56 Action of diuretics Flashcards
Where do the main therapeutically useful diuretics act on? (3)
- Thick ascending loop of Henle
- Early distal consulted tubules
- Collecting tubules and ducts
What are the general action of diuretics? (3)
- Direct action on cells of the nephron to alter ionic pumps or indirectly to modify the content of the filtrate
- Decrease net absorption of Na+ and Cl+ ions from he filtrate to cause natriuresis causing diuresis
- Increase excretion of Na+ and water
What is the most powerful diuretic?
Loop diuretics
What are 2 examples of loop diuretics?
Furosemide
Bumetanide
How quickly do loop diuretics act?
Within 1 hour
Where do loop diuretics act on?
Thick ascending limb of loop of Henle
What is the mechanism of action of loop diuretics?
- Inhibit Na+/K+/2Cl- carrier in luminal membrane
- Thereby inhibiting transport of NaCl out of tubule into interstitial tissue
- Dissipates osmotic gradient in medulla of kidney: not able to recover water in the collecting tubules and ducts
- Increases delivery of Na+ to distal tubule casting loss of H+ and K+
What may loop diuretics produce?
Metabolic alkalosis
What are the indications for loop diuretics? (2)
- Oedema due to heart failure
2. Resistant hypertension
What are the side effects of loop diuretics? (4)
- Dehydration
- Electrolyte disturbances - e.g. hypokalaemia, hyponatraemia
- Gout
- Renal impairment if dose too high
Where do thiazide diuretics act on?
Distal tubule
What are 2 examples of thiazide diuretics?
Bendroflumethiazide
Indapamide
What is the mechanism of action of thiazide diuretics?
- Decrease absorption of Na+ and Cl- by binding to the Na+ / Cl- co-transport system
- Thereby inhibit co-transport’s action
Which diuretics also produces vasodilation
Thiazide diuretics
What are the indications of thiazide diuretics? (4)
- Hypertension
- Mild heart failure
- Severe resistant oedema
- Nephrogenic diabetes insipidus
What are the side-effects of thiazide diuretics?
Metabolic and electrolyte disturbances:
- ↑ cholesterol, glucose, uric acid, calcium
- ↓potassium, sodium, magnesium, BP
- metabolic alkalosis
Where do potassium sparing diuretics act?
Collecting tubules
Which is the weakest diuretic?
Potassium sparing diuretic
What are 2 examples of potassium sparing diuretic?
Amiloride
Spironolactone
What is the mechanism of action of potassium sparing diuretics? (Amiloride and triamterene)
Blocking sodium channels controlled by aldosterone’s protein mediator
What is the mechanism of action of potassium sparing diuretics? (Spironolactone and eplerenone)
Antagonists at aldosterone receptor
Which diuretic doesn’t produce hypokalaemia?
Potassium sparing diuretic
What are indications of potassium sparing diuretics? (4)
- Alongside K+ losing diuretics (loop or thiazide) to prevent K+l loss
Spironolactone:
- Heart failure
- Conn’s (primary hyperaldosteronism)
- Secondary hyperaldosteronism
What are the side-effects of K+ sparing diuretics? (3)
- Hyperkalaemia
- GI upset
- Metabolic acidosis
What is an example of osmotic diuretics?
Mannitol
What are the indications for osmotic diuretics? (2)
- Cerebral oedema
2. Raised intra-ocular pressure
What is an example of carbonic anhydrase inhibitors?
Acetazolamide (very weak diuretic)
What are the indications for carbonic anhydrase inhibitors? (2)
- Glaucoma
2. Altitude sickness
What is syndrome of inappropriate ADH secretion (SIADH)?
Inappropriate ADH secretion from posterior pituitary or from ectopic source despite low serum osmolarity
What is SIADH associated with (3)
- ↓ sodium
- ↑ urine osmolality
- euvolaemia
What is SIADH caused by? (4)
- Neurological causes - tumour, trauma, infection , GBS, MS, SLE
- Pulmonary causes - lung small cell ca, mesothelioma, pneumonia
- Malignancy - stomach, pancreatic ca
- Drugs - thiazide and loop diuretics , ACE - is, SSRIs and PPIs
What is the presentation of SIADH? (6)
- Nausea
- Vomiting
- Cramps/ tremors
- Depressed mood, irritability, personality change, memory issues, hallucinations
- Seizures
- Coma
What is the treatment of SIADH?
- Correct underlying cause, monitor plasma osmolality, serum Na+ and bodyweight
- Fluid restrict (500-100ml daily)
- Drugs - demeclocycline, tolvaptan
- Hypertonic NaCl in sever cases only
How does demeclocyline work? And what does it treat?
- Inhibits action of vasopressin on kidney, anti-ADH action
* SIADH
How does tolvaptan work? And what does it treat?
- Vasopressin V2 antagonist in renal collecting ducts
* SIADH
What is the function erythropoietin (EPO)?
Hormone that promotes RBC formation in bone marrow
What is erythropoietin driven by?
Anoxia
Where is erythropoietin produced?
- Kidney (peritubular interstitial cells)
* Liver (different form from kidney)
What occurs in moderate-severe renal impairment regarding EPO?
Kidneys produce less EPO resulting in anaemia
What is the treatment of less EPO production resulting in anaemia?
