibodies
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ATG
OKT3 alemtuzumab rituximab |
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IL2 receptior antibodies
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daclizumab
basiliximab |
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calcineurin antagonists
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tacrolimus
cyclosporine |
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antiproliferation agents
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azathioprine
mycophenoloic acid |
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Fuck theres another drug class what is it and what are drugs in it
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mTOR inhibitors
Sirolimus Everolimus |
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Induction therapy
what, why, length, SE |
antibodies for potent immune suppression inital 7-14 days after transplant
decrease reject rate SE- cytokine release, potential infections, antibodies against antibodies possible |
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Induction therapy
drug subtypes |
Polyclonal antibodies
(ATG, Thymoglobulin) Monoclonal antibodies (OKT3, Daclizumab, Basiliximab) NOTE sum of these are IL2s and sum are depleting... get to that soon |
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Polyclonal antibodys
info, MOA, where from, SE |
MOA-destroy all T cell types, enhanced by steriods
induction or rejection w/ APAP, cortico, antihistamines SE- aplastic anemia, nephrotox, thrombocytopenia, pulm edema...infection ATG-horse Thymoglobulin-rabbit |
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Monoclonal antibodies
3 of them 2 still availible... infos -OKT3 |
OKT3- mouse
SE- cytokine release syndrome MAJOR for induction, steroid resist reject, not chronic MOA-bind CD3 forms complex w/ t cell receptor (TCR) |
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Monoclonal antibodies
3 of them 2 still availible... infos -Daclizumab |
no longer availible!!!!
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Monoclonal antibodies
3 of them 2 still availible... infos -Basiliximab |
INDUCTION only
chimeric no dose adjust renal or gender MOA- IL2 antag, comped inhib, note ignores quintesent T cells 40mg day 0 and day 4.... SE constipation, rare thrombosis... |
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maintenance therapy
whats standard |
2 or 3 drugs for life
if no reject attempt to reduce if reject then up dose or switch class |
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Maintnenace based off 3 signal model
Each signal and what drugs act there |
BOTH 1 and 2 req T cell activation
Signal1- Calcineurin pathway- gen IL2 from T cell seeing antigen Drugs- inhibitors- Cyclosporine, tacrolimus S2- Costimulation path- CD40 and CD28 bind with stuff on opposite cells Drugs-target those- Balacacet (we dont go over it...) S3- IL2 on CD25 receptor - creates mammalian target of rapamycin(mTOR) mTOR inhibs- Sirolimus and Everolimus |
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Calcineuin inhibitors
what are they again? what signal? what do they basically do eventully |
Cylcosporine and Tacrolimus
signal 1 eventually inhib IL2 production hepatic metab, P450s watch, NOT DIALIZABLE |
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Cyclosporin
target when use info |
target 100-400 mcg/ml
interacts cyclophilin to inactivate calcineurin...no NF-AT highly protein bound (really thats both) variable absorb so microemusion (Neoral) use in borderline diabetics!!! |
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Tacrolimus
target when use specific SE |
5-15 mcg/ml
interact FKBP inactivate calcinurin..no NF-AT ...fuck i already wrote this more predictable absorb MORE POTENT, CHILD USAGE SE- gingival hypertrophy, allopecia..worse nephrotox |
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Calcineurin inhib SE
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less IV cuz nephrotox- PO 3x that dose
nephrotox kill kidney- acute tube necro, interstitial fibrosis, all that shit busted nuerotox- nightmares, some hepato, HTN hyperchol, hypergly DI- P450s think about it, and avoid nephrotox drugs and NSAIDs, no lovastatin |
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Antiproliferation agents are...
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Azathioprine
Mycophenolate mofetil |
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Azathioprine
MOA, what is it SE watch? |
immunosuppressive antimetabolite 6MP formed
nonselective DNA/RNA syn in rapid dividing cells like T and B cells for renal homotrans SE-dose depend BMS, reversible hepatotox watch XO watch bactrim or ganciclovir or BMSers |
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Mycophenolic acid
also called MOA indication |
cellcept- oral or inj
inhib syn IMPDH, block purine syn prevent T B cell proliferation- in S phase i think for Rebal, liver, cardiac trans |
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Mycophenolic acid
special? SE |
can use for chronic reject
ENTEROHEPATIC circulation- double peaks (cyclosporine will prevent this) SE diarrhea... vomit, leukopenia, sepsis...also BMS |
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reason to use azathioprine over mycophenolic acid?
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there isnt one the studies dont say shit
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mTOR inhibitors
are? what are they basically preventing |
Sirolimus aka Rapamycin (macrolide...)
