L31 Renal Pharmacology Flashcards
How is blood pressure sensed in the kidney?
80% of glomeruli lie in the cortex with an afferent arteriole going into it and an efferent artery coming out of each glomeruli. The macula dense and juxtaglomerular apparatus sit where the blood is entering; there is a sensory mechanisms to sense the changes in the concentration of sodium, chloride in the blood and the osmolarity. When it detects things are changing, it can lead to the release to renin. If there is damage to the kidney you can get hypertension, causing CKD which causes hypotension - and then a cycle.
What is renin secretion stimulated by?
Renin secretion stimulated by
• Pressure changes in afferent arteriole - this can occur after surgery (from anesthetics), times of stress, hypotension etc.
• Sympathetic tone
• Macula densa
• Chloride
• Osmotic concentration
Local prostaglandin and nitric oxide release
How does a ACEi work?
Inhibits vasoconstrictive effect of angiotensin II
• Acts on efferent arteriole
• Modulates intraglomerular pressure - pressure responsible for the ultrafiltrate occurring. Too much pressure exerted can damage the glomerulus.
Increases sodium and water excretion
What are the side effects of an ACEi?
Hypotension and Hypokalaemia - this is the same for ARBs. This is through the inhibition the action of aldosterone.
What are the contraindications for ARBs?
Women who are trying to get pregnant as it can lead to foetal abnormalities
What are the different sites of diuretics?
- Loop Diuretics
- Carbonic anhydrase inhibitors
- On the distal convoluted tubule
- Osmotic diuretics
What is the action of loop diuretics?
The loop diuretic act on the ascending loop of Henle and act on the sodium, potassium, 2 chloride cotransporter. The transporter would otherwise carry water across into the blood. The loop diuretic means that water is lost through the tubule and salts (diuresis). This helps treat oedema caused by heart failure. The heart can then start to function better (starlings curve). They are also used in the treatment of CKD, nephrotic syndrome, hypertension and liver failure (ascites). Most of these present with oedema.
Give examples of loop diuretics. What is the possible side effects of loop diuretics?
Examples: Furosemide and Bumetanide
Side effects: Hypovolaemia (if you give too much and therefore a deterioration in kidney function, therefore check the kidney function) and Hypokalaemia - can be used with potassium sparing diuretics
What are thiazides? Give the method of action, examples, indications and possible side effects.
Thiazides inhibit sodium uptake at the DCT. They remove sodium and water. They are a weak diuretic. They are also used as an anti-hypertensive. They have direct effects on the vasculature as well as indirect effects. Can also be used to lower eGFRs.
Indications: CKD, Nephrotic Syndrome, Hypertension and Cardiac Failure
Side effects: Hypovolaemia and Hyponatraemia
What is Spironolactone? Give the method of action, examples, indications and possible side effects.
Spironolactone
Inhibits aldosterone. It prevents sodium reabsorption in exchange for potassium - it has a ‘Potassium sparing effect.’ In contrast to sodium, potassium has very little effect on osmotic pressure. Often used together with loop diuretics as they can cause hypokalaemia
Indications: Cardiac failure and liver cirrhosis (ascites)
Side effects: Hyperkalaemia
What is Amiloride? Give the method of action, examples, indications and possible side effects.
Inhibits sodium reabsorption in exchange for potassium. It removes sodium and water. It is a weak diuretic in contrast to loop diuretics. The loop diuretics are a potent diuretic when you need to get rid of a lot of fluid quickly.
Indications to prevent hypokalaemia
Side effects Hyperkalaemia
What drugs are used in the treatment of CKD?
- Vitamin D analogues (such as Alpha Calcidol - side effects include hypercalcaemia and hyperphosphatemia).
- Erthyropoitein. Side effects: Hypertension and pure red cell aplasia (antibodies are produced to the epo - this is very rare). We do not put the haemoglobin back to normal as there is then a risk of stroke.
Why are NSAIDs nephrotoxic in CKD?
In patients with CKD or at risk of AKI there is an increased reliance on the intra-renal haemodynamics to maintain perfusion pressure. There is a pressure gradient between the afferent and efferent arteriole produced to allow for ultrafiltration. This pressure gradient is regulated all the time depending on blood pressure and sodium concentration for example. In reduced renal perfusion (hypotension, haemorrhage, vomiting, diarrhoea, trauma etc.), there is reduced pressure in the glomerulus and so there is not as much urine produced - developing AKI (become oligemic - reduced total blood volume).
Prostaglandins cause vasodilation of the afferent arteriole. NSAIDS inhibit prostaglandins and so vasodilation does not occur. In patients with heart failure or CKD, NSAIDs are not good drugs to use as they will reduce the perfusion and the pressure to the kidney.
Why are ACEi and ARBs nephrotoxic?
The physiological response to reduced kidney perfusion is to increase the back pressure i.e. increase the pressure of the efferent arteriole to allow ultrafiltration. ACEi and ARBs inhibit efferent arteriole vasoconstriction. This decreases transglomerular pressure and decreases GFR. This may be dangerous in a patient with AKI, as blood just passes through, no perfusion through the kidney and the damage gets worse. You wait from them to cover and then you can reinstate the ACEi or ARB.
Which drugs are removed by the kidney?
- Penicillin except Flucloxacillin - accumulation of penicillins can lead to CNS side effects.
- Opiod analgesics especially morphine, codeine and pethidine. Overdose can lead to increases incidence of CNS side effects and respiratory depression such that there is a respiratory arrest.
- Digoxin
- Hypoglycaemic agents- accumulation can lead to hypoglycaemia.
- Metformin - accumulation can lead to hypoglycaemia
- Herbal preparations
