4. Action of diuretics

Question 1

Action of diuretics on the kidney?

Answer 1

Increase excretion of Na+ and water from he body by an anion on the kidney.
Decrease net absorption of Na+ and Cl- ions from the filtrate to cause natriuresis
Water loss (diuresis) is secondary to natriuresis

Action by altering ionic pumps

Question 2

Where do the following diuretics act in the nephron:
Loop diuretics?
Thiazides?
Potassium sparing?

Answer 2

1. Thick ascending loop of Henle: Loop diuretics
2. Early distal convoluted tubule: Thiazides
3. Collecting tubules and ducts: Potassium sparing

Question 3

Main example of loop diuretics?

Answer 3

Furosemide, acts within 1 hour

Question 4

What is the mechanism of loop diuretics?

Answer 4

Inhibits reabsorption in the thick ascending limb of the loop of Henle.

Inhibits reabsorption:

• Inhibits the Na+/K+/2Cl- carrier in the luminal membrane
• So inhibits the transports of NaCl out of the tubule into the interstitial tissue (Blood)
• DIssipates the osmotic gradient in the medulla of the kidney, hence water isn’t recovered
• Increases delivery of Na+ to the distal tubule causing loss of H+ and K+

Question 5

Risk of loop diuretic use on acid base balance?

Answer 5

May produce metabolic alkalosis

Question 6

Clinical indications of loop diuretics?

Answer 6

• Pulmonary oedema due to LVF
• Chronic heart failure
• Resistant hypertension (not first line for HT)
• Oedema

Question 7

How are loop diuretics in cardiac failure?

Answer 7

Reduce pre-load and contribute to venodilation (helps after load)
Helps to maintain bp when LV filling decreases

Question 8

Side effects of loop diuretics?

Answer 8

• Hypokalaemia
• Hypotension
• Urinary retention (if enlarged prostate)
• Gout

Question 9

Action of thiazide diuretics?

Answer 9

Acts on distal tubule
Decrease reabsorption of Na+ and Cl- by inhibiting to the Na+/Cl- co-transport system
Also produces vasodilatation

Question 10

Main example of thiazide diuretics?

Answer 10

Bendroflumethiazide, indapamide

Question 11

Indication of thiazide diuretics?

Answer 11

• Hypertension
• Mild heart failure
• Severe resistant oedema
• Nephrogenic diabetes insipidus

Question 12

Side effects of thiazide diuretics?

Answer 12

Metabolic and electrolyte disturbances

• Increase in cholesterol, glucose, uric acid and calcium
• Decrease in potassium, sodium, magnesium, bp
• Metabolic alkalosis

Question 13

Action of potassium sparing diuretics?

Answer 13

Act in the collecting tubules

Question 14

Mechanism of action for amiloride and triamterene?

Answer 14

Block the apical sodium channel to decrease Na reabsorption

Question 15

Mechanism of action of spironolactone and eplerenone?

Answer 15

Compete with aldosterone for binding to intracellular receptors. Results in:

1. Decreased gene expression and reduced synthesis of a protein mediator that activates Na+ channels in the apical membrane
2. Decreased numbers of Na+/K+ATPase pumps in the basolateral membrane

Question 16

Why are K+ sparing diuretics used?

Answer 16

Alongside K+ losing diuretics (loop or thiazide) to prevent K+ loss

Question 17

Indications for use of spironolactone?

Answer 17

Heart failure
Conn’s (primary hyperaldosteronism)
Secondary hyperaldosteronism

Question 18

Side effects of K+ sparing diuretics?

Answer 18

Hyperkalaemia
GI upset
Metabolic acidosis

Question 19

Example of an osmotic diuretic?

Answer 19

Mannitol

Question 20

What are the indictions for the use of mannitol, an osmotic diuretic?

Answer 20

Cerebral oedema

Raising intra-ocular pressure

Question 21

What diuretics combine to for co-amilofruse?

Answer 21

Amiloride

Furosemide

Question 22

What are the indications for use of co-amilofruse?

Answer 22

Oedema

Poorly medication compliant patients (1 pill vs 2)

Question 23

Example of an carbonic anhydrase inhibitor?