Everolimus stops signal 3 from recruiting all those immune bastards: cytokines more antibodies and shit |
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Sirolimus
specific MOA SE dose consid DI |
inhib T lympho activation and proliferation via cytokines, also inhib antibody production
1-2g a day, double for AA follow troughs 8-12 SE CV rxns-HTN, hyperlipid, hyper TG DI- stagger w/ cyclosporin 4 h, watch p450s major staggering or can get all f'ed (keto specially) |
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Everolimus
MOA indication |
hyperactivation kinase AKT via inhib mTOR neg feedback loop sum thing sumthin.
.. like Sirolimus for heart transplant |
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Corticosteroid use...
when not effective whatlimits |
prevent and tx rejection episodes
not in chronic inteferes cytokine signals and induce apotposis inflam cells high dose and taper SE limit hypo K Na..weakness, BMS... watch P450 inducers |
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Tx of acute rejection...
types |
cellualr reject
acute humoral reject |
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Tx of acute rejection...
cellular tx |
M/M- methylprednisolone pulse dose
3-5 days high IV dose then taper S- thymoglobulin IV 1.5mg/kg qd 5 days, or.. OKT 5mg IV qd 5 days (rare) |
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Tx of acute rejection...
humoral tx |
antibody mediated
plasmapheresis (remove antibodies), IVIG infusion or rituxamab |
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Rituxamab
MOA dose? |
modulate B cell lysis
chimeric monoclonal ab for CD 20 375mg/M2 qwk for 4 wks |
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Chronic rejection
called diff stuff for diff organs tx |
banishing bile duct sydrim
accellerated atheroscerosis broncholitis obliterans syndrome no good tx, can add sirolimus |
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medical complications from chronic tx and what to do.....
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theres a nice chart in my review, look at it.... i think its rather importnat
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Organ transplant complication
where it all goes downhill whats main one... and when happen |
infection
usually 1-6 months- viral or fungal maybe if less than normal easy bacteria |
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transplant infection tx
bacteria |
common agents- 3rd gen ceph,
extended spec PCN blactamase combo FQ use broad spectrum empirically bascially same as usual tx |
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Viral complications
whats shitty bout them which ones |
higher reject rate
herpes family : CMV HSV EBV VZV also polyoma viruss----BK virus |
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CMV
disease vs infection how avoid dx |
disease- symptomatic or tissue invasive
infection usually asymptomatic if positive host to neg donor give prophlyaxis dx difficult |
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CMV tx
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prevent w/
ganciclovir acyclovir valganciclovir (950mg) or can use vaccine immunoglobulin prep- can inactivate liver vaccines... |
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CMV tx adverse effects
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carinogencity
BMS seizures u know fun stuff |
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BK virus!!!! neuropathy
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in most ppl controled but immunosupress does that
tubulointerstitial nephritis, ureteral stenosis happens watch for renal issues |
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BK virus!!!! neuropathy
tx |
reduce immunos!!!
leflunomide- pyrimidine syn inhib cidofovir IVIG |
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Tx for...
HSV VZV EBV |
acyclovir
antivirals same shit basically...sorta |
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Fungal infections w/ transplants
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tx is poor
surgical debridement minimize immunosuppress use antifungals..cyclosporine can increase tox |
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PCP
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use bactrim....
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Cancer w/ transplant
which ones increased how prevent? and...well |
common ones not increase- karposi sarcoma got fuckin huge tho
mimize sun exposure lymphoma can cuz- cyclosporin, FK, OKT3, ATG, or EBV infection stop or reduce immunosuppress, consider Rituximab i think ur gonna die lets be serious about this |
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Pregnancy and transplant
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D/C mycophenolic acid
not that other ones are good for your baby or anything but thats what he said... |
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Whats a big issue with transplant
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noncompliance
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Sepsis and its definitions
SIRS Sepsis Severe Sepsis Septic Shock |
systemic inflam response syndrome
2 or more: hypo/hyper thermic, HR>90, RR>20, WBC wacked Sepsis- SIRS w/ infection Severe Sepsis- SIRS, infection, and organ dysfunction Shock- all above and PERSISTANT hypotensive despite resuscitation |
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Pathophysio of sepsis
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microbe factors:
high infection burden, superantigen, resistance to opsonization, phagocytosis Host factors: proinflammatory (TNF!!) sum antiinflamm compensatory mechs histamine release coagulation factors (PROcoag) |
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Early vs Late sepsis
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in early- compensatory mechs seen
tachy, chills, NnV, myalgias, fever, hyperglycemia, proteinuria, hyperbilirubiemia late-start to see damage done lactic acidosis, oliguria, leukopenia, myocardia depress, pulmonary edema, hypotension, hypoglycemia, gI bleed, COMA |
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Prognosis for sepsis
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APACHE II score or
