Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
51 Cards in this Set
- Front
- Back
|
Diuretics
|
Inc UOP by DEC NaCl reabsor (and water) at diff places in nephron
Each part of nephron has a unique sodium entry mechanism. Diuretics work by inhibiting these mechanisms |
|
|
Diuretics: how do they work
|
Protein bound--how do they get into tubule then...
They are secreted by proximal tubule anion pump that allows proteins to pass In patients with renal insuff, the tubules don't work properly and they develop diuretic resistance |
|
|
Osmotic Diuretics--Mannitol
|
Most commonly used osmotic diuretic
Six carbon sugar Fully filtered--filtered at glomerulus unlike the others that are protein bound Only means of clearance is via renal tubules |
|
|
Mannitol--how does it work
|
Increases osmolarity of renal tubules and plasma--has two effects:
1) decreases water reabs in renal tubules leading to relative water diuresis--losing mostly water, little bit of Na, Cl, HCO3 2) expands intravascular volume by drawing water from intracellular sites. Leads to inc RBF and decreased brain bulk |
|
|
Mannitol--why do we use it
|
1) To reduce intracranial pressure
Cranial vault is a fixed structure. Inc in brain, blood, or CSF may be offset by a dec in antoher |
|
|
Mannitol--When do we use it
|
To reduce ICP
0.25 - 1gm/kg (usually 0.5g/kg) Draws water from tissues in brain Dec CSF volume by dec fluid formation effect within 10-15 min Duration 2 hr Infuse slowly bc in theory you could develop acute inc in ICP d/t rapid fluid shifts Must have intact BBB b/c it could get trapped in brain and fluid couldn't get out ? |
|
|
Other Uses of Mannitol
|
1) Reduce IOP
-glycerin typically used here -can lead to INC in blood glucose as it's metabolized 2)Differential diagnosis of Acute Oliguria -if cause is dec volume (pre-renal) then mannitol should work -if damage is in glomerulus or tubes mannitol will not work 3) Convert oliguric to non-oliguric renal failure 4) Prophylaxis agst ARF in setting of CV surgery, aortic surgery, or trauma--giving mannitol before ischemic insults seems to dec damage |
|
|
Mannitol--who should we worry about
|
Pts with heart failure--volume overload
Electrolyte changes following admin--hyponatremia, hypokalemia, and hypovolemia Pts without an intact BBB |
|
|
Loop Diuretics
|
Powerful diuretics that work on the L of H
Sulfonamide derivates WATCH WITH SULFA ALLERGY |
|
|
Loop Diuretics--how does it work
|
1) Inhibit NaCl reabs via competition with Cl for its postioin on Na K 2Cl transporters
-located on teh thick ascending limb and early distal tubule -effect in 2-10 min -at max doses can cause excretion of 20% of flitered sodium load -ultimate effect: hypotonic urine, losses of sodium, potassium, calcium |
|
|
Loop Diuretics--when do we use them
|
1) Mobilize edema
-help reduce pulm and cardiac overload in pts with heart failure, cirrhosis, renal insuff, and nephrotic syndrome -causes peripheral dilation even prior to diuresis activ which is great for pulm edema -helps forward flow, breathe better even before they start diuresing 2)Dec cerebral edema -Dec total fluid volume -dec CSF prod -Dec Na transport to glial tissue -not as good as mannitol, best if used together -doesn't matter if BBB intact--no change in CBF or osmolarity 3) Tx of HTN 4)Eval of acute oliguria -will help if problem was redistribution of blood flow to medulla -if prob was hypovolemia then you just made matters worse 5) Tx of hypercalcemia -ca reabs in loop is passive and gradient is created by the NaCl transporter. So, calcium reabs is inhibited wtih Loop diuretics |
