Week 3 - J - Drugs Acting on the kidney 2 - K+Sparing, CAinhibtors, ADH, OSmotics

Question 1

Why can loop diuretics / thiazide diuretics be bad for increasing sodium loss? (both mechanisms)

Answer 1

Both cause increased sodium loss and therefore in an effort to increase sodium reabsorption via aldosterone, potassium is lost

Question 2

What class of diuretics can reduce the fluid load however maintain the potassium levels?

Answer 2

Potassium sparing diuretics

Question 3

name side effects that thiazides and loop diuretics share?

Answer 3

Hypokalaemia, hypomagnaesemia,

Question 4

Potassium sparing diuretics are weak diuretics on their own Compound preparations with Thiazide or loop diuretics (which activate the renin-angiotensin-aldosterone system in response to natriuresis and hypovolemia) What are the four types of potassium sparing diuretics?

Answer 4

Amiloride and triamterene Spironolactone and eplerenone

Question 5

Which two of the potassium sparing diuretics block the sodium channels (eg Na+/H+ exchanger and Na+/K+ exchanger) at the apical membrane?

Answer 5

Amiloride and triamterene

Question 6

Which two of the potassium antagonists compete with aldosterone for binding to intracellular receptors?

Answer 6

Spironolactone and epleronone

Question 7

What effect do the spironolactone have on the epleronone have on the the sodium channels at the apical and basolateral membrane?

Answer 7

Apical mebrane - decreases gene expression and reduced key protein synthesis for apical sodium channels Basolateral membrane - decreased numbers of Na+/K+/ATPase at the basolateral membrane

Question 8

Run through again How do amiloride and triamterene exert their effects? How do spironolactone and epleronone exert their effects?

Answer 8

Amiloride and traimterene - block sodium channels at the apical membrane of the distal tubule and collecting duct Spironolactone and epleronone - decrease expression and decreased synthesis of a protein that regulate the apical sodium channels Decreased number of Na+/K+/ATPase channels at the basolateral membrane

Question 9

Loop diuretics, thiazide diuretics, potassium sparing diuretics Which is the only to work on the basolateral membrane and name the drugs?

Answer 9

Only potassium sparing diuretics - drugs are spironolactone and epleronone

Question 10

Amiloride & Triamterene Block luminal sodium channels in late DT and collecting tubules. Thiazides and loops entered the tubular lumen via organic anion transporters as they are acidic How do amiloride and traimterene enter?

Answer 10

Enter via organic cation transporters in the proximal tubule

Question 11

Spironolactone and epleronone are steroid compounds and are competitive antagonists of the the cytoplasmic aldosterone receptors Do they gain access to the cytoplasm via apical or basolateral receptors?

Answer 11

They gain access via basolteral receptors

Question 12

Amiloride 10 times more potent than Triamterene Which is better reabsorbed in the GI tract and is therefore better for long term oral use?

Answer 12

Triamterene

Question 13

Spironolactone rapidly metabolised in the liver to active metabolite canrenone which accounts for ½ to 2/3 rd action of the drug What does spironolactone bind to outside the kidneys that can cause hormonal imbalances?

Answer 13

Binds to androgen receptors

Question 14

What are side effects of spironolactone? (if experiencing these side effects can change to triamterene)

Answer 14

Causes gynaecomastia, impotence and menstrual irregularities

Question 15

What are aldosterone antagnoists first line in the treatment of? What are the aldosterone antagnoists?

Answer 15

They are first line in the treatment of primary hyperaldosteronism - Conn’s syndrome (where the patinet has bilateral adrenal hyperplasia or unilateral but surgery is contraindicated) Aldosterone antagonists are spironolactone and epleronone

Question 16

What else apart from primary hyperaldosteronism can aldosterone antagonists be given in?

Answer 16

Can be given in ascites

Question 17

What other hypertensive medication are potassium sparing diuretics needed to be watched when given with and why?

Answer 17

Watch if giving it when the patinet has an ACEi Can cause hypotension as both have effects to decrease aldosterone effect

Question 18

Carbonic anhydrase inhibitors – have a diuretic action but not used as it What are they used in the treatment of?

