Kidney and drugs Flashcards
What is a juxtaglomerular apparatus?
Structure which regulates the functioning of the nephron. The cells here synthesise the hormone renin.
What does the juxtaglomerular apparatus consist of?
Specialised kidney structure of smooth muscle cells formed by the DCT and glomerular afferent arteriole. it is located near the glomerulus.
Action of macula densa in response to high Na+?
Macula densa causes contraction of the afferent arteriole to reduce GFR by releasing adenosine.
What is the role of aldosterone?
Increases reabsorption of Na+ and H20
Increases secretion of K+ and H+ into the urine
What is filtering in the glomerulus?
Movement of substances from glomerular capillaries to the nephron filtrate
What is secretion?
Movement of substances from the bloodstream to the filtrate in the kidney nephron post-glomerulus.
What is reabsorption?
Uptake of substances from filtrate in nephron to the bloodstream, where majority of this occurs in the PCT
Which substances are not typically reabsorbed?
Ionised drugs which remain in the tubules. Lipid-soluble drugs are mainly reabsorbed.
Which substances are reabsorbed into the bloodstream in the PCT?
Na+, K+, CL-, glucose, urea, amino acids
How does secretion occur in the PCT?
Site where many toxic substances such as drugs, bile salts, urates enter the tubular lumen be removed via the urine
Which substances in the PCT rely on the H+ antiporter for secretion?
The organic cations via the H+/Organic cation antiporter for:
Creatinine
Drugs- trimethoprim, quinine and cimetidine
Which organic anions (-) are secreted in the PCT?
Bile, urea, ketoacids, paraminohippuric acid
Drugs: penicillin, cephalosporins, diuretics
What is an important diagnostic tool for the measurement renal plasma flow?
Para aminohippuric acid which is freely filtered by the kidneys and secreted by PCT tubular cells into the lumen
What is transport maximum?
Limit for uptake by PCT carriers of glucose from the kidney to bloodstream. Carriers are oversaturated and glucose becomes excreted in urine.
Which drug is affected by albumin?
Warfarin and penicillin are highly bound to albumin. Hypoalbuminemia leads to disrupted levels of free warfarin and penicillin.
What is the role of the PCT?
Reabsorption in the tubule, specifically of water and sodium.
How does absorption occur from PCT lumen to the inside of the proximal tubule?
Na+/H+ exchanger for Na+ uptake into the PCT.
Co transport of glucose and Na+/ H+ exchanger.
Overall, efflux of H+ out for Na+ and glucose entry into the PCT.
What are the ion transporters in the DCT?
NA+/K+/Cl- symporter from nephron to tubular space.
From there, Na+/K+ ATPase exchanger for Na+ entry into the blood.
Cl- directly enters blood via basolateral channels
Mg and Ca2+ directly move from nephron to bloodstream via basolateral channel
What are the endogenous anions?
Urate, bile salts and ketoacids
What is exogenous anions?
Drugs such as penicillin excreted by the PCT.
What is urate?
Metabolite of purines
What is clearance?
Measure of rate which substance is completely removed from plasma. Renal clearance is determined by creatinine levels.
How is clearance calculated?
Cu x Vu/ Cp
Urinary conc x urinary volume/plasma conc
What determines Cu?
Concentration of urine determined by reabsorption from tubular fluid and entrance of drug into tubular fluid.
What is Vu?
Volume of urine
What is normal urine pH?
pH of 4.5 -> 7.8
What causes alkaline urine pH?
Vegan diet excess in fruit which causes increase in alkaline pH
Vomiting with loss of H+
What causes acidic urine pH?
Protein based diet due to excess amino acids
Starvation and diabetes mellitus generates acidic ketones via beta-oxidation
Loop and thiazide diuretics
How does acidic urine pH affect clearance?
More readily ionises and clears alkaline drugs from plasma such as Phenobarbital; acidic drugs remain unionised and therefore have a slower clearance rate.
How does alkaline urine pH affect clearance?
More readily ionised and clears acidic drugs from plasma such as amphetamines; alkaline drugs remain unionised and therefore have a slower clearance rate
Which drug is exclusively cleared by the kidney?
Aminoglycosides like gentamicin- nephrotoxicity leads to steady state concentration and cause hearing damage.
What is a diuretic?
Drug which increases water loss in urine to decrease BP. There are loop diuretics and thiazide diuretics
What is a loop diuretic?
Inhibits the Na+/K+/Cl- co-transporter in the ascending limb of loop of Henle which creates high conc filtrate to be excreted in the urine, increasing volume. It also inhibits the Cl- channel on the basolateral membrane.
What are loop diuretics given for?
Chronic heart failure: loop diuretics will decrease BP to normal levels
Pulmonary oedema in left ventricular heart failure: loop diuretics reduce reabsorption of ions
When should loop diuretics be avoided?
Severe hypokalemia/hyponatremia
Renal failure
-> anuria (no urine production)
Liver cirrhosis
What is a thiazide diuretic?
Inhibits Na+/Cl- cotransporter in the DCT which increases Na+ loss in the urine. There is associated decrease in calcium to compensate for loss of sodium and hypokalemia.
What is the effect of low-dose thiazide?
Lowers blood pressure
What are the effect of high dose thiazide diuretics?
Hyponatremia, hypocalcemia and hypokalemia with little benefit to BP
Why do thiazide diuretics cause K+ loss?
Low levels of sodium reabsorption to the blood means more is retained in the PCT. This induces aldosterone release and results in K+ loss.
What is osmotic diuresis?
Drugs which increase urination due to the presence of substances which increase osmolarity of kidney filtrate. Without drugs, this is achieved via glucose.
It increases the permeability of the PCT and the ascending loop of Henle to water to promote water loss.
When is osmotic diuresis used?
Excess urination to:
Decrease intracranial pressure for neurosurgery
Intraocular pressure
Treatment of cerebral oedema when blood glucose concentration is variable
They can only be given intravenously because they are poorly absorbed by the GI tract and cause diarrhoea.
WHat is an aldosterone agonist?
Amiloride
K+ sparing diuretics
Weak diuretics which affects the Na+/K+ pump. Primarily it targets sodium channels in the DCT or inhibits aldosterone receptors to reduce sodium reabsorption and K+ and H+ secretion. In the DCT, k+ FREELY FLOWS BETWEEN CHANNELS.
How to determine steady state concentration on a graph?
Maximum point
How can acute kidney disease be determined at an early stage?
Reduced urine output.
What is the effect of oestrogen on the kidneys?
Enhances Na+ and Cl- reabsorption from the tubules, causing fluid retention in pregnancy.
What is the effect of progresterone on the kidneys?
Promotes Na+ and water loss, competing with aldosterone for binding.
What is the effect of glucocorticoids on the kidneys?
Increase GFR and reabsorption of Na+.
What is the issue with IV administration of a drug?
No absorption phase for the drug which is delivered directly to the bloodstream.
How do carbonic anhydrase inhibitors work?
They act as a diuretic on the PCT because they prevent the breakdown of CO2 and H20 -> H+ and HC03-. This ensures more water is leaving the nephron and that less H+ is formed which can be exchanged with Na+ for more water retention. This includes acetazolomide.
What is indapamide?
Thiazide-like diuretic.
What is a milo ride?
Potassium sparing diuretic which inhibits sodium reabsorption in the DCT and collecting duct.