|
|
Loop Diuretics--what do we worry about
|
1) Hypokalemia
2) hypercalcuria--can cause stones 3) Enhance non-depolarizer--may act on presyn nerve endings causing dec release of Ach 4) enhances renal conc of aminoglycosides and cephalosporins--enhancing toxicity risk 5) SULFA ALLERGY 6) INC risk of lithium and dig toxicity 7) Deafness |
|
|
Thiazides
|
Lower potency diuretic that works on distal tubule
|
|
|
Thiazides--how does it work
|
Competes for Cl site on NaCl luminal carrier protein at distal tubule
-results in an inc excretion of Na, Cl, and HCO3 ions -leads to an excretion of 3-5% of filtered sodium load -augment calcium reabs in distal tubule -usually ok to take DOS |
|
|
Thiazides--when do we use it
|
1) Manage essential HTN
-initially dec ECF volume -peripheral dilation 2 to diminished sympathetic nervous system--overall dec in total body Na (needed for APs) thought to reduce sympth activ 2) Edema -only if state is 2 to sodium overload 3) Hypercaluria--to reduce stone formation 4) Tx Nephrogenic DI -ability to impair diluting capacity of tubules |
|
|
Thiazides--what should we worry about
|
1) Hypokalemia, hypochloremia, metabolic alkalosis
-cardiac dysrhythmias, skeletal muscle weakness, GI ileus, dig toxicity, potentiation of non-dep 2) Be wary of hypovolemia, orthostatic hypotension, and hemoconcentrated labs 3) hyperglycemia--inhibits insulin release from pancreas |
|
|
Potassium sparing Diuretics
|
even more weak diuretics that spare potassium via effect on Na resabs in collecting tubules
|
|
|
Potassium sparing diuretics---how does it work
|
1) act on principal cells in cortical collecting tubule decreasing the # of open sodium channels--so Na leaves and K doesn't
-Amiloride and Triamterene--directly dec sodium channel activity -Spironolactone and Eplerenone--inhibit mineralocorticoid receptors---where aldosterone works Only about 1-2% of filtered Na load excreted |
|
|
Potassium sparing diuretics--when do we use it---Triamterene and Amiloride
|
1) HTN--combined with thiazides to prevent hypokalemia
2) CHF--added to loop diuretics to preven hypokalemia |
|
|
Potassium sparing diuretics---when do we use it--Spironolactone
|
1) Primary and secondary Hyperaldosteronism
- direct antagonist to aldosterone therefore effect tx for edema assoc with above states 2) Pts with secondary ascites (liver failure and heart failure) |
|
|
Potassium sparing diuretics--what should we worry about
|
1) Hyperkalemia
2)Metabolic acidosis 3) diarrhea and n/v 4) gynecomastia and sexual dysfxn |
|
|
Carbonic anhydrase inhibitors
|
Diamox (Acetazolamide)
Summary: Work by impairing H secretion in proximal tubule and impair HCO3 reabsor. Used to treat metabolic alkalosis and alkalinize the urine Produce HYPERCHOLREMIC METABOLIC ACIDOSIS |
|
|
Anesthesia and Surgery--Effect on the Kidneys
|
RBF, GFR, UOP, Na excretion all REVERSIBLY DECLINE under both general and regional anesthesia
MAINTENANCE OF NORMAL BP AND INTRAVASCULAR VOLUME IS KEY!!! |
|
|
Cardiovascular influences
|
Inhaled agents--
DOSE DEPENDENT MYOCARDIAL DEPRESSION AND VASODILATION regional anesthesia-- HYPOTENSION AND LOSS OF VENOUS CAPACITANCE Kidneys autregulate at MAP 80-180 -decreased GFR, RBF, UOP, and Na excretion outside this range -RBF ceases at 40-50 MAP So what do we do to help...IVFs! |
|
|
Nervous System influences
|
Pts are SYMPATHETICALLY ACTIVATED!