Answer 18

Primary open angle glaucoma Acute angle closure glaucoma

Question 19

Carbonic anhydrase inhibtors inhibit the enzyme CAase, what does this cause the excretion of if used for the kidneys?

Answer 19

Bicarbonate, potassium, sodium and water (can lead to very low potassium levels)

Question 20

Name a topical carbonic anyhdrase inhibitor and a systemic one

Answer 20

Topical - dorzalamide Systemic - acetalozamide

Question 21

What class of diuretics have their major effect on the proximal convoluted tubule? Cannot be given orally, only IV

Answer 21

These are the osmotic diuretics

Question 22

How do osmotic diuretics affect the proximal convoluted tubule?

Answer 22

They increas esodium and water loss in the proximal convoluted tubule

Question 23

Osmotic diuretics are used mainly in raised intracranial pressure What is a side effect?

Answer 23

Hyponatraemic headaches

Question 24

ADH is secreted by posterior pituitary and produced in the hypothalamus What are the different receptors that ADH binds to?

Answer 24

Binds to vasopressin 1 receptors on smooth muscle causing vasoconstriction Binds to vasopressin 2 receptors on the basolateral membrane of the DCT and collecting duct

Question 25

Name 2 vasopressin analogues?

Answer 25

Desmorpressin and terlipressin (used in hepatorenal syndrome)

Question 26

What is hepatorenal syndrome where terlipressin is uded?

Answer 26

a life-threatening medical condition that consists of rapid deterioration in kidney function in individuals with cirrhosis or fulminant liver failure. (patient can be anuric)

Question 27

Cirrhosis of the liver causes portal hypertension which can lead to renal failure Variceal bleeding in portal hypertension can be controlled by ADH analogue terlipressin How does this work? Name a cutaenous sign of portal hypertension?

Answer 27

Works by binding to the vasopressin type 1 receptors causing smooth muscle constriction to stop bleeding Cutaneous sign is caput medusae

Question 28

What is the treatment of neurogenic (central) diabetes insipidus?

Answer 28

Desmopressin - ADH analogue causes ADH production for kidneys to act on

Question 29

Nephrogenic diabetes insipidus – inability of the nephron to respond to vasopressin. What drug is given for this and how does it work?

Answer 29

Managed by thiazide diuretics Causes the loss of sodium and water from the distal tubule leading to reabsorption in the proximal tubule

Question 30

What is a drug that can cause nephrogenic diabetes insipidus?

Answer 30

Lithium - ie patient for bipolar disorder

Question 31

62 year old man with alcohol related cirrhosis and alcoholic hepatitis who is anuric and his CVP is 12. what is suitable treatment

Answer 31

Terlipressin anuric means no urine production

Question 32

Competitive antagonists of vasopressin receptors (which occur as V1A, V1B & V2 subtypes) What are these drugs?

Answer 32

Aquaretics/Vaptans Competitive antagonists of the ADH stopping their effects by binding to the receptors at the basolateral membrane

Question 33

What is the treatment of SIADH?

Answer 33

SIADH treatment - fluid restriction and saline and can give a vaptan (vasopressin receptor antagonist) If this fails - may require demeclocycline

Question 34

What is demeclocycline?

Answer 34

It is a tetracycline antibiotic is an ADH antagonist as it causes nephrogenic diabetes insipidus - makes the kidneys non responsive to ADH

Question 35

What is an IV vaptan? (and is non slective)

Answer 35

Conivaptan -non selective

Question 36

Which is the only thiazide diretic you can add to loop in renal failure?

Answer 36

Metolazone

Question 37

If you had an acidic drug poisoning, which diuretic causes alkalosis? To give something for water loss without affecting sodium levels ie in a patient with hypernatraemia, which drug?

Answer 37

Diuretic causing alkalosis - carbponic annhydrase inhibitor ADH analogue does not affect sodium levels

Question 38

What side effects can a patient develop to spironolactone? What would they be switched to?

Answer 38

Side effects - gynaecomastia, impotence and menstrual irregularities cause it binds to androgen receptors outside the kidneys Patient would be switched to amiloride or triamterene (amiloride and triamterene are usually only used in late hypertensive treatment or congestive heart failure)