Answer 23

Acetazolamide

Question 24

Indications for the use of acetazolamide?

Answer 24

Mountain sickness

Glaucoma

Question 25

SIADH?

Answer 25

Syndrome of inappropriate ADH secretion?

Question 26

What 3 signs are associated to SIADH?

Answer 26

Decrease Na Increased urine osmolality Euvolaemia

Question 27

4 possible causes for SIADH?

Answer 27

Neurological causes e.g. tumour, trauma, infection, GBS, MS, SLE Pulmonary causes e.g. lung SCC, mesothelioma, pneumonia Malignancy e.g. stomach, pancreatic ca Drugs e.g. thiazide and loop diuretics, ACEI, SSRIs and PPIs

Question 28

What is GBS?

Answer 28

Guillain-Barré syndrome (GBS) is a disorder in which the body's immune system attacks part of the peripheral nervous system.

Question 29

What is SLE

Answer 29

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that has protean manifestations and follows a relapsing and remitting course. Autoimmune disease

Question 30

Symptoms of SIADH?

Answer 30

``` Nausea Vomiting Cramps/tremors Depressed mood, irritability, personality change, memory issues, hallucinations Seizures Coma ```

Question 31

What is EPO?

Answer 31

Erythropoietin Hormone produced by the kidney (peritubular interstitial cells) that promotes RBC formation in the bone marrow. Process driven by anoxia

Question 32

What are the adrenal hormones?

Answer 32

Cortical hormones: - Glucocorticoids e.g. cortisol - Mineralocorticoids e.g. aldosterone - Androgens Medullary hormones (i.e. catecholamines) - Adrenaline - Noradrenaline

Question 33

What are the two main groups of synthetic agents (corticosteroid hormones)?

Answer 33

Glucocorticoids and mineralocorticoids

Question 34

What is is the classification of glucocorticoids? and name examples for each

Answer 34

Topical steroids e.g. belcomethasone Inhaled steroids e.g. budeonide Oral or parenteral steroids e.g. Hydrocortisone, prednisone, dexamethasone

Question 35

Name an example of a mineralocorticoid?

Answer 35

Fludrocortisone

Question 36

Indications for the use of glucocorticoids of the following classifications: Topical? Inhaled? Oral?

Answer 36

Topical steroid: Inflammatory skin conditions e.g. eczema , psoriasis Inhaled: Asthma Oral: IBD, asthma, acute transplant rejection, congenital adrenal hyperplasia, cerebral oedema/raised ICP

Question 37

Side effects of synthetic glucocorticoids?

Answer 37

* In topical treatment can thin the skin * Adrenal suppression/atrophy → withdrawal risk * Psychiatric effects * Diabetes * Osteoporosis * Cushing’s syndrome * Growth restriction (children) * Peptic ulceration * Increase susceptibility to infections Lead to suppressive action on hypothalamic-pituitary-adrenal axis

Question 38

What is the HPA axis?

Answer 38

Hypothalamus, ant Pituitary, Adrenal cortex Hypothalamus -- (CRH, corticotropin releasing hormone) --> ant Pituitary -- (ACTH, Asrenocorticotropic Hormone) --> Adrenal cortex -- ( CORT, cortisol) --> body Negative feedback along axis

Question 39

Side effects and indications of mineralocorticoids?

Answer 39

Indications for fludrocortisone: Mineralocorticoid replacement in adrenocortical insufficiency, Addison's Side effects: Hypertension, Na and H2O retention, K and Ca loss

Question 40

Which diuretic: An 80 year old female patient in hospital post total knee replacement develops shortness of breath, 4 pillow orthopnoea and paroxysmal nocturnal dyspnoea. Which medication would you prescribe?

Answer 40

Furosemide

Question 41

Which diuretic: A 79 year old male patient has marked peripheral oedema and a K+ of 2.5. He is requesting medication to treat his condition. Which agent would you choose?

Answer 41

Spironolactone

Question 42

Which diuretic: A 60 year old female caucasian patient presents to the practice nurse for a new patient check. Her blood pressure is 160/100. It is measured on 2 further actions and remains at a similar level. Which medication may you prescribe?

Answer 42

Bendroflumethiazide