W06: PHARMACOLOGY, RENAL REPLACEMENT, ORGAN DONATION Flashcards
Discuss the principles of drug therapy in the presence of renal insufficiency.
risk of rapdi build up of ACTIVE drug and TOXIC METABs.
* on the contrary = Benzylpenicillin wide range/low tox.
de novo renal impairment d/t sick, hypotensive, and polypharmacy
GFR dysfunc.
- 1/2L prolonging = accumulation esp. w/ narrow therapeutic range
- ⇩protein binding
BBB more permeable + greater sens + synergistic effects
State how drug-induced nephrotoxicity can be limited
- infants, young children, elderly
- pt with pre-existing dysfunction/ CVD therefore !hypotensive
- use of drugs w/ WIDE therapeutic index
- ⇩ loading & maintenance dose / frequency
- ⇧therapeutic drug monitoring
- non-renal clearance mode preferred
Give examples of drug induced renal disease
GENTAMICIN. = renal/ ototoxicitiy
DIGOXIN = arrhythmia, nausea, death
LITHIUM = renal tox and death
TACROLIMUS = renal and CNS tox.
Drug Induced Renal Effects
- AKI
- NEPHROTIC SYNDROME
- RENAL TUBULAR DYSFUNCT. W/ POTASSIUM WASTING
- CHRONIC RENAL FAILURE
Pre-Renal Causes of AKI
- DIURETICS, laxatives, lithium, NSAIDS
- Steroids, tetracyclines = ⇧catabolism
- oestrogens/ OCP = vascular occlusion
= deterioration in renal function which results in a rapid rise in creatinine; fall in volume
Intrinsic causes of AKI
- ACUTE TUBULAR NECROSIS d/t
aminoglycoside antibiotics, cisplatin (chemoT), statin drugs + immunosuppr. (cyclosporin) - ACUTE INTERSTITIAL NEPHRITIS d/t
onset after drug 3-5d; PENICILLLIN, CEPHALOSPORIN, NSAID, OMEPRAZOLE, CHINESE HERBS, COCAINE - THROMBOTIC MICROANGIOPATHY (thrombotic microvasc) d/t
cyclosporin, tacrolimus, estrogen contraceptives, cocaine, clopidogrel
Post Renal Causes of AKI
- OBSTRUCTIVE UROPATHY
crystal formation within tubules or ureters OR retroperitoneal fibrosis (methysergide)
ACYCLOVIR, SULFONAMIDES, METHOTREXATE, EXCESS VITAMIN C
Drug causes of Nephrotic Syndrome
NSAIDs
Gold
Interferon
Hospital Acquired Renal Insufficiency Drug Causes
AMINOGLYCOSIDES for gram-ve sepsis therefore TDrugMonitoring ensure good limits
NSAIDs = prerenal RFailure = haemodynamic/ acute tubular necrosis
OR immune mediated = acute interstitial nephritis
• HT, hyperkalaemia = arrythmia, papillary necrosis
Explain the principles of dialysis and its main modalities.
solute composition of a solution, A, is altered by exposing solution A to a second solution, B, through a SEMIPERMEABLE membrane.
+ Diffusion to achieve equilibrium w/ Pt and dialysate + ultrafiltration via oncotic pressure and gradient drag.
- membrane, blood exposure, dialysis access, anticoag required
- IJV line common
Primarily want to remove creatinine and urea, as well as small K+, and to correct and give HCO3-
Principles of management of the patient receiving dialysis
RESTRICTIONS include:
- Fluid restriction = based off residual urine output, and interdialytic weight gain (fluid gain)
500-800ml/24hr intake restriction (haemo)
more liberal in PDial.
- Dietary restriction = potassium, sodium, phosphate
MEDICATIONS:
+ ERYTHROPOIETIN INJECTION
+ IV iron suppl.
+ ACTIVATED VITAMIN D (calcitriol)
+ Phosphate binders w/ meals
+HEPARIN
+VITAMINS (aq)
+ Antihypertensives to combat fluid-overload or hypovolaemia
Principles of renal replacement therapy (RRT)
indicated when eGFR <10 ml/min.
