Metabolic Block - MasterClass 1 Flashcards
AKI criteria
Increase in serum creatinine by >26.5micromol/L within 48 hours
Or
Increase in serum creatinine to >1.5times baseline which is known or presumed to have occurred within prior 7 days
Or
Urine volume <0.5ml/kg/h for 6 hrs
AKI stages
1-3
Stage 1- Creatinine - 1.5 to 1.9x Baseline/ >26 mm OR Urine output <0.5 for 6-12 hrs
Stage 2- Creatinine- 2.0 to 2.9x baseline OR urine output <0.5 for >12hrs
Stage 3- 3x baseline or >354mm/l OR <0.3 for >24hrs or Anuria for >12hrs or RRT
Or in children less than 18yrs old - decr In GFR <35ml/L
Immediate therapy for AKI
IV Fluid therapy - 500ml 0.9% NaCI over 15 mins - saline solution.
Withdrawal of nephrotoxins (ACE inhibitors and NSAIDS)
Withdrawal of hypotensive agents and diuretics
Withdrawal of statins
Causes of hyperkalemia
Reduced renal potassium excretion due to AKI combined with the actions of spironolactone and ramipril which cause a relative reduction in aldosterone effect
4 major causes of hyperkalemia due to reduced urinary potassium secretion are:
1- reduced aldosterone effect
2- reduced response to aldosterone (aldosterone resistance)
3- reduced distal sodium and water delivery as occurs in effective arterial blood volume depletion
4- acute and chronic disease in which one or more of the above factors are present
Spironolactone
Aldosterone antagonist
Competes with aldosterone for receptor sites (mineralocorticoid receptor)in the distal renal tubules , increasing NaCI and water excretion while conserving potassium and hydrogen ions , May block the effect of aldosterone on arteriolar smooth muscle as well.
potassium sparing Diuretic
Eplerenone
Indications:
systolic heart failure
Temporary treatment of Conn’s syndrome
Liver failure (oedema)
Management of oedema associated with excessive aldosterone excretion or with congestive heart failure unresponsive to other therapies , HTN, primary hyperaldosteronism (for pts awaiting surgery or for whom surgery is not an option) , hypokalemia , cirrhosis of liver accompanied by oedema or ascites(spironolactone is 1st line), nephrotic syndrome, severe HF
Side effects: Hyperkalemia Gynaecomastia Liver impairment Jaundice Stevens Johnson’s syndrome (T cell mediated hypersensitivity reaction)
CI/cautions :
severe renal impairment
Hyperkalemia
Addison’s disease (who are aldosterone deficient)
Pregnant or lactating women (crosses placenta and appears in breast milk)
Interactions:
ACE inhibitors and ARBs - are used together but with careful monitoring
Potassium supplements
Furosemide
Loop diuretic
Inhibits reabsorption of sodium and chloride in the ascending loop of henle and distal renal tubule; interfering with the chloride- binding co transport system, thus causing increased excretion of water, sodium, Chloride, mg and Ca.
Block luminal Na/K+/2CI co transporter and
inhibit upto 25% of filtered Na reabsorption
Side effects: Dehydration Hypotension Hyponatraemia Hypokalemia Hypochloraemia Hypomagnesaemia Metabolic alkalosis Gout
Uncommon but important:
Deafness
Tinnitus
Indications for loop diuretics: Acute pulmonary oedema Chronic heart failure Oedematous states (liver/ renal disease) Resistant hypertension(rarely used)
Ramipril
ACE inhibitor
Prevents formation of ANG II (vasoconstrictor) from ANG I
Competitive reversible inhibitor
Indications: Hypertension Chronic heart failure Secondary prevention in IHD / AMI /stroke Diabetic nephropathy /microalbuminuria Chronic kidney disease
Side effects: Hypotension(esp 1st dose) Hyperkalemia Cough Worsening renal function
Uncommon but important:
Angioedema
Anaphylactoid reactions
Interactions:
ACE/ARB - if used together can cause dangerous hyperkalemia
Potassium supplements and potassium sparing diuretics - hyperkalemia
NSAIDs - AKI
Pharmacodynamic
Pharmacodynamic drug interactions occur when interacting drugs have either additive effects in which case overall effect is increased or opposing effects in which case the overall effect is decreased or even cancelled out
Is what drug does to the body
Pharmacokinetic
Is what body does to the drug
Pharmacokinetic drug-drug interactions occur when one drug changes the systemic concentration of another drug, altering how much and for how long it is present at the site of action
Pharmacodynamic interactions of ACE inhibitors
BP lowering with diuretics or other antihypertensive drugs(used deliberately to aid treatment of hypertension)- hypotension
Increase in plasma potassium if used alongside a potassium sparing diuretic or an ARB- hyperkalemia
How can NSAIDs (analgesic and anti inflammatory benefits) contribute to the development of AKIs
NSAID inhibition of COX enzymes with subsequent reduction in PG synthesis can lead to reversible ischaemia and AKI
NSAIDs can also cause acute interstitial nephritis
Affect the afferent - cause vasoconstriction
ACE inhibitors act on efferent so if both used together then constriction of afferent and dilatation of efferent so reduction in GFR
How could you measure or estimate GFR
Estimated using measurements of urinary clearance or an ideal filtration marker such as inulin - amount filtered at the glomerulus which is equal to amount excreted in urine which can be measure but expensive and short supply.
So use measurement of creatinine clearance and estimation equations based upon serum creatinine such as the Cockcroft-Gault equation
CrCI- F(1.04 for F and 1.23 for males)x (140-age) x weight (kg) / plasma creat (micromol/L)
Which is more accurate - eGFR (MDRD formula)or CrCI by Cockcroft Gault - creatinine clearance
Probably CrCI as it used weight to add further information but may over estimate by 10-40%
However CrCI estimates serum creatinine in a patient with stable serum creatinine
Two ways of measuring renal function
eGFR used more commonly in practice
Important to know eGFR or CrCI to safely prescribe drugs that could be affected by abnormal renal function
eGFR can be made more accurate by correcting for an individual’s body surface area - estimated GFRx estimated body surface area / 1.73 to get estimated GFR mL/min
You can use CrCI with patients at extreme of body mass
For drugs excreted by the kidney - what effect will sig renal impairment have on the half life of a drug and what does this mean for time taken to reach steady state plasma concentrations
Increased half life so longer to reach steady state
How much you alter prescription of a drug that is mostly excreted through kidney in a patient with sig renal impairment
Give loading dose if needed to reach steady state quickly but lower dose at more frequent intervals or