1) INC SVR 2) Activ of Renin-Angiotensin system 3) INC Na and water retention 4) Redistrib of blood flow from cortex to medulla |
|
|
Endocrine influences
|
Stress response:
1) Increase in circ catecholamines--epi and norepi 2) Increases in renin-angio syst 3) Inc in ADH, Aldosterone, ACTH, and cortisol TAKE HOME: Endocrine system intimately responsible for the renal changes seen under anesthesia |
|
|
Flouride induced nephrotoxicity
|
A state of high output renal insufficiency charac by polyuria, dehydration, hypernatremia, hyperosmolality, and eleveated BUN and Crt.
Difficult to treat. Causative agents: 1) Methoxyflurane--extensive metab in the kidney leads to high plasma level of flourine causing renal injury 2) Enflurane--less metab than methoxy but is assoc with transient inc in flouride 3) Sevoflurane--even less metab <5%, can cause small inc in plasma flouride |
|
|
Flouride induced nephrotoxicity
|
Severity of injury is related to:
1) Peak plasma flouride concentrations--want less than 50 micromoles 2) Duration of elevated plasma conc -Methoxy has longest duration of elevation 3) Specific location for metab of the agent -Methoxy undergoes much metab in the kidney by specific renal related cytochrome p450 enzymes |
|
|
Flouride induced nephrotoxicity
|
TAKE HOME MESSAGE:
Methoxyflurane and Enflurane are the only anesthetics that have been clinically assoc with flouride induced nephrotoxicity or high levels of plasma flouride concentrations |
|
|
Sevoflurane and Compound A
|
-CO2 absorbants degrade Sevo into this compound
-production of Comp A is enhanced by LOW FLOWS & WARM/DRY CO2 ABSORBANT -Barium Lime makes MORE than Soda Lime -High Levels of Comp A in rats have been shown to cause nephrotoxicity by causing cell necrosis of tubules |
|
|
More about Compound A
|
Use Sevo if you want.
Most data on animals. Recent studies with humans found no indications of renal effects Average conc of Comp A during low flow Sevo is 8-24 ppm/hr |
|
|
IV agents and renal changes during surgery
|
OPIATES/BARBS--same effect as inhaled agents when compared with N2O
KETAMINE--can help preserve renal fxn in settings of trauma d/t sympathomimetic effect PROPOFOL & ETOMIDATE--safe to use if BP stays within autoregulation OTHERS: -Ketorolac--inhibit prostaglandins which normally act on afferent arteriole to inc RBF -ACE inhibitors--potentiate anesthetic effects on kidneys, block Ang 2 mediated kidney protection ABX--pay attention to redosing guidelines |
|
|
Certain surgeries affecting Renal Function
|
1) Laparascopic--pneumoperitoneum causes compartment syndrome state in abdomen and therefore produces oliguria
2) CPB 3) Cross clamping of aorta 4) Clamping in and around renal vessels 5) Neurosurgical procedures around the pituitary can also affect UOP (SIADH) |
|
|
Summary: Anesthesia and Healthy Kidneys
|
1) Use any agent you like--Sevo 2L/min flows recc
2) Use any IV induction agent appropriate 3) Use whatever narcotic you like 4) Maintain MAP 80-180 to preserve GFR and Give IVFs to compensate for surgical and anesthetic renal effects |
|
|
Anesthesia and Sick Kidneys---Induction agents
BARBITURATES |
Metabolism in liver hepatocytes and to a small extent renal--metabolites are usually INACTIVE and water soluble
Decreased protein stores=increased free circ drug=exaggerated clinical effects Chronic acidosis thought to facilitate fast brain uptake of non-ionized portions of drug |
|
|
Thiopental
|
Most commonly used BARB
Highly lipid soluble Most protein bound 72-86% REDUCE DOSE--reduce to 75% of normal dose (ex. if normal dose is 100mg then give 75mg) |
|
|
Sick kidneys and Induction Agents
