Pharmacology of the Kidney Flashcards
When do the kidneys release renin?
When blood pressure drops
The kidneys secrete renin to retain salt and water to increase BP
What is the role of renin?
It converts angiotensinogen into angiotensin I
What happens to angiotensin I?
It is converted into angiotensin II by ACE
Angiotensin II is a potent vasoconstrictor
How does angiotensin II affect the adrenal gland?
It binds to an angiotensin II receptor and causes aldosterone release
Aldosterone increases sodium retention
How do ACE inhibitors work?
Why is a cough a common side effect?
They block ACE which converts AngI to AngII in the lungs
In some people, ACEi will block breakdown of bradykinin which causes a cough
Where do ARBs work?
On the adrenal gland and the surface of blood vessels
Where do beta blockers work?
They work on the kidney to inhibit renin release
What is the role of aldosterone?
It stimulates sodium uptake and potassium loss
What are the roles of the macula densa and juxtaglomerular apparatus in the cortex?
They sense changes in the concentration of Na+ and Cl- and the osmolality
They trigger the release of renin when there is a change
Where are granular cells found and what is their role?
They line the afferent arteriole leading to the glomerulus
They contain renin
When do granular cells release renin?
What stimulates this?
They release renin when triggered by macula densa cells
This is triggered by decreased pressure
e.g. blood loss, hypotension, stress, vomiting, anaesthetics
How do anaesthetics affect the kidneys during surgery?
Anaesthetics reduce the blood pressure
This leads to the kidneys being underperfused during surgery
What will stimulate renin secretion from the granular cells?
- pressure changes in afferent arteriole
- sympathetic tone
- macula densa sensing changes in Cl- and osmotic concentration
- local prostaglandin and nitric oxide release
Where do ACEis work?
What actions do they result in?
They work on the efferent arteriole
They inhibit the vasoconstrictive effect of AngII by:
- modulating intraglomerular pressure
- increasing Na+ and water excretion
When may ACEi be prescribed?
- hypertension
- cardiac failure
- chronic kidney disease - to reduce intra-renal pressure
What are the side effects of ACEi?
- hypotension
2. hyperkalaemia
What are examples of ACEi?
Ramipril and Lisinopril
“pril” ending
When should women not be prescribed ACEi?
If they are planning on becoming pregnant
They cause foetal abnormalities
Why do ARBs and ACEi cause hyperkalaemia?
They inhibit the action of aldosterone
Aldosterone leads to K+ excretion
What is the role of ARBs?
Where do they work?
They inhibit the vasoconstrictive effect of AngII
They work on the efferent arteriole
They modulate intraglomerular pressure and increase Na+ and water excretion
When may ARBs be prescribed?
- hypertension
- cardiac failure
- chronic kidney disease
They are only prescribed if a patient does not respond well to an ACEi
What are the side effects of ARBs?
- hypotension
2. Hyperkalaemia due to inhibition of aldosterone
What are examples of ARBs?
Valsartan and Irbesartan
“sartan” ending
What is an example of an osmotic diuretic?
Where does it act?
Mannitol
Acts at the Bowman’s capsule to modify the contents of the filtrate
Where to loop diuretics work?
What are examples?
They work on the Na+K+Cl- transporter to inhibit the reuptake of ions and water
e.g. furosemide and bumetanide
Why are loop diuretics used to relieve an oedema?
They block the reuptake of Na+, K+, Cl- and water
This leads to diuresis - the loss of salt and water in urine
This relieves the fluid build-up in a patient
What is an example of a carbonic anhydrase inhibitor?
How do they work?
Acetazolamide
They inhibit Na+ reabsorption in the distal and proximal convoluted tubules
This is because there is no H+ to exchange with Na+
What is the role of thiazides?
They block the uptake of sodium in the distal convoluted tubule
How do amiloride and spironolactone work?
They block the effects of aldosterone
This prevents sodium reabsorption and loss of K+ in urine
When may loop diuretics be prescribed?
- chronic kidney disease
- nephrotic syndrome
- hypertension
- cardiac failure
- liver failure (ascites)
What are the side effects of loop diuretics?
- hypovolaemia
2. hypokalaemia
What may loop diuretics often be prescribed alongside?
Potassium-sparing diuretics
This prevents hypokalaemia
What is the action of thiazides?
They inhibit sodium uptake
This leads to the removal of sodium and water
When are thiazides prescribed?
- chronic kidney disease
- nephrotic syndrome
- hypertension
- cardiac failure
They are a weak diuretic and are also used as an antihypertensive
What are the side effects of thiazides?