Artificial versions of EPO - ESAs (erythropoiesis stimulation agents)
-boosts production of RBCs, improve survival, reduce cardiovascular morbidity, enhance quality of life
What are 2 examples of ESAs (erythropoiesis stimulating agents)?
- Epoetin Alfa
* Darbapoietin
What are 2 examples of vasopressin receptor agonists?
- Desmopressin
* Terlipressin
What does demopressin treat?
Diabetes insipidus
What does terlipressin treat?
Oesophageal varices
What is an example of sodium-glucose co-transporter-2 (SGLT-2) Inhibitors? And what does it treat?
- Canagliflozin
* Type 2 diabetes mellitus
What is an example of uricosuric drug? And what does it treat?
- Sulphinpyrazone
* Gout
What are examples of drugs affecting pH of urine? And what does it treat?
- Ascorbic acid (acidify)
- Potassium citrate(alkalinise):
• for urine infection symptoms or kidney stone formation
What is the main organ for drug elimination from body?
Kidneys
What occurs if kidneys are damaged regarding drugs?
Affects pharmacokinetics of many drugs
How is the severity of renal impairment gauged?
- Estimate glomerular filtration rate
* Use lab-quoted eGFR
What occurs to some renal excreted drugs in renal impairment?
Stay in body for longer and can accumulate - toxic
What is the management of acute kidney injury (AKI)? (6)
- Treat any sepsis or uro obstruction
- Aim for good fluid/ electrolyte balance
- Optimise BP
- With-hold/ stop toxins
- Review drug doses and side effect profile
- Monitor U&Es, refer nephrology/ urology if worsening
Nephrotoxic drugs
- Some drugs can help or worsen renal function - e.g. ACE inhibitors
- Some can help reno-protect - e.g. ACE inhibitors
- Reduced renal excretion of a drug and its metabolites may cause toxicity
- Increased risk of adverse drug reactions
What are some drug reduced renal impairments?
- Pre-renal
- Obstructive uropathy
- Allergic or immunological damage
- Direct nephrotoxicity
Drug induced renal impairment (pre-renal)?
- Water/ electrolyte loss
- Increased catabolism
- Vascular occlusion
- Altered renal haemodynamics
Drug induced renal impairment (obstructive uropathy)?
Bleeding/clots
Drug induced renal impairment (allergic or immunological damage)?
- Hypersensitivity reactions resulting in vasculitis
- Interstitial nephritis
- Glomerulonephritis
Drug induced renal impairment (direct nephrotoxicity)?
- Giving rise to acute tubular or interstitial damage
* Renal papillary necrosis
Examples of potentially nephrotoxic drugs
use with caution or avoid in renal impairment
- ACE inhibitors, Angiotensin II blockers
- NSAIDs - ibuprofen
- Lithium (bipolar disorders)
- Digoxin
- Aminoglycosides - gentamicin
- Vancomycin
- Metformin (T2DM)
- Iodinated contrast media
- Opiods - morphine
Examples of drugs that reduce renal perfusion
- Diuretics (esp. loop diuretics)
- NSAIDs
- ACE inhibitors
How do diuretics reduce renal perfusion?
Causing excessive fluid loss
How do NSAIDs reduce renal perfusion?
Inhibit prostaglandin synthesis leading to vasoconstriction, poor renal blood flow, reduced GFR and urine volume
How do ACE inhibitors reduce renal perfusion?
Prevent angiotensin II mediated vasoconstriction and cause vasodilation of efferent arteriole leading to a reduction in GFR (important in reno vascular disease)
What are “Medicine sick day rules”?
- Help reduce the risk of acute kidney injury through patient education
- If patient gets dehydrated and on ACE inhibitor/ ARBs/ NSAIDs/ Diuretics/ Metformin - risk of AKI
Examples of ACE inhibitors
Medicine names ending in “pril”
• Lisinopril
• Ramipril
Examples of ARBs
Medicine names ending in “sartan”
• Losartan
• Candesartan
• Valsartan
Examples of NSAIDs
Anti-inflammatory pain killers
• Ibuprofen
• Diclofenac
• Naproxen
Examples of diuretics
"Water pills" • Furosemide • Spironoloactone • Indapamide • Bendeoflumethiazide
What is metformin used for?
Diabetes
Prescribing in renal impairment:
if drug is really excreted or has active metabolites that are really excreted?
- Consider stopping nephrotoxic drugs
- If continuing, reduce dose or increase dosing interval
- Use therapeutic drug monitoring to guide dose/ frequency if appropriate
- Monitor U&Es, eGFR, BP, and clinical response0 adjust subsequent doses accordingly
Prescribing in chronic kidney disease (CKD)
- CKD classified stage 1 (mild) –> 5 (severe impairment)
- Important risk factor for CVD
Aim to:
• Normalise BP with anti-hypertensives
• Prevent or reverse worsening
• Review all meds, check doses appropriate for patient’s eGFR
• Manage concurrent conditions e.g. sepsis, diabetse, heart failure, renal anaemia, bone disease, electrolyte and acid-base disturbances
Patients on renal replacement therapy
- Some drugs actively removed during dialysis - will affect dose and timing of drug
- Many variables - what kind of dialysis?
- Is drug removed from circulation during dialysis?
- What is dialysed membrane, blood and dialyse flow rate?
- Refer to specialist renal team
