Drugs and the Kidney Flashcards
What is the mechanism of action of loop diuretics and some examples?
- inhibits Na-K-2Cl co-transporter in luminal membrane of thick ascending limb of Henle’s loop
- inhibiting salt transport out of tubule and into interstitial tissue reducing the osmotic gradient in the medulla causing diuresis
- eg. furosemide, bumetanide
What are the indications for loop diuretics?
- oedema (heart failure/pulmonary/ascites/nephrotic syndrome/renal failure)
- resistant hypertension
- hypercalcaemia
What are the side effects of loop diuretics?
- hypovolaemia
- hypotension
- electrolyte disturbances
- can produce metabolic alkalosis due to loss of H+
- hyperuricaemia (gout)
- renal impairment
What is the mechanism of action of thiazide diuretics and some examples?
- inhibits NaCl co-transporter in distal tubule resulting in less Na and Cl absorbed, resulting in moderate diuresis (reduces oedema and BP)
- direct relanant effect on vascular smooth muscle
- eg. bendroflumethiazide, indapamide
What are the indications for thiazide diuretics?
- hypertension
- mild heart failure
- severe resistant oedema (plus loop diuretic)
- nephrogenic diabetes insipidus
What are the side effects of thiazide diuretics?
- hypotension
- hypovolaemia
- low Na, K and Mg
- calcium retention
- metabolic alkalosis
- gout
- erectile dysfunction
- hyperglycaemia, hyperlipidaemia
What is the mechanism of action of aldosterone antagonists and some examples?
- in CT, antagonise aldosterone receptor
- eg. spironolactone, epleronone
What are the indications for aldosterone antagonists?
- oedema
- hypertension
- Conn’s syndrome
What are the side effects of aldosterone antagnosists?
- renal impairment
- hyperkalaemia
- hyponaturaemia
- GI upset
- metabolic acidosis
- gynaecomastia (with spironolactone)
What is the mechanism of action of osmotic diuretics, its indications and an example?
- modify filtrate content to increase amount of water excreted
- indicated in cerebral oedema and raised intra-ocular pressure
- eg. mannitol (IV)
What is the mechanism of action of carbonic anhydrase inhibitors, its indications and an example?
- very weak diuretic
- indicated in glaucoma and altitude sickness
- eg. acetazolamide
What is the mechanism of action of amiloride?
- potassium-sparing weak diuretic
- acts directly by blocking epithelial Na channels in collecting tubule so less Na reabsorbed causing diuresis
- usually combined with thiazide or loop diuretic
What are the indications and side effects of amiloride?
- indicated in oedema including ascites and hypertension
- side effects: high potassium, GI upset, metabolic acidosis, renal impairment
What happens with the syndrome of inappropriate ADH secretion (SIADH)?
- excess ADH secreted by posterior pituitary gland
- hyponaturaemia (<135)
- low plasma osmolality
- inappropriately elevated urine osmolality
- euvolaemia
What are the symptoms of SIADH?
Mild:
- nausea, vomiting, headaches, anorexia
Moderate:
- muscle cramps, weakness, tremor, mental health disorders
Severe:
- drowsiness, seizures, coma
What are the causes of SIADH?
- neurological causes (tumour, trauma, meningitis)
- pulmonary causes (lung small cell carcinoma, pneumonia)
- malignancy
- hypothyroidism
- drugs (thiazide and loop diuretics, ACEIs, SSRIs, PPIs)
How would you treat SIADH?
- correct underlying cause, monitor plasma osmolality, serum sodium and bodyweight
- fluid restriction
- declocycline (antibiotics, inhibits ADH action on kidney)
- tolvaptan (vasopressin V2 antagonist in renal collecting ducts)
- hypertonic NaCl in severe cases
What happens in anaemia of renal disease?
kidneys produce less EPO (hormone that promotes RBC formation in bone marrow) resulting in anaemia
How would you treat anaemia of renal disease?
- erythropoietin stimulating agents (ESA)
- eg. epoetin, alfa, darbpoetin
- IV/SC route
What are the advantages of ESAs?
- reduce need for blood transfusions
- boost production of RBCs
- improve survival
- reduce CV morbidity
- enhance quality of life
Why is it important to prescribe safely in renal impairment?
- reduced renal excretion of the drug and metabolites can cause build up resulting in toxicity
- kidneys sensitivity to some drugs is increased
- increased risk of adverse reactions
- some drugs not effective due to reduced renal function
- chronic kidney disease increases risk of drug induced kidney disorders
What are the considerations before prescribing for renal impairment
- degree of renal impairment
- whether acute or chronic kidney disease
- proportion of drug renally excreted
- does drug have narrow or wide therapeutic window
- is drug potentially nephrotoxic
- is patient established on renal replacement therapy
What are some potentially nephrotoxic drugs?
- ACEis
- angiotensin II blockers
- diuretics
- lithium
- digoxin
- aminoglycosides
- vancomycin
- metformin
- iodinated contrast media
- opiods
What ways can you estimate renal function?
- creatinine clearance (good for narrow therpeutic index drugs)
- eGFR (good for chronic kidney disease and most patients and drugs)
What are the risks of giving the wrong dose of drug?
- too high: bleeding risk
- too low: increase in embolic events and strokes
What are the principles of prescribing in renal impairment?
- check U’s and E’s, including eGFR and creatinine
- look at baseline and trends in renal function
- consider stopping or with-holding nephrotoxic drugs
- check resources
- choose non-nephrotoxic if possible
- reduce size of dose or increase dosing interval or stop or withhold
- use therapeutic drug monitoring to guide dose/frequency
- continue to monitor Us and E’s, BP and clinical response
How would you manage acute kidney injury?
- treat any sepsis/uro obstruction
- aim for good fluid/electrolyte balance
- optimise BP
- with-hold/stop toxins
- review drug doses/side effect profile
- monitor Es and Es, refer nephrology/urology if worsening