- hypovolaemia
2. hyponatremia
What is the action of spironolactone?
It inhibits aldosterone
This prevents sodium reabsorption in exchange for potassium
What type of diuretic is spironolactone?
Potassium-sparing
When may spironolactone be prescribed?
- cardiac failure
2. liver cirrhosis - ascites
What are the side effects of spironolactone?
- hyperkalaemia
What is the action of amiloride?
It inhibits sodium reabsorption in exchange for potassium
This leads to the removal of sodium and water
When may amiloride be prescribed?
Alongside a loop diuretic to prevent hypokalaemia
It is a potassium-sparing diuretic
What are the side effects of amiloride?
Hyperkalaemia
Why can calcium and phosphate not be absorbed if the kidneys are not functioning properly?
The kidneys activate vitamin D
Vitamin D is needed for Ca2+ and phosphate absorption
What happens to vitamin D analogues when they enter the body?
They are hydroxylated by the liver to an active form
What is the action of vitamin D analogues?
They increase the uptake of calcium and phosphate from the gut
What are the side effects of vitamin D analogues?
- hypercalcaemia
2. hyperphosphataemia
What is an example of a vitamin D analogue?
Alpha calcidol
When is erthyropoietin usually released from the kidneys?
It is produced by cells in the interstitium
Secretion is stimulated by hypoxia as it stimulates erythropoiesis
When may erythropoietin be administered to a patient?
How is it administered
When eGFR < 15 in CKD patients that have developed anaemia
Administered through subcutaneous injection
What are the side effects of erythropoietin?
- hypertension
2. pure red cell aplasia
Why is hypertension as a result of erythropoietin dangerous?
You want to keep Hb levels slightly lower than normal
Hypertension can lead to a stroke if Hb levels are brought back to normal
What is meant by pure red blood cell aplasia?
Antibodies develop to the Epo
RBC levels will not rise despite administering Epo
In patients with CKD, or at risk of AKI, why are some drugs potentially harmful to the kidneys?
There is an increased reliance on the intra-renal haemodynamics to maintain perfusion pressure
What is meant by intra-renal haemodynamics?
Blood flows into the glomerulus via an afferent arteriole and out through an efferent arteriole
There is a pressure gradient which allows ultrafiltrate to form
This pressure is regulated at all times
How does reduced renal perfusion affect intra-renal haemodynamics?
Reduced transglomerular pressure
Reduced GFR
How do prostaglandins affect intra-renal haemodynamics?
They cause vasodilation of the afferent arteriole
This increases renal perfusion
Why are NSAIDs potentially harmful to the kidneys?
They inhibit prostaglandins
This impairs vasodilation of the afferent arteriole, leading to a reduced renal perfusion
How does activation of the renin-angiotensin system restore GFR?
It causes efferent arteriolar vasoconstriction
This increases transglomerular pressure and restores GFR
How may ACEi and ARBs affect intra-renal haemodynamics?
They inhibit efferent arteriolar vasoconstriction
This decreases transglomerular pressure
This leads to a decreased GFR
What types of penicillins are excreted by the kidneys?
ALL penicillins except for flucloxacillin
Why should a reduced dose of penicillin be given in patients with CKD or AKI?
It the penicillin accumulates this can lead to CNS side effects
This includes seizures and hypoxic brain injury
What are examples of opioid analgesics?
Why does a reduced dose need to be given in patients with CKD and AKI?
Morphine, pethidine, codeine
Accumulation of active metabolites can lead to CNS side effects and respiratory depression
What opiates are preferred in people with reduced kidney function?
Opiates with minimal renal excretion
- fentanyl
- oxycodone
- hydromorphone
In someone with reduced kidney function, why should digoxin be avoided?
It can accumulate and lead to:
- bradycardia
- visual disturbances
- mental confusion
it also aggravates hyperkalaemia
Under what conditions is digoxin used in patients with reduced kidney function?
A reduced dose is used and the drug level is monitored
Under what conditions are hypoglycaemic agents used in patients with reduced kidney function?
- avoid longer acting agents
- reduced dose
- monitoring of blood glucose levels as they may accumulate and lead to hypoglycaemia
What may metformin lead to in patients with reduced kidney function?
Lactic acidosis
Accumulation also leads to hypoglycaemia
When should metformin not be given to patients with reduced kidney function?
When GFR < 30 ml/min
What type of Chinese herbal medicine should be avoided?
Herbal medicines containing aristocholic acid
This is implicated in interstitial nephritis
What is Cat’s Claw?
What is the problem with using this herbal remedy?
It has anti-inflammatory properties
It is implicated in causing AKI and hypotension with antihypertensives
