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Flashcards in medicines and the kidney Deck (20):
1

summary of the nephron

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

2

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

3

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

4

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

5

calculation of kidney function

Biochem labs report eGFR by MDRD formula

Prescribing based on CrCl (Cockcroft-Gault formula)

Similar but NOT the same

6

Dose Adjustment Options in Renal Decompensation

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

7

what happens in accumulation of morphine and metabolites in renal disease

respiratory depression

8

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

9

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.

10

• 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)

11

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)
• NSAIDs

12

Glomerulonephritis

- inflammation of the glomerulus
• Gold salts
• Penicillamine •

13

Interstitial Nephritis

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

14

Nephrogenic Diabetes Insipidus

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

15

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

16

what are loop diuretics used to treat

pulmonary oedema

hypertension

hypercalcaemia

renal failure

17

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

18

thiazides used for?

hypertension uncomplicated

mild heartfailure
hypercalcuria
nephrogenic diabetes insipidus

19

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)

20

what are K+ sparing diuretics used for

hypokalaemia
hypertension
hyperaldosteronism