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Flashcards in medicines and the kidney Deck (20):

summary of the nephron

bowmans capsule -filtration of all drugs of low molecular weight
loop of henle - reabsorption of water
DCT - passive tubular reabsorption
collecting duct - water soluble drugs and metabolites


Elimination of drugs and the kidney

Most drugs unless highly plasma protein bound freely filtered

Most drugs esp. weak acids actively secreted into proximal tubule

Lipid soluble drugs passively resorbed by diffusion across tubule- not excreted in urine a lot

Weak acids more easily excreted in alkaline urine and vice versa


Effect of Impaired Renal Function on Drug Therapy. what are the relevant factors

1. Toxicity
2. Ineffective treatment

1.impaired drug absorption
2. impaired elimination
3. effect of renal dysfunction on hepatic drug metabolism
4. increased tissue sensitivity
5. protein binding


stages of chronic kidney disease

normal GFR >90 ml/min/1.73m2

early CKD GFR60-89 ml/min/1.73m2

moderate CKD GFR 30-59ml/min/1.73m2

severe CKD GFR 15-29 ml/min/1.73m2

endstage CKD GFR <15 ml/min/1.73m2


calculation of kidney function

Biochem labs report eGFR by MDRD formula

Prescribing based on CrCl (Cockcroft-Gault formula)

Similar but NOT the same


Dose Adjustment Options in Renal Decompensation

decrease dose - decreased peak concentration
increase dose interval - decreased trough concentration


what happens in accumulation of morphine and metabolites in renal disease

respiratory depression


selecting appropriate drugs in renal failure

drug that is predominantly eliminated via hepatic/biliary

less than 25% excreted unchanged in kidneys

no active metabolites

widespread therapeutic margin

disposition unaffected by protein binding changes or by fluid balance changes

drugs that are not nephrotoxic


Reduced clearance - leads to toxicity if the drug remains in the circulation at high concentrations. • This leads to accumulation of drugs and metabolites “normally” excreted and a change in the drug distribution. This leads to:

• Impaired drug absorption - fluid retention in the kidney with oedema of the bowel wall can lead to reduced absorption of drugs given orally.
• Decreased protein binding - proteinuria/albuminuria, causes decreased proteins available for binding to drugs in the plasma, hence increase plasma concentrations of that drug.
• Impaired kidney metabolism - some drugs are metabolised in the liver e.g. insulin. Impaired kidney function will lead to increased half lives of drugs, thus raising the plasma concentration with every dose.


• Prescribing drugs in CKD must be carefully monitored, with eGFR calculated to estimate renal function. There are 2 methods of dealing with dosage regimes:

• Decrease the dose, keeping the interval constant (lower peak concentrations)
• Keep the dose constant, and increase the dose interval. (lower trough concentrations)


what is Acute Tubular Necrosis

death of tubular epithelial cells and is one of the most common causes of acute kidney injury (AKI).
• Aminoglycosides (Gentamicin)



- inflammation of the glomerulus
• Gold salts
• Penicillamine •


Interstitial Nephritis

inflammation of the interstitium surrounding the tubules (acute/chronic)
• Furosemide
• Penicillins
• Thiazide


Nephrogenic Diabetes Insipidus

excessive thirst and excretion of large amounts of dilute urine.
• Lithium
• Demeclocycline


how do loop diuretics work

they are the most powerful of diuretics , capable of causing the excretion of 15-20% of filtered Na+

they act on the thick ascending loop of henle , inhibiting the action of NK2CL carrier in the lumen membrane e.g. furosemide


what are loop diuretics used to treat

pulmonary oedema



renal failure


thiazide diuretics

these are less powerful than loop diuretics but better tolerated

preferred treatment in uncomplicated hypertension

they act on the distal tubule , inhibiting the Na+/Cl- co transporter , causing natriuresis (excretion of sodium)

therefore sodium and chloride are lost in the urine
e.g. bendroflumethiazide


thiazides used for?

hypertension uncomplicated

mild heartfailure
nephrogenic diabetes insipidus


how do potassium sparing diuretics work

WORK by competing with aldosterone for its intracellular receptor , therefore inhibiting Na+ retention and inhibiting K+ secretion .
the distal Na+/K+ exchanger only accounts for 2% of filtered Na , limited action.
spironalactone (mineralocorticoid receptor antagonist )
amiloride (sodium channel blocker that blocks eNaC in collecting duct)


what are K+ sparing diuretics used for