- Transplant
best option as it resolves issues but not available for everyone
*IN ILIAC FOSSA with anastomosis to iliac vessels while native kidneys remain in-situ - removal only indicated specifically
preservation
Patient and graft survival is better with living compared to deceased donation.
!bleeding risk; imm suppr sfx
- Haemodialysis: home / satellite
* permanent access: arteriovenous fistula, AV proesthetic graft
* temp: venous catheter
* anticoag! - Peritoneal: CAPD; intermittent peritoneal dialysis
* ideally at pelvis via catheter using PERITONEAL MESOTHELIUM (membrane)
* drain in w/ fresh dialysate to correct metabolites
+ glucose as osmotic agent for ultrafiltration
* continuous - Conservative Kidney Mgmt
Supportive care: symptoms, holistic, anticipatory
Pt informed choice + factors
- intraabdo surgeries affecting PD
- vascular access issues affecting haemodial.
- PD favoures better urine output
- social factors
*increasing morbidity and mortality with dialysis
Advanced CKD
aka URAEMIA involving multi-organs, 1st sympt = MALAISE, FATIGUE
*CKD could be asymptomatic until stage 4 or 5
Complications of PD
!infection @ exit
PERITONITIS
gram+ (skin) more common than neg.
gram- (bowel)
- failure of ultrafiltration
- encapsulating peritoneal sclerosis
> intreperitoneal Vancomycin + Oral Ciproflox.
MECHANICAL malfunctions
Indications for dialysis in ESRD
Advanced uraemia, (GFR 5-10 ml/min)
Severe acidosis (bicarbonate <10 mmol/l)
Treatment resistant hyperkalaemia (K >6.5 mmol/l)
Treatment resistant fluid overload
Complications of haemodialysis
CV problems: hypotension and cramps (intra-dial.); arrythmias
COAGULATION: clotting of vascular access, heparin
ALLERGY
Common bleeding complication of transplant
BLEEDING @ ANASTOMOTIC SITES, perirenal haematoma
Immunosuppression SFX
CORTICO. - HT, hyperglc., infections, bone loss, GI bleeding
TACROLIMUS - hyperglc., AKI, tremor
Transplant Imm Suppr. Protocol
- BASILIXIMAB
- maintained by TACROLIMUS + MYCOPHENOLATE + STEROIDS
Steroid-free is possible
Brain-death criteria
Coma, unresponsive to stimuli Apnoea off ventilator (with oxygenation) despite build up of CO2 Absence of cephalic reflexes pupillary oculocephalic oculovestibular (caloric) corneal gag purely spinal reflexes may be present Body temperature above 34 C Absence of drug intoxication
Expanded criteria donors
Donor aged > 60y Donor aged 50-59 + history of hypertension death from cerbrovascular accident terminal creatinine of >133µmol/L
Risks to Donor
Negligible/minor risk
Kidney function becomes normal, but chances of albuminuria esp in high BMIs and male donors.
Main complications of transplant
REJECTION
- T-cell med. rejection = arteritis; art. fibrinoid necrosis
- acute antibody mediated rejection = cap./glomerular inflamm.; arterial inflamm. (C4d+)
INFECTIVE
- cytomegalovirus common: active transmission / reactivation latent
> antiviral (cidofovir)
reduce imm. suprr.
CARDIOVASCULAR
MALIGNANCY
Discuss the principles, practicalities and ethical considerations of organ donation
Duty to Inquire - ensure latest views are expressed and respected, ensures appt. checks undertaken
*if no written decision of donation, safeguards are in place to ensure transplantation can continue
CHILDREN UNDER 12 - parental + similar agreement
12-16y/o - record their own decision but parents should be consulted
+ nearest relative heirachy
- Death by neurological criteria
- Donation after cardiac death
Describe the principles involved in renal replacement therapy and state the social, economic and psychological implications of dialysis and renal transplantation.
Renal transplantation much more symptomatically effective as well as economically.