KETAMINE |
Metabolism--hepatic to Norketamine 1/3 potency, then hydroxylated to water soluble form for excretion
Prob not a good choice for HTn pts. TAKE HOME: Renal dysfxn has no effect on drug |
|
|
Sick Kidneys and Induction Agents
PROPOFOL |
Metabolism--hepatic, rapid, and extensive--inactive metabolites
TAKE HOME: Renal dysfxn does not affect clearance of propofol |
|
|
Sick Kidneys and Induction Agents
ETOMIDATE |
Metabolism--lipid soluble with large volume of distribution
76% bound to albumin--pharmacology may be enhanced but not significantly TAKE HOME: Safe to use in renal pts and a good choice when cardiac failure is present |
|
|
Sick kidneys and benzos
MIDAZOLAM |
Extensively protein bound--therefore inc free fraction in renal dx
exaggerated resp to benzos MIDAZOLAM-- -highly lipid soluble, ext protein bound -metab extensively by hydroxylation in liver to 1 & 4-hydroxymidazolam and ACTIVE METABOLITE TAKE HOME: Pts will have exagg effects so DECREASE DOSE. Elimination and clearance not altered by renal failure. CAN USE IT BUT USE LESS |
|
|
Sick kidneys and opiods
FENTANYL |
Lipid soluble, extensively protein bound
Liver metab with no active metabolites REDUCE DOSE. Good choice for ESRD. |
|
|
Sick kidneys and opiods
SUFENTANIL |
lipid soluble, even more protein bound
Liver metab--ACTIVE metabolite, desmethyl sufentanil 10% as potent -Prolong depression of ventilation can be seen with renal failure |
|
|
Sick kidneys and opiods
ALFENTANIL |
Renal failure does not alter clearance or elimination
|
|
|
Sick kidneys and opiods
REMIFENTANIL |
Ester hydrolysis to weakly potent compound, makes safe choice in renal failure
|
|
|
MORPHINE and renal failure
|
Hepatic metabolism to:
Morphine-3-glucoronide (85%) INACTIVE Morpine-6-glucoronide (10%) ACTIVE Morphine-6-Glucoronide: Potency and duration are GREATER than Morphine--elimination of this metabolite IMPAIRED in renal failure TAKE HOME: Not a good choice. Use sparingly |
|
|
MEPERIDINE and renal failure
|
Extensive hepatic demethylation to less potent but active normeperidine
Normeperedine has elimination half-time of 15 hrs in normal pt Normeperidine aslo produces CNS stim and is assoc with seizures TAKE HOME: Not a good choice. Do NOT use. |
|
|
Sick kidneys and Muscle Relaxants
|
SUCCINYLCHOLINE: safe to use with K<5
CISATRACURIUM, ATRACURIUM, MIVACURIUM: Drug of choice in renal failure d/t non-organ dep metab--ester hydrolysis and Hoffman elimination VECURONIUM & ROCURONIUM: Both undergo primarily hepatic metab, 20% eliminated in urine. Use smaller doses. PANCURONIUM: renal dependent excretion--don't use if you have to use small doses. |
|
|
Moderate Renal Failure
|
-Monitor blood loss closely, replete volume and maintain BP
-Avoid large amts of phenylephrine, use as temp measure to inc BP and maintain RBF VOLUME OVERLOAD IS EASIER TO TREAT THAN ARF |
|
|
Crt levels and renal impairment
|
MILD RENAL IMPAIRMENT:
CrCl= 40-60 mL/min MODERATE RENAL IMPAIRMENT CrCl = 25-40 mL/min FOCUS IS ON PRESERVING WHATEVER RENAL FUNCTION IS LEFT |
|
|
Moderate Renal Failure: Preoperative Preparation
|
consider generous hydration coupled with solute diuresis
consider diuretics like mannitol 0.5 g/kg--has renal presrevation properties d/t solute diuresis Consider having Dopamine agonists available Maintain adequate UOP--0.5 mL/kg/hr) prevent fluid overload |
|
|
Induction
|
Most IV agents are acceptable. Adjust dose as needed
Make sure adequately hydrated before induction to avoid a sudden decrease in RBF and RPP Remember the sympathetic innervation our pts exhibit pre-op is detrimental to healthy renal fxn and even worse if diminished fxn |