Sequential Organ failure assessment (SOFA) |
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standards of care in sepsis
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initial resuscitation (6 hours)
antibiotic therapy source control hemodynaimc support (fluids, vasopressors, inotropes) -other stuff |
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sepsis
EDGT what do we want |
Early directed goal therapy
-w/i first 6 hours CVP 8-12 MAP >65 Urine output >5ml/kg/h SvO2 >70% HCT >30% delay equals organ dysfunc, longer stay etc |
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Antimicrobials
-where source -what microbes most liekly -how start |
usually respiratory
usually +ve followed by negative obtain cultures before initiation w/i first hour |
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Antimicrobials sepsis empirical choices
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one or more drug activity against likely pathogens (combo in pseudomonas)
penetrate source reassess/ desclate in 48-72 hours typical duration 7-10 days- stop if noninfectious cause drain abscesses and remove infected hardware |
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Hemodynamical issues
what are they what are ways to fix |
CVP down
CO up SVR (systemic vascular resist way down) fluid resuscitation and vasopressors and inotropes |
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Fluid resuscitation
what used and such |
done first
6-10 L cyrstalloid fluids SE-edemas 2-4 L colloids soln (no mortality diff) SE renal failure and expensive hourly boluss over 24h, assess after each remember EDGT goals, CVP, MAP, urine output, SvO2 |
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Vasopressors and ionotropes used why
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want perfusion back so organs don fin die
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Vasopressors
do? are? |
vasoconstriction--MAP >60-65
adrenergics- NE, Dopamine, EPI, phenylephrine Nonadrenergic- vasopressin |
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Iontropes
are when do what |
not used as much
will increase CO Dobutamine Dopamine |
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Norepinephrine
acts on helps SE |
mainly alpha 1
up MAP, up SVR, maybe urine output 1st line!!!! SE organ ischemia, arrhythmias preferred over dopamine |
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Dopamine
acts on helps SE |
precursor NE
stim DA1, B1, B2, a1 effects dose dependant- alpha 1 >10 mcg/kg/min 1st line more tachy low dose is not recommended for renal perfusion |
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EPI
acts on doing when to use |
a1, b1, b2
ups MAP, up CO, up HR, up SVR alpha predominates above 0.05mcg/kg/ml SE organ ischemia ... elevate serum lactate, tachy from beta USE: refractory hypotensive |
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Phenylephrine
acts on does when use |
a1 exclusive
up MAP and SVR SE HTN w/ reflex brady cardia USE: when worried about tachys |
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Vasopressin
acts does when |
V1
up MAP, up SVR, maybe urine...maybe think of it as supplement since naturally depleted in sepsis like stuff WILL POTENTIATE OTHER VASOPRESSORS- use in refractory septic shock |
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Dobutamine
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B1, B2, minimal a1
up CO, down SVR, up HR more for cardiogenic shock combo with NE USE if inadequate CO |
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Hypothalamic Pituitary adrenal axis
.. what is is why do we fuckin care |
release of corticotropin releasing hormine if stasis threatened (gets u cortisol)
-this ups glucose, catecholamines, glucagon, BP, vasopressor sens, lipolysis -with relative adrenal insuff- reversible- we dont have enough cortisol to handle the issues |
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HPA cortisol def in sepsis
who to tx |
suspected adrenal insuff w/ pt on vasopressors despite fluid resus
intermittent 50mg IV q6h, +/- fludrocortisone 50mcg >7 days then taper no ACTH stim test DO NOT USE AT ALL UNLESS SHOCK!!! |
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Glucose control
tx in spesis and why hapen |
hyperglycemia disrupt immune func and promote inflam
use IV insulin to control hyperglycemia in pt w/ severe sepsis following stabilization try to keep blood glucose <180, provide glucose caloric source and monitor glucose q1-2 h if receiving insulin |
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Analgesia in sepsis
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hemodynamic instability indiction for it
fentanyl, hydromorphone, morphine (careful in RF) pain scale, FLACC scale, subject assessment |
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sedation
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only after provided aqequate analgesia and physiologic causes, use valid sale and define tx
Propofol, Dexmedetomidine, Benzos Lorazepam- formulated with propylene glycol- damage kidney pt acidotic (renal issues) wake up and CNS daily, determine min dose, sedation vacation |
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NMB- neuro musclualr blocker
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surgical relax, mech ventilation, down o2 consumption
Depolarizing-Succinylcholine Nondepolarizing- the curoniums-- pancuronium, vecuronium, rocuronium benzylisoquinliums-WTF... tubocurarine, cosatracurium, atracurium important monitor w/ train of 4 (4 pulses 2 twitches) need baseline |
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VTE
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if anything disposes them to clot
graduated compresion stockings-fit them properly sequential compression devices- squeezers, cant be ambulatory risks : low , mod , high USE low dose UFH or LMWH (preferred) unless CI if CI mech prop best to use LMWH and mech |
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stress ulcer prop
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if mech ventilate >48h or coagulopathy INR>1.5
no studys w severe sepsis H2 or PPI to prevent upper GI bleed- should prolly do it it seems benefits mut outweight risks.. chance of ventilator associated pneumonia VAP